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IntroductionChronic viral infection may lead to an immunosuppressive microenvironment, whereas the association between virus-related indicators and treatment response in hepatocellular carcinoma(HCC) patients undergoing immune checkpoint inhibitors(ICIs) therapy remains a topic of debate. We aim to investigate the influence of hepatitis virus on the ICI efficiency in HCC patients through a meta-analysis.MethodsWe searched PubMed, Cochrane Library, Embase, and Web of Science until 14 July 2024 to identify cohort studies involving ICIs treatments in HCC patients. We extracted data from the literature related to hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, baseline HBV load, and antiviral therapy. Overall survival (OS) and progression-free survival (PFS) were considered as the primary endpoints, while objective response rate (ORR) was regarded as a secondary endpoint.ResultsWe included 55 cohort studies published between 2019 and 2024, involving a patient population of 7180 individuals. Summarized hazard ratio (HR) comparing HBV infection with non-HBV infection in the context of ICIs therapy revealed no significant association between HBV infection and either mortality risk or progression risk with the pooled HR for OS of 1.04(95%CI: 0.93-1.16, P=0.483) and the pooled HR for PFS of 1.07(95%CI:0.96-1.20, P=0.342). HBV infected patients with HCC may have better tumor response than non-HBV infected patients receiving ICIs with the combined relative risk(RR) for ORR was 1.94 (95%CI: 1.12-3.38, P=0.002). High baseline HBV load is associated with poor survival outcomes in patients with HCC who receive ICIs with the pooled HR for OS was 1.74 (95%CI: 1.27-2.37, P=0.001), thereby antiviral therapy has the potential to significantly enhance prognostic outcomes with the pooled HR for OS was 0.24 (95% CI: 0.14-0.42 P

BackgroundCupping therapy has been indicated effective in reducing muscle fatigue after 24 h based on the spectral analyses of surface electromyography (sEMG). However, there is no sufficient evidence showing changes of sEMG nonlinear indexes at more time points after cupping therapy. Furthermore, it is unclear whether the intervention timings of cupping therapy affect the recovery from muscle fatigue. The purpose of this study was to use the sEMG nonlinear analysis to assess the difference of time response of cupping therapy between different intervention timings after muscle fatigue.Materials and methodsThis randomized controlled trial recruited 26 healthy volunteers. Cupping therapy (−300 mmHg pressure for 5 min by the 45 mm-diameter cup) was applied before (i.e., pre-condition) or after (i.e., post-condition) muscle fatigue induced by performing repeated biceps curls at 75% of the 10 repetitions of maximum (RM) on the non-dominant upper extremity. Subjects were randomly allocated to the pre-condition group or the post-condition group. The sEMG signals during the maximal voluntary isometric contractions (MVC) of the biceps were recorded at four time points (i.e., baseline; post 1: immediate after cupping-fatigue/fatigue-cupping interventions; post 2: 3 h after cupping-fatigue/fatigue-cupping interventions; post 3: 6 h after cupping-fatigue/fatigue-cupping interventions). Two nonlinear sEMG indexes (sample entropy, SampEn; and percent determinism based on recurrence quantification analysis, %DET) were used to evaluate the recovery from exercise-introduced muscle fatigue. The Friedman test followed by the Nemenyi test and the Mann-Whitney U test were applied in statistics.ResultsThe SampEn and %DET change rate did not show any significant differences at four time points in the pre-condition group. However, there were significant delayed effects instead of immediate effects on improving muscle fatigue in the post-condition group (SampEn change rate: baseline 0.0000 ± 0.0000 vs. post 2 0.1105 ± 0.2253, p < 0.05; baseline 0.0000 ± 0.0000 vs. post 3 0.0627 ± 0.4665, p < 0.05; post 1–0.0321 ± 0.2668 vs. post 3 0.0627 ± 0.4665, p < 0.05; and %DET change rate: baseline 0.0000 ± 0.0000 vs. post 2–0.1240 ± 0.1357, p < 0.01; baseline 0.0000 ± 0.0000 vs. post 3 0.0704 ± 0.6495, p < 0.05; post 1 0.0700 ± 0.3819 vs. post 3 0.0704 ± 0.6495, p < 0.05). Moreover, the SampEn change rate of the post-condition group (0.1105 ± 0.2253) was significantly higher than that of the pre-condition group (0.0006 ± 0.0634, p < 0.05) at the post 2 time point. No more significant between-groups difference was found in this study.ConclusionThis is the first study demonstrating that both the pre-condition and post-condition of cupping therapy are useful for reducing muscle fatigue. The post-condition cupping therapy can e ffectively alleviate exercise-induced muscle fatigue and there is a significant delayed effect, especially 3 h after the interventions. Although the pre-condition cupping therapy can not significantly enhance muscle manifestations, it can recover muscles into a non-fatigued state.

Psoriasis and atopic dermatitis (AD) are prevalent inflammatory skin disorders, each stemming from diverse factors, and characterized by recurring episodes. In certain complex cases, the clinical and pathological features exhibit overlapping and atypical characteristics, making accurate clinical diagnosis and targeted treatment a challenge. Psoriasiform dermatitis is the term used to describe such cases. Moreover, when patients have a history of malignancy, the situation becomes even more intricate, resulting in limited treatment options. Biologic therapies have transformed the management of immune-mediated inflammatory diseases, including psoriasis and AD. Meanwhile, the safety of biologics in special populations, especially among patients with a history of malignancy, should be underlined. The selective Janus kinase 1 (JAK1) inhibitor abrocitinib has been approved for the treatment of AD and has showed satisfying efficacy and safety in the treatment of psoriasis in clinical trials. Although unreported, JAK1 inhibitors are thought to have the potential to increase the risk of potential tumors. Apremilast, an oral phosphodiesterase (PDE)-4 inhibitor, is approved for moderate to severe plaque psoriasis. It has been investigated for its efficacy in AD, and is not contraindicated in malignancy. This report presents three cases of psoriasiform dermatitis in patients with a history of malignancy, showcasing significant improvement following treatment with systemic glucocorticoid, abrocitinib, or apremilast.

ObjectThe hepatitis C virus (HCV) is prevalent across China, with a distinctive genotypic distribution that varies by geographical region and mode of transmission. Yunnan is one such geographical region wherein the local population continues to experience a high level of HCV infection, severely straining public health resources. This high prevalence is likely due to the increased incidence of intravenous drug use in that region, as Yunnan is a major point of entry for illegal heroin into China.MethodsWe investigated 510 individuals with chronic HCV infections in Yunnan Province from 2008 through 2018. Using reverse transcription PCR and Sanger sequencing to amplify and sequence samples. Bayesian analyses was performed to estimate the common ancestors and Bayesian skyline plot to estimate the effective viral population size. Molecular network was conducted to explore the characteristics of HCV transmission.ResultsWe successfully amplified and sequenced a total of 503 viral samples and genotyped each as either 3b (37.6%), 3a (21.9%), 1b (19.3%), 2a (10.5%), HCV-6 (10.1%), or 1a (0.6%). Over this 11-year period, we observed that the proportion of 3a and 3b subtypes markedly increased and, concomitantly, that the proportion of 1b and 2a subtypes decreased. We also performed Bayesian analyses to estimate the common ancestors of the four major subtypes, 1b, 2a, 3a, and 3b. Finally, we determined that our Bayesian skyline plot and transmission network data correlated well with the changes we observed in the proportions of HCV subtypes over time.ConclusionsTaken together, our results indicate that the prevalence of HCV 3a and 3b subtypes is rapidly increasing in Yunnan, thus demonstrating a steadily growing public health requirement to implement more stringent preventative and therapeutic measures to curb the spread of the virus.

