Ropivacaine synergizes with sorafenib to induce apoptosis of hepatocellular carcinoma cells via the IL-6/STAT3 pathway.

The development of resistance in hepatocellular carcinoma (HCC) cells limits the effectiveness of sorafenib, but combination therapy with other drugs may have a positive effect. However, the effect of ropivacaine combined with sorafenib on the treatment of HCC cells and its potential regulatory mechanisms remain unclear. The proliferation and apoptosis of HCC cells treated with ropivacaine, sorafenib, and ropivacaine plus sorafenib were analyzed by cell-counting kit 8 and flow cytometry. The protein levels were measured by Western blot. The antitumor effect of ropivacaine, sorafenib, and their combination was verified by a tumor xenograft model. Ropivacaine and sorafenib markedly impeded the viability of HCC cells in a concentration-dependent manner. Compared with ropivacaine or sorafenib treatment alone, ropivacaine and sorafenib combination treatment impeded HCC cell proliferation, facilitated apoptosis, enhanced cleaved caspase-3, cleaved caspase-9, and cyclin D1 protein expression, while it reduced IL-6 and p-STAT3 expression and inhibited tumor growth in vivo. Importantly, the activation of the IL-6/STAT3 pathway could reverse the repressive or stimulative effects of ropivacaine and sorafenib on the proliferation and apoptosis in HCC cells. In summary, ropivacaine synergistically induces sorafenib-stimulated apoptosis of HCC cells via the IL-6/STAT3 pathway. Ropivacaine is a potential drug for the treatment of HCC when combined with sorafenib.

Mild therapeutic hypothermia upregulates the O-GlcNAcylation level of COX10 to alleviate mitochondrial damage induced by myocardial ischemia-reperfusion injury.

OBJECTIVE: Mild therapeutic hypothermia (MTH) is an important method for perioperative prevention and treatment of myocardial ischemia-reperfusion injury (MIRI). Modifying mitochondrial proteins after protein translation to regulate mitochondrial function is one of the mechanisms for improving myocardial ischemia-reperfusion injury. This study investigated the relationship between shallow hypothermia treatment improving myocardial ischemia-reperfusion injury and the O-GlcNAcylation level of COX10. METHODS: We used in vivo Langendorff model and in vitro hypoxia/reoxygenation (H/R) cell model to investigate the effects of MTH on myocardial ischemia-reperfusion injury. Histological changes, myocardial enzymes, oxidative stress, and mitochondrial structure/function were assessed. Mechanistic studies involved various molecular biology methods such as ELISA, immunoprecipitation (IP), WB, and immunofluorescence. RESULTS: Our research results indicate that MTH upregulates the O-GlcNACylation level of COX10, improves mitochondrial function, and inhibits the expression of ROS to improve myocardial ischemia-reperfusion injury. In vivo, MTH effectively alleviates ischemia-reperfusion induced cardiac dysfunction, myocardial injury, mitochondrial damage, and redox imbalance. In vitro, the OGT inhibitor ALX inhibits the OGT mediated O-GlcNA acylation signaling pathway, downregulates the O-Glc acylation level of COX10, promotes ROS release, and counteracts the protective effect of MTH. On the contrary, the OGA inhibitor ThG showed opposite effects to ALX, further confirming that MTH activated the OGT mediated O-GlcNAcylation signaling pathway to exert cardioprotective effects. CONCLUSIONS: In summary, MTH activates OGT mediated O-glycosylation modified COX10 to regulate mitochondrial function and improve myocardial ischemia-reperfusion injury, which provides important theoretical basis for the clinical application of MTH.

Genetic algorithm-based optical proximity correction for DMD maskless lithography.

We present an optical proximity correction (OPC) method based on a genetic algorithm for reducing the optical proximity effect-induced pattern distortion in digital micromirror device (DMD) maskless lithography. Via this algorithm-assisted grayscale modulation of the initial mask at the pixel level, the exposure pattern can be enhanced significantly. Actual exposure experiments revealed that the rate of matching between the final exposure pattern and the mask pattern can be increased by up to 20%. This method's applicability to complex masks further demonstrates its universality for mask pattern optimization. We believe that our algorithm-assisted OPC could be highly helpful for high-fidelity and efficient DMD maskless lithography for microfabrication.

Future Directions in Optimizing Anesthesia to Reduce Perioperative Acute Kidney Injury.

