Mining of neurological adverse events associated with valbenazine: A post-marketing analysis based on FDA adverse event reporting system.

PURPOSE: Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine. METHODS: Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale. RESULTS: The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles. CONCLUSIONS: The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.

Dehydration of Organic Solvents from Ternary Mixtures Containing Toluene/Methanol/Water by Pervaporation.

The separation of a toluene/methanol/water ternary mixture is a difficult task due to the toluene/water and toluene/methanol azeotropes. In this article, low-energy pervaporation is proposed for the separation of the ternary azeotrope toluene-methanol-water. This work investigates the effects of feed temperature, feed flow rate, and vacuum on pervaporation and compares the energy consumption of pervaporation with that of distillation. The results showed that at the optimized flow rate of 50 L/h and a permeate side vacuum of 60 kPa at 50 °C, the water and methanol content in the permeate was about 63.2 wt.% and 36.8 wt.%, respectively, the water/ methanol separation factor was 24.04, the permeate flux was 510.7 g/m2·h, the water content in the feed out was reduced from 2.5 wt.% to less than 0.66 wt.%, and the dehydration of toluene methanol could be realized. Without taking into account the energy consumption of pumps and other power equipment, pervaporation requires an energy consumption of 43.53 kW·h to treat 1 ton of raw material, while the energy consumption of distillation to treat 1 ton of raw material is about 261.5 kW·h. Compared to the existing distillation process, the pervaporation process consumes much less energy (about one-sixth of the energy consumption of distillation). There is almost no effect on the surface morphology and chemical composition of the membrane before and after use. The method provides an effective reference for the dehydration of organic solvents from ternary mixtures containing toluene/methanol/water.

Pregnane X receptor (PXR) deficiency promotes hepatocarcinogenesis via induction of Akr1c18 expression and prostaglandin F2α (PGF2α) levels.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Pregnane X receptor (PXR), a xenobiotic-sensing nuclear receptor, plays a critical role in the metabolism of endogenous and exogenous substances in the liver. Here, we investigate whether PXR plays a role in pathogenesis of HCC. We show that liver tumors were developed in diethylnitrosamine (DEN)-treated in PXR knockout (KO) mice. Hepatic levels of prostaglandin F2α (PGF2α) and aldo-keto reductase family 1 member C18 (Akr1c18), a prostaglandin synthase of catalyzing reduction of PGH2 to PGF2α, were significantly elevated in DEN-treated PXR KO mice. Hepatic mRNA levels of alpha fetoprotein (AFP), cyclin D1 (Ccnd1), fibroblast growth factor 21 (FGF21), and inflammatory cytokine interleukin 6 (IL-6) were significantly increased in DEN-treated PXR KO mice. Other members of Akr1c family, liver metabolizing enzymes including Cyp1a2, Cyp2b10 and Cyp3a11, and bile acid synthesis enzyme Cyp7a1 mRNA levels were significantly decreased in DEN-treated PXR KO mice. Our findings revealed that PXR deficiency promoted DEN-induced HCC in mice via induction of Akr1c18 expression and PGF2α levels and the increased PGF2α levels synthetized by Akr1c18 enhanced hepatocytes proliferation and induced inflammatory cytokine production, which accelerated liver tumor development after DEN treatment, suggesting that PXR deficiency may create a microenvironment that is more prone to DEN-induced liver tumors and targeting PXR and Akr1c18 to reduce PGF2α biosynthesis may be a potential and novel therapeutic strategy for HCC.

Chromosomal-level genome assembly and annotation of the tropical sea cucumber Holothuria scabra.

