Abstract:Modern neuroscience tends to regard the brain as a predictor of the external environment, which can actively infer forthcoming sensory information based on both the prior knowledge and current sensory inputs, interacting with the external environment effectively. The predictive coding stands at the center of theories describing the mechanism of prediction. Reviewing the studies about the predictive coding, especially the ones in visual and auditory modality, can offer a new theoretical perspective for a more in-depth comprehension of the brain’s operational mode. This article first described the content of the predictive coding. And then it reviewed typical studies on the interactions between the predictions and sensory inputs, in terms of common paradigms, typical phenomena, and controversies. The third part introduced the endogenous neural representations of prediction, which are stimulus-independent, mainly from two aspects, i.e., the neural representations of prediction when the stimulus was omission, and prediction-related neural oscillation patterns. Furthermore, this review presented major neurophysiological evidence and neural structures that support the hierarchical structure. Finally, the development of the predictive coding related research is prospected from the aspects of deepening theoretical research, helping disease diagnosis and treatment, and inspiring the brain-computer interface technology. It is believed that a deeper comprehension of the computational model and neural representations of prediction coding in visual and auditory neural activity would offer up new perspectives on how perceptual neural activity in the brain functions.

Abstract:Research has shown that in addition to the classical visual cortical pathway, there is an “ancient”, rapid subcortical pathway responsible for the rapid processing of emotion-related information both consciously and unconsciously. This pathway consists of the superior colliculus, pulvinar, and amygdala and bypasses the primary visual cortex. Our study shows that this pathway is also responsible for processing visual topological information, and that the visual cortex is not related to topological information processing. Based on these findings, we believe that in early stage of vision, the brain detects signals involving life or safety, putting the brain into an alert state, which is essential for the survival of the species. Therefore, in the early stage of vision, the objects to be detected are only “appearing” and “disappearing”, not “texture”, “shape”, etc. Both “appearance” and “disappearance” are changes in topological features. The presence of topological perception and subcortical pathways may be the neural basis for early warning. In primates, the peripheral area of retina is distributed mainly with rod cells, the visual information processing in this area is mainly processed by subcortical visual pathway, this type of retinal structure appeared in more than one hundred million years ago. The area close to the center of the retina is the fovea, the visual information processing in this area is mainly processed by visual cortex, cone cell density increased greatly, the visual spatial resolution becomes very high. This structure emerged only 50 million years ago, so our eyes span at least 50 million years from the peripheral region to the central region. It is a Mosaic of an older structure and a younger one, and their coexistence gives us perfect vision. When we consider the significance of the existence of subcortical visual pathway, we should also consider the function of cortical pathways.

Abstract:Overweight and obesity are risks for many metabolic diseases, posing a serious threat to human health and life. It is now clear that obesity is the result of genome-environment interaction. Obesity is a highly heritable and genetically heterogeneous disorder in humans and rodents. The high-fat diet is an important contributor to weight gain and the development of obesity. Previous studies found that high-fat diet can induce two completely distinct phenotypes in rodents, named diet-induced obesity (DIO) and diet-induced resistance (DR), which has different characteristics in weight, body composition, energy metabolism, feeding preference, etc. However, its internal mechanism is not fully known. Several studies suggested that lipid metabolism in liver, adipose tissue, intestinal tract, and skeletal muscle may contribute to the difference between DIO and DR. Additionally, the changes of gastrointestinal hormone secretion and intestinal inflammation would cause these two phenotypes. Moreover, there was a significant reduction in gut microbiota richness and diversity in DIO mice but not in DR mice, which may play an important role in the development of the obese phenotype. The gut-brain axis made the contributions to the control of food intake and obesity. And the hypothalamic-pituitary-thyroid (HPT) axis function and deiodinases activity might be involved in different propensities to obesity. Difference of NPY/AGRP, POMC/CART and their receptor gene expressions in hypothalamic arcuate nucleus was also the basis of the difference between the two phenotypes. But all these changes of physiology are strongly related to genetic mutations and genotype.

