Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination.

Nonalcoholic fatty liver disease (NAFLD) is a global health concern with no approved drugs. High-protein dietary intervention is currently the most effective treatment. However, its underlying mechanism is unknown. Here, using Drosophila oenocytes, the specialized hepatocyte-like cells, we find that dietary essential amino acids ameliorate hepatic steatosis by inducing polyubiquitination of Plin2, a lipid droplet-stabilizing protein. Leucine and isoleucine, two branched-chain essential amino acids, strongly bind to and activate the E3 ubiquitin ligase Ubr1, targeting Plin2 for degradation. We further show that the amino acid-induced Ubr1 activity is necessary to prevent steatosis in mouse livers and cultured human hepatocytes, providing molecular insight into the anti-NAFLD effects of dietary protein/amino acids. Importantly, split-intein-mediated trans-splicing expression of constitutively active UBR2, an Ubr1 family member, significantly ameliorates obesity-induced and high fat diet-induced hepatic steatosis in mice. Together, our results highlight activation of Ubr1 family proteins as a promising strategy in NAFLD treatment.

Genome-wide investigation of the TGF-ß superfamily in scallops.

BACKGROUND: Transforming growth factor ß (TGF-ß) superfamily genes can regulate various processes, especially in embryogenesis, adult development, and homeostasis. To understand the evolution and divergence patterns of the TGF-ß superfamily in scallops, genome-wide data from the Bay scallop (Argopecten irradians), the Zhikong scallop (Chlamys farreri) and the Yesso scallop (Mizuhopecten yessoensis) were systematically analysed using bioinformatics methods. RESULTS: Twelve members of the TGF-ß superfamily were identified for each scallop. The phylogenetic tree showed that these genes were grouped into 11 clusters, including BMPs, ADMP, NODAL, GDF, activin/inhibin and AMH. The number of exons and the conserved motif showed some differences between different clusters, while genes in the same cluster exhibited high similarity. Selective pressure analysis revealed that the TGF-ß superfamily in scallops was evolutionarily conserved. The spatiotemporal expression profiles suggested that different TGF-ß members have distinct functions. Several BMP-like and NODAL-like genes were highly expressed in early developmental stages, patterning the embryonic body plan. GDF8/11-like genes showed high expression in striated muscle and smooth muscle, suggesting that these genes may play a critical role in regulating muscle growth. Further analysis revealed a possible duplication of AMH, which played a key role in gonadal growth/maturation in scallops. In addition, this study found that several genes were involved in heat and hypoxia stress in scallops, providing new insights into the function of the TGF-ß superfamily. CONCLUSION: Characteristics of the TGF-ß superfamily in scallops were identified, including sequence structure, phylogenetic relationships, and selection pressure. The expression profiles of these genes in different tissues, at different developmental stages and under different stresses were investigated. Generally, the current study lays a foundation for further study of their pleiotropic biological functions in scallops.

Plastic substrate and residual time of microplastics in the urban river shape the composition and structure of bacterial communities in plastisphere.

The widespread secondary microplastics (MPs) in urban freshwater, originating from plastic wastes, have created a new habitat called plastisphere for microorganisms. The factors influencing the structure and ecological risks of the microbial community within the plastisphere are not yet fully understood. We conducted an in-site incubation experiment in an urban river, using MPs from garbage bags (GB), shopping bags (SB), and plastic bottles (PB). Bacterial communities in water and plastisphere incubated for 2 and 4 weeks were analyzed by 16S high-throughput sequencing. The results showed the bacterial composition of the plastisphere, especially the PB, exhibited enrichment of plastic-degrading and photoautotrophic taxa. Diversity declined in GB and PB but increased in SB plastisphere. Abundance analysis revealed distinct bacterial species that were enriched or depleted in each type of plastisphere. As the succession progressed, the differences in community structure was more pronounced, and the decline in the complexity of bacterial community within each plastisphere suggested increasing specialization. All the plastisphere exhibited elevated pathogenicity at the second or forth week, compared to bacterial communities related to natural particles. These findings highlighted the continually evolving plastisphere in urban rivers was influenced by the plastic substrates, and attention should be paid to fragile plastic wastes due to the rapidly increasing pathogenicity of the bacterial community attached to them.