Holothuria scabra, a commercially valuable yet ecologically vulnerable tropical holothuroid, has experienced a severe decline in its wild populations, especially in China. Genomic resources are crucial for the development of effective genomic breeding projects and stock conservation strategies to restore these natural populations. Until now, a high-quality, chromosome-level reference genome for H. scabra has not been available. Here, we employed Oxford Nanopore and Hi-C sequencing technologies to assemble and annotate a high-quality, chromosome-level reference genome of H. scabra. The final genome comprised 31 scaffolds with a total length of 1.19 Gb and a scaffold N50 length of 53.52 Mb. Remarkably, 1,191.67 Mb (99.95%) of the sequences were anchored to 23 pseudo-chromosomes, with the longest one spanning 79.75 Mb. A total of 34,418 protein-coding genes were annotated in the final genome, with BUSCO analysis revealing 98.01% coverage of metazoa_odb10 genes, marking a significant improvement compared to the previous report. These chromosome-level sequences and annotations will provide an essential genomic basis for further investigation into molecular breeding and conservation management of H. scabra.

The first chromosomal-level genome assembly and annotation of white suckerfish Remora albescens.

Remora albescens, also known as white suckerfish, recognized for its distinctive suction-cup attachment behavior and medicinal significance. In this study, we produced a high-quality chromosome-level genome assembly of R. albescens through the integration of 23.87 Gb PacBio long reads, 64.54 Gb T7 short reads, and 88.63 Gb Hi-C data. Initially, we constructed a contig-level genome assembly totaling 605.30 Mb with a contig N50 of 23.12 Mb. Subsequently, employing Hi-C technology, approximately 99.68% (603.38 Mb) of the contig-level genome was successfully assigned to 23 pseudo-chromosomes. Through the integration of homologous-based predictions, ab initio predictions, and RNA-sequencing methods, we successfully identified a comprehensive set of 22,445 protein-coding genes. Notably, 96.36% (21,629 genes) of these were effectively annotated with functional information. The genome assembly achieved an estimated completeness of 98.1% according to BUSCO analysis. This work promotes the applicability of the R. albescens genome, laying a solid foundation for future investigations into genomics, biology, and medicinal importance within this species.

[Rapid determination of 15 N-nitrosamines in air-dried yak meat using one-step QuEChERS-gas chromatography-triple quadrupole mass spectrometry].

A method based on gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) coupled with one-step QuEChERS technique was developed for the simultaneous determination of 15 N-nitrosamines in air-dried yak meat. The hydration volume, extraction solvent, extracting salt, and cleaning material were optimized according to the characteristics of the N-nitrosamines and sample matrix. The optimized conditions were as follows: 10 mL of purified water for sample hydration, acetonitrile as the extraction solvent for the sample after hydration, 4.0 g of anhydrous MgSO4 and 1.0 g of NaCl as extracting salts, 500 mg of MgSO4+25 mg of C18+50 mg of PSA as cleaning materials. Favorable recoveries of the 15 N-nitrosamines were obtained when the extraction solution was incompletely dried. Thus, the final extract was dried to below 0.5 mL under a mild nitrogen stream and then redissolved to 0.5 mL with acetonitrile. After filtration, 200 µL of the sample was transferred to an autosampler vial for GC-MS/MS analysis. The 15 N-nitrosamines were determined using GC-MS/MS on a DB-HeavyWAX column (30 m×0.25 mm×0.25 µm) with an electron impact ion source in multiple-reaction monitoring (MRM) mode, and quantified using an external standard method. Under the optimized experimental conditions, the results showed that the calibration curves exhibited good linearities for the 15 N-nitrosamines, with correlation coefficients (r2) greater than 0.9990. The limits of detection (LODs) and the limits of quantification (LOQs) ranged from 0.05 to 0.20 µg/kg and from 0.10 to 0.50 µg/kg, respectively. At spiked levels of 1LOQ, 2LOQ, and 10LOQ, the average recoveries were 79.4%-102.1%, 80.6%-109.5%, and 83.0%-110.6%, respectively, and the relative standard deviations were in the range of 0.8%-16.0%. The low matrix effects of the 15 N-nitrosamines indicated the high sensitivity of the proposed method. The method was applied to detect representative commercial air-dried yak meat samples obtained using different processing techniques. Seven N-nitrosamines, including N-nitrosodimethylamine, N-nitrosodiisobutylamine, N-nitrosodibutylamine, N-methyl-N-phenylnitrous amide, N-ethyl-N-nitrosoaniline, N-nitrosopyrrolidine, and N-nitrosodiphenylamine were detected in all samples. The average contents of the seven N-nitrosamines was 0.08-20.18 µg/kg. The detection rates and average contents of the N-nitrosamines in cooked air-dried yak meat samples were higher than those in traditional raw air-dried yak meat samples. Compared with the manual QuEChERS method, the one-step QuEChERS method developed integrated the extraction and clean-up procedures into one single run, and the detection efficiency was considerably improved. The developed method is simple, rapid, highly sensitive, and insusceptible to human errors. Thus, it is useful for the determination of N-nitrosamines in air-dried yak meat and can be extended to the qualitative and quantitative analysis of N-nitrosamines in other meat products. It also provides method support and a data reference for the general determination of N-nitrosamines, which is of great significance for food safety.

