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Abstract 抽象 Lymphangioleiomyomatosis (LAM) is a rare, slowly progressing, low-grade metastatic tumor primarily affecting women. Currently, vascular endothelial growth factor–D (VEGF-D) is the only validated diagnostic biomarker, enabling diagnosis of LAM without the need for lung biopsy in appropriate clinical settings. However, VEGF-D concentrations are normal in about 30% of patients, rendering it insufficient for diagnosing all cases of LAM. There remains a need to identify more non-invasive, safe, sensitive, and specific biomarkers associated with LAM. Therefore, it is imperative to explore novel non-invasive, safe, and specific diagnostic methods for LAM. This article aims to review biomarkers associated with LAM, including potential biomarkers newly discovered or showing advancements in classical biomarkers widely used in LAM, and discuss their application in LAM diagnosis, assessment of disease severity, prediction of treatment response, and prognosis.淋巴管平滑肌瘤病 （LAM） 是一种罕见的、进展缓慢的低级别转移性肿瘤，主要影响女性。目前，血管内皮生长因子-D （VEGF-D） 是唯一经过验证的诊断生物标志物，无需在适当的临床环境中进行肺活检即可诊断 LAM。然而，约 30% 患者的 VEGF-D 浓度正常，不足以诊断所有 LAM 病例。仍然需要确定与 LAM 相关的更多无创、安全、敏感和特异性的生物标志物。因此，当务之急是探索新型无创、安全和特异性的 LAM 诊断方法。本文旨在回顾与 LAM 相关的生物标志物，包括新发现的潜在生物标志物或显示出 LAM 中广泛使用的经典生物标志物的进展，并讨论它们在 LAM 诊断、疾病严重程度评估、治疗反应预测和预后中的应用。

ABSTRACT Vulvovaginal candidiasis (VVC) is a common vaginal infectious disease caused by Candida. The high recurrence rate of VVC is a great clinical challenge, with recurrent VVC (RVVC) defined as four or more episodes within a year. In this study, we recruited 31 RVVC patients, 28 VVC patients, and 29 healthy women. Vaginal samples were collected for metagenomic and metabolic analysis. RVVC and VVC groups presented similar clinical symptoms, with only a significantly increased incidence of swelling in the VVC group. Vaginal microbiota in VVC/RVVC exhibited a decreased abundance of Lactobacillus and increased bacterial vaginosis-associated bacteria, such as Gardnerella, Prevotella, and Atopobium. Notably, Lactobacillus iners was higher in RVVC, suggesting not all Lactobacillus species are protective. Healthy women showed lower overall microbiota diversity, emphasizing single-species dominance for stability. Glycogen metabolism pathways were enriched in RVVC/VVC, and were correlated with Atopobium vaginae, Prevotella bivia, and Lactobacillus jensenii. Peptidoglycan synthesis pathways, associated with P. bivia, were enriched, with the substrate L-glutamate elevated in RVVC, possibly promoted by L. iners. These findings shed light on potential therapeutic targets for recurrent VVC, contributing to the understanding of the intricate interplay between the metabolism of vaginal microbiome and disease.IMPORTANCEThis study enhances our knowledge of the vaginal microbiota dynamics and the role of associated metabolites in individuals with vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis through shotgun sequencing and multi-omics analysis. The relationship between metabolites and vaginal microbiota and disease state was revealed. The accumulation of L-glutamate generated in glycogen metabolism, which is governed by Lactobacillus iners or bacterial vaginosis-associated bacteria, may contribute to the incidence and recurrence of VVC. Such insights have the potential to impact the treatment and prevention strategies for these common yet distressing conditions, potentially leading to targeted therapies and improved patient outcomes.

Abstract Geminiviruses are an important group of viruses that infect a variety of plants and result in heavy agricultural losses worldwide. The homologs of C4 (or L4) in monopartite geminiviruses and AC4 (or AL4) in bipartite geminiviruses are critical viral proteins. The C4 proteins from several geminiviruses are the substrates of S-acylation, a dynamic post-translational modification, for the maintenance of their membrane localization and function in virus infection. Here we initiated a screening and identified a plant protein ABAPT3 (Alpha/Beta Hydrolase Domain-containing Protein 17-like Acyl Protein Thioesterase 3) as the de-S-acylation enzyme of C4 encoded by BSCTV (Beet severe curly top virus). Overexpression of ABAPT3 reduced the S-acylation of BSCTV C4, disrupted its plasma membrane localization, inhibited its function in pathogenesis, and suppressed BSCTV infection. Because the S-acylation motifs are conserved among C4 from different geminiviruses, we tested the effect of ABAPT3 on the C4 protein of ToLCGdV (Tomato leaf curl Guangdong virus) from another geminivirus genus. Consistently, ABAPT3 overexpression also disrupted the S-acylation, subcellular localization, and function of ToLCGdV C4, and inhibited ToLCGdV infection. In summary, we provided a new approach to globally improve the resistance to different types of geminiviruses in plants via de-S-acylation of the viral C4 proteins and it can be extendedly used for suppression of geminivirus infection in crops.

