Four-Year Treatment Effect of Custom-Made Foot Orthosis on Pediatric Symptomatic Accessory Navicular Bone Combined with Flexible Flatfoot.

Purpose: Congenital accessory navicular bone (ANB) is a common variant in the foot and is prone to cause several clinical symptoms. Wearing custom-made foot orthosis is considered a desirable option; however, there is limited evidence of its effectiveness. This study aims to report the mid-term effect of foot orthosis for symptomatic pediatric ANBs. Methods: School-age children with symptomatic ANBs combined with flexible flatfoot in the authors' institute were recruited and got custom-made foot orthosis treatment. They were followed up over 4 years. The general characteristics of these children were collected before treatment, including age, gender, and body mass index (BMI). The indicators of foot symptoms, including frequency and location of pain, visual analogue scale (VAS), arch index (AI), and hind foot valgus angle (HVA), were measured during pretreatment and at the last follow-up. Results: Twenty-seven children were recruited for this study. After 4 years of custom-made foot orthosis treatment, significant improvements showed in pain frequency, VAS, AI, and HVA (P < 0.001). Type II ANBs showed a higher pain index pretreatment (P < 0.001) and reduced after treatment (P < 0.001). Conclusion: Mid-term effect of custom-made foot orthosis is inspiring in clinical symptoms of pediatric congenital ANBs combined with flexible flatfoot and may be an optional nonoperative treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-024-01210-7.

Flavonoid Profiles in the Pulp of Different Lemon Cultivars and Their Antioxidant Activity Based on UPLC-Q-TOF-MS.

Previous studies have indicated that there may be differences among the varieties of lemon flavonoids, but the details have not yet been made clear, which limits the comprehensive use of different cultivated lemon varieties. In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) and ultraviolet-visible spectroscopy (UV-Vis) were used to investigate the types and contents of flavonoids in the flesh of the main cultivated variety (Eureka) and five common lemon varieties, as well as their in vitro antioxidant activity. A total of 21 compounds were identified, five of which were common compounds. Among them, Verna, Lisbon, and Bearss each have characteristic components that can serve as potential criteria for variety identification. Each of the six varieties of lemon has strong antioxidant activity. The antioxidant activity of different lemon varieties is related to flavonoids. Therefore, Eureka and the other five varieties of lemon are good natural antioxidants, and the cultivation and industrial production of lemons should consider the needs and selection of suitable varieties.

Discovery of Cell Number-Interstitial Fluid Volume (CIF) Ratio Reveals Secretory Autophagy Pathway to Supply eHsp90α for Wound Healing.

Cell secretion repairs tissue damage and restores homeostasis throughout adult life. The extracellular heat shock protein-90alpha (eHsp90α) has been reported as an exosome cargo and a potential driver of wound healing. However, neither the mechanism of secretion nor the genetic evidence for eHsp90α in wound healing has been substantiated. Herein, we show that tissue injury causes massive deposition of eHsp90α in tissues and secretion of eHsp90α by cells. Sequential centrifugations of conditioned medium from relevant cell lines revealed the relative distributions of eHsp90α in microvesicle, exosome and trypsin-sensitive supernatant fractions to be approximately <2%, <4% and >95%, respectively. Establishing the cell-number-to-interstitial-fluid-volume (CIF) ratio for the microenvironment of human tissues as 1 × 109 cells: 1 mL interstitial fluid enabled us to predict the corresponding tissue concentrations of eHsp90α in these fractions as 3.74 µg/mL, 5.61 µg/mL and 178 µg/mL. Remarkably, the 178 µg/mL eHsp90α matches the previously reported 100-300 µg/mL of recombinant eHsp90α whose topical application promotes maximum wound healing in animal models. More importantly, we demonstrate that two parallel secretory autophagy-regulating gene families, the autophagy-regulating (AR) genes and the Golgi reassembly-stacking protein (GRASP) genes work together to mediate the secretion of the physiological concentration of eHsp90α to promote wound healing. Thus, utilization of the CIF ratio-based extrapolation method may enable investigators to rapidly predict biomarker targets from cell-conditioned-medium data.

Recent Progress on Flexible Self-Powered Tactile Sensing Platforms for Health Monitoring and Robotics.