TLR2 Stimulation Increases Cellular Metabolism in CD8+ T Cells and Thereby Enhances CD8+ T Cell Activation, Function, and Antiviral Activity.

TLR2 serves as a costimulatory molecule on activated T cells. However, it is unknown how the functionality and antiviral activity of CD8+ T cells are modulated by direct TLR2 signaling. In this study, we looked at the TLR2-mediated enhancement of TCR-driven CD8+ T cell activation in vitro and in woodchuck hepatitis virus transgenic mice. In vitro stimulation of CD8+ T cells purified from C57BL/6 mice showed that TLR2 agonist Pam3CSK4 directly enhanced the TCR-dependent CD8+ T cell activation. Transcriptome analysis revealed that TLR2 signaling increased expression of bioenergy metabolism-related genes in CD8+ T cells, such as IRF4, leading to improved glycolysis and glutaminolysis. This was associated with the upregulation of genes related to immune regulation and functions such as T-bet and IFN-γ. Glycolysis and glutaminolysis were in turn essential for the TLR2-mediated enhancement of T cell activation. Administration of TLR2 agonist Pam3CSK4 promoted the expansion and functionality of vaccine-primed, Ag-specific CD8+ T cells in both wild type and transgenic mice and improved viral suppression. Thus, TLR2 could promote CD8+ T cell immunity through regulating the energy metabolism.

Comparative Transcriptome Profiling Reveals Changes of microRNAs Response to Exercise in Rats with Neuropathic Pain.

There is accumulating evidence showing that exercise therapy may play an active role in peripheral neuropathic pain (NP), but its mechanism is still unclear. Studies have found that microRNAs (miRNAs) may play a role in NP by regulating pain-related target genes. Therefore, we aimed to explore the changes of miRNA and mRNA of dorsal root ganglion (DRG) after NP in response to exercise with transcriptome technology. The chronic constriction injury (CCI) model was established, and rats were randomly allocated into three groups, namely, the sham-operated, CCI, and CCI-exercised groups. L4-L6 DRG tissue was taken for RNA-sequencing, and the differentially expressed genes (DEGs) were determined through bioinformatics analysis. Real-time PCR was used to confirm the accuracy. A total of 4 overlapping differentially expressed miRNAs and 186 overlapping differentially expressed mRNAs were identified in the two comparisons of the sham-operated group versus the CCI group and the CCI group versus the CCI-exercised group. Among these DEGs, miR-145-5p, miR-341, miR-300-5p, miR-653-5p, Atf3, Cacna2d1, Gal, and Ctss related to NP were validated by real-time PCR. DEGs between the CCI and CCI-exercised groups were enriched in HIF-1 signaling pathway, Rap1 signaling pathway, and neurotrophin signaling pathway. This study provides an understanding of the adaptive mechanisms after exercise of NP, and these DEGs in DRG might play a role in NP by stimulating the enriched pathways.

The hotspots and trends of coronavirus disease 2019 (COVID-19) and physical therapy: a bibliometric and visual analysis.

[Purpose] With the COVID-19 pandemic, more and more articles have been published to explore the role of physical therapy on COVID-19. In order to analyze the research hotspots and the trends of physical therapy and COVID-19, we conducted bibliometric and visual analysis. [Methods] Data were collected from the Science Citation Index Expanded (SCI-EXPANDED) and Social Sciences Citation Index (SSCI) of the Web of Science Core Collect (WoSCC) from 2019 to 2021. CiteSpace and VOSviewer were used to perform the visual analysis of keywords and references to help quickly get key information. [Results] A total of 466 publications were retrieved. Exercise, sedentary behavior, and mental health were research hotspots. The relationship between exercise and immunity, as well as the management of COVID-19 patients after discharge were the research trends. [Conclusion] This study provided relevant information for future research. Findings suggested that physical therapy is beneficial for suspected or confirmed COVID-19 patients during isolation. It is hoped that academic exchanges can be quickly established in the face of infectious diseases. And in the future, we should focus on the rehabilitation of discharged patients.

TLR5 activation in hepatocytes alleviates the functional suppression of intrahepatic CD8+ T cells.