IntroductionHyperbaric oxygen therapy (HBOT) is one of the common clinical treatments, but adverse effects have hampered and limited the clinical application and promotion of hyperbaric oxygen therapy. A systematic review and meta-analysis of the adverse effects of hyperbaric oxygen therapy have conducted by our group to provide a theoretical basis for clinical treatment.MethodsThree electronic databases (PubMed, Web of Science, and The Cochrane Library) were comprehensively searched for randomized clinical trials (RCTs) from March 2012 to October 2022. Two reviewers independently screened titles and abstracts for eligibility and assessed the quality of the included studies. The meta-analysis was performed using RevMan 5.3.ResultsA total of 24 RCTs involving 1,497 participants were identified. ① The HBOT group reported more adverse effects (30.11% vs. 10.43%, p 10 sessions, the incidence of adverse effects was higher than that of the control group; when the course of HBOT was ≤10 sessions, the adverse effects caused by hyperbaric oxygen were comparatively lower. ④ When the chamber pressure is above 2.0 ATA, the incidence of adverse effects is higher than that of the control group. While the chamber pressure is lower than 2.0 ATA, HBOT is relatively safe compared with the previous one.ConclusionHyperbaric oxygen therapy (HBOT) is more likely to cause adverse reactions when the chamber pressure is above 2.0 ATA. More attention should be paid to the possible occurrence of related adverse effects if the treatment course is >10 sessions.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316605.

Extracellular vesicles (EVs) including exosomes are vesicular vesicles with phospholipid bilayer implicated in many cellular interactions and have the ability to transfer multiple types of cargo to cells. It has been found that EVs can package various molecules including proteins and nucleic acids (DNA, mRNA, and noncoding RNA). The discovery of EVs as carriers of proteins and various forms of RNA, such as microRNAs (miRNA) and long noncoding RNAs (lncRNA), has raised great interest in the field of drug delivery. Despite the underlying mechanisms of neuropathic pain being unclear, it has been shown that uncontrolled glial cell activation and the neuroinflammation response to noxious stimulation are important in the emergence and maintenance of neuropathic pain. Many studies have demonstrated a role for noncoding RNAs in the pathogenesis of neuropathic pain and EVs may offer possibilities as carriers of noncoding RNAs for potential in neuropathic pain treatment. In this article, the origins and clinical application of EVs and the mechanism of neuropathic pain development are briefly introduced. Furthermore, we demonstrate the therapeutic roles of EVs in neuropathic pain and that this involve vesicular regulation of glial cell activation and neuroinflammation.

Background and objectivesThe benefits of physical activity (PA) for asthmatic children were increasingly recognized, and as the design of studies on PA and asthma has become more refined in recent years, the latest evidence needed to be updated. We performed this meta-analysis to synthesize the evidence available from the last 10 years to update the effects of PA in asthmatic children.MethodsA systematic search was conducted in three databases, PubMed, Web of Science, and Cochrane Library. Randomized controlled trials were included, and two reviewers independently conducted the inclusion screening, data extraction, and bias assessment.ResultsA total of 9 studies were included in this review after 3,919 articles screened. PA significantly improved the forced vital capacity (FVC) (MD 7.62; 95% CI: 3.46 to 11.78; p

BackgroundChronic systemic inflammation may be associated with neurocognitive decline, but the relationships between inflammatory bowel disease and related medications and the risk of Alzheimer's disease remain unclear.MethodsWe performed a meta-analysis to evaluate the associations of ulcerative colitis, Crohn's disease and related medications with risk of Alzheimer's disease. We identified cohort and case-control studies by searching PubMed, Embase and Web of Science up to August 2022.ResultsSeven eligible studies with 20,174 cases of Alzheimer's disease were included in the meta-analysis. Six studies reported the association between ulcerative colitis and risk of Alzheimer's disease; five studies reported the association between Crohn's disease and risk of Alzheimer's disease. Meta-analysis combining these studies did not reveal any significant association of ulcerative colitis or Crohn's disease with risk of Alzheimer's disease. The pooled relative risks were 1.16 (95%CI: 0.96, 1.41) and 1.17 (95%CI: 0.84, 1.62) for ulcerative colitis and Crohn's disease, respectively. High heterogeneity was detected across the studies. Of note, there was an inverse association between inflammatory bowel disease related medication exposure and risk of Alzheimer's disease. The pooled relative risk of three studies for Alzheimer's disease was 0.86 (95%CI: 0.75, 0.99). No publication bias was detected.ConclusionThis study does not support the association of ulcerative colitis and Crohn's disease with the risk of Alzheimer's disease. However, medications for the treatment of inflammatory bowel disease might be associated with a lower risk of Alzheimer's disease.

After peripheral nerve injury, pain signals are transmitted from primary sensory neurons in the dorsal root ganglion (DRG) to the central nervous system. Epigenetic modification affects neuropathic pain through alterations in the gene expression in pain-related areas and glial cell activation. Recent studies have shown that non-coding RNA and n6-methyladenosine (m6A) methylation modification play pivotal regulatory roles in the occurrence and maintenance of neuropathic pain. Dysregulation of the RNA m6A level via dynamic changes in methyltransferase and demethylase after central or peripheral nerve injury commonly regulates pain-associated genes, contributing to the induction and maintenance of neuropathic pain. The dynamic process has significant implications for the development and maintenance of neuropathic pain. However, the underlying mechanisms by which non-coding RNA and m6A RNA modification regulate neuropathic pain are not well-characterized. This article elucidates the multiple mechanisms of non-coding RNA and m6A methylation in the context of neuropathic pain, and summarizes its potential functions as well as recent advances.

ObjectiveCalcium is present in serum mainly in filterable and bound forms, and Ca2+ is a major key to modulate signaling pathways that control oncogenesis and oncochannels associated with several types of cancer. However, the biological significance of serum calcium and its related mechanism with estrogen in endometrial cancer (EC) still remains elusive. This study aims to ascertain the relationship between serum calcium and clinicopathology in EC.MethodsRetrospective assessment of a total of 502 patients diagnosed with EC after surgery in Peking University People's Hospital from 2010 to 2018. Preoperative serum ionized calcium and the albumin corrected calcium was calculated in quartiles for various postoperative clinicopathological characteristics, logistic regression adjusted for potential confounders. Intracellular calcium homeostasis change induced by estrogen was detected by confocal analysis. Downstream pathways were analyzed by transcriptome and proteomics. Mitochondrial Ca2+ and ROS (reactive oxygen species) level was detected by confocal and flow cytometry. Lysosomal morphological and membrane changes were verified by confocal or Western blot assays.ResultsHigh level of albumin-corrected serum calcium was significantly correlated with EC clinicopathological characteristics progression include lymph vascular space invasion, lymph nodes metastasis, myometrial invasion, and cervical invasion. Calcium homeostasis regulated by estrogen in EC cells derived from extracellular calcium influx but not the release of the endoplasmic reticulum. Proteomic and bioinformatic analysis revealed the calcium influx might be involved in the regulation of autophagy and mitochondrial-related pathways. Mechanistic investigation demonstrated that calcium influx acted on the function of mitochondrial ROS and lysosomal activity.ConclusionOur findings revealed that serum calcium level was significantly related to poor outcomes. The extracellular calcium influx induced by estrogen was targeted to mitochondrial ROS and lysosome activity, which should be oriented to improve EC therapeutic strategies.