Abstract Background Myocardial ischemia/reperfusion injury (MIRI) is an important complication of reperfusion therapy, and has a lack of effective prevention and treatment methods. Oleuropein (OP) is a natural strong antioxidant with many protective effects on cardiovascular diseases, but its protective effect on MIRI has not yet been studied in depth. Methods Tert-Butyl hydroperoxide (tBHP) was used to establish an in vitro oxidative stress model. Cell viability was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH). Flow cytometry and fluorescence assays were performed for evaluating the ROS levels and mitochondrial membrane potential (MMP). Immunofluorescence analysis detected the NRF2 nuclear translocation and autophagy indicators. Further, Western blotting and quantitative real-time PCR were performed to evaluate the expression levels of proteins and mRNAs. Molecular docking, CETSA, and molecular interaction analysis explored the binding between OP and TLR4. The protective effects of OP in vivo were determined using a preclinical MIRI rat model. Results OP protected against tBHP-treated injury, reduced ROS levels and reversed the damaged MMP. Mechanistically, OP activated NRF2-related antioxidant pathways, inhibited autophagy and attenuated the TLR4/MAPK signaling pathway in tBHP-treated H9C2 cells with a high binding affinity to TLR4 (K D = 37.5 µM). The TLR4 inhibitor TAK242 showed a similar effect as OP. In vivo, OP could alleviate cardiac ischemia/reperfusion injury and it ameliorated adverse cardiac remodeling. Consistent with in vitro studies, OP inhibited TLR4/MAPK and autophagy pathway and activated NRF2-dependent antioxidant pathways in vivo. Conclusion This study shows that OP binds to TLR4 to regulate oxidative stress and autophagy for protecting damaged cardiomyocytes, supporting that OP can be a potential therapeutic agent for MIRI.

The P2X7 receptor (P2X7R), an ATP-gated ion channel, has emerged as a crucial player in neuroinflammation and a promising therapeutic target for neurodegenerative disorders. This review explores the current understanding of P2X7R’s structure, activation, and physiological roles, focusing on its expression and function in microglial cells. The article examines the receptor’s involvement in calcium signaling, microglial activation, and polarization, as well as its role in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis. The review highlights the complex nature of P2X7R signaling, discussing its potential neuroprotective and neurotoxic effects depending on the disease stage and context. It also addresses the development of P2X7R antagonists and their progress in clinical trials, identifying key research gaps and future perspectives for P2X7R-targeted therapy development. By providing a comprehensive overview of the current state of knowledge and future directions, this review serves as a valuable resource for researchers and clinicians interested in exploring the therapeutic potential of targeting P2X7R for the treatment of neurodegenerative disorders.

Vaginitis, characterized by pathogenic invasion and a deficiency in beneficial lactobacilli, has recognized lactobacilli supplementation as a novel therapeutic strategy. However, due to individual differences in vaginal microbiota, identifying universally effective Lactobacillus strains is challenging. Traditional methodologies for probiotic selection, which heavily depend on extensive in vitro experiments, are both time-intensive and laborious. The aim of this study was to pinpoint possible vaginal probiotic candidates based on whole-genome screening. We sequenced the genomes of 98 previously isolated Lactobacillus strains, annotating their genes involved in probiotic metabolite biosynthesis, adherence, acid/bile tolerance, and antibiotic resistance. A scoring system was used to assess the strains based on their genomic profiles. The highest-scoring strains underwent further in vitro evaluation. Consequently, two strains, Lactobacillus crispatus LG55-27 and Lactobacillus gasseri TM13-16, displayed an outstanding ability to produce d-lactate and adhere to human vaginal epithelial cells. They also showed higher antimicrobial activity against Gardnerella vaginalis, Escherichia coli, Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa compared to reference Lactobacillus strains. Their resilience to acid and bile environments highlights the potential for oral supplementation. Oral and vaginal administration of these two strains were tested in a bacterial vaginosis (BV) rat model at various doses. Results indicated that combined vaginal administration of these strains at 1 × 106 CFU/day significantly mitigated BV in rats. This research offers a probiotic dosage guideline for vaginitis therapy, underscoring an efficient screening process for probiotics using genome sequencing, in vitro testing, and in vivo BV model experimentation.

Panel pad bending is a critical process to improve the screen-to-body ratio of an active-matrix organic light-emitting diode (AMOLED) panel. The failure analysis of the metal wirings is the key to ensure the reliability of signal transmission when the pad be bent to the back of the panel. In the present work, the sub-modeling technique combined with the periodic boundary condition was used to simulate the stress distribution of the bending area of the pad. The progressive failure of bent metal wirings was investigated by the extended finite element method. It is proved to be rational to prevent the wirings damage if the interlayer dielectric is replaced by an organic layer. In order to reduce stress of metal wirings, it is a measure to replace the original ultraviolet (UV) curable adhesive with a higher-modulus UV adhesive. The simulated results also show that rectangular perforations can avoid the stress concentration caused by the holes compared with circular perforations. For better stress distribution of metal wirings, it is necessary to increase the lengths of the rectangular holes and decrease the widths of that to a certain extent, which is helpful for restraining crack propagation by means of low-stress zones and holes.

Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the intestine. A higher abundance of Prevotella timonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.

BackgroundFat-soluble vitamins (A, D, and E) are essential for the proper functioning of the immune system and are of central importance for infection risk in humans. Vitamins A, D, and E have been reported to be associated with the immune response following vaccination; however, their effects on the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination remain unknown.MethodsWe measured the neutralizing antibody titers against wild type and omicron within 98 days after the third homologous boosting shot of inactivated SARS-CoV-2 vaccine (BBIBP-CorV or CoronaVac) in 141 healthy adults in a prospective, open-label study. High-performance liquid chromatography-tandem mass spectroscopy was used to determine the concentrations of plasma vitamins A, D, and E.ResultsWe found that the anti-wide-type virus and anti-omicron variant antibody levels significantly increased compared with baseline antibody levels (P < 0.001) after the third vaccination. 25(OH)D3 was significantly negatively associated with the baseline anti-wide-type virus antibody concentrations [beta (95% CI) = −0.331 (−0.659 ~ −0.003)] after adjusting for covariates. A potentially similar association was also observed on day 98 after the third vaccination [beta (95% CI) = −0.317 (−0.641 ~ 0.007)]. After adjusting for covariates, we also found that 25(OH)D3 was significantly negatively associated with the seropositivity of the anti-omicron variant antibody at day 98 after the third vaccination [OR (95% CI) = 0.940 (0.883 ~ 0.996)]. The association between plasma 25(OH)D3 with anti-wild-type virus antibody levels and seropositivity of anti-omicron variant antibodies were persistent in subgroup analyses. We observed no association between retinol/α-tocopherol and anti-wide-type virus antibody levels or anti-omicron variant antibody seropositive in our study.ConclusionThe third inactivated SARS-CoV-2 vaccination significantly improved the ability of anti-SARS-CoV-2 infection in the human body. Higher vitamin D concentrations could significantly decrease the anti-wide-type virus-neutralizing antibody titers and anti-omicron variant antibody seropositive rate after the inactivated SARS-CoV-2 vaccination in people with adequate levels of vitamin D, better immune status, and stronger immune response; further studies comprising large cohorts of patients with different nutritional status are warranted to verify our results.

The molecular landscape in breast cancer is characterized by large biological heterogeneity and variable clinical outcomes. Here, we performed an integrative multi-omics analysis of patients diagnosed with breast cancer. Using transcriptomic analysis, we identified three subtypes (cluster A, cluster B and cluster C) of breast cancer with distinct prognosis, clinical features, and genomic alterations: Cluster A was associated with higher genomic instability, immune suppression and worst prognosis outcome; cluster B was associated with high activation of immune-pathway, increased mutations and middle prognosis outcome; cluster C was linked to Luminal A subtype patients, moderate immune cell infiltration and best prognosis outcome. Combination of the three newly identified clusters with PAM50 subtypes, we proposed potential new precision strategies for 15 subtypes using L1000 database. Then, we developed a robust gene pair (RGP) score for prognosis outcome prediction of patients with breast cancer. The RGP score is based on a novel gene-pairing approach to eliminate batch effects caused by differences in heterogeneous patient cohorts and transcriptomic data distributions, and it was validated in ten cohorts of patients with breast cancer. Finally, we developed a user-friendly web-tool (https://sujiezhulab.shinyapps.io/BRCA/) to predict subtype, treatment strategies and prognosis states for patients with breast cancer.

BackgroundColon cancer is a highly heterogeneous disease, and identifying molecular subtypes can provide insights into deregulated pathways within tumor subsets, which may lead to personalized treatment options. However, most prognostic models are based on single-pathway genes.MethodsIn this study, we aimed to identify three clinically relevant subtypes of colon cancer based on multiple signaling pathways-related genes. Integrative multi-omics analysis was used to explain the biological processes contributing to colon cancer aggressiveness, recurrence, and progression. Machine learning methods were employed to identify the subtypes and provide medication guidance for distinct subtypes using the L1000 platform. We developed a robust prognostic model (MKPC score) based on gene pairs and validated it in one internal test set and three external test sets. Risk-related genes were extracted and verified by qPCR.ResultsThree clinically relevant subtypes of colon cancer were identified based on multiple signaling pathways-related genes, which had significantly different survival state (Log-Rank test, p

Neurodegenerative diseases (NDs) are disorders characterized by degenerative degeneration of neurons and loss of their function. NDs have a complicated pathophysiology, of which neuroinflammation and neuronal death are significant factors. The inflammatory process known as pyroptosis (“fiery death”) is caused by a family of pore-forming proteins called Gasdermins (GSDMs), which