The liver is an immune-privileged organ with a tolerogenic environment for maintaining liver homeostasis. This hepatic tolerance limits the intrahepatic CD8+ T-cell response for eliminating infections. The tolerant microenvironment in the liver is orchestrated by liver-specific immunoregulatory cells that can be functionally regulated by pathogen-associated molecular patterns (PAMPs). Here, we report that flagellin, a key PAMP of gut bacteria, modulates the intrahepatic CD8+ T-cell response by activating the TLR5 signalling pathway of hepatocytes. We found that mice treated with Salmonella-derived recombinant flagellin (SF) by hydrodynamic injection had a significantly elevated IFN-γ production by the intrahepatic lymphocytes in 7 days after injection. This was correlated with a reduced immune suppressive effect of primary mouse hepatocytes (PMHs) in comparison with that of PMHs from mock-injected control mice. In vitro co-culture of SF-treated PMHs with splenocytes revealed that hepatocyte-induced immune suppression is alleviated through activation of the TLR5 but not the NLRC4 signalling pathway, leading to improved activation and function of CD8+ T cells during anti-CD3 stimulation or antigen-specific activation. In an acute HBV replication mouse model established by co-administration of SF together with an HBV-replicating plasmid by hydrodynamic injection, SF significantly enhanced the intrahepatic HBV-specific CD8+ T-cell response against HBV surface antigen. Our results clearly showed that flagellin plays a role in modulating the intrahepatic CD8+ T-cell response by activating the TLR5 pathway in PMHs, which suggests a potential role for gut bacteria in regulating liver immunity.

Deciphering the archaeal communities in tree rhizosphere of the Qinghai-Tibetan plateau.

BACKGROUND: The Qinghai-Tibetan Plateau represents one of the most important component of the terrestrial ecosystem and a particularly vulnerable region, which harbouring complex and diverse microbiota. The knowledge about their underground microorganisms have largely been studied, but the characteristics of rhizosphere microbiota, particularly archaeal communities remains unclear. RESULTS: High-throughput Illumina sequencing was used to investigate the rhizosphere archaeal communities of two native alpine trees (Picea crassifolia and Populus szechuanica) living on the Qinghai-Tibetan Plateau. The archaeal community structure in rhizospheres significantly differed from that in bulk soil. Thaumarchaeota was the dominant archaeal phylum in all soils tested (92.46-98.01%), while its relative abundance in rhizospheres were significantly higher than that in bulk soil. Ammonium nitrogen, soil organic matter, available phosphorus and pH were significantly correlated with the archaeal community structure, and the deterministic processes dominated the assembly of archaeal communities across all soils. In addition, the network structures of the archaeal community in the rhizosphere were less complex than they were in the bulk soil, and an unclassified archaeal group (Unclassified_k_norank) was identified as the keystone species in all archaeal networks. CONCLUSIONS: Overall, the structure, assembly and co-occurrence patterns of archaeal communities are significantly affected by the presence of roots of alpine trees living on the Qinghai-Tibetan Plateau. This study provides new insights into our understanding of archaeal communities in vulnerable ecosystems.

Network and pathway-based analysis of microRNA role in neuropathic pain in rat models.

The molecular mechanisms underlying neuropathic pain (NP) remain poorly understood. Emerging evidence has suggested the role of microRNAs (miRNAs) in the initiation and development of NP, but the specific effects of miRNAs in NP are largely unknown. Here, we use network- and pathway-based methods to investigate NP-induced miRNA changes and their biological functions by conducting a systematic search through multiple electronic databases. Thirty-seven articles meet the inclusion criteria. Venn analysis and target gene forecasting are performed and the results indicate that 167 overlapping target genes are co-regulated by five down-regulated miRNAs (rno-miR-183, rno-miR-96, rno-miR-30b, rno-miR-150 and rno-miR-206). Protein-protein interaction network analysis shows that 77 genes exhibit interactions, with cyclic adenosine monophosphate (cAMP)-dependent protein kinase catalytic subunit beta (degree = 11) and cAMP-response element binding protein 1 (degree = 10) having the highest connectivity degree. Gene ontology analysis shows that these target genes are enriched in neuron part, neuron projection, somatodendritic compartment and nervous system development. Moreover, analysis of Kyoto Encyclopedia of Genes and Genomes reveals that three pathways, namely, axon guidance, circadian entrainment and insulin secretion, are significantly enriched. In addition, rno-miR-183, rno-miR-96, rno-miR-30b, rno-miR-150 and rno-miR-206 are consistently down-regulated in the NP models, thus constituting the potential biomarkers of this disease. Characterizing these miRNAs and their target genes paves way for their future use in clinical practice.