Axons in the central nervous system often fail to regenerate after injury due to the limited intrinsic regeneration ability of the central nervous system (CNS) and complex extracellular inhibitory factors. Therefore, it is of vital importance to have a better understanding of potential methods to promote the regeneration capability of injured nerves. Evidence has shown that non-coding RNAs play an essential role in nerve regeneration, especially long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). In this review, we profile their separate roles in axon regeneration after CNS injuries, such as spinal cord injury (SCI) and optic nerve injury. In addition, we also reveal the interactive networks among non-coding RNAs.

Marfan syndrome (MFS) is an inherited disorder that affects the connective tissues and mainly presents in the bones, eyes, and cardiovascular system, etc. Aortic pathology is the leading cause of death in patients with Marfan syndrome. The fibrillin-1 gene (FBN1) is a major gene involved in the pathogenesis of MFS. It has been shown that the aortic pathogenesis of MFS is associated with the imbalances of the transforming growth factor-beta (TGF-β) signaling pathway. However, the exact molecular mechanism of MFS is unclear. Animal models may partially mimic MFS and are vital to the study of MFS. Several species of animals have been used for MFS studies, including chicks, cattle, mice, pigs, zebrafishes, Caenorhabditis elegans, and rabbits. These models were developed spontaneously or in combination with genetic engineering techniques. This review is to describe the TGF-β signaling pathway in MFS and the potential application of animal models to provide new therapeutic strategies for patients with MFS.

IntroductionNon-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, with high morbidity and mortality. The rapidly increasing incidence of NAFLD is becoming an essential precursor of HCC globally. MicroRNAs (miRNAs) are involved in the progression of NAFLD and HCC.MethodPotential miRNAs associated with NAFLD in HCC tumorigenesis were identified through a systematic review, and their roles were evaluated by data mining analysis. The biological function of the potential miRNA and its target genes in NAFLD and HCC were evaluated by bioinformatic analysis.ResultMIR122 was identified as the potential miRNA associated with NAFLD and HCC. Then, MIR122 expression was significantly lower in HCC patients, and higher MIR122 levels were associated with significantly better overall survival. Next, the biological functions of MIR122 and target genes were predicted to be involved in inflammation, fibrosis, cell proliferation, invasion, metastasis, and apoptosis. In particular, the FOXO signaling pathway may regulate the above biological functions.ConclusionMIR122 was suggested to be involved in progressing from NAFLD to HCC through the PI3K/AKT/FOXO pathway.Systematic review registrationPROSPERO, identifier: CRD 42024517940.

BackgroundTraditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating gallstone risk. This study investigated the association between novel anthropometric indices and gallstone risk among 6,848 participants from the National Health and Nutrition Examination Survey in the United States.MethodsMeasures calculated included weight (WT), BMI, waist circumference (WC), waist-to-height ratio (WtHR), conicity index (CI), A Body Shape Index (ABSI), Body Roundness Index (BRI), Abdominal Volume Index (AVI), and Weight-adjusted Waist Index (WWI). Logistic regression and smooth curve fitting assessed the relationships between these indices and gallstones, complemented by receiver operating characteristic (ROC) curve analysis to evaluate their discriminative power.ResultsThe results indicated significant differences between study groups, with a positive and independent correlation identified between gallstones and all measures except ABSI. Specifically, per 1 SD increase in WC, WT, BMI, WtHR, and AVI was associated with a 57%, 59%, 52%, 53%, and 53% increased risk of gallstones, respectively. Dose-response analysis confirmed a positive correlation between these indices and gallstone risk. ROC analysis highlighted WtHR and BRI as having superior discriminative abilities (AUC = 0.6703). Further, among participants with a BMI < 30 kg/m2, elevated levels of WT, WtHR, CI, BRI, and WWI significantly increased the risk of gallstones (P < 0.001). Likewise, elevated BMI heightened the risk at low levels of WT, WC, WtHR, BRI, AVI, and CI (P < 0.001).ConclusionThis study supports the positive association between various anthropometric indicators and gallstones, recommending that newer anthropometric indices be considered more extensively to enhance gallstone prevention and treatment strategies.

BackgroundCong-Chi decoction (CCD) is made using Allium ascalonicum L. (shallot) bulbs and Sojae Semen Praeparatum (SSP). Shallot bulbs and SSP are both used regularly in traditional Chinese medicine; however, there are no recent pharmacological studies on their synergistic effects. Despite their roles in the treatment of the common cold for thousands of years, their pharmacological mechanisms of action against wind-cold-type common cold are yet to be explored comprehensively.MethodsA mouse model was standardized using wind-cold modeling equipment to study the anti-inflammatory, antioxidant, and antiapoptotic effects of CCD. Then, 16S rRNA sequencing was employed to analyze the association between Lactobacillus murinus and changes in body temperature. Additionally, the antipyretic effects of L. murinus were validated via animal experiments.ResultsThe results indicate that CCD improves the symptoms of wind-cold by reducing fever, levels of pro-inflammatory factors, and cellular apoptosis, as well as increasing the blood leukocyte and lymphocyte counts, thereby alleviating lung tissue damage. The effects of CCD are mediated by upregulation of pulmonary Nrf2 and HO-1 expressions, thereby reducing oxidative damage in the lungs, in addition to other anti-inflammatory mechanisms. Furthermore, CCD increases the abundance of L. murinus in the intestinal tract. The animal experiments confirm that L. murinus ameliorates fever in mice.ConclusionCCD exhibits remarkable antioxidant and anti-inflammatory properties for effectively treating wind-cold-type common cold. Furthermore, its regulatory effects on L. murinus represent a novel mechanism for product development.