BACKGROUND: Perioperative acute kidney injury (AKI) is common in surgical patients and is associated with high morbidity and mortality. There are currently few options for AKI prevention and treatment. Due to its complex pathophysiology, there is no efficient medication therapy to stop the onset of the injury or repair the damage already done. Certain anesthetics, however, have been demonstrated to affect the risk of perioperative AKI in some studies. The impact of anesthetics on renal function is particularly important as it is closely related to the prognosis of patients. Some anesthetics can induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. Propofol, sevoflurane, and dexmedetomidine are a few examples of anesthetics that have protective association with AKI in the perioperative period. SUMMARY: In this study, we reviewed the clinical characteristics, risk factors, and pathogenesis of AKI. Subsequently, the protective effects of various anesthetic agents against perioperative AKI and the latest research are introduced. KEY MESSAGE: This work demonstrates that a thorough understanding of the reciprocal effects of anesthetic drugs and AKI is crucial for safe perioperative care and prognosis of patients. However, more complete mechanisms and pathophysiological processes still need to be further studied.

Food-derived peptides as novel therapeutic strategies for NLRP3 inflammasome-related diseases: a systematic review.

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), a member of the nucleotide-binding domain (NOD) and leucine-rich repeat sequence (LRR) protein (NLR) family, plays an essential role in the inflammation initiation and inflammatory mediator secretion, and thus is also associated with many disease progressions. Food-derived bioactive peptides (FDBP) exhibit excellent anti-inflammatory activity in both in vivo and in vitro models. They are encrypted in plant, meat, and milk proteins and can be released under enzymatic hydrolysis or fermentation conditions, thereby hindering the progression of hyperuricemia, inflammatory bowel disease, chronic liver disease, neurological disorders, lung injury and periodontitis by inactivating the NLRP3. However, there is a lack of systematic review around FDBP, NLRP3, and NLRP3-related diseases. Therefore, this review summarized FDBP that exert inhibiting effects on NLRP3 inflammasome from different protein sources and detailed their preparation and purification methods. Additionally, this paper also compiled the possible inhibitory mechanisms of FDBP on NLRP3 inflammasomes and its regulatory role in NLRP3 inflammasome-related diseases. Finally, the progress of cutting-edge technologies, including nanoparticle, computer-aided screening strategy and recombinant DNA technology, in the acquisition or encapsulation of NLRP3 inhibitory FDBP was discussed. This review provides a scientific basis for understanding the anti-inflammatory mechanism of FDBP through the regulation of the NLRP3 inflammasome and also provides guidance for the development of therapeutic adjuvants or functional foods enriched with these FDBP.

Examining the Persuasive Effects of Health Communication in Short Videos: Systematic Review.

BACKGROUND: The ubiquity of short videos has demonstrated vast potential for health communication. An expansion of research has examined the persuasive effect of health communication in short videos, yet a synthesis of the research is lacking. OBJECTIVE: This paper aims to provide an overview of the literature by examining the persuasive effect of health communication in short videos, offering guidance for researchers and practitioners. In particular, it seeks to address 4 key research questions: What are the characteristics of short videos, samples, and research designs in short video-based health communication literature? What theories underpin the short video-based health communication literature? What are the persuasive effects of health communication in short videos? and What directions should future research in this area take? METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, an electronic search of 10 databases up to March 10, 2023, generated 4118 results. After the full-text screening, 18 articles met the eligibility criteria. RESULTS: The current research lacks a uniform definition of short videos, demonstrates sample biases in location and education, and adopts limited methodologies. Most studies in this synthesis are theoretically grounded or use theoretical concepts, which are predominantly well examined in persuasion research. Moreover, relevant topics and suitable themes are effective in persuasive health communication outcomes, whereas the impact of diverse narrative techniques remains ambiguous. CONCLUSIONS: We recommend that future research extends the definition of short videos beyond time constraints and explores non-Western and less-educated populations. In addition, researchers should consider diverse methods to provide a more comprehensive examination and investigate the impact of audience targeting and narrative techniques in short video health communication. Finally, investigating how the unique aspects of short videos interact with or challenge traditional persuasion theories is essential.

Genome-Wide Identification, Evolutionary Analysis, and Functional Studies of APX Genes in Melon (Cucuis melo L.).