A Bioinformatic Analysis of MicroRNAs' Role in Human Intervertebral Disc Degeneration.

Objectives The aim of our study was to ascertain the underlying role of microRNAs (miRNAs) in human intervertebral disc degeneration (IDD). Design Bioinformatic analysis from multiple databases. Methods Studies of the association of miRNAs and IDD were identified in multiple electronic databases. All potential studies were assessed by the same inclusion and exclusion criteria. We recorded whether miRNA expression was commonly increased or suppressed in the intervertebral disc tissues and cells of IDD subjects. We used String to identify biological process and cellular component pathways of differentially expressed genes. Results We included fifty-seven articles from 1,277 records in this study. This report identified 40 different dysregulated miRNAs in 53 studies, including studies examining cell apoptosis (26 studies, 49.06%), cell proliferation (15 studies, 28.3%), extracellular matrix (ECM) degradation (10 studies, 18.86%), and inflammation (five studies, 9.43%) in IDD patients. Three upregulated miRNAs (miR-19b, miR-32, miR-130b) and three downregulated miRNAs (miR-31, miR-124a, miR-127-5p) were considered common miRNAs in IDD tissues. The top three biological process pathways for upregulated miRNAs were positive regulation of biological process, nervous system development, and negative regulation of biological process, and the top three biological process pathways for downregulated miRNAs were negative regulation of gene expression, intracellular signal transduction, and negative regulation of biological process. Conclusions This study revealed that miRNAs could be novel targets for preventing IDD and treating patients with IDD by regulating their target genes. These results provide valuable information for medical professionals, IDD patients, and health care policy makers.

Effects of Whole-Body Vibration on Lumbar-Abdominal Muscles Activation in Healthy Young Adults: A Pilot Study.

BACKGROUND This study investigated how whole-body vibration (WBV), exercise, and their interactions influence core muscle activity in healthy young adults. MATERIAL AND METHODS Twenty-three healthy young adults (8 males and 15 females; age: 21.87±2.33 years) participated in the study. The activities of muscle multifidi (MM), rectus abdominis muscle (RM), erector spinae (ES), abdominis obliquus externus (AOE), and abdominis obliquus internus (AOI) were measured through surface electromyography (sEMG) while participants were performing 4 different exercise forms under 3 WBV conditions (condition 1: 5 Hz, 2 mm; condition 2: 10 Hz, 2 mm; and condition 3: 15 Hz, 2 mm) and a no-WBV condition in single experimental sessions. RESULTS The WBV frequency of 15 Hz is the best vibration stimulation for core muscles in all of the exercises (P<0.05). Single bridge is a better exercise for RM and AOE (P<0.05) compared with other exercises, and crunches is the best exercise for MM, AOI, and ES (P<0.05). Significant interaction effect was observed in different frequencies and exercises (P>0.05) except for AOI (F=0.990, P=0.378). CONCLUSIONS High vibration frequencies can lead to enhanced exercise benefits within an appropriate frequency range, and different exercises have diverse effects on various muscles. Single bridge and crunches are appropriate exercise forms for lumbar-abdominal muscles.

Surgical versus non-operative treatment for lumbar disc herniation: a systematic review and meta-analysis.