BackgroundA high risk of developing mild cognitive impairment (MCI) is faced by elderly patients with type 2 diabetes mellitus (T2DM). In this study, independent risk factors for MCI in elderly patients with T2DM were investigated, and an individualized nomogram model was developed.MethodsIn this study, clinical data of elderly patients with T2DM admitted to the endocrine ward of the hospital from November 2021 to March 2023 were collected to evaluate cognitive function using the Montreal Cognitive Assessment scale. To screen the independent risk factors for MCI in elderly patients with T2DM, a logistic multifactorial regression model was employed. In addition, a nomogram to detect MCI was developed based on the findings of logistic multifactorial regression analysis. Furthermore, the accuracy of the prediction model was evaluated using calibration and receiver operating characteristic curves. Finally, decision curve analysis was used to evaluate the clinical utility of the nomogram.ResultsIn this study, 306 patients were included. Among them, 186 patients were identified as having MCI. The results of multivariate logistic regression analysis demonstrated that educational level, duration of diabetes, depression, glycated hemoglobin, walking speed, and sedentary duration were independently correlated with MCI, and correlation analyses showed which influencing factors were significantly correlated with cognitive function (p

IntroductionIgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally. While nephrotic syndrome (NS) is uncommon in IgAN, its significance remains unclear.MethodsWe conducted a retrospective analysis of 170 IgAN patients, classifying them into NS (n = 85) and non-NS (n = 85) groups. Our study aims to compare their clinical characteristics, treatment responses, and prognoses. Patients were selected based on renal biopsy from 2003 to 2020. Propensity score matching ensured comparability. Clinical, pathological, and immunological data were analyzed. Composite endpoints were defined as end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR).ResultsNS patients showed higher eGFR (74.3 ± 36.8 vs. 61.5 ± 33.6 mL/min.1.73 m2, p = 0.02), severe hematuria (35.0 (4.7,147.5) vs. 4.0 (1.8,45,0) cells/μl, p

In the field of medical image analysis within deep learning (DL), the importance of employing advanced DL techniques cannot be overstated. DL has achieved impressive results in various areas, making it particularly noteworthy for medical image analysis in healthcare. The integration of DL with medical image analysis enables real-time analysis of vast and intricate datasets, yielding insights that significantly enhance healthcare outcomes and operational efficiency in the industry. This extensive review of existing literature conducts a thorough examination of the most recent deep learning (DL) approaches designed to address the difficulties faced in medical healthcare, particularly focusing on the use of deep learning algorithms in medical image analysis. Falling all the investigated papers into five different categories in terms of their techniques, we have assessed them according to some critical parameters. Through a systematic categorization of state-of-the-art DL techniques, such as Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs), Generative Adversarial Networks (GANs), Long Short-term Memory (LSTM) models, and hybrid models, this study explores their underlying principles, advantages, limitations, methodologies, simulation environments, and datasets. Based on our results, Python was the most frequent programming language used for implementing the proposed methods in the investigated papers. Notably, the majority of the scrutinized papers were published in 2021, underscoring the contemporaneous nature of the research. Moreover, this review accentuates the forefront advancements in DL techniques and their practical applications within the realm of medical image analysis, while simultaneously addressing the challenges that hinder the widespread implementation of DL in image analysis within the medical healthcare domains. These discerned insights serve as compelling impetuses for future studies aimed at the progressive advancement of image analysis in medical healthcare research. The evaluation metrics employed across the reviewed articles encompass a broad spectrum of features, encompassing accuracy, sensitivity, specificity, F-score, robustness, computational complexity, and generalizability.

Planting aromatic plant might be a promising strategy for safely utilizing heavy metal (HM)-contaminated soils, as HMs in essential oil could be completely excluded using some special technologies with ease. Clove basil (Ocimum gratissimum L.) is an important aromatic plant used in essential oil production. Improving cadmium (Cd) tolerance in clove basil can increase its production and improve the utilization efficiency of Cd-contaminated soils. However, the lack of genomic information on clove basil greatly restricts molecular studies and applications in phytoremediation. In this study, we demonstrated that high levels of Cd treatments (0.8, 1.6 and 6.5 mg/L) significantly impacted the growth and physiological attributes of clove basil. Cd contents in clove basil tissues increased with treatment concentrations. To identify Cd stress-responsive genes, we conducted a comparative transcriptomic analysis using seedlings cultured in the Hoagland’s solution without Cd ion (control) or containing 1.6 mg/L CdCl2 (a moderate concentration of Cd stress for clove basil seedlings). A total of 104.38 Gb clean data with high-quality were generated in clove basil under Cd stress through Illumina sequencing. More than 1,800 differential expressed genes (DEGs) were identified after Cd treatment. The reliability and reproducibility of the transcriptomic data were validated through qRT-PCR analysis and Sanger sequencing. KEGG classification analysis identified the “MAPK signaling pathway,” “plant hormone signal transduction” and “plant-pathogen interaction” as the top three pathways. DEGs were divided into five clusters based on their expression patterns during Cd stress. The functional annotation of DEGs indicated that downregulated DEGs were mainly involved in the “photosynthesis system,” whereas upregulated DEGs were significantly assigned to the “MAPK signaling pathway” and “plant-pathogen interaction pathway.” Furthermore, we identified a total of 78 transcription factors (TFs), including members of bHLH, WRKY, AP2/ERF, and MYB family. The expression of six bHLH genes, one WRKY and one ERF genes were significantly induced by Cd stress, suggesting that these TFs might play essential roles in regulating Cd stress responses. Overall, our study provides key genetic resources and new insights into Cd adaption mechanisms in clove basil.

Fresh-cut taros are prone to browning even though they are stored at low temperatures, which leads to the quality deterioration and markedly limits the shelf life. The browning control of fresh-cut food with natural substances has received much attention. This study evaluated anti-browning potential of peppermint extracts in fresh-cut taro during cold storage. The results showed that both peppermint leaf and shoot extract (LE and SE) treatments could effectively retard the browning of fresh-cut taros. Furthermore, LE and SE treatments reduced the activities of phenylalanine ammonialyase and lipoxygenase, the contents of total phenolic compound (TPC), total flavonoids, soluble quinones, malondialdehyde and hydrogen peroxide, enhanced peroxidase activity and antioxidant capacity in taro slices. The TPC contents were reduced by 4.05 and 17.71%, and the T-AOC was enhanced by 28.73 and 28.82% as compared to the control at 12 d. These results together suggested that peppermint extract treatments reduced phenolic biosynthesis but enhanced antioxidant activity. However, LE and SE treatments did not inhibit polyphenol oxidase (PPO) activity, suggesting that peppermint extract treatments reduced taro browning was not through inhibition of phenolic oxidation. More than 240 phenolic-related compounds including caffeic acid, ferulic acid and p-Coumaric acid were identified in peppermint extracts through UPLC–MS/MS analysis, suggesting that phenolics may be bioactive substances reducing taro browning. In conclusion, this study demonstrates that peppermint extract is a promising natural anti-browning ingredient and phenolic compounds may function on taro browning inhibition.

Background and aimsComplement activation is essential for tuberculosis pleural effusion. However, little is known about the value of complement regulatory protein (CD46, CD55, and CD59) in the differential diagnosis of tuberculosis.Materials and methodsNinety-nine patients with exudative pleural effusion admitted to Xiangya Hospital of Central South University from June 1, 2021to November 14, 2022 were enrolled. The expression levels of soluble CD46 (sCD46), soluble CD55 (sCD55), and soluble CD59 (sCD59) in pleural effusion were quantified by enzyme-linked immunosorbent assay, and the receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic and co-diagnostic values.ResultsThe ADA level is higher in TPE patients than non-TPE patients. It is well-found that TPE patients had lower levels of sCD46, sCD55, and sCD59 compared with non-TPE patients. Moreover, the expression of sCD46, sCD55, and sCD59 in pleural effusion was negatively correlated with ADA. In addition, the diagnostic efficacy of sCD46, sCD55 and sCD59 was comparable to that of ADA, with 0.896, 0.857, 0.858 and 0.893, respectively. Furthermore, combine detection of sCD46, sCD55, sCD59 and ADA could improve the diagnostic accuracy.ConclusionsComplement regulatory factors (CD46, CD55, and CD59) were validated by this project to be promising candidate biomarkers for the diagnosis of TPE with high accuracy. The combination of the CD46, CD55, and CD59 and ADA assay exist a better diagnostic value in TPE.