The antioxidative enzyme ascorbate peroxidase (APX) exerts a critically important function through scavenging reactive oxygen species (ROS), alleviating oxidative damage in plants, and enhancing their tolerance to salinity. Here, we identified 28 CmAPX genes that display an uneven distribution pattern throughout the 12 chromosomes of the melon genome by carrying out a bioinformatics analysis. Phylogenetic analyses revealed that the CmAPX gene family comprised seven different clades, with each clade of genes exhibiting comparable motifs and structures. We cloned 28 CmAPX genes to infer their encoded protein sequences; we then compared these sequences with proteins encoded by rice APX proteins (OsAPX2), Puccinellia tenuiflora APX proteins (PutAPX) and with pea APX proteins. We found that the CmAPX17, CmAPX24, and CmAPX27 genes in Clade I were closely related, and their structures were highly conserved. CmAPX27 (MELO3C020719.2.1) was found to promote resistance to 150 mM NaCl salt stress, according to quantitative real-time fluorescence PCR. Transcriptome data revealed that CmAPX27 was differentially expressed among tissues, and the observed differences in expression were significant. Virus-induced gene silencing of CmAPX27 significantly decreased salinity tolerance, and CmAPX27 exhibited differential expression in the leaf, stem, and root tissues of melon plants. This finding demonstrates that CmAPX27 exerts a key function in melon's tolerance to salt stress. Generally, CmAPX27 could be a target in molecular breeding efforts aimed at improving the salt tolerance of melon; further studies of CmAPX27 could unveil novel physiological mechanisms through which antioxidant enzymes mitigate the deleterious effects of ROS stress.

Comparative Transcriptome Analysis Identified Key Pathways and Genes Regulating Differentiated Stigma Color in Melon (Cucumis melo L.).

Stigma color is an important morphological trait in many flowering plants. Visual observations in different field experiments have shown that a green stigma in melons is more attractive to natural pollinators than a yellow one. In the current study, we evaluated the characterization of two contrasted melon lines (MR-1 with a green stigma and M4-7 with a yellow stigma). Endogenous quantification showed that the chlorophyll and carotenoid content in the MR-1 stigmas was higher compared to the M4-7 stigmas. The primary differences in the chloroplast ultrastructure at different developmental stages depicted that the stigmas of both melon lines were mainly enriched with granum, plastoglobulus, and starch grains. Further, comparative transcriptomic analysis was performed to identify the candidate pathways and genes regulating melon stigma color during key developmental stages (S1-S3). The obtained results indicated similar biological processes involved in the three stages, but major differences were observed in light reactions and chloroplast pathways. The weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs) uncovered a "black" network module (655 out of 5302 genes), mainly corresponding to light reactions, light harvesting, the chlorophyll metabolic process, and the chlorophyll biosynthetic process, and exhibited a significant contribution to stigma color. Overall, the expression of five key genes of the chlorophyll synthesis pathway-CAO (MELO03C010624), CHLH (MELO03C007233), CRD (MELO03C026802), HEMA (MELO03C011113), POR (MELO03C016714)-were checked at different stages of stigma development in both melon lines using quantitative real time polymerase chain reaction (qRT-PCR). The results exhibited that the expression of these genes gradually increased during the stigma development of the MR-1 line but decreased in the M4-7 line at S2. In addition, the expression trends in different stages were the same as RNA-seq, indicating data accuracy. To sum up, our research reveals an in-depth molecular mechanism of stigma coloration and suggests that chlorophyll and related biological activity play an important role in differentiating melon stigma color.

Resequencing of 297 melon accessions reveals the genomic history of improvement and loci related to fruit traits in melon.

Domestication and improvement are two important stages in crop evolution. Melon (Cucumis melo L.) is an important vegetable crop with wide phenotypic diversity in many horticultural traits, especially fruit size, flesh thickness and aroma, which are likely the results of long-term extensive selection during its evolution. However, selective signals in domestication and improvement stages for these remarkable variations remain unclear. We resequenced 297 wild, landrace and improved melon accessions and obtained 2 045 412 high-quality SNPs. Population structure and genetic diversity analyses revealed independent and two-step selections in two subspecies of melon: ssp. melo and ssp. agrestis during melon breeding. We detected 233 (~18.35 Mbp) and 159 (~17.71 Mbp) novel potential selective signals during the improvement stage in ssp. agrestis and spp. melo, respectively. Two alcohol acyltransferase genes (CmAATs) unique to the melon genome compared with other cucurbit crops may have undergone stronger selection in ssp. agrestis for the characteristic aroma as compared with other cucurbits. Genome-wide association analysis identified eight fruit size and seven flesh thickness signals overlapping with selective sweeps. Compared with thin-skinned ssp. agrestis, thick-skinned ssp. melo has undergone a stronger selection for thicker flesh. In most melon accessions, CmCLV3 has pleiotropic effects on carpel number and fruit shape. Findings from this study provide novel insights into melon crop evolution, and new tools to advance melon breeding.