Reconstructing parent genomes using siblings and other relatives.

Reconstructing the DNA of ancestors from their descendants has the potential to empower phenotypic analyses (including association and genetic nurture studies), improve pedigree reconstruction, and shed light on the ancestral population and phenotypes of ancestors. We developed HAPI-RECAP, a method that reconstructs the DNA of parents from full siblings and their relatives. This tool leverages HAPI2's output, a new phasing approach that applies to siblings (and optionally one or both parents) and reliably infers parent haplotypes but does not link the ungenotyped parents' DNA across chromosomes or between segments flanking ambiguities. By combining IBD between the reconstructed parents and the relatives, HAPI-RECAP resolves the source parent of these segments. Moreover, the method exploits crossovers the children inherited and sex-specific genetic maps to infer the reconstructed parents' sexes. We validated these methods on research participants from both 23andMe, Inc. and the San Antonio Mexican American Family Studies. Given data for one parent, HAPI2 reconstructs large fractions of the missing parent's DNA, between 77.6% and 99.97% among all families, and 90.3% on average in three- and four-child families. When reconstructing both parents, HAPI-RECAP inferred between 33.2% and 96.6% of the parents' genotypes, averaging 70.6% in four-child families. Reconstructed genotypes have average error rates < 10-3, or comparable to those from direct genotyping. HAPI-RECAP inferred the parent sexes 100% correctly given IBD-linked segments and can also reconstruct parents without any IBD. As datasets grow in size, more families will be implicitly collected; HAPI-RECAP holds promise to enable high quality parent genotype reconstruction.

Use of human Caco-2 cells and HPAE-PAD for α-glucosidase assay.

To measure α-glucosidase activity, rat intestinal acetone powder is commonly used as a source of α-glucosidase, and the mutarotase-glucose oxidase (GOD) methods commonly used to quantitate glucose produced by enzymatic hydrolysis of the substrates. In this study, we compared human Caco-2 cell extracts with rat intestinal acetone powder extracts. We also compared high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) with the mutarotase-GOD method. The sensitivity of HPAE-PAD was higher than that of mutarotase-GOD. The glucose concentration quantified by HPAE-PAD was similar to that quantified using the mutarotase-GOD method. In the maltase reaction, 1-deoxynojirimycin (1-DNJ) exerted a more potent inhibitory effect on human enzymes than on rat enzymes. This order was reversed during the sucrase reaction. These results suggested that the combined use of Caco-2 cell extracts and HPAE-PAD is advantageous for use in α-glucosidase-related basic research.

Modification Strategies of High-Energy Li-Rich Mn-Based Cathodes for Li-Ion Batteries: A Review.