Over the past decades, tactile sensing technology has made significant advances in the fields of health monitoring and robotics. Compared to conventional sensors, self-powered tactile sensors do not require an external power source to drive, which makes the entire system more flexible and lightweight. Therefore, they are excellent candidates for mimicking the tactile perception functions for wearable health monitoring and ideal electronic skin (e-skin) for intelligent robots. Herein, the working principles, materials, and device fabrication strategies of various self-powered tactile sensing platforms are introduced first. Then their applications in health monitoring and robotics are presented. Finally, the future prospects of self-powered tactile sensing systems are discussed.

Chlorhexidine gluconate versus povidone-iodine for nasal bacteria decolonization before transsphenoidal surgery in patients with pituitary neuroendocrine tumors: A prospective, randomized, double-blind, non-inferiority trial.

BACKGROUND: This study aimed to compare the nasal decolonization efficacy and comfort between chlorhexidine gluconate (CHG) and povidone-iodine (PVP) to provide an evidence basis for clinical guidance. METHODS: A prospective, randomized, single-blinded, noninferior clinical trial was conducted in 174 patients with pituitary neuroendocrine tumors (PitNETs) who were scheduled to undergo transsphenoidal surgery. The noninferiority margin was δ=-0.1. The primary outcome was the effective rate of disinfection. The secondary outcomes included post-operative inflammatory indicators, the intracranial infection rate, and the proportion of intracranial infection. RESULTS: The effective clearance rate of post-operative nasal bacteria was nonsignificantly different between the CHG and PVP groups (88.64% vs. 82.56%; between-group difference 6.10%; 95% CI [-5.30 to 17.50]). There was no significant difference in the incidence of post-operative central nervous system infections or serum inflammation-related indications between the two groups, but sterilization tended to occur quicker and last longer in the CHG group. CHG seemed to have advantages in terms of comfort, including less nasal irritation, less pungency, and better intranasal coloration. CONCLUSION: CHG and PVP have equal efficacy in nasal decolonization before transsphenoidal surgery, but CHG seems to have comfort-related advantages in terms of less nasal irritation, less pungency, and better intranasal coloration.

Epidermal stem cells: skin surveillance and clinical perspective.

The skin epidermis is continually influenced by a myriad of internal and external elements. At its basal layer reside epidermal stem cells, which fuels epidermal renovation and hair regeneration with powerful self-renewal ability, as well as keeping diverse signals that direct their activity under surveillance with quick response. The importance of epidermal stem cells in wound healing and immune-related skin conditions has been increasingly recognized, and their potential for clinical applications is attracting attention. In this review, we delve into recent advancements and the various physiological and psychological factors that govern distinct epidermal stem cell populations, including psychological stress, mechanical forces, chronic aging, and circadian rhythm, as well as providing an overview of current methodological approaches. Furthermore, we discuss the pathogenic role of epidermal stem cells in immune-related skin disorders and their potential clinical applications.

SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2.

Sirtuin 1 (SIRT1) is a histone deacetylase and plays diverse functions in various physiological events, from development to lifespan regulation. Here, in Parkinson's disease (PD) model mice, we demonstrated that SIRT1 ameliorates parkinsonism, while SIRT1 knockdown further aggravates PD phenotypes. Mechanistically, SIRT1 interacts with and deacetylates pyruvate kinase M2 (PKM2) at K135 and K206, thus leading to reduced PKM2 enzyme activity and lactate production, which eventually results in decreased glial activation in the brain. Administration of lactate in the brain recapitulates PD-like phenotypes. Furthermore, increased expression of PKM2 worsens PD symptoms, and, on the contrary, inhibition of PKM2 by shikonin or PKM2-IN-1 alleviates parkinsonism in mice. Collectively, our data indicate that excessive lactate in the brain might be involved in the progression of PD. By improving lactate homeostasis, SIRT1, together with PKM2, are likely drug targets for developing agents for the treatment of neurodegeneration in PD.

Rise of Metal-Organic Frameworks: From Synthesis to E-Skin and Artificial Intelligence.

Metal-organic frameworks (MOFs) have attained broad research attention in the areas of sensors, resistive memories, and optoelectronic synapses on the merits of their intriguing physical and chemical properties. In this review, recent progress on the synthesis of MOFs and their electronic applications is introduced and discussed. Initially, the crystal structures and properties of MOFs encompassing optical, electrical, and chemical properties are discussed in brief. Subsequently, advanced synthesis methods for MOFs are introduced, categorized into hydrothermal approach, microwave synthesis, mechanochemical synthesis, and electrochemical deposition. After that, the various roles of MOFs in widespread applications, including sensing, information storage, optoelectronic synapses, machine learning, and artificial intelligence, are discussed, highlighting their versatility and the innovative solutions they provide to long-standing challenges. Finally, an outlook on remaining challenges and a future perspective for MOFs are proposed.