LncRNA KCNQ1OT1 knockdown inhibits viability, migration and epithelial-mesenchymal transition in human lens epithelial cells via miR-26a-5p/ITGAV/TGF-beta/Smad3 axis.

BACKGROUND: Long noncoding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) takes part in diabetic cataract progression. This research aims to analyze the function and mechanism of KCNQ1OT1 on viability, migration and epithelial-mesenchymal transition (EMT) in lens epithelial cells. METHODS: 20 diabetic cataract posterior lens capsule tissues and normal samples were collected. Lens epithelial cells (SRA01/04) were stimulated via high glucose (HG). The levels of KCNQ1OT1, miR-26a-5p, integrin αV (ITGAV), TGF-ß, Smad3 and phosphorylated (p)-Smad3 were measured via quantitative real-time polymerase chain reaction or Western blot. Cell viability, migration and EMT were analyzed via MTT, wound healing, transwell and Western blot assays. The target relationship between miR-26a-5p and KCNQ1OT1 or ITGAV was determined via luciferase reporter assay. RESULTS: KCNQ1OT1 was up-regulated and miR-26a-5p level was reduced in diabetic cataract tissues and HG-treated SRA01/04 cells. Silence of KCNQ1OT1 or miR-26a-5p up-regulation repressed cell viability, migration and EMT in SRA01/04 cells stimulated via HG. KCNQ1OT1 could target miR-26a-5p and controlled cell viability, migration and EMT via regulating miR-26a-5p. ITGAV was targeted via miR-26a-5p and positively regulated via KCNQ1OT1. ITGAV overexpression promoted cell viability, migration and EMT in HG-treated SRA01/04 cells, which were mitigated by KCNQ1OT1 silence. KCNQ1OT1 knockdown mitigated HG-induced the activation of TGF-ß/Smad3 signaling by regulating miR-26a-5p. CONCLUSION: KCNQ1OT1 knockdown represses cell viability, migration and EMT through miR-26a-5p/ITGAV/TGF-ß/Smad3 axis in SRA01/04 cells under HG condition, providing a new target for the treatment of diabetic cataract.

Comparative transcriptome analysis of two contrasting watermelon genotypes during fruit development and ripening.

BACKGROUND: Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is an economically important crop with an attractive ripe fruit that has colorful flesh. Fruit ripening is a complex, genetically programmed process. RESULTS: In this study, a comparative transcriptome analysis was performed to identify the regulators and pathways that are involved in the fruit ripening of pale-yellow-flesh cultivated watermelon (COS) and red-flesh cultivated watermelon (LSW177). We first identified 797 novel genes to extend the available reference gene set. Second, 3958 genes in COS and 3503 genes in LSW177 showed at least two-fold variation in expression, and a large number of these differentially expressed genes (DEGs) during fruit ripening were related to carotenoid biosynthesis, plant hormone pathways, and sugar and cell wall metabolism. Third, we noted a correlation between ripening-associated transcripts and metabolites and the key function of these metabolic pathways during fruit ripening. CONCLUSION: The results revealed several ripening-associated actions and provide novel insights into the molecular mechanisms underlying the regulation of watermelon fruit ripening.

Identification of Chromosomal Regions and Candidate Genes for Round leaf Locus in Cucumis melo L.