Li-rich manganese-based oxide (LRMO) cathode materials are considered to be one of the most promising candidates for next-generation lithium-ion batteries (LIBs) because of their high specific capacity (250 mAh g-1) and low cost. However, the inevitable irreversible structural transformation during cycling leads to large irreversible capacity loss, poor rate performance, energy decay, voltage decay, etc. Based on the recent research into LRMO for LIBs, this review highlights the research progress of LRMO in terms of crystal structure, charging/discharging mechanism investigations, and the prospects of the solution of current key problems. Meanwhile, this review summarizes the specific modification strategies and their merits and demerits, i.e., surface coating, elemental doping, micro/nano structural design, introduction of high entropy, etc. Further, the future development trend and business prospect of LRMO are presented and discussed, which may inspire researchers to create more opportunities and new ideas for the future development of LRMO for LIBs with high energy density and an extended lifespan.

Integrating image and gene-data with a semi-supervised attention model for prediction of KRAS gene mutation status in non-small cell lung cancer.

KRAS is a pathogenic gene frequently implicated in non-small cell lung cancer (NSCLC). However, biopsy as a diagnostic method has practical limitations. Therefore, it is important to accurately determine the mutation status of the KRAS gene non-invasively by combining NSCLC CT images and genetic data for early diagnosis and subsequent targeted therapy of patients. This paper proposes a Semi-supervised Multimodal Multiscale Attention Model (S2MMAM). S2MMAM comprises a Supervised Multilevel Fusion Segmentation Network (SMF-SN) and a Semi-supervised Multimodal Fusion Classification Network (S2MF-CN). S2MMAM facilitates the execution of the classification task by transferring the useful information captured in SMF-SN to the S2MF-CN to improve the model prediction accuracy. In SMF-SN, we propose a Triple Attention-guided Feature Aggregation module for obtaining segmentation features that incorporate high-level semantic abstract features and low-level semantic detail features. Segmentation features provide pre-guidance and key information expansion for S2MF-CN. S2MF-CN shares the encoder and decoder parameters of SMF-SN, which enables S2MF-CN to obtain rich classification features. S2MF-CN uses the proposed Intra and Inter Mutual Guidance Attention Fusion (I2MGAF) module to first guide segmentation and classification feature fusion to extract hidden multi-scale contextual information. I2MGAF then guides the multidimensional fusion of genetic data and CT image data to compensate for the lack of information in single modality data. S2MMAM achieved 83.27% AUC and 81.67% accuracy in predicting KRAS gene mutation status in NSCLC. This method uses medical image CT and genetic data to effectively improve the accuracy of predicting KRAS gene mutation status in NSCLC.

A robust framework for enhancing cardiovascular disease risk prediction using an optimized category boosting model.

Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and it is of utmost importance to accurately assess the risk of cardiovascular disease for prevention and intervention purposes. In recent years, machine learning has shown significant advancements in the field of cardiovascular disease risk prediction. In this context, we propose a novel framework known as CVD-OCSCatBoost, designed for the precise prediction of cardiovascular disease risk and the assessment of various risk factors. The framework utilizes Lasso regression for feature selection and incorporates an optimized category-boosting tree (CatBoost) model. Furthermore, we propose the opposition-based learning cuckoo search (OCS) algorithm. By integrating OCS with the CatBoost model, our objective is to develop OCSCatBoost, an enhanced classifier offering improved accuracy and efficiency in predicting CVD. Extensive comparisons with popular algorithms like the particle swarm optimization (PSO) algorithm, the seagull optimization algorithm (SOA), the cuckoo search algorithm (CS), K-nearest-neighbor classification, decision tree, logistic regression, grid-search support vector machine (SVM), grid-search XGBoost, default CatBoost, and grid-search CatBoost validate the efficacy of the OCSCatBoost algorithm. The experimental results demonstrate that the OCSCatBoost model achieves superior performance compared to other models, with overall accuracy, recall, and AUC values of 73.67%, 72.17%, and 0.8024, respectively. These outcomes highlight the potential of CVD-OCSCatBoost for improving cardiovascular disease risk prediction.

Diagnosis of pulmonary hemorrhagic leptospirosis complicated by invasive pulmonary aspergillosis complemented by metagenomic next-generation sequencing: a case report.