[Methodological and reporting quality of randomized controlled trials on the treatment of benign prostatic hyperplasia with traditional Chinese medicine].

OBJECTIVE: To systematically evaluate the methodological quality and reporting quality of randomized controlled trials (RCT) on the treatment of BPH with traditional Chinese medicine (TCM), in order to provide some methodological reference for clinical practice and research. METHODS: We searched CNKI, VIP, Wanfang Data and PubMed for RCTs on the treatment of BPH with TCM published in China from January 2013 to November 2023. Two researchers screened the literature separately, and evaluated the methodological and reporting quality of the RCTs based on the Cochrane bias risk assessment tool and CONSORT TCM compound. RESULTS: Totally, 88 RCTs were included in this study. In terms of methodological quality, according to the Cochrane bias risk assessment tool, 27 biases in the process of randomization were identified as of low-risk and the other 61 of a certain risk. Among the allocation-related biases deviating from the established interventions, 76 were of low risk, 10 of a certain risk and 2 of high risk; among the compliance-related biases deviating from the established interventions, 76 were of low risk and 12 of a certain risk; among the biases due to missing outcome data, 86 were of low risk and 2 of a certain risk, while all the biases due to outcome measurement were of low risk; and among the biases from selective reporting, 65 were of low-risk, 2 of a certain risk and 21 of high-risk. In terms of reporting quality, according to the evaluation criteria of consort TCM compound, appropriate key words were used in 1 RCT (0.01%), the random assignment sequence method described in 27 (30.68%), the details of assignment limitation given in 5 (5.68%), assignment concealment mentioned in 3 (3.41%), the blind method and assignment concealment employed in 3 (3.41%), fall-offs recorded in 10 (11.36%), adverse events reported in 38 (43.18%), and limitations of the trials analyzed in 18 (20.45%). All the RCTs lacked complete intervention measures, subject flow chart, clinical trial registration and research schemes. CONCLUSION: At present, the methodological quality and reporting quality of RCTs on the treatment of BPH with TCM are generally low, with the main problems of incomplete experimental designs, lack of detailed description of randomized and blind methods, and insufficient TCM symptom evaluation of outcome indicators. Researchers should be cautious in adopting and applying the results reported, follow the CONSORT statement in design, registration, implement and reporting of the scheme, fully consider the clinical characteristics of TCM in the treatment of BPH, and reasonably design and report the evaluation indicators.

Subtyping of gastric cancer based on basement membrane genes that stratifies the prognosis, immune infiltration and therapeutic response.

Gastric cancer (GC) is highly heterogeneous and prone to metastasis, which are obstacles to the effectiveness of treatment. The basement membrane (BM) acts as a barrier to tumor cell invasion and metastasis. It is critical to investigate the relationship between BM status, metastasis, and patient prognosis. In several large cohorts, we investigated BM gene expression-based molecular classification and risk-prognosis models for GC, examined tumor microenvironment (TME) differences among different molecular subtypes, and developed risk models in predicting prognosis, immunotherapy effectiveness, and chemotherapy resistance. Three GC subtypes (BMclusterA/B/C) based on BM gene expression status were discovered. Each of the three GC subtypes has unique immune infiltration and activated oncogenic signals. Moreover, a 6-gene score (BMscore) predictive model was developed. The low BMscore group had a high tumor mutation burden, high immunogenicity, and low RHOJ expression levels, implying that individuals with GC in this category may be more susceptible to immunotherapy and treatment. The EMT subtype showed a considerably higher BMscore than the other subtypes in the Asian Organization for Research on Cancer (ACRG) molecular classification. Endothelial cells, smooth muscle cells, and fibroblasts may be engaged in regulating BM reorganization in GC progression, according to single-cell transcriptome analyses. In conclusion, we defined a novel molecular classification of GC based on BM genes, developed a prognostic risk model, and elucidated the cell subpopulations involved in BM remodeling at the single-cell level. This study has deepened the understanding of the relationship between GC metastasis and BM alterations, achieved prognostic stratification, and guided therapy.

How do students of different self-efficacy regulate learning in collaborative design activities? An epistemic network analysis approach.