OBJECTIVE: To investigate the effects of surgical versus non-operative treatment on the physical function and safety of patients with lumbar disc herniation. DATA SOURCES: PubMed, Cochrane Library, Embase, EBSCO, Web of Science, China National Knowledge Infrastructure and Chinese Biomedical Literature Database were searched from initiation to 15 May 2017. METHODS: Randomized controlled trials that evaluated surgical versus non-operative treatment for patients with lumbar disc herniation were selected. The primary outcomes were pain and side-effects. Secondary outcomes were function and health-related quality of life. A random effects model was used to calculate the pooled mean difference with 95% confidence interval. RESULTS: A total of 19 articles that involved 2272 participants met the inclusion criteria. Compared with non-operative treatment, surgical treatment was more effective in lowering pain (short term: mean difference = -0.94, 95% confidence interval = -1.87 to -0.00; midterm: mean difference = -1.59, 95% confidence interval = -2.24 to -9.94), improving function (midterm: mean difference = -7.84, 95% confidence interval = -14.00 to -1.68; long term: mean difference = -12.21, 95% confidence interval = -23.90 to -0.52) and quality of life. The 36-item Short-Form Health Survey for physical functions (short term: mean difference = 6.25, 95% confidence interval = 0.43 to 12.08) and bodily pain (short term: mean difference = 5.42, 95% confidence interval = 0.40 to 10.45) was also utilized. No significant difference was observed in adverse events (mean difference = 0.82, 95% confidence interval = 0.28 to 2.38). CONCLUSION: Low-quality evidence suggested that surgical treatment is more effective than non-operative treatment in improving physical functions; no significant difference was observed in adverse events. No firm recommendation can be made due to instability of the summarized data.

Tai Chi for improving cardiopulmonary function and quality of life in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

OBJECTIVE: To examine the effect of Tai Chi on cardiopulmonary function and quality of life in chronic obstructive pulmonary disease. DATA SOURCES: Cochrane Library, PUBMED, EMBASE, China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang database. METHODS: Articles on randomized controlled trials comparing Tai Chi with other treatments or no treatment were identified. A random-effects model was used to calculate the pooled mean difference (MD) with 95% confidence interval (CI). RESULTS: Fifteen articles involving 1354 participants were included. Compared with the control group, Tai Chi was more effective in improving exercise capacity on 6-minute walking distance (short term: MD = 16.02, 95% CI 2.86 to 29.17; mid term: MD = 30.90, 95% CI 6.88 to 54.93; long term: MD = 24.63, 95% CI 2.30 to 46.95), as well as pulmonary functions on forced expiratory volume in the first second (mid term: MD = 0.10; 95% CI 0.01 to 0.19), and forced vital capacity (mid term: MD = 0.20; 95% CI 0.04 to 0.36). Concerning quality of life, we found Tai Chi was better than the control group for the Chronic Respiratory Disease Questionnaire dyspnoea score (short term: MD = 0.90; 95% CI 0.51 to 1.29), fatigue score (short term: MD = 0.75; 95% CI 0.42 to 1.09), and total score (short term: MD = 1.92; 95% CI 0.54 to 3.31). CONCLUSIONS: Tai Chi may improve exercise capacity in the short, mid, and long terms. However, no significant long term differences in pulmonary function and quality of life were observed for patients with chronic obstructive pulmonary disease.

Resveratrol Inhibits Zinc Deficiency-Induced Mitophagy and Exerts Cardiac Cytoprotective Effects.

Resveratrol (Res) possesses various beneficial effects, including cardioprotective, anti-inflammatory, anti-aging, and antioxidant properties. However, the precise mechanism underlying these effects remains unclear. Here we investigated the protective effects of resveratrol on cardiomyocytes, focusing on the role of Zn2+ and mitophagy. Using the MTT/lactate dehydrogenase assay, we found that addition of a zinc chelator TPEN for 4 h induced mitophagy and resulted in a significant reduction in cell viability, increased cytotoxicity, and apoptosis in H9c2 cells. Notably, resveratrol effectively mitigated these detrimental effects caused by TPEN. Similarly, Res inhibited the TPEN-induced expression of mitophagy-associated proteins, namely P62, LC3, NIX, TOM20, PINK1, and Parkin. The inhibitory action of resveratrol on mitophagy was abrogated by the mitophagy inhibitor 3-MA. Additionally, we discovered that silencing of the Mfn2 gene could reverse the inhibitory effects of resveratrol on mitophagy via the AMPK-Mfn2 axis, thereby preventing the opening of the mitochondrial permeability transition pore (mPTP). Collectively, our data suggest that Res can safeguard mitochondria protection by impeding mitophagy and averting mPTP opening through the AMPK-Mfn2 axis in myocardial cells.