Leaf morphology plays a crucial role in plant classification and provides a significant model for studying plant diversity while directly impacting photosynthetic efficiency. In the case of melons, leaf shape not only influences production and classification but also represents a key genetic trait that requires further exploration. In this study, we utilized forward genetics to pinpoint a recessive locus, dubbed Cmrl (Round leaf), which is responsible for regulating melon leaf shape. Through bulked segregant analysis sequencing and extensive evaluation of a two-year F2 population, we successfully mapped the Cmrl locus to a 537.07 kb region on chromosome 8 of the melon genome. Subsequent genetic fine-mapping efforts, leveraging a larger F2 population encompassing 1322 plants and incorporating F2:3 phenotypic data, further refined the locus to an 80.27 kb interval housing five candidate genes. Promoter analysis and coding sequence cloning confirmed that one of these candidates, MELO3C019152.2 (Cmppr encoding a pentatricopeptide repeat-containing family protein, Cmppr), stands out as a strong candidate gene for the Cmrl locus. Notably, comparisons of Cmrl expressions across various stages of leaf development and different leaf regions suggest a pivotal role of Cmrl in the morphogenesis of melon leaves.

Clorf Encodes Carotenoid Isomerase and Regulates Orange Flesh Color in Watermelon (Citrullus lanatus L.).

Flesh color is a significant characteristic of watermelon. Although various flesh-color genes have been identified, the inheritance and molecular basis of the orange flesh trait remain relatively unexplored. In the present study, the genetic analysis of six generations derived from W1-1 (red flesh) and W1-61 (orange flesh) revealed that the orange flesh color trait was regulated by a single recessive gene, Clorf (orange flesh). Bulk segregant analysis (BSA) locked the range to ∼4.66 Mb, and initial mapping situated the Clorf locus within a 688.35-kb region of watermelon chromosome 10. Another 1,026 F2 plants narrowed the Clorf locus to a 304.62-kb region containing 32 candidate genes. Subsequently, genome sequence variations in this 304.62-kb region were extracted for in silico BSA strategy among 11 resequenced lines (one orange flesh and ten nonorange flesh) and finally narrowed the Clorf locus into an 82.51-kb region containing nine candidate genes. Sequence variation analysis of coding regions and gene expression levels supports Cla97C10G200950 as the most possible candidate for Clorf, which encodes carotenoid isomerase (Crtiso). This study provides a genetic resource for investigating the orange flesh color of watermelon, with Clorf malfunction resulting in low lycopene accumulation and, thus, orange flesh.

Intervention effects and related mechanisms of glycyrrhizic acid on zebrafish with Hirschsprung-associated enterocolitis.

BACKGROUND: The prevention and treatment of Hirschsprung-associated enterocolitis (HAEC) is a serious challenge in pediatric surgery. Exploring the mechanism of HAEC is conducive to the prevention of this disease. AIM: To explore the possible mechanism of glycyrrhizic acid (GA) and its therapeutic effect on HAEC. METHODS: We developed a model of enteritis induced by trinitrobenzenesulfonic acid (TNBS) in zebrafish, and treated it with different concentrations of GA. We analyzed the effect of GA on the phenotype and inflammation of zebrafish. RESULTS: After treatment with TNBS, the area of the intestinal lumen in zebrafish was significantly increased, but the number of goblet cells in the intestinal lumen was significantly reduced, but these did not increase the mortality of zebrafish, indicating that the zebrafish enteritis model was successfully developed. Different concentrations of GA protected zebrafish with enteritis. In particular, high concentrations of GA were important for the prevention and control of HAEC because it significantly reduced the intestinal luminal area, increased the number of goblet cells in the intestinal lumen, and reduced the levels of interleukin (IL)-1ß and IL-8. CONCLUSION: GA significantly reduced the intestinal luminal area, increased the number of intestinal goblet cells, and decreased IL-1ß and IL-8 in zebrafish, and is important for prevention and control of HAEC.

Elucidation of interactions between myofibrillar proteins and κ-carrageenan as mediated by NaCl level: Perspectives on multiple spectroscopy and molecular docking.