Abstract:Heart failure is a complex cardiac disease without effect therapeutic methods, which causes a huge economic and social burden. It is urgent to identify new diagnostic biomarker and develop new therapeutic method. Mitochondria dysfunction is closely associated with the development of heart failure. About 95% ATP consumed by heart are derived from mitochondrial oxidative phosphorylation. The deficiency of myocardial energy supply caused by mitochondrial injury is the key factor linking the mitochondrial dysfunction to heart failure, which involves mitochondrial mediated metabolism disorder, calcium imbalance, oxidative stress, apoptosis and mitophagy. It has been demonstrated that non-coding RNA (ncRNA) playing a critical role in modulating epigenetic modification, post-transcription, translation modification and so on. Many researches showed that ncRNA express abnormally during the heart development and cardiac disease, and exhibit important regulating roles in the regulation of mitochondrial structure and function. Among them, miRNA has been demonstrated widely. Most miRNA, originated from either nuclear or mitochondrial genome, showed important roles in regulating heart pathophysiology change through mitochondrial dysfunction and structure disruption via targeting mRNA or protein. While lncRNA and circRNA play diverse roles in the regulation of mitochondrial structure and function by ncRNA-miRNA-mRNA triple networks, which provide us more perspective to understand the explicit role of ncRNA in mitochondria and heart pathophysiology. However, only a little ncRNA encoded by mitochondrial genome have been confirmed in the process of heart failure. Besides, it is still unclear that how does the ncRNA encoded by nuclear genome transport to mitochondria and vice versa. Moreover, recent studies discovered many other mitochondria encoded ncRNA, such as piRNA and small ncRNA shorter than 200 nucleotides derived from tRNA, rRNA or lncRNA, play important roles in many diseases. It has a broad prospect in investigating the various roles of mitochondria encoded ncRNA. Therefore, this work aims to provide some new ideas and targets for the clinical research and therapy for heart failure via reviewing the newly recent researches about the regulation mechanism of new ncRNAs on mitochondria function in the process of heart failure.

Abstract:Chimeric antigen receptor T cells (CAR-T) have achieved remarkable success in the treatment of hematological cancers, but little progress in solid tumors. Meanwhile, innate immune cells-based tumor immunotherapy has been scarcely developed. Macrophages detect and clear malignant cells through phagocytosis and innate immune sensing, thus being potential targets for cancer immunotherapy. Promising evidence from preclinical studies have shown chimeric antigen receptor macrophages (CAR-M) as an effective therapeutic strategy in solid tumors. This review sketches the prospect of CAR-immune cell therapeutics and emphasizes current status and perspective of CAR-M cell therapy trials and limitations associated with CAR-M. We also describe CAR-M can be manufactured from pre-existing cell lines or induced pluripotent stem cells, while transfection vectors for CAR-M show different characteristics, highlighting CAR-M as a next-generation therapeutic modality linking the closely intertwined innate and adaptive immunity to induce efficacious anti-tumor immune responses.

Abstract:Malignant tumors have become serious threatens to human health and life. Although radiation therapy and chemotherapy are commonly used to treat tumors in clinical practice, which could inhibit the growth and metastasis of tumors to a certain extent, but there are still some drawbacks to overcome. For example, the traditional chemotherapy drugs lack targeting and have serious side effects during the administration process. Moreover, most chemotherapy drugs are poorly water-soluble and thus have limited effects, and repeated administration of high doses lead to drug resistance. Importantly, the single-mode treatment strategy does not work well. Recently, the construction of targeted intelligent multi-functional nano-drug carrier system to achieve accurate diagnosis and treatment of tumors has become a research hotspot. Among various materials, porphyrin mental-organic frameworks (MOFs) materials have the characteristics of high porosity, large specific surface area, and surface modification, making it promising platforms for constructing targeted stimulus-responsive drug carrier. Moreover, porphyrin MOFs can avoid self-aggregation of porphyrin molecules and self-quenching in the excited state, and also have a wide spectral response range of porphyrin molecules, which is a class of solid photosensitizers with broad application prospects. Therefore, porphyrin MOFs have become an important platform for building targeted intelligent multifunctional nano-drug delivery systems in recent years. Herein, the recent research progress of porphyrin MOFs-based multifunctional nano-platforms triggered by stimulation of endogenous components (such as pH, enzymes, oxidation reduction species) and exogenous factors (such as sound, magnetism and light) for the precise diagnosis and treatment of tumors in recent years are summarized, and the challenges and opportunities faced by porphyrin MOFs in future tumor treatment are also discussed. Compared to traditional drug delivery systems, endogenous and exogenous stimuli-responsive systems can significantly improve the biosafety and the efficiency of tumor treatment. Typically, multimodal synergistic therapies using porphyrin MOFs as platform, such as combining photodynamic therapy (PDT) with chemotherapy, photothermal therapy (PTT), immunotherapy or sonodynamic therapy could achieve synergistic effects and maximize the therapeutic effect and safety.