Introduction: Students' self-regulation skills and self-efficacy are linked to performance and are considered essential for lifelong learning. Understanding these skills and their development is crucial for educational success and long-term personal growth. Methods: In this study, 60 students attending a university-level collaborative design course were recruited as participants. They were initially classified into three groups [high, mixed, and low self-efficacy (SE)] based on the initial test results. Students' written reflections were then analyzed using epistemic network analysis (ENA), aiming to explore the characteristics and developmental trajectories of self-regulated learning (SRL). Results: Comparing with the other two groups, the high self-efficacy (HSE) group demonstrated: (1) more behavioral characteristics of SRL in the performance and self-reflection stages, (2) an earlier development of interest 91 in the task and recognition of its value during collaborative design activities, 92 followed by the utilization of more cognitive and metacognitive strategies; and (3) an "anticipation-behavior-reflection" loop in the self-regulation process. Discussion: These findings highlight the importance of fostering high self-efficacy among students to enhance their self-regulated learning capabilities and overall academic performance. Strategies for improving learners' SRL and future research directions were provided accordingly.

SEC16A Variants Predispose to Chronic Pancreatitis by Impairing ER-to-Golgi Transport and Inducing ER Stress.

Chronic pancreatitis (CP) is a complex disease with genetic and environmental factors at play. Through trio exome sequencing, a de novo SEC16A frameshift variant in a Chinese teenage CP patient is identified. Subsequent targeted next-generation sequencing of the SEC16A gene in 1,061 Chinese CP patients and 1,196 controls reveals a higher allele frequency of rare nonsynonymous SEC16A variants in patients (4.90% vs 2.93%; odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26-2.33). Similar enrichments are noted in a French cohort (OR, 2.74; 95% CI, 1.67-4.50) and in a biobank meta-analysis (OR, 1.16; 95% CI, 1.04-1.31). Notably, Chinese CP patients with SEC16A variants exhibit a median onset age 5 years earlier than those without (40.0 vs 45.0; p = 0.012). Functional studies using three CRISPR/Cas9-edited HEK293T cell lines show that loss-of-function SEC16A variants disrupt coat protein complex II (COPII) formation, impede secretory protein vesicles trafficking, and induce endoplasmic reticulum (ER) stress due to protein overload. Sec16a+/- mice, which demonstrate impaired zymogen secretion and exacerbated ER stress compared to Sec16a+/+, are further generated. In cerulein-stimulated pancreatitis models, Sec16a+/- mice display heightened pancreatic inflammation and fibrosis compared to wild-type mice. These findings implicate a novel pathogenic mechanism predisposing to CP.

Selective extraction of genomic DNA from leopard cat (Prionailurus bengalensis), hairy-crowned deer (Elaphodus cephalophus) and muntjac (Muntiacus reevesi) using hydrophobic magnetic deep eutectic solvents.

Wild animals, as a vital component of our natural world, serve a crucial role in preserving ecological equilibrium and biodiversity. By delving into the genetic constitution of wild animal populations, the evolutionary history, genetic diversity, and adaptation mechanisms could be explored, thereby informing conservation strategies and safeguarding the future of these species. In order to study the genetic information of wild animals, it is necessary to extract high purity and high concentration of wild animal genomic DNA. In this work, a hydrophobic magnetic deep eutectic solvent (HMDES) based vortexed extraction was developed for the extraction of genomic DNA from leopard cat (Prionailurus bengalensis), hairy-crowned deer (Elaphodus cephalophus) and muntjac (Muntiacus reevesi) muscle tissue, respectively. Extraction conditions like the pH value, extraction time, temperature and the amount of HMDES used were optimized by single-factor experiments. Under the optimized condition, genomic DNA could be selectively extracted from the three animal tissues. The limits of detection (LOD) and limits of quantification (LOQ) of the proposed method were 2.86 ng/µL and 8.66 ng/µL, respectively. Meanwhile, the relative standard deviation (RSD) of the method precision and repeatability were 1.64 % and 5.57 % at 20 ng/µL, showing the method has good precision and repeatability. After extraction, the DNA extracted into the HMDES droplets can be quickly recovered and the HMDES can be recycled and reused. The method proposed is a fast, environmental-friendly and high efficient extraction strategy for purification and enrichment of genomic DNA from leopard cat, hairy-crowned deer and muntjac tissues.

Aluminum-Lithium Alloy Fillers Enhancing the Room Temperature Performances of Polymer Electrolytes for All-Solid-State Lithium Batteries.