The present study was aimed to investigate the intermolecular interaction between myofibrillar proteins (MP) and κ-carrageenan (KC) as mediated by KC concentration (0.1, 0.2, 0.3, and 0.4 %, w/w) and NaCl levels (0.3 and 0.6 M) based on the multiple spectroscopy and molecular docking. The results showed that the incorporation of KC increased the turbidity, zeta-potential, and surface hydrophobicity of MP-KC mixed sols with a dose-dependent manner, as well as significantly decreasing the protein solubility (P < 0.05), which indicated that the interaction between KC and MP promoted the expansion of protein structure and exposed more hydrophobic groups. Fluorescence spectra result revealed that the interaction between MP and KC was a static quenching in the fluorescence quenching process, which affected the aromatic amino acids residue microenvironment of MP. Moreover, the existence of KC decreased the α-helix contents of MP (P < 0.05), contributing to the transformation from random structure to organized configuration of MP. In addition, molecular forces, the molecular docking and thermodynamic parameters indicated that hydrophobic interactions, van der Waals force, and hydrogen bonding were considered as the main interaction forces between MP and KC. Furthermore, 0.6 M NaCl level rendered higher solubility and particle size, as well as lower turbidity and the surface hydrophobicity of MP-KC mixed sols than those with 0.3 M NaCl level (P < 0.05), which promoted the unfolding of MP molecule and subsequently increased the numbers of binding sites between MP and KC, facilitating the intermolecular interactions between MP and KC in mixed sols.

Role of NLRP3 inflammasome in diabetes and COVID-19 role of NLRP3 inflammasome in the pathogenesis and treatment of COVID-19 and diabetes NLRP3 inflammasome in diabetes and COVID-19 intervention.

2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A "cytokine storm", i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotide-binding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients.

Effects of high-intensity interval training, moderate-intensity continuous training, and guideline-based physical activity on cardiovascular metabolic markers, cognitive and motor function in elderly sedentary patients with type 2 diabetes (HIIT-DM): a protocol for a randomized controlled trial.

Background and objective: Sedentary behavior is of increasing concern in older patients with type 2 diabetes mellitus (T2DM) due to its potential adverse effects on cardiovascular health, cognitive function, and motor function. While regular exercise has been shown to improve the health of individuals with T2DM, the most effective exercise program for elderly sedentary patients with T2DM remains unclear. Therefore, the objective of this study was to assess the impact of high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and guideline-based physical activity programs on the cardiovascular health, cognitive function, and motor function of this specific population. Methods: This study will be a randomized, assessor-blind, three-arm controlled trial. A total of 330 (1:1:1) elderly sedentary patients diagnosed with T2DM will be randomly assigned the HIIT group (10 × 1-min at 85-95% peak HR, intersperse with 1-min active recovery at 60-70% peak HR), MICT (35 min at 65-75% peak HR), and guideline-based group (guideline group) for 12 weeks training. Participants in the guideline group will receive 1-time advice and weekly remote supervision through smartphones. The primary outcomes will be the change in glycosylated hemoglobin (HbA1c) and brain-derived neurotrophic factor (BDNF) after 12-weeks. Secondary outcomes will includes physical activity levels, anthropometric parameters (weight, waist circumference, hip circumference, and body mass index), physical measurements (fat percentage, muscle percentage, and fitness rate), cardiorespiratory fitness indicators (blood pressure, heart rate, vital capacity, and maximum oxygen), biochemical markers (high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and HbA1c), inflammation level (C-reactive protein), cognitive function (reaction time and dual-task gait test performance), and motor function (static balance, dynamic balance, single-task gait test performance, and grip strength) after 12 weeks. Discussion: The objective of this study is to evaluate the effect of 12 weeks of HIIT, MICT, and a guideline-based physical activity program on elderly sedentary patients diagnosed with T2DM. Our hypothesis is that both HIIT and MICT will yield improvements in glucose control, cognitive function, cardiopulmonary function, metabolite levels, motor function, and physical fitness compared to the guideline group. Additionally, we anticipate that HIIT will lead to greater benefits in these areas. The findings from this study will provide valuable insights into the selection of appropriate exercise regimens for elderly sedentary individuals with T2DM. Ethics and dissemination: This study has been approved by the Ethics Review Committee of the Reproductive Hospital Affiliated with China Medical University (approval number: 202203). Informed consent will be obtained from all participants or their guardians. Upon completion, the authors will submit their findings to a peer-reviewed journal or academic conference for publication. Clinical trial registration: Chinese Clinical Trial Registry, identifier ChiCTR2200061573.

Insights into monkeypox pathophysiology, global prevalence, clinical manifestation and treatments.