Abstract:Knee osteoarthritis (KOA) is a degenerative disease characterized by degeneration of articular cartilage. So far, there is no effective drug to treat KOA. Extracellular vesicles (EVs) are spherical membranous vesicles formed by the envelopment of lipid bilayers released from cells, which can deliver bioactive molecules such as nucleic acids and proteins between cells. Mesenchymal stem cell derived EVs can be used as an effective way in KOA treatment by reducing inflammation and promoting cartilage repair. Compared with mammalian-derived EVs, plant-derived EVs have attracted much attention in the field of drug carrier delivery research because of their wide and economical sources. It is worth noting that vesicles derived from Chinese herbal medicine have great prospects in disease treatment. Modification of EVs for drug delivery by genetic engineering and other methods can greatly improve drug delivery efficiency and its efficacy. In addition, the hybrid vesicles prepared by membrane fusion can efficiently deliver CRISPR/Cas9 plasmids for KOA treatment. Because of its diversified functions and modifiability, EVs have great prospects in disease treatment and drug delivery. This paper reviews the progress of EVs from animals and plants in the treatment of KOA, focusing on the research and development of engineered EVs as drug delivery carriers in KOA treatment, in order to provide a reference for the use of EVs in the treatment of KOA.

Abstract:Tetrodotoxin (TTX) is a highly toxic alkaloid natural neurotoxin that selectively blocks sodium ion channels. As a poison, TTX has lethal effects when ingested in humans, with lethal doses ranging from 1.5 mg to 2.0 mg (9 μg/L in plasma). However, when TTX is administered to patients at levels well below its median lethal dose (LD₅₀), it can treat a variety of medical diseases, including heroin and cocaine withdrawal symptoms, spinal cord injury, traumatic brain injury, tumor, neuropathic pain, and visceral pain. Cancer pain is generally treated with opioids, but it has certain dependence and addiction. After decades of unremitting exploration, researchers have made gratifying progress in the application of TTX in the field of biomedicine, especially in the treatment of cancer-related pain. Here we first review voltage-gated sodium channels (VGSCs), which are transmembrane proteins composed of a large α subunit and one or more β subunits. VGSCs play an important role in pain and are typically classified as TTX-sensitive or TTX-resistant channels. Furthermore, we focus on roles of three VGSC subtypes Nav1.7, Nav1.8 and Nav1.9, and present the current status of research progress in the field of cancer-related pain. We also discuss the binding sites, tolerability, delivery and supply of TTX. Finally, we summarize the most relevant recent advances in the clinical development, efficacy and safety of TTX as a drug for relieving cancer pain, showing the promise of TTX in cancer pain relief. On this basis, the limitations of existing research are pointed out, and the research directions of TTX in relieving cancer pain and the development of targeted analgesic drugs in the future are prospected.

Abstract:High-intensity interval training (HIIT) is a type of exercise characterized by short periods of time, high intensity, and short intervals of rest or recovery. Compared with aerobic exercise and resistance exercise, HIIT is more convenient and time-saving to regulate skeletal muscle mass and function, so it has attracted people’s attention. Current studies have shown that long-term HIIT can up-regulate or delay the reduction of skeletal muscle mass in different age groups. However, to obtain accurate results, future detection needs to pay attention to whether it is the site of exercise, the level of subjects’ training and the combined use of detection instruments. It is worth noting that it is difficult to simulate the movement mode of HIIT on cells, and the gene knockout mice have not been reported in the field of HIIT. Therefore, if we want to further study the specific mechanism of HIIT, the gene knockout mice may be the breakthrough point. Studies have shown that HIIT may activate satellite cell proliferation independent of muscle fiber hypertrophy and subsequently mediate remodeling of cell repair, whereas the effect on myocyte nuclei may depend on the state of the subject. In addition, HIIT can up-regulate PGC-1α, and our group has previously demonstrated that PGC-1α can up-regulate the expression of MOTS-C, which has recently been reported to be closely related to the transformation of fast to slow muscles. This may be a new mechanism for the transformation of HIIT fibers. HIIT can promote skeletal muscle angiogenesis and blood perfusion, but its regulation effect on oxygenation index is still contradictory. The effect of HIIT on mitochondrial morphology and function is mediated by multiple pathways. It is still questionable to evaluate the effectiveness of training based on the change of single marker. Different intensity and duration of HIIT have different order of influence on mitochondrial function and function in skeletal muscle. HIIT may be an effective way to improve the strength of exercise-sensitive people, and its mechanism may be around muscle growth, anti-atrophy, increasing sensitivity to calcium ions, and upregulation of the tensile strength of extracellular matrix. But its strength gain is limited by where it is exercised. HIIT supplementation with protein effectively promoted muscle synthesis independent of upregulated mitochondrial function, although this conclusion remains to be confirmed since only sprint interval training (SIT) has been reported. This article reviews the relationship between HIIT and skeletal muscle mass and function, in order to provide theoretical basis and application strategies for HIIT to prevent and improve muscle loss and function decline.