Role of Exercise on Neuropathic Pain in Preclinical Models: Perspectives for Neuroglia.

The benefits of exercise on neuropathic pain (NP) have been demonstrated in numerous studies. In recent studies, inflammation, neurotrophins, neurotransmitters, and endogenous opioids are considered as the main mechanisms. However, the role of exercise in alleviating NP remains unclear. Neuroglia, widely distributed in both the central and peripheral nervous systems, perform functions such as support, repair, immune response, and maintenance of normal neuronal activity. A large number of studies have shown that neuroglia play an important role in the occurrence and development of NP, and exercise can alleviate NP by regulating neuroglia. This article reviewed the involvement of neuroglia in the development of NP and their role in the exercise treatment of NP, intending to provide a theoretical basis for the exercise treatment strategy of NP.

Vancomycin-loaded hydrogels with thermal-responsive, self-peeling, and sustainable antibacterial properties for wound dressing.

Wound dressings play an important role in wound healing. However, many wound dressings lack antibacterial properties and are difficult to remove from newly grown tissues, causing secondary wound injuries and repeated medical treatment. This study reports a new type of thermal-responsive hydrogel dressing consisting of vancomycin-loaded gelatin nanospheres (GNs) and poly((N-isopropylacrylamide)-co-N-(methylol acrylamide)) functional components that could impart self-peeling and sustainable antibacterial properties. SEM images showed that the prepared hydrogel possessed a porous microstructure and the homogeneous distribution of GNs in its network. Excellent swelling ratios and thermal-induced self-peeling characteristics were confirmed by qualitative analysis. The GNs not only enhanced the strain at break of the hydrogel, but also acted as drug carriers to slow down the drug release from the hydrogel, achieving sustainable antibacterial properties and balanced biocompatibility. Therefore, this vancomycin-loaded hydrogel with self-peeling characteristics provides an effective way of preventing wound infection and can be used as a novel platform for wide-ranging applications of wound dressings.

Remodeling Intestinal Microbiota Alleviates Severe Combined Hyperlipidemia-Induced Nonalcoholic Steatohepatitis and Atherosclerosis in LDLR-/- Hamsters.

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain. In this study, CHL was induced in low-density lipoprotein receptor-deficient (LDLR-/-) hamsters through an 8-week high-fat and high-cholesterol (HFHC) diet or a 4-month high-cholesterol (HC) diet. Placebo or antibiotics were administered through separate or cohousing approaches. Analysis through 16S rDNA sequencing revealed that intermittent antibiotic treatment and the cohousing approach effectively modulated the gut microbiota community without impacting its overall abundance in LDLR-/- hamsters exhibiting severe CHL. Antibiotic treatment mitigated HFHC diet-induced obesity, hyperglycemia, and hyperlipidemia, enhancing thermogenesis and alleviating nonalcoholic steatohepatitis (NASH), concurrently reducing atherosclerotic lesions in LDLR-/- hamsters. Metabolomic analysis revealed a favorable liver lipid metabolism profile. Increased levels of microbiota-derived metabolites, notably butyrate and glycylglycine, also ameliorated NASH and atherosclerosis in HFHC diet-fed LDLR-/- hamsters. Notably, antibiotics, butyrate, and glycylglycine treatment exhibited protective effects in LDLR-/- hamsters on an HC diet, aligning with outcomes observed in the HFHC diet scenario. Our findings highlight the efficacy of remodeling gut microbiota through antibiotic treatment and cohousing in improving obesity, NASH, and atherosclerosis associated with refractory CHL. Increased levels of beneficial microbiota-derived metabolites suggest a potential avenue for microbiome-mediated therapies in addressing CHL-associated diseases.

Zero-shot learning enables instant denoising and super-resolution in optical fluorescence microscopy.