BackgroundDepression is a serious risk for cardiovascular disease (CVD). Improving depression can alleviate cardiac symptoms and improve quality of life. Studies have shown that acupuncture has a positive effect on depression and CVD. This systematic review and meta-analysis will evaluate the efficacy and safety of acupuncture in the treatment of depression complicated with CVD.MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and China Biomedical Literature databases. Randomized controlled trials of acupuncture vs. standard care or sham acupuncture or antidepressants were included. The retrieval time is from database construction to 07 April 2022. We used the “risk of bias” tool of Cochrane Collaboration, and the Review Manager (RevMan.) Version 5.4.1 for statistics analysis. Primary outcomes included Hamilton scale for depression (HAMD), self-rating depression scale (SDS), and the effective rate of depression. Secondary outcomes included frequency of angina pectoris and visual analogue scale (VAS) scores for angina pain.ResultsA total of 2,366 studies were screened based on the search strategy. Twelve eligible studies with a total of 1,203 participants have been identified. The result showed that acupuncture reduced the HAMD score [weighted mean difference (WMD): −3.23; 95% confidence interval (CI): −5.38 to −1.09; P = 0.003] and the SDS score (WMD: −1.85; 95% CI: −2.14 to −1.56; P < 0.00001) in patients with depression complicated with CVD. Acupuncture also improved the effective rate of depression (risk ratio: 1.15; 95% CI: 1.03 to 1.29; P = 0.01). The result also showed that acupuncture reduced the attack frequency of angina pectoris (WMD: −4.54; 95% CI: −5.96 to −3.11; P < 0.00001) and the VAS score for angina pain (WMD: −0.72; 95% CI: −1.06 to −0.38; P < 0.0001). This article reviewed the significant advantages of acupuncture for depression and the superiority of acupuncture over no-intervention therapy, antidepressant therapy, and psychotherapy in reducing angina frequency and pain intensity in patients with CVD.ConclusionThis systematic review suggested that acupuncture was a good complementary and alternative therapy for CVD complicated with depression. Considering the limitations of the included research literature, it is still necessary to perform multi-center, large-sample, and double-blind high-quality studies to provide higher-level evidence in the later stage.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022304957].

Glioblastoma (GBM) is the most malignant glioma in brain tumors with low survival and high recurrence rate. Irigenin, as an isoflavone compound extracted from Shegan, has shown many pharmacological functions such as antioxidant, anti-inflammatory and anti-tumor. However, the effects of irigenin on GBM cells and the related molecular mechanisms remain unexplored. In this study, we found that irigenin inhibited the proliferation of GBM cells in a dose-dependent manner by several assays in vitro. Subsequently, we found that irigenin arrested cell cycle at G2/M phase and induced apoptosis of GBM cells in vitro. In addition, irigenin inhibited the migration of GBM cells. Mechanically, we found that irigenin treatment decreased the expression of YAP (yes-associated protein), suppressed β-catenin signaling. Furthermore, overexpression of YAP partially restored the anti-tumor effects of irigenin on GBM cells in vitro. Finally, we found that irigenin inhibited the growth of tumor in GBM xenograft mice model through inactivation of YAP. Taken together, these results suggest that irigenin exerts its anticancer effects on GBM via inhibiting YAP/β-catenin signaling, which may provide a new strategy for the treatment of GBM.

The browning on the cut surface is a big problem reducing the quality of fresh-cut taro (FCT), which causes severe postharvest losses and may raise environmental impacts. Citronellal (CA) is a natural compound in several aromatic plants. This study investigated the effects of CA treatments in different concentrations (0.2, 0.5, and 1 mL/L) on the browning of FCT under cold storage at 5°C. The results indicated that low-dose (0.2 mL/L) CA treatment showed best anti-browning effects, reflecting at the maintained L* values but the reduced a*, b* and browning index values by CA treatment during cold storage. A repeated experiment using 0.2 mL/L CA confirmed fine anti-browning effects again. Furthermore, CA (0.2 mL/L) treatment markedly reduced the contents of total phenolic compounds and soluble quinones, restrained the activities of phenylalanine ammonia lyase, peroxidase and polyphenol oxidase, down-regulated the gene expression of 18 browning-related enzymes in FCT. These results together strongly demonstrate the validity of CA on FCT browning prevention. Given that CA is a natural compound existing in plants, low concentration of CA possesses strong anti-browning effects on FCT and also inhibitory effects on pathogens, implying that its application has potentiality to preserve high quality of fresh-cut produce for processing and storage. Moreover, CA treatment significantly decreased malondialdehyde contents and lipoxygenase activity. Correlation analysis indicated that the lipid peroxidation of cell membrane was mostly correlated with FCT browning. The results suggest that membrane lipid peroxidation was a possible reason for FCT browning and CA treatment reduced browning, in part, through alleviating the lipid peroxidation of cell membrane. Overall, our results demonstrate that CA is a novel browning mitigator for FCT under cold storage condition.

BackgroundMonocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.Methods30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.ResultsCompared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys.ConclusionEnhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.

Cardiac mast cells (CMCs) are multifarious immune cells with complex roles both in cardiac physiological and pathological conditions, especially in cardiac fibrosis. Little is known about the physiological importance of CMCs in cardiac homeostasis and inflammatory process. Therefore, the present review will summarize the recent progress of CMCs on origin, development and replenishment in the heart, including their effects on cardiac development, function and ageing under physiological conditions as well as the roles of CMCs in inflammatory progression and resolution. The present review will shed a light on scientists to understand cardioimmunology and to develop immune treatments targeting on CMCs following cardiac injury.

Awake rodent fMRI is becoming a promising non-invasive brain imaging module when investigating large-scale brain function given behavioral tasks. Previous studies have either applied sedatives during scanning or pre-treatment of anesthetics, e.g., isoflurane, to reduce the motion of animals, which could confound the brain function of “awake” states in rodents. Here, we have established a long training awake mouse fMRI-pupillometry paradigm/setup without the initial use of anesthesia. To validate the awake mouse fMRI platform, evoked BOLD-fMRI was performed to identify brain activation in the visual cortex, dorsal lateral geniculate nuclei, and superior colliculus. Furthermore, pupil signal fluctuation was investigated during scanning, showing a less dilated pupil after 5–8 weeks of intermittent training. Thus, using the awake mouse fMRI with real-time pupillometry provides a longitudinal functional mapping tool to study fully conscious mice.