Abstract:Due to the remarkable properties of fluorine atoms, the physicochemical properties of many molecules can be significantly improved after introducing the fluorine atoms. Therefore, fluorine atom is more and more widely used in pharmaceutical field. In addition, 80% of pharmaceutical compounds are chiral molecules. It should be mentioned that chiral fluorinated alcohols are commonly uslized to bulid chiral pharmacecutical ingredients. Hence, the research exploring the synthesis methods of such structures is of great importance. Asymmetric reduction of fluorinated ketones is a common method for obtaining this structure. Compared with chemical reduction, biocatalytic reduction shows many advantages, such as high enantioselectivity and yield, easy separation and purification. Biocatalysis, especially enzyme-catalyzed reduction of fluorinated ketones, has grown a research hotspot in the field of preparing chiral compounds. At present, biocatalysis methods have some disadvantages. The reaction time is relatively long and the price of biological enzymes and coenzymes is expensive. Accordingly, the scientists should work on shortening the reaction time, recycling biological enzymes and developing more efficient and economical coenzyme regeneration systems. In this paper, the recent development of biocatalytic reduction of fluorine-substituted ketones to fluorinated chiral alcohols is reviewed from the aspects of purified enzyme catalysis and whole-cell catalysis. Moreover, the effect of fluorination on the biocatalytic reduction of ketones is highlighted and the prospect of catalytic reduction method is also put forward in this review.

Abstract:As a new interdisciplinary subject, microbial synthetic biology aims to transform existing microbial cells or create new microbial cells to provide them with specific physiological functions or the ability to produce target products. To achieve this process, efficient, rapid and accurate gene manipulation tools are important. Since its creation, CRISPR/Cas9 system has been widely used in synthetic biology in recent years due to its ability to accurately identify and cut specific DNA sequences, as well as its characteristics of simple operation, low cost, high efficiency and diverse functions. In this paper, various gene editing techniques derived from CRISPR/Cas9 and their specific applications in microbial synthetic biology are reviewed. At the same time, the commonly used industrial model microorganisms and the corresponding transformation methods of chassis cells are introduced. A variety of industrial microbial chassis cells exist in nature and have their own metabolic characteristics to produce suitable products. However, natural chassis cells also have problems such as intermediate metabolite toxicity, end-product feedback inhibition, and branch pathway, which lead to low target yield, or the host itself does not have the ability to produce the product. Therefore, it is necessary to modify chassis cells by gene editing method, so as to obtain more excellent strains. The advantages of the edited cells compared to the control in the synthesis of target products were listed, and the characteristics of each gene editing technology were summarized in order to select the appropriate gene editing methods for the researchers in the transformation of microbial chassis cells. Finally, the existing problems of CRISPR gene editing technology, such as PAM dependence, off-target effect and universality of application, are put forward.

Abstract:Because of its advantages of high sensitivity, simple method and easy operation, colorimetric biosensing technology has been widely used in many fields such as the detection of pollutants in the biological environment, the detection of important markers in the organism and cancer screening. The colorimetric biosensor based on nanozymes mainly uses the catalytic ability of nanozymes to simulate peroxidase-like activities, oxidize the chromogenic agent to form a colored solution, so as to realize visual detection, and obtain the content of related substances through the detection of its absorbance. Compared with colorimetric biosensors without nanozymes, colorimetric biosensors based on nanozymes have the advantages of higher selectivity, faster detection and higher sensitivity. Nanozymes, on the other hand, are more and more widely studied for their natural enzyme activity while also having the advantages of low cost, good stability, and easy synthesis. At present, colorimetric biosensors based on nanozymes have become an important method to assist related medical detection, and are also widely used in portable and real-time related detection, providing important support and guarantee for medical detection. In order to improve the sensitivity and application range of colorimetric biosensors, researchers are also working on increasing the variety of substances to be detected and diversifying the types of nanozymes. This paper mainly introduces the detection principle of nanozyme-based colorimetric biosensors, several typical used nanozymes, and the application and research progress of nanozyme-based colorimetric biosensors in the field of biomedical detection.