Poly(ethylene oxide) (PEO) electrolytes usually suffer from low room temperature (RT) ionic conductivity and a narrow voltage window, which limits the improvement of energy density and practical applications in all-solid-state batteries. Composite polymer electrolytes (CPEs) are regarded as the common method to reduce the crystallinity of polymers and increase the lithium ion conductivity. Compared with active or inert ceramic material fillers in previous studies, aluminum-lithium alloy fillers are used to prepare composite electrolytes in this study, showing excellent performance at room temperature. The conductivity of the PEO-based electrolytes increases by a factor of 3.62-3.62× 10-4 S cm-1 at RT with 5 wt % Al-Li alloy. The transference number of Li+ is increased to 0.524. The characteristics of the Al-Li alloy and higher conductivity enable the composite electrolyte to stabilize the interface with the electrodes, reducing the polarization of solid-state batteries. The all-solid-state Li/PEO-5%/LiFePO4 cells show the highest initial discharge capacity of 153 mAh g-1 and the highest stable discharge capacity of 147 mAh g-1 with the initial Coulombic efficiency of more than 100%. It also exhibits the best rate capacity and cycle performance (90% capacity retention rate after 100 cycles).

Previously Unrecognized and Potentially Consequential Challenges Facing Hsp90 Inhibitors in Cancer Clinical Trials.

Targeting the Hsp90 chaperone machinery in various cancers with 200 mono- or combined- therapy clinical trials since 1999 has yet yielded any success of FDA approval. Blames for the failures were unanimously directed on the Hsp90 inhibitors or tumors or both. However, analyses of recent cellular and genetic studies together with the Hsp90 data from the Human Protein Atlas database suggest that the vast variations in Hsp90 expression among different organs in patients might have been the actual cause. It is evident now that Hsp90ß is the root of dose-limiting toxicity (DLT), whereas Hsp90α is a buffer of penetrated Hsp90 inhibitors. The more Hsp90α, the safer Hsp90ß and the lower DTL are for the host. Unfortunately, the dramatic variations of Hsp90, from total absence in eye, muscle, pancreas and heart to abundance in reproduction organs, lung, liver and gastrointestinal track, would cause the selection of any fair toxicity biomarker and an effective maximum tolerable dose (MTD) of Hsp90 inhibitor extremely challenging. In theory, a safe MTD for the organs with high Hsp90 could harm the organs with low Hsp90. In reverse, a safe MTD for organs with low or undetectable Hsp90 would have little impact on the tumors, whose cells exhibit 3-7% Hsp90 over 2-3% Hsp90 in normal cells. Moreover, not all tumor cell lines tested follow the "inhibitor binding-client protein degradation" paradigm. It is likely why the oral Hsp90 inhibitor TAS-16 (Pimitespib), which bypasses blood circulation and other organs, showed some beneficiary efficacy by conveniently hitting tumors along the gastrointestinal track. The critical question is what the next step will be for Hsp90 chaperone as a cancer therapeutic target.

Mapping and analysis of protein and gene profiles identify the important role of TGF-ß in synovial invasion in pigmented villonodular synovitis.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare benign proliferative disease affecting the soft tissue lining the synovial joints and tendons. Its etiology is poorly understood, largely limiting the availability of current therapeutic options. Here, we mapped the synovial gene and protein profiles of patients with PVNS, revealed a link between synovial inflammation and invasion, and elucidated the potential molecular mechanism involved. METHODS: The expression of synovial genes from six control individuals, seven OA patients, and nineteen PVNS patients was analyzed via RNA sequencing. Protein profiles from five control individuals, ten OA patients, and thirty-two PVNS patients were analyzed using label-free proteomics. Microarray and RT-PCR analyses and immunohistochemical staining were used to evaluate inflammatory cytokine and target gene expression levels in synovial tissue, epithelial cells, and synovial fibroblasts (FLSs) derived from PVNS tissue. Various signaling pathway inhibitors, siRNAs, and western blots were used for molecular mechanism studies. Transwell migration and invasion assays were subsequently performed. RESULTS: In total, 522 differentially expressed proteins were identified in the PVNS tissues. By integrating RNA sequencing and microarray analyses, significant changes in the expression of EMT-related genes, including TGFBI, N-cadherin, E-cadherin, SNAIL, and TWIST, were confirmed in the PVNS tissue compared to the control tissue. In vitro, TGF-ß induced EMT and increased epithelial cell migration and invasion. Moreover, TGF-ß not only promoted interactions between epithelial cells and FLSs but also directly increased the migration and invasion abilities of FLSs by activating the classical Smad2/3 and nonclassical JNK/AKT signaling pathways. CONCLUSION: This study provides overall protein and gene profiles of PVNS and identifies the crucial role of TGF-ß in synovial invasion pathology. Exploring the related molecular mechanism may also reveal a new strategy or target for PVNS therapy.