Probiotics have received widespread attention as a healthy ingredient. The preventive effect of Bifidobacterium lactis TY-S01 on loperamide-induced constipation in mice was investigated in this study. TY-S01 accelerated the peristalsis of intestine, maintained the humidity of faeces, and prevented the destruction of gut barrier. TY-S01 also maintained the 5-HT, MTL and SP at normal levels in constipated mice. Simultaneously, TY-S01 up-regulated the mRNA expressions of 5-HT4R, SERT, and MUC-2, while down-regulated the mRNA expressions of pro-inflammatory genes remarkably. The levels of short-chain fatty acids in the feces of constipated mice were also increased because of the intervention with TY-S01. Moreover, TY-S01 prevented gut microbiological dysbiosis in constipated mice. Spearman’s correlation analysis revealed that there was an obvious association between metabolic biomarkers and gut microbiota. In summary, TY-S01 regulated gut microbiota and the production of intestinal metabolites to prevent loperamide-induced constipation.

ObjectivesConverging evidence points towards a role of the complement system in the pathogenesis of diabetic nephropathy (DN). The classification system of diabetic kidney lesions devised by the Renal Pathology Society (RPS) in 2010 are based on the pathogenic process of DN. Therefore, we investigated the correlation between glomerular C3 deposits and RPS DN classification and the combined deleterious effects thereof on kidney function.MethodsThe study analyzed data from 217 diabetic patients who underwent renal biopsy between 2010 and 2021 and were found to have DN as the only glomerular disease. C3 deposition was considered positive if the glomerular C3 immunofluorescence intensity was at the trace or ≥1+ level. We divided DN into five glomerular lesion classes and separately evaluated the degree of interstitial and vascular involvement. The primary outcome was the composite of a ≥50% decline from the initial estimated glomerular filtration rate, end-stage renal disease, and death.ResultsNone of the patients were classified into class I, and few were classified into classes IIa (7.8%) and IV (9.2%). Most patients were classified as IIb (30.9%) and III (52.1%). C3 deposition was detected in 53.9% of patients. Multivariate logistic regression analysis showed that DN class was significantly correlated with C3 deposits [odds ratio, 1.59; 95% confidence interval (CI), 1.08–2.36; p = 0.02). During a median follow-up of 22 months, 123 (56.7%) patients reached the composite outcome. The endpoints occurred more frequently in patients with C3 deposition (69.2 vs. 42%) compared with those without C3 deposition. Patients with C3 deposition in either class IIb [hazards ratio (HR), 3.9 (95% CI, 1.14–13.17) vs. 2.46 (95% CI, 0.68–8.89)] or III [HR, 4.98 (95% CI, 1.53–16.23) vs. 2.63 (95% CI, 0.77–9.0)] had a higher risk of adverse kidney outcomes than those without C3 deposition. The prognostic accuracy of the combination of DN class and C3 deposits at 1 and 3 years was higher than that for DN class only.ConclusionsComplement deposition together with DN class predicts more rapid deterioration of kidney function in DN, which underlines the clinical significance of the DN phenotype according to the RPS classification.

IntroductionKey genes involved in tubulointerstitial injury may influence the development and progression of diabetic nephropathy (DN). We investigated whether complement-related genes are linked to the mechanism underlying tubulointerstitial injury in DN.MethodsWe analyzed the microarray data of 17 tubulointerstitial tissue samples from DN patients and 21 normal controls from the Gene Expression Omnibus. A gene co-expression network was constructed, and genes were divided into modules by weighted gene co-expression network analysis (WGCNA). We also investigated the association of C3 and C1q deposits in kidney tissues with a composite outcome of end-stage renal disease or a 50% reduction in the estimated glomerular filtration rate (eGFR) in DN patients. Finally, we performed immunohistochemical analyses of C3, C1q, C5b-9, mannose-binding lectin (MBL), and factor B in kidney tissues.ResultsNine co-expression modules were constructed using 12,075 genes from the 38 human tubulointerstitial tissue samples. Black module with more genes was positively correlated with tubulointerstitial injury in DN. C3, one of the top 10 genes in tubulointerstitial injury, was verified in an independent dataset; C3 was significantly overexpressed in tubulointerstitial tissue from patients with DN compared to the normal controls. The mRNA level of C3 in renal tubulointerstitium was negatively correlated with eGFR in DN patients (r = −0.75; p = 0.001). Analysis of the follow-up data of 54 DN patients demonstrated that codeposits of C3 and C1q in kidney tissues were independently associated with the renal outcome in DN (hazard ratio, 2.3, 95% confidence interval, 1.01–5.2, p < 0.05). Immunohistochemical analysis showed that patients with higher C1q, C3, C5b-9, MBL, or factor B expression in renal tubulointerstitium were more likely to progress to kidney failure.ConclusionLocal complement activation of the classical, lectin and alternative pathways appears linked to tubulointerstitial injury and disease progression in DN.

Wound healing, a highly complex pathophysiological response to injury, includes four overlapping phases of hemostasis, inflammation, proliferation, and remodeling. Initiation and resolution of the inflammatory response are the primary requirements for wound healing, and are also key events that determines wound quality and healing time. Currently, the number of patients with persistent chronic wounds has generally increased, which imposes health and economic burden on patients and society. Recent studies have found that microRNA(miRNA) plays an essential role in the inflammation involved in wound healing and may provide a new therapeutic direction for wound treatment. Therefore, this review focused on the role and significance of miRNA in the inflammation phase of wound healing.

Most species in Rosaceae usually need to undergo several years of juvenile phase before the initiation of flowering. After 4–6 years’ juvenile phase, cultivated loquat (Eriobotrya japonica), a species in Rosaceae, enters the reproductive phase, blooms in the autumn and sets fruits during the winter. However, the mechanisms of the transition from a seedling to an adult tree remain obscure in loquat. The regulation networks controlling seasonal flowering are also largely unknown. Here, we report two RELATED TO ABI3 AND VP1 (RAV) homologs controlling juvenility and seasonal flowering in loquat. The expressions of EjRAV1/2 were relatively high during the juvenile or vegetative phase and low at the adult or reproductive phase. Overexpression of the two EjRAVs in Arabidopsis prolonged (about threefold) the juvenile period by repressing the expressions of flowering activator genes. Additionally, the transformed plants produced more lateral branches than the wild type plants. Molecular assays revealed that the nucleus localized EjRAVs could bind to the CAACA motif of the promoters of flower signal integrators, EjFT1/2, to repress their expression levels. These findings suggest that EjRAVs play critical roles in maintaining juvenility and repressing flower initiation in the early life cycle of loquat as well as in regulating seasonal flowering. Results from this study not only shed light on the control and maintenance of the juvenile phase, but also provided potential targets for manipulation of flowering time and accelerated breeding in loquat.