Abstract:Hepatocellular carcinoma (HCC) is the most common and lethal liver malignancy. The treatment of this disease has been hampered by its heterogeneity, which severely limits progress in its personalized therapy. Therefore, it is necessary to divide highly heterogeneous HCC into molecular subtypes with similar characteristics for its clinical treatment. With the development of high-throughput technologies, integrative multi-omics data can deepen our comprehension of the biological mechanisms behind HCC pathogenesis. And it can also open new ideas for HCC stratification studies. Cluster analysis has been the main algorithm of cancer subtypes research for many years. Based on the number of input clustering algorithm omics, we summarize the current multi-omics HCC stratification methods into two major strategies: “from single-to-multi (S To M)” and “from multi-to-multi (M To M)”. Among them, the S To M strategy is to stratify HCC using different features of single omics and then combine multi-omics data to find the differential molecules among different HCC subtypes and verify the authenticity of their differences and the association with tumor biological phenomena. Feature selection is the core of the S To M strategy. Over the years, there are 3 approaches to the selection of stratified features in the S To M strategy: data distribution-based, biological features, and multi-omics approaches. Unlike S To M strategy, M To M strategy is based on the concept of systems biology and presents a landscape of the differences and associations between different omics within different subtypes. The core step of the M To M strategy is data dimensionality reduction, which puts multi-omics data into a low-dimensional stacked matrix, providing input for the subsequent cluster analysis. Generally, M To M strategy stratification algorithms can be classified into three categories: similarity-based, integration-based, and deep learning. We believe that both S To M and M To M need to pay attention to the combination of data and the applicability and practicality of related software when using it for cancer subtype analysis. In the end, we summarized the current multi-omics characteristics of HCC subtypes. We found that HCC subtypes obtained by different methods may have a common feature, which suggests that more studies are needed in the future to summarize the more representative subclasses among them.

Abstract:Objective The unclear mechanism of depression occurrence and the undesired clinical efficacy of drugs are the difficult problems all over the world. Previous studies have found that gaseous formaldehyde (FA) exposure or intraperitoneal injection of FA can directly induce depression-like behaviors in mice. Whether endogenous FA leads to depression is unclear. This study was to explore whether lipopolysaccharide (LPS) induces depression-like behaviors in mice by stimulating endogenous FA generation, and to observe whether non-invasive physical therapy——630 nm red light irradiation can activate FA dehydrogenase and degrade FA, thereby attenuate depression-like behaviors in mice.Methods Male adult C57BL/6J mice were randomly divided into: (1) control group, intraperitoneal injection of phosphate buffered saline (PBS); (2) depression model group, intraperitoneal injection of LPS at a concentration gradient; (3) red light intervention group, these mice were intraperitoneally injected with LPS and treated with 630 nm red light irradiation. The depression-like behaviors of mice were evaluated by open field test, sucrose preference test, tail suspension test and forced swimming test. The concentration and distribution of FA in brain tissue of mice were detected by FA fluorescence (Na-FA, specific FA fluorescent probe) quantitative method and whole brain FA fluorescence imaging. The concentrations of IL-1β, TNF-α, IL-6 and semicarbazide-sensitive amine oxidase (SSAO) were detected by ELISA.Results One hour after acute injection of LPS, FA accumulated rapidly in the whole brain, especially in the midbrain. With the increase of IL-1β and TNF-α content; 24-hour depression-like behaviors, for example, open field total movement distance, central area movement time (distance) decreased significantly; the total immobility time of tail suspension test and forced swimming test were increased. However, 630 nm red light treatment significantly attenuated LPS-induced depression-like behavior in mice accompanied by a decrease in midbrain inflammatory factors IL-1β and TNF-α.Conclusion The accumulation of FA in the midbrain is an initiating factor for depression, stimulating a large release of inflammatory factors and leading to depression-like behaviors. However, red light irradiation can scavenge FA and reduce neuroinflammation. It is a promising new strategy for non-invasive treatment of depression.

Abstract:Objective To investigated the effects of obesity on the structure of seminiferous tubules, autophagy and apoptosis-related proteins in testes tissue, and the effect of exercise on autophagy and apoptosis in testis and regulatory mechanism.Methods Fifty 6-week-old SD male rats were randomly divided into the standard diet group (SD, n=20) and the high-fat diet group (HFD, n=30). HFD group was fed 8 weeks to establish an obesity model of rats, and 20 rats were randomly selected to exercise intervention. Rats in SD and HFD groups were randomly divided into normal diet control group (CC), normal diet+exercise group (CE), high-fat diet control group (OC), and high-fat diet+exercise group (OE), 10 rats in each group. The rats in the CE and OE groups underwent moderate intensity treadmill training for 60 min/d, 5 d/week. CC and OC groups maintained the same feeding conditions. After 48 h of the last exercise, the rats were anesthetized intraperitoneally and weighed, the testes were taken from both sides of the rats, weighed and the testicular index was calculated. Paraffin sections of the testes were prepared to discover the testicular tissue structure by HE staining. Western blot was used to detect the protein expression of p62, LC3II, LC3I, BCL-2, Bax, and AMPK in testicular tissue, and the ratio of LC3II/LC3I was calculated. Immunofluorescence was used to detect LC3 and BCL-2 protein expression positions in the testis.Results The testicular index was reduced; HE staining revealed a significant decrease in the diameter of the seminiferous tubules (P<0.01), spermatocytes, and lipid droplet deposition in the testicular tissue; the protein expression of p62 and Bax were significantly increased (P<0.01), AMPK, LC3II/LC3I ratio, and BCL-2 were significantly decreased (P<0.01), and the number of LC3 proteins on sperm cells were significantly reduced in the testis tissue of rats in the OC group compared with the CC group. After exercise intervention, the testicular index was increased in the OE group; HE staining showed that the diameter of seminiferous tubules (P<0.01) and the number of spermatogonia (P<0.05) were significantly increased, and the structure of seminiferous tubules was improved; the protein expression of p62 and Bax were significantly decreased (P<0.01), AMPK, LC3II/LC3I ratio, and BCL-2 were significantly increased (P<0.01); the level of BCL-2 proteins on spermatocytes and sperm cells increased significantly in the OE group compared with OC group. AMPK was strongly correlated with p62, LC3II/LC3I, and Bax in all rat testicular tissue.Conclusion High-fat diet-induced obesity inhibits autophagy and promotes apoptosis in rat testes; 8 weeks of moderate-intensity exercise may activate autophagy and inhibit apoptosis in testis tissue via AMPK, correcting the adverse changes in spermatogenesis caused by obesity.