Background: Leptospirosis is a bacterial zoonosis with variable clinical manifestations. Pulmonary diffuse hemorrhagic leptospirosis often occurs rapidly and, when not promptly diagnosed and treated, it can be life-threatening. Aspergillus flavus is an opportunistic fungus that is commonly seen in immunosuppressed patients. Invasive pulmonary aspergillosis also progresses rapidly. This case study describes a patient with severe pneumonia caused by pulmonary hemorrhagic leptospirosis combined with invasive pulmonary aspergillosis. We have found almost no clinical reports to date on these two diseases occurring in the same patient. Case presentation: A 73-year-old male arrived at our hospital complaining of fever, general malaise, and hemoptysis that had lasted 4 days. The patient was initially diagnosed with severe pneumonia in the emergency department, but he did not respond well to empiric antibiotics. Subsequently, the patient's condition worsened and was transferred to the ICU ward after emergency tracheal intubation and invasive ventilator. In the ICU, antibacterial drugs were adjusted to treat bacteria and fungi extensively. Although the inflammatory indices decreased, the patient still had recurrent fever, and a series of etiological tests were negative. Finally, metagenomic next-generation sequencing (mNGS) of bronchial alveolar lavage fluid detected Leptospira interrogans and Aspergillus flavus. After targeted treatment with penicillin G and voriconazole, the patient's condition improved rapidly, and he was eventually transferred out of the ICU and recovered. Conclusion: Early recognition and diagnosis of leptospirosis is difficult, especially when a patient is co-infected with other pathogens. The use of mNGS to detect pathogens in bronchial alveolar lavage fluid is conducive to early diagnosis and treatment of the disease, and may significantly improve the prognosis in severe cases.

N-of-1 medicine.

ABSTRACT: The fields of precision and personalised medicine have led to promising advances in tailoring treatment to individual patients. Examples include genome/molecular alteration-guided drug selection, single-patient gene therapy design and synergy-based drug combination development, and these approaches can yield substantially diverse recommendations. Therefore, it is important to define each domain and delineate their commonalities and differences in an effort to develop novel clinical trial designs, streamline workflow development, rethink regulatory considerations, create value in healthcare and economics assessments, and other factors. These and other segments are essential to recognise the diversity within these domains to accelerate their respective workflows towards practice-changing healthcare. To emphasise these points, this article elaborates on the concept of digital health and digital medicine-enabled N-of-1 medicine, which individualises combination regimen and dosing using a patient's own data. We will conclude with recommendations for consideration when developing novel workflows based on emerging digital-based platforms.

IFN-α armed gE elicits superior immunogenicity compared to unmodified antigens and flagellin armed gE in mice.

Herpes zoster (HZ) induces significant pain and discomfort, which can seriously affect the quality of life of patients. At present, there is no specific treatment for HZ, and the mosteffective HZ control is vaccination. The main obstacle to developing an effective HZ vaccine is poorly induced cellular immune response. In this study, the IFN-α-gE-Fc fusion protein induced higher levels of humoral and cellular immunity compared to the unengineered gE antigen and higher levels of cellular immunity compared to the flagellin-gE-Fc fusion protein in a murine model. Compared with the marketed recombinant herpes zoster vaccine (Shingrix), IFN-α-gE-Fc can replace current used MPL adjuvant. At the same time, the immunogenicity of the IFN-α-gE-Fc + AQ was not weaker than that of the marketed recombinant zoster vaccine. The novel fusion protein provides a candidate entity for the development of a safe and effective novel HZ vaccine.

Rutin promotes M2 phenotype microglia polarization by suppressing the JAK/STAT3 signaling to protect against retinal ischemia-reperfusion injury.