BackgroundEctopic adrenocorticotropic hormone (ACTH)-secreting lung tumors represent the most common cause of ectopic Cushing syndrome (ECS). Pulmonary opportunistic infections are associated with ECS. The present study aimed to evaluate the usefulness of 18F-FDG PET/CT for differentiating ectopic ACTH-secreting lung tumors from tumor-like pulmonary infections in patients with ECS.MethodsWe retrospectively reviewed the imaging data of 24 patients with ECS who were suspected to have ACTH-secreting lung tumors and underwent 18F-FDG PET/CT between 2008 and 2019. Eleven patients with lung tumors and 4 with pulmonary infections also had additional somatostatin receptor imaging (99mTc-HYNIC-TOC SPECT/CT or 68Ga-DOTATATE PET/CT).ResultsIn total, 18 patients had lung tumors and six had pulmonary infections. The primary source of ECS remained occult in the six patients with pulmonary infections. The maximum standardized uptake value (SUVmax) for pulmonary infections was significantly higher than that for tumors (P = 0.008). Receiver operating characteristic analysis revealed that a cut-off SUVmax of 4.95 helped in differentiating ACTH-secreting lung tumors from infections with 75% sensitivity and 94.4% specificity. For the 11 patients with ACTH-lung tumors, somatostatin receptor imaging (SRI) was positive in 6; while for the 4 with pulmonary infections, SRI was positive in 2. The sensitivity and specificity of somatostatin receptor imaging (SRI) for detecting ACTH-secreting lung tumor was 54.5% and 50%.ConclusionsOur findings suggest that pulmonary infections exhibit significantly higher FDG uptake than ACTH-secreting lung tumors in 18F-FDG PET/CT. An SUVmax cut-off value of 4.95 may be useful for differentiating the two conditions. Our results also suggested that SRI may not be an effective tool for differentiating the two conditions given the relatively low specificity.

Flowering is an integral part of the life cycle of flowering plants, which is essential for plant survival and crop production. Most woody fruit trees such as apples and pears bloom in spring, but loquat blooms in autumn and winter. Gibberellin (GA) plays a key role in the regulation of plant flower formation. In this study, we sprayed loquat plants with exogenous GA3, which resulted in vigorous vegetative growth rather than floral bud formation. We then performed a comprehensive RNA-seq analysis on GA3-treated and control-treated leaves and buds over three time periods to observe the effects of exogenous GA3 application on floral initiation and development. The results showed that 111 differentially expressed genes (DEGs) and 563 DEGs were down-regulated, and 151 DEGs and 506 DEGs were up-regulated in buds and leaves, respectively, upon treatment with GA3. Among those that are homologs of the DELLA-mediated GA signal pathway genes, some may be involved in the positive regulation of flower development, including EjWRKY75, EjFT, EjSOC1, EjAGL24, EjSPL, EjLFY, EjFUL, and EjAP1; while some may be involved in the negative regulation of flower development, including EjDELLA, EjMYC3, EjWRKY12, and EjWRKY13. Finally, by analyzing the co-expression of DEGs and key floral genes EjSOC1s, EjLFYs, EjFULs, EjAP1s, 330 candidate genes that may be involved in the regulation of loquat flowering were screened. These genes belong to 74 gene families, including Cyclin_C, Histone, Kinesin, Lipase_GDSL, MYB, P450, Pkinase, Tubulin, and ZF-HD_dimer gene families. These findings provide new insights into the regulation mechanism of loquat flowering.

GLCCI1 plays a significant role in modulating glucocorticoid (GC) sensitivity in asthma. This project determines the underlying mechanism that GLCCI1 deficiency attenuates GC sensitivity in dexamethasone (Dex)-treated Ovalbumin (OVA)-induced asthma mice and epithelial cells through upregulating binding of IRF1:GRIP1 and IRF3:GRIP1. Dexamethasone treatment led to less reduced inflammation, airway hyperresponsiveness, and activation of the components responsible for GC activity, as determined by decreased GR and glucocorticoid receptor interacting protein 1 (GRIP1) expression but augmented IRF1 and IRF3 expression in GLCCI1−/− asthmatic mice compared with wild type asthmatic mice. Moreover, the recruitment of GRIP1 to GR was downregulated, while the individual recruitment of GRIP1 to IRF1 and IRF3 was upregulated in GLCCI1−/− Dex-treated asthmatic mice compared to wild type Dex-treated asthmatic mice. We also found that GLCCI1 knockdown reduced GR and GRIP1 expression but increased IRF1 and IRF3 expression in Beas2B and A549 cells. Additionally, GLCCI1 silencing increased the interactions between GRIP1 with IRF1 and GRIP1 with IRF3, but decreased the recruitment of GRIP1 to GR. These studies support a critical but previously unrecognized effect of GLCCI1 expression on epithelial cells in asthma GC responses by which GLCCI1 deficiency reduces the GR and GRIP1 interaction but competitively enhances the recruitment of GRIP1 to IRF1 and IRF3.

Wang Bi tablet (WBT) is used to treat rheumatoid arthritis (RA) in China. We employed integrative pharmacology, including rapid analysis of chemical composition, pharmacological experiment, and network pharmacology analysis, to elucidate the active components and mechanism underlying the effect of WBT against RA. The chemical fingerprint of WBT was revealed by UPLC-QTOF-MS/MS, and the chemical composition was identified. The anti-inflammatory effect of WBT was evaluated in TNF-α-stimulated RAW264.7 cells by ELISA and transcriptome sequencing. Network pharmacology analysis, functional enrichment analysis, and network visualization were performed. A total of 293 chemical constituents were preliminarily identified or tentatively characterized in WBT extract, and they effectively inhibited inflammatory response in TNF-α-stimulated RAW264.7 cells. Forty-eight key active constituents were identified based on high-frequency binding to hub targets and their corresponding targets number. Next, 135 corresponding hub genes, which may be the putative targets of WBT in treating RA, were selected. Functionally, the putative targets were significantly associated with the inflammatory immune response regulation module, energy metabolism regulation module, and cell function regulation module, corresponding to the traditional efficacy of WBT. In summary, this study revealed, for the first time using integrative pharmacology, that WBT may attenuate RA through the inflammation-immune regulation system.

With the rapid development of the world’s aerospace technologies, a high-power and high-reliability space high-voltage power supply is significantly required by new generation of applications, including high-power electric propulsion, space welding, deep space exploration, and space solar power stations. However, it is quite difficult for space power supplies to directly achieve high-voltage output from the bus, because of the harshness of the space environment and the performance limitations of existing aerospace-grade electronic components. This paper proposes a high-voltage power supply module design for space welding applications, which outputs 1 kV and 200 W when the input is 100 V. This paper also improves the efficiency of the high-voltage converter with a phase-shifted full-bridge series resonant circuit, then simulates the optimized power module and the electric field distribution of the high-voltage circuit board.

Background and purpose: Early mobilization is considered to have favorable outcomes for stroke patients, but there is currently a lack of specific data to guide this early mobilization, including the initiation time, intensity, frequency, and duration of each activity. Therefore, the optimal strategy for early mobilization is unclear. In this study, we investigated the best combination of different factors to achieve early mobilization, to develop the optimal program.Methods: We conducted an L9 (33) orthogonal experiment with a blinded follow-up assessment. Patients with ischemic stroke, admitted to a stroke unit within 24–72 h of its onset, were recruited. Eligible subjects were randomly assigned to one of nine different programs of early mobilization. The outcomes were assessed at baseline, discharge, and 1 and 3 months after discharge to observe the changes in various efficacy indicators and determine the main factors affecting outcome.Results: We analyzed 57 of 63 patients, after six were excluded for poor compliance, failure to cooperate with the study, or worsening of the disease. The initiation time, intensity, and frequency of mobilization were the main factors affecting outcome (all P < 0.05), and the duration of each activity was a secondary factor (P > 0.05). A comprehensive analysis of the various parameters showed that the optimal level of the early mobilization program was an initiation time: 24–48 h after stroke; intensity: bed and chair transfer, sitting out of bed, standing and walking or climbing stairs when mobility permitted; frequency: 2–3 times/day; duration of each mobilization: determined according to the actual situation of the patient.Conclusions: Early rehabilitation with high-intensity physical exercise at 24–48 h after the onset of stroke, 2–3 times/day, may benefit stroke patients. Applying the optimized program of early mobilization to stroke patients effectively alleviated their symptoms of neurological deficit, improved their capacity for self-care, restored their self-efficacy, improved their quality of life and social participation, and reduced post-stroke fatigue at 3 months.