Abstract:Objective To investigate the effects of Polygonatum odoratum (Mill.) Druce extract (POD) on ovarian function and inflammation of rats with polycystic ovary syndrome (PCOS).Methods Three-week-old female SD rats were used in this study. PCOS model was established by gavage of letrozole for 21 d. Then PCOS model rats were treated with different concentrations of POD by gavage. The changes of water and food intake, body mass and estrous cycle were recorded, blood related indicators were detected, serum testosterone level was measured, glucose tolerance was detected, and the morphological changes of ovarian tissue were observed by HE staining. Western blot (WB), fluorescent quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to detect the expression of anti-Mullerian hormone (AMH), inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in ovarian tissues.Results Compared with the control group, the PCOS model rats had disordered estrous cycle, polycystic ovarian changes, significantly increased serum testosterone level, up-regulated ovarian AMH expression, and impaired glucose tolerance (P<0.01). The expression of IL-1β and TNF-α was increased (P<0.01). After the PCOS model rats were treated with different concentrations of POD, the estrous cycle gradually returned to normal, the number of corpus luteum in the ovary increased, the number of cystic follicles decreased, the serum testosterone level decreased, and the impaired glucose tolerance was alleviated (P<0.01). The expression of inflammatory cytokines IL-1β and TNF-α in ovarian tissue was down-regulated.Conclusion POD can improve the ovarian function of PCOS model rats and inhibit inflammatory response, and has a certain therapeutic effect on PCOS model rats.

Abstract:Objective Deinococcus radiodurans (D. radiodurans) is an extremophile with strong resistance to ultraviolet (UV), ionization, desiccation and chemical reagents. However, the molecular responses of this bacterium in the early recovery stage after UV irradiation are not fully understood. The aim of this work is to reveal the transcriptomic responses of D. radiodurans at this stage.Methods In this study, the transcriptomes of D. radiodurans under normal and UV irradiation culture conditions were determined by using RNA-seq technique. To identify the key genes and their regulatory relationships among the differentially expressed genes (DEGs), functional enrichment analysis was performed. Some key DEGs were selected and validated by real-time quantitative PCR. The transcriptome data from previous studies were adopted to find DEGs common to UV irradiation, ionizing radiation and desiccation stresses. The protein-protein interaction (PPI) network of DEGs was constructed; the hub genes and major modules in the PPI network were identified; functional enrichment analysis was performed for these hubs and modules.Results The results showed that the number of up-regulated genes was more than twice that of down-regulated genes in the early recovery stage after UV irradiation, and most of them were related to stress response and DNA repair. The main repair pathways in the early stage of recovery include single-strand annealing (SSA) pathway (involving genes ddrA-D), nonhomologous end joining (NHEJ) pathway (involving genes ligB and pprA) and nucleotide excision repair (NER) pathway (involving genes uvrA-C), the first two of which are for homologous recombination (HR), while the NER pathway removes pyrimidine dimers caused by UV irradiation. By comparing the transcriptome data under UV irradiation, ionizing radiation and desiccation stresses, it was found that the common responsive DEGs mainly involve Deinococcus-specific genes and the genes related to DNA/RNA metabolism. Several important hub genes and interaction modules were identified from the PPI network of DEGs, whose functions are concentrated in double-strand break repair, DNA topological change and replication.Conclusion These results indicate that in the early recovery stage after UV irradiation, a variety of genes in D. radiodurans undergo responses at transcriptome level, several repair pathways are initiated to cope with this stress, and some repair pathways are common to other stress conditions.