We aimed to investigate the neuroprotective effect of rutin on retinal ganglion cells (RGCs) under ischemia-reperfusion (I/R) conditions and the underlying mechanisms involving microglia polarization and JAK/STAT3 signaling. RGCs isolated from C57/Bl6 mice were co-cultured with BV2 microglial cells under normal or in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) conditions. Rutin's effects were evaluated by assessing cell viability, apoptosis rates, cytokine levels, microglial polarization markers and JAK/STAT3 phosphorylation levels. The specific target is confirmed through the inhibitory effect of rutin on the respectively activated signaling factors. Furthermore, molecular docking analyses elucidated rutin-JAK1 interactions. OGD/R conditions significantly reduced RGC viability, exacerbated by BV2 co-culture. However, both 1 µM and 5 µM rutin treatment dose-dependently enhanced RGC viability, reduced apoptosis, and suppressed pro-inflammatory cytokine levels. Western blot analysis indicated that rutin promoted the M2 microglial phenotype and suppressed JAK/STAT3 signaling. Notably, rutin selectively inhibited JAK1 phosphorylation without affecting STAT3. Molecular docking highlighted potential interaction sites between rutin and specific JAK1 pseudokinase domain. Rutin exerts neuroprotective effects against retinal I/R injury by promoting M2 microglial polarization, potentially through the selective inhibition of JAK1 phosphorylation within the JAK/STAT3 signaling pathway. These findings provide a foundation for the therapeutic potential of rutin in retinal I/R injuries.

Solvation enhanced long-range proton transfer in aqueous phase for glycolaldehyde hydrogenation over Ru/C catalyst.

The catalytic hydrogenation of biomass-derived chemicals is essential in chemical industry due to the growing demand for sustainable and renewable energy sources. In this study, we present a comprehensive theoretical investigation regarding the hydrogenation of glycolaldehyde to ethylene glycol over a Ru/C catalyst by employing density functional theory and ab initio molecular dynamics simulations. With inclusion of explicit solvation, we have demonstrated that the glycolaldehyde hydrogenation is significantly improved due to the fast proton transfer through the hydrogen bond network. The enhanced activity could be attributed to the participation of the solvent water as the hydrogen source and the highly positively charged state of a Ru cluster in an aqueous phase, which are critical for the activation of aldehyde groups and proton-assisted hydrogenation. Overall, our findings provide valuable insights into glycolaldehyde hydrogenation over Ru/C catalysts in the aqueous phase, highlighting the importance of solvation effects in the biomass conversion.

Aerobic Exercise Attenuates Pressure Overload-Induced Myocardial Remodeling and Myocardial Inflammation via Upregulating miR-574-3p in Mice.

BACKGROUND: Exercise training can promote cardiac rehabilitation, thereby reducing cardiovascular disease mortality and hospitalization rates. MicroRNAs (miRs) are closely related to heart disease, among which miR-574-3p plays an important role in myocardial remodeling, but its role in exercise-mediated cardioprotection is still unclear. METHODS: A mouse myocardial hypertrophy model was established by transverse aortic coarctation, and a 4-week swimming exercise training was performed 1 week after the operation. After swimming training, echocardiography was used to evaluate cardiac function in mice, and histopathologic staining was used to detect cardiac hypertrophy, myocardial fibrosis, and cardiac inflammation. Quantitative real-time polymerase chain reaction was used to detect the expression levels of miR-574-3p and cardiac hypertrophy markers. Western blotting detected the IL-6 (interleukin-6)/JAK/STAT inflammatory signaling pathway. RESULTS: Echocardiography and histochemical staining found that aerobic exercise significantly improved pressure overload-induced myocardial hypertrophy (n=6), myocardial interstitial fibrosis (n=6), and cardiac inflammation (n=6). Quantitative real-time polymerase chain reaction detection showed that aerobic exercise upregulated the expression level of miR-574-3p (n=6). After specific knockdown of miR-574-3p in mouse hearts with adeno-associated virus 9 using cardiac troponin T promoter, we found that the protective effect of exercise training on the heart was significantly reversed. Echocardiography and histopathologic staining showed that inhibiting the expression of miR-574-3p could partially block the effects of aerobic exercise on cardiac function (n=6), cardiomyocyte cross-sectional area (n=6), and myocardial fibrosis (n=6). Western blotting and immunohistochemical staining showed that the inhibitory effects of aerobic exercise on the IL-6/JAK/STAT pathway and cardiac inflammation were partially abolished after miR-574-3p knockdown. Furthermore, we also found that miR-574-3p exerts cardioprotective effects in cardiomyocytes by targeting IL-6 (n=3). CONCLUSIONS: Aerobic exercise protects cardiac hypertrophy and inflammation induced by pressure overload by upregulating miR-574-3p and inhibiting the IL-6/JAK/STAT pathway.