[Exploration of cancer biological characteristics in people with different five movements and six climates constitution based on pan-cancer Bulk RNA-Seq].

According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.

Quercetin alleviates inflammation induced by porcine reproductive and respiratory syndrome virus in MARC-145 cells through the regulation of arachidonic acid and glutamine metabolism.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) infection causes severe inflammatory response, respiratory disease and sow reproductive failure. Quercetin is among the widely occurring polypheno found abundantly in nature. Quercetin has anti-inflammatory, anti-oxidative and anti-viral properties. OBJECTIVES: This study aimed to explore the effect and mechanism of quercetin on PRRSV-induced inflammation in MARC-145 cells. METHODS: Observing the cytopathic effect and measurements of inflammatory markers in MARC-145 cells collectively demonstrate that quercetin elicits a curative effect on PRRSV-induced inflammation. Liquid chromatography-mass spectrometry was further used for a non-targeted metabolic analysis of the role of quercetin in the metabolic regulation of PRRSV inflammation in MARC-145 cells. RESULTS: It was shown that quercetin attenuated PRRSV-induced cytopathy in MARC-145 cells. Quercetin treatment inhibited PRRSV replication in MARC-145 cells in a dose-dependent manner. We also found that quercetin inhibited PRRSV-induced mRNA expression and secretion levels of tumour necrosis factor-α, interleukin 1ß and interleukin 6. Metabolomics analysis revealed that quercetin ameliorated PRRSV-induced inflammation. Pathway analysis results revealed that PRRSV-induced pathways including arachidonic acid metabolism, linoleic acid, glycerophospholipid and alanine, aspartate and glutamate metabolism were suppressed by quercetin. Moreover, we confirmed that quercetin inhibited the activation of NF-κB/p65 pathway, probably by attenuating PLA2, ALOX and COX mRNA expression. CONCLUSIONS: These results provide a crucial insight into the molecular mechanism of quercetin in alleviating PRRSV-induced inflammation.

Exploring the wound-healing potential and seasonal chemical variability of the Formosan Callery pear Pyrus calleryana: implications for therapeutic applications.

CONTEXT: Pyrus calleryana Decne (Rosaceae), renowned for its therapeutic properties, is known to moisturize the lungs (removing dryness; relieving cough), clear heat (acting as an antipyretic; febrifuge) and aid in detoxification (relieving pyogenic inflammation; eliminating toxins). However, scientific evidence supporting its efficacy in wound healing is lacking. OBJECTIVE: This study investigated P. calleryana samples collected over a year to explore metabolite variations and their impact on skin wound-healing activities. MATERIALS AND METHODS: P. calleryana (PC) twigs and leaves were collected from the Matsu Islands, Taiwan, spanning 2018-2020. Extracts were prepared using 95% ethanol or water, and we assessed the chemical composition, total phenolic/triterpenoid contents and antioxidant properties. Metabolites were analysed via LC-MS/MS and molecular networking. Wound healing potential was evaluated on WS-1 cells through MTT and migration assays, and gene expression analyses, with tests including control (DMSO), compounds 1 (3'-hydroxylbenzyl-4-hydroxybenzoate-4'-O-ß-glucopyranoside) and 2 (vanilloylcalleryanin) (100 µM), and a positive control (ascorbic acid, 100 µM) for 24 h. RESULTS: Significant variations in extract compositions were observed based on the solvent used, with distinct metabolomic profiles in extracts collected during different months. Notably, compounds 1 and 2 showed no cytotoxic effects on human dermal fibroblast cells and significantly accelerated wound closure at 100 µM. A gene expression analysis indicated upregulation of wound healing-associated genes, including MMP-1 (matrix metalloproteinase-1) and COL1A1 (collagen, type 1, alpha 1). CONCLUSIONS: This study reports the first evidence of PC compounds aiding wound healing. Utilizing Global Natural Products Social Molecular Networking (GNPS) and principal component analysis (PCA) approaches, we unveiled metabolomic profiles, suggesting the potential to expedite wound-healing.

Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice.

H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.