Abstract:Objective In this study, we propose three-dimensional electrical impedance tomography (3D-EIT) combined with two-dimensional electrical impedance tomography (2D-EIT) to study the electrical characteristics of gastric volume changes and the response to changes in the gastroesophageal liquid condition with the objective of investigating the possibility of applying EIT technique to monitor gastroesophageal reflux disease (GERD).Methods Eight subjects were asked to fast 4 h before the experiment to ensure that the gastric was in an emptying condition at the start of the experiment. The subject was asked to drink 400 ml of rehydration water in two parts, 3D-EIT was applied to detect the conductivity distribution in the 3D space of the abdominal cavity at the condition of 200 ml intake and at the condition of 400 ml intake, respectively. In order to quantify the variation of electrical characteristics in different conditions, the spatial-mean conductivity () of 3D-EIT was analysed by using a paired-samples t-test. In addition, numerical simulation tools were used to establish two sizes of gastric volume models to verify that the cause of conductivity changes in the 3D space of the subject’s abdominal cavity in the experimental results is due to the changes in gastric volume. The trends of electrical characteristics when gastric cavity was filled with different ratios of rehydration water were investigated, and 2D-EIT numerical simulation was applied to reconstruct the conductivity distribution image σ.Results The results of the paired-sample t-test for spatial-mean conductivity ) in the abdominal 3D-EIT experiment in eight subjects show that the spatial-mean conductivity increased from ^{200 ml}=0.226 in the C^{200 ml} case to ^{400 ml}=0.387 in the C^{400 ml} case (n=8, P<0.05). Thus, the of subject’s abdominal gastric region increased significantly with increasing gastric volume. The 2D-EIT numerical simulation results show that the measured voltage difference (ΔV) is decreased gradually with increasing the rehydration water ratio of the gastric lumen filling. ΔV is sensitive to the ratio of gastric lumen filling rehydration water. The average voltage difference is smaller in the big gastric lumen model with the same ratio of gastric lumen filling rehydration water compared to the small gastric lumen model. is sensitive to the size of gastric lumen model. In the small gastric lumen model, the spatial-mean conductivity is increased with the ratio of gastric lumen filled with rehydration water, from _A=-0.29 for 25% filling to _D=-0.41 for filling 100%; in the big gastric lumen model, the is also increased with the ratio of gastric lumen filled with rehydration water, from _E=-1.85 for 25% filling to _H=-2.12 for filling 100%.Conclusion The 3D-EIT satisfactorily monitors the differences in electrical characteristics of different gastric volumes by 3D-EIT images. 2D-EIT shows the same trend according to ΔV, , and in different gastric volume models. Therefore, we conclude that 3D-EIT combined with 2D-EIT technique satisfactorily monitors liquid condition changes in the different gastric volumes.

Abstract:Objective Detecting the detailed behaviors of single viruses is essential for uncovering the underlying mechanisms guiding virus life cycle, which significantly benefits developing therapeutic methods against viral infection. The advent of atomic force microscopy (AFM) provides a novel powerful tool to characterize the structures and mechanical properties of single viruses with unprecedented spatial resolution, and applications of AFM in single-virus assay have contributed much to the field of physical virology. Nevertheless, the mechanical cues of single native viruses during viral activities are still not fully understood, and particularly studies of utilizing multiparametric AFM imaging to investigate the behaviors of single viruses are still scarce. Here, multiparametric AFM imaging was combined with AFM indentation assay to investigate the structural and mechanical dynamics of single native virus particles in response to chemical stimuli under aqueous conditions.Methods The poly-L-lysine was used to coat the coverslips to attach lentivirus particles onto the coverslips, and then the virus particles were probed by AFM in pure water. Single virus particles were imaged at the peak force tapping (PFT)-based multiparametric AFM imaging mode, in which the topographical images and mechanical maps of the virus particles were obtained simultaneously. Under the guidance of AFM’s topographical imaging, the AFM probe was moved to the central area of the virus particle to perform indentation assay for measuring the mechanical properties of the virus. The alcohol solution (75%) was used as an example of chemical stimulus to treat virus particles, after which the structural and mechanical changes of individual virus particles were revealed by AFM.Results The structures and mechanical properties of single virus particles could be well characterized by AFM under aqueous conditions, and the virus particles exhibited different elastic and adhesive properties in air and in liquid. After the treatment of alcohol, the shape of virus particles became irregular, and the virus particles became stiffer as well as less deformable.Conclusion The research provides a novel way to investigate the structures and nanomechanical properties of single native viruses in liquids based on AFM, which will have general implications for the field of virology.