On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent of monkeypox, is a zoonotic, linear, double-stranded DNA virus. In 1970, the Democratic Republic of the Congo reported the first case of MPV infection. Human-to-human transmission can happen through sexual contact, inhaled droplets, or skin-to-skin contact. Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs, including the skin, gastrointestinal tract, genitals, lungs, and liver. By September 9, 2022, more than 57,000 cases had been reported in 103 locations, especially in Europe and the United States. Infected patients are characterized by physical symptoms such as red rash, fatigue, backache, muscle aches, headache, and fever. A variety of medical strategies are available for orthopoxviruses, including monkeypox. Monkeypox prevention following the smallpox vaccine has shown up to 85% efficacy, and several antiviral drugs, such as Cidofovir and Brincidofovir, may slow the viral spread. In this article, we review the origin, pathophysiology, global epidemiology, clinical manifestation, and possible treatments of MPV to prevent the propagation of the virus and provide cues to generate specific drugs.

Identification of Candidate Chromosome Region Related to Melon (Cucumis melo L.) Fruit Surface Groove Trait Through Biparental Genetic Mapping and Genome-Wide Association Study.

The melon fruit surface groove (fsg) not only affects peel structure and causes stress-induced fruit cracking but also fits consumers' requirements in different regions. In this study, genetic inheritance analysis of three F2 populations derived from six parental lines revealed that the fsg trait is controlled by a simple recessive inherited gene. Through bulked segregant analysis sequencing (BSA-seq), the Cmfsg locus was detected in an 8.96 Mb interval on chromosome 11 and then initially mapped to a region of approximately 1.15 Mb. Further fine mapping with a large F2 population including 1,200 plants narrowed this region to 207 kb containing 11 genes. A genome-wide association study (GWAS) with 187 melon accessions also produced the same chromosome region for the Cmfsg locus. Due to the rare molecular markers and lack of mutations in the coding and promoter regions of the 11 candidate genes in the fine-mapped interval, we conducted in silico BSA to explore the natural melon panel to predict candidate genes for the Cmfsg locus. A 1.07 kb segment upstream of MELO3C019694.2 (annotated as the AGAMOUS MADS-box transcription factor) exhibited a correlation with the grooved and non-grooved accessions among the F2 individuals, and a natural panel consisted of 17 melon accessions. The expression level of MELO3C019694.2 in the pericarp was higher in grooved lines than in non-grooved lines and was specifically expressed in fruit compared with other tissues (female flower, male flower, root, and leaf). This work provides fundamental information for further research on melon fsg trait formation and molecular markers for melon breeding.

[Effects of blocking activation of IGF-1-Stat3 signaling pathway in guinea pig sclera fibroblast by AG490 on expression of MMP-2 and Integrinß(1)].

OBJECTIVE: To explore the effect of Blocking activation of IGF-1-Stat3 signaling pathway in guinea pig sclera fibroblast (GSFs) by AG490 on expressions of MMP-2, Integrinß(1). METHODS: Cultured GSFs were divided into four groups: group A(control group: only DMEM without IGF-1), group B (only IGF-1 group), group C(IGF-1 + PBS group), group D (IGF-1 + 25 µmol/L AG490 group). The expressions of Stat3, p-Stat3, MMP-2, Integrinß(1) protein induced by IGF-1 and inhibited by AG490 in GSFs were detected by Western blot. The levels of Stat3, MMP-2 and Integrinß(1)mRNA were detected by RT-PCR. RESULTS: Compared with Groups A and D, Stat3, p-Stat3, MMP-2 protein expression in groups B and C were expressed at higher level (t(pr) = -32.324, -26.284, -32.876, -26.345, -68.668, -58.724, -187.481, -58.842, -110.264, -120.256, -121.345, -120.286; t(mRNA) = -31.554, -31.178, -31.286, -31.198, -12.076, -14.969, -11.896, -14.546, P < 0.05), but the expression levels were not obviously different between groups B and C (t(p) = -32.720, -32.816, -68.668, -187.481, -110.264, -121.345; t(mRNA) = -0.692, -0.579, P > 0.05), which were similar to mRNA level. The Integrinß(1) protein and mRNA were expressed in groups A, B, C and D but no significant difference among them respectively (F(pr) = 0.214;F(mRNA) = 0.045, P > 0.05). CONCLUSIONS: Activation of Stat3 signaling pathway may be involved in up-modulating the expression of MMP-2 in GSFs, and not affect the Integrinß(1) protein and mRNA changes. The results reveal that Stat3 signaling transduction pathway may play a critical role in sclera remodeling by means of modulating MMP-2 expression.