Computational super-resolution methods, including conventional analytical algorithms and deep learning models, have substantially improved optical microscopy. Among them, supervised deep neural networks have demonstrated outstanding performance, however, demanding abundant high-quality training data, which are laborious and even impractical to acquire due to the high dynamics of living cells. Here, we develop zero-shot deconvolution networks (ZS-DeconvNet) that instantly enhance the resolution of microscope images by more than 1.5-fold over the diffraction limit with 10-fold lower fluorescence than ordinary super-resolution imaging conditions, in an unsupervised manner without the need for either ground truths or additional data acquisition. We demonstrate the versatile applicability of ZS-DeconvNet on multiple imaging modalities, including total internal reflection fluorescence microscopy, three-dimensional wide-field microscopy, confocal microscopy, two-photon microscopy, lattice light-sheet microscopy, and multimodal structured illumination microscopy, which enables multi-color, long-term, super-resolution 2D/3D imaging of subcellular bioprocesses from mitotic single cells to multicellular embryos of mouse and C. elegans.

Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters.

Background: ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity and triglyceride-rich lipoproteins (TRLs). Although the role of ApoA5 in extrahepatic triglyceride (TG) metabolism in circulation has been well documented, the relationship between ApoA5 and nonalcoholic fatty liver disease (NAFLD) remains incompletely understood and the underlying molecular mechanism still needs to be elucidated. Methods: We used CRISPR/Cas9 gene editing to delete Apoa5 gene from Syrian golden hamster, a small rodent model replicating human metabolic features. Then, the ApoA5-deficient (ApoA5-/-) hamsters were used to investigate NAFLD with or without challenging a high fat diet (HFD). Results: ApoA5-/- hamsters exhibited hypertriglyceridemia (HTG) with markedly elevated TG levels at 2300 mg/dL and hepatic steatosis on a regular chow diet, accompanied with an increase in the expression levels of genes regulating lipolysis and small adipocytes in the adipose tissue. An HFD challenge predisposed ApoA5-/- hamsters to severe HTG (sHTG) and nonalcoholic steatohepatitis (NASH). Mechanistic studies in vitro and in vivo revealed that targeting ApoA5 disrupted NR1D1 mRNA stability in the HepG2 cells and the liver to reduce both mRNA and protein levels of NR1D1, respectively. Overexpression of human NR1D1 by adeno-associated virus 8 (AAV8) in the livers of ApoA5-/- hamsters significantly ameliorated fatty liver without affecting plasma lipid levels. Moreover, restoration of hepatic ApoA5 or activation of UCP1 in brown adipose tissue (BAT) by cold exposure or CL316243 administration could significantly correct sHTG and hepatic steatosis in ApoA5-/- hamsters. Conclusions: Our data demonstrate that HTG caused by ApoA5 deficiency in hamsters is sufficient to elicit hepatic steatosis and HFD aggravates NAFLD by reducing hepatic NR1D1 mRNA and protein levels, which provides a mechanistic link between ApoA5 and NAFLD and suggests the new insights into the potential therapeutic approaches for the treatment of HTG and the related disorders due to ApoA5 deficiency in the clinical trials in future.

Research trends and hotspots of neuropathic pain in neurodegenerative diseases: a bibliometric analysis.

Background: Neuropathic pain is caused by a neurological injury or disease and can have a significant impact on people's daily lives. Studies have shown that neuropathic pain is commonly associated with neurodegenerative diseases. In recent years, there has been a lot of literature on the relationship between neuropathic pain and neurodegenerative diseases. However, bibliometrics is rarely used in analyzing the general aspects of studies on neuropathic pain in neurodegenerative diseases. Methods: The bibliometric analysis software CiteSpace and VOSviewer were used to analyze the knowledge graph of 387 studies in the Science Citation Index Expanded of the Web of Science Core Collection Database. Results: We obtained 2,036 documents through the search, leaving 387 documents after culling. 387 documents were used for the data analysis. The data analysis showed that 330 papers related to neuropathic pain in neurodegenerative diseases were published from 2007-2022, accounting for 85.27% of all published literature. In terms of contributions to the scientific study of neuropathic pain, the United States is in the top tier, with the highest number of publications, citations, and H-indexes. Conclusion: The findings in our study may provide researchers with useful information about research trends, frontiers, and cooperative institutions. Multiple sclerosis, Parkinson's disease, and Alzheimer's disease are the three most studied neurodegenerative diseases. Among the pathological basis of neurodegenerative diseases, microglia-regulated neuroinflammation is a hot research topic. Deep brain stimulation and gamma knife radiosurgery are two popular treatments.