MicroRNA sequencing analysis reveals immune responses in hepatopancreas of Fenneropenaeus penicillatus under white spot syndrome virus infection.

White Spot Disease is one of the most harmful diseases of the red tail shrimp, which can cause devastating economic losses due to the highest mortality up to 100% within a few days. MicroRNAs (miRNAs) are large class of small noncoding RNAs with the ability to post-transcriptionally repress the translation of target mRNAs. MiRNAs are considered to have a significant role in the innate immune response of crustaceans, particularly in relation to antiviral defense mechanisms. Numerous crustacean miRNAs have been verified to be required in host immune defense against viral infection, however, till present, the miRNAs functions of F. penicillatus defense WSSV infection have not been studied yet. Here in this study, for the first time, miRNAs involved in the F. penicillatus immune defense against WSSV infection were identified using high-throughput sequencing platform. A total of 432 miRNAs were obtained including 402 conserved miRNAs and 30 novel predicted miRNAs. Comparative analysis between the WSSV-challenged group and the control group revealed differential expression of 159 microRNAs in response to WSSV infection. Among these, 48 were up-regulated and 111 were down-regulated. Ten candidate MicroRNAs associated with immune activities were randomly selected for qRT-PCR analysis, which confirming the expression profiling observed in the MicroRNA sequencing data. As a result, most differentially expressed miRNAs were down-regulated lead to increase the expression of various target genes that mediated immune reaction defense WSSV infection, including genes related to signal transduction, Complement and coagulation cascade, Phagocytosis, and Apoptosis. Furthermore, the genes expression of the key members in Toll and Imd signaling pathways and apoptotic signaling were mediated by microRNAs to activate host immune responses including apoptosis against WSSV infection. These results will help to understand molecular defense mechanism against WSSV infection in F. penicillatus and to develop an effective WSSV defensive strategy in shrimp farming.

Efficacy of acellular fish skin graft in the management of chronic ulcer: a systematic review and meta-analysis.

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.

Safety and immunogenicity of homologous prime-boost CoronaVac vaccine in people living with HIV in China: A multicenter prospective cohort study.

People living with HIV (PLWH) are particularly vulnerable to SARS-CoV-2. This multicentre prospective cohort study evaluated the long-term immunogenicity and safety of a third homologous dose of Sinovac CoronaVac in PLWH in China. A total of 228 PLWH and 127 HIV-negative controls were finally included and followed up for 6 months. Fewer participants reported mild or moderate adverse reactions, and no serious adverse events were observed. The median levels of neutralizing antibodies (nAbs) and immunoglobulin G against the receptor-binding domain of the spike protein (S-IgG) in PLWH (655.92 IU/mL, IQR: 175.76-1663.55; 206.83 IU/mL, IQR: 85.20-397.82) were comparable to those in control group (1067.16 IU/mL, IQR: 239.85-1670.83; 261.70 IU/mL, IQR: 77.13-400.75), and reached their peak at 4 weeks, exhibiting a delayed peak pattern compared to the 2-week peak in control group. After then, the immune titres gradually decreased over time, but most participants still maintained positive seroconversion at the 6-month mark. Multivariable generalized estimating equation analysis indicated that CD4+T cell count, HIV viral load, and antiretroviral therapy (ART) were independent factors strongly associated with immune response (each p < 0.05). We suggested that PLWH should maintain well-controlled HIV status through ART and receive timely administration of the second booster dose for optimal protection.