Abstract:Objective Tunneling nanotubes are membrane-tubule-like structures that exist between cells and have a direct long-distance biological information exchange function. Because the structure of TNTs is easily destroyed, exists for a short period of time and is unstable after formation, it is difficult to observe its dynamic formation and function. This study used the high content analysis system (HCA) combined with laser scanning confocal microscopy (LSCM) to try to observe the dynamic process of TNTs formation and its function of vesicular material transport.Methods Human lung adenocarcinoma A549 and cisplatin-resistant A549/DDP cells were labeled using fluorescent probes. Subsequently, HCA was used to observe the formation process of TNTs, LSCM to observe the three-dimensional structure of TNTs, and HCA combined with LSCM to analyze the vesicular material transport function of TNTs, respectively.Results TNTs structures can be formed between tumor cells of the same types (A549 or A549/DDP) or between different subtypes of tumor cells (A549 and A549/DDP). TNTs formed between A549/DDP cells were longer, thicker and had a higher formation index compared to A549 cells ( the length, diameter and formation index of TNTs for A549 and A549/DDP were 14.71 μm, 2.27 μm, 4 and 25.44 μm, 2.59 μm, 11, respectively). TNTs are formed in two steps: first, two cell cytoplasmic membranes first come into contact with each other and then fuse, and as the two cells translocate in opposite directions, the fused regions of the membranes are continuously elongated and narrowed, resulting in the formation of TNTs; second, two cells extend filopodia-like membrane projections and fuse when they come into contact with each other’s membrane projections, resulting in the formation of TNTs or one cell extends filopodia-like membrane projections and fuses after contacting the other cell membrane, thus forming TNTs. The transport of vesicles by TNTs is bidirectional. During transport, the rate and amounts of vesicles being transported vary depending on the stage of transport and the donor cell. The vesicular translocation from A549/DDP cells to A549 cells showed a fast initial rate and a slow terminal rate. A549 cells, as donor cells, transit vesicles to recipient A549/DDP cells in a higher number and proportion than A549/DDP as donor cells in the opposite direction.Conclusion The dynamic formation process and vesicular substance transport function of TNTs could be observed and analyzed by HCA combined with LSCM effectively.

Abstract:Objective It is an urgent need for patients with mechanical ventilation and clinicians to monitor the process of pulmonary ventilation with real-time continuous images at the bedside. Electrical impedance imaging (EIT) of the lung can reflect the distribution of changes in the electrical characteristics of the chest caused by breathing, which has a natural advantage in the monitoring of pulmonary ventilation. The purpose of this paper is to establish a radial basis function neural network (RBFNN) based weighted frequency-difference EIT (wfd-EIT) method to achieve high spatial resolution imaging of pulmonary ventilation.Methods The wfd-EIT method was used to describe the conductivity distribution of the thoracic cavity in real time, and then the target region was visualized and its boundary information was accurately identified by the RBFNN. Firstly, through numerical analysis and simulation, 2 028 simulation samples were established by COMSOL and MATLAB software at each excitation frequency, which were divided into training set and test set to verify the feasibility and effectiveness of the proposed imaging method. Secondly, in order to verify the simulation results, a lung physical model was established. Biological tissues with low conductance characteristics were selected to simulate the ventilation area of the lung, and the imaging experiment was conducted on it. The quantitative data of image correlation coefficient (ICC) and lung region ratio (LRR) were used to measure the accuracy of the imaging method.Results The wfd-EIT method can reconstruct the image at any time and accurately reflect the electrical characteristics distribution of the target region. The algorithm based on RBFNN can enhance the imaging accuracy of the target region with ICC reaching over 0.94, which can better highlight the boundary contour information.Conclusion The wfd-EIT imaging method utilizes the simultaneous measurement of multi-frequency impedance spectra to realize rapid visualization of the target area, and combines the advantages of the RBFNN in approximating arbitrary non-linear functions to achieve accurate identification of the electrical characteristics changes in the target area, which lays theoretical and technical foundations for EIT image monitoring of clinical pulmonary ventilation in the next step.

Abstract:Ability of clinical decision-making is one of the essential capacities of doctors, as well as one of the necessary and important training objectives in medical education. At present, there is no complete system for training this ability of medical students. Usually, it is too late to arrange the training program in the senior stage. It is worth exploring and researching how to integrate the cultivation of clinical decision-making ability into the basic courses in lower grades, in order to training as soon as possible. This study took the course of medical genetics as an example, combined the characteristics of inquiry teaching method, simulated various sub-modules of clinical decision-making thinking process, optimized course design, and explored the integration of clinical decision-making ability cultivation in lower grade courses. The results suggest that inquiry teaching design can fully mobilize students’ initiative and increase their investment diving in analysis and thinking. Under the guidance of teachers, it can effectively promote students’ training in the process of clinical decision-making thinking process. Finally, the ideas for thinking strand design and practice were analyzed, the design principles and key points were summarized, and the gains and losses in teaching were reflected as well.