Hydroxysafflower yellow A (HSYA), as a principal natural ingredient extracted from safflower (Carthamus tinctorius L.), has significant pharmacological activities, such as antioxidant, anti-inflammatory, anticoagulant, and anticancer effects. However, chemical instability and low bioavailability have been severely hampering the clinical applications of HSYA during the treatment of cardiovascular and cerebrovascular disease. Therefore, this present review systematically summarized the materials about HSYA, including acquisition methods, extraction and detection methods, pharmacokinetics, pharmacological effects and molecular mechanism, especially focus on the possible causes and resolutions about the chemical instability and low bioavailability of HSYA, in order to provide relatively comprehensive basic data for the related research of HSYA.

TERMINAL FLOWER1 (TFL1), a key factor belonging to the phosphatidyl ethanolamine-binding protein (PEBP) family, controls flowering time and inflorescence architecture in some plants. However, the role of TFL1 in loquat remains unknown. In this study, we cloned two TFL1-like genes (EjTFL1-1 and EjTFL1-2) with conserved deduced amino acid sequences from cultivated loquat (Eriobotrya japonica Lindl.). First, we determined that flower bud differentiation occurs at the end of June and early July, and then comprehensively analyzed the temporal and spatial expression patterns of these EjTFL1s during loquat growth and development. We observed the contrasting expression trends for EjTFL1s and EjAP1s (APETALA 1) in shoot apices, and EjTFL1s were mainly expressed in young tissues. In addition, short-day and exogenous GA3 treatments promoted the expression of EjTFL1s, and no flower bud differentiation was observed after these treatments in loquat. Moreover, EjTFL1s were localized to the cytoplasm and nucleus, and both interacted with another flowering transcription factor, EjFD, in the nucleus, and EjTFL1s-EjFD complex significantly repressed the promoter activity of EjAP1-1. The two EjTFL1s were overexpressed in wild-type Arabidopsis thaliana Col-0, which delayed flowering time, promoted stem elongation, increased the number of branches, and also affected flower and silique phenotypes. In conclusion, our results suggested that EjTFL1-1 and EjTFL1-2 do not show the same pattern of expression whereas both are able of inhibiting flower bud differentiation and promoting vegetative growth in loquat by integrating GA3 and photoperiod signals. These findings provide useful clues for analyzing the flowering regulatory network of loquat and provide meaningful references for flowering regulation research of other woody fruit trees.

Traumatic brain injury, a common cause of acquired epilepsy, is typical to find necrotic cell death within the injury core. The dynamic changes in astrocytes surrounding the injury core contribute to epileptic seizures associated with intense neuronal firing. However, little is known about the molecular mechanisms that activate astrocytes during traumatic brain injury or the effect of functional changes of astrocytes on seizures. In this comprehensive review, we present our cumulated understanding of the complex neurological affection in astrocytes after traumatic brain injury. We approached the problem through describing the changes of cell morphology, neurotransmitters, biochemistry, and cytokines in astrocytes during post-traumatic epilepsy. In addition, we also discussed the relationship between dynamic changes in astrocytes and seizures and the current pharmacologic agents used for treatment. Hopefully, this review will provide a more detailed knowledge from which better therapeutic strategies can be developed to treat post-traumatic epilepsy.

Long non-coding RNAs (lncRNAs) play a significant role in stress responses. To date, only a few studies have reported the role of lncRNAs in insect-pathogenic fungi. Here, we report a genome-wide transcriptional analysis of lncRNAs produced in response to heat stress in Metarhizium robertsii, a model insect-pathogenic fungus, using strand-specific RNA sequencing. A total of 1655 lncRNAs with 1742 isoforms were identified, of which 1081 differentially expressed (DE) lncRNAs were characterized as being heat responsive. By characterizing their genomic structures and expression patterns, we found that the lncRNAs possessed shorter transcripts, fewer exons, and lower expression levels than the protein-coding genes in M. robertsii. Furthermore, target prediction analysis of the lncRNAs revealed thousands of potential DE lncRNA–messenger RNA (mRNA) pairs, among which 5381 pairs function in the cis-regulatory mode. Further pathway enrichment analysis of the corresponding cis-regulated target genes showed that the targets were significantly enriched in the following biological pathways: the Hippo signaling pathway and cell cycle. This finding suggested that these DE lncRNAs control the expression of their corresponding neighboring genes primarily through environmental information processing and cellular processes. Moreover, only 26 trans-regulated lncRNA–mRNA pairs were determined. In addition, among the targets of heat-responsive lncRNAs, two classic genes that may be involved in the response to heat stress were also identified, including hsp70 (XM_007821830 and XM_007825705). These findings expand our knowledge of lncRNAs as important regulators of the response to heat stress in filamentous fungi, including M. robertsii.

The MADS-box transcription factor SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) integrates environmental and endogenous signals to promote flowering in Arabidopsis. However, the role of SOC1 homologs in regulating flowering time in fruit trees remains unclear. To better understand the molecular mechanism of flowering regulation in loquat (Eriobotrya japonica Lindl.), two SOC1 homologs (EjSOC1-1 and EjSOC1-2) were identified and characterized in this work. Sequence analysis showed that EjSOC1-1 and EjSOC1-2 have conserved MADS-box and K-box domains. EjSOC1-1 and EjSOC1-2 were clearly expressed in vegetative organs, and high expression was detected in flower buds. As observed in paraffin-embedded sections, expression of the downstream flowering genes EjAP1s and EjLFYs started to increase at the end of June, a time when flower bud differentiation occurs. Additionally, high expression of EjSOC1-1 and EjSOC1-2 began 10 days earlier than that of EjAP1s and EjLFYs in shoot apical meristem (SAM). EjSOC1-1 and EjSOC1-2 were inhibited by short-day (SD) conditions and exogenous GA3, and flower bud differentiation did not occur after these treatments. EjSOC1-1 and EjSOC1-2 were found to be localized to the nucleus. Moreover, ectopic overexpression of EjSOC1-1 and EjSOC1-2 in wild-type Arabidopsis promoted early flowering, and overexpression of both was able to rescue the late flowering phenotype of the soc1-2 mutant. In conclusion, the results suggest that cultivated loquat flower bud differentiation in southern China begins in late June to early July and that EjSOC1-1 and EjSOC1-2 participate in the induction of flower initiation. These findings provide new insight into the artificial regulation of flowering time in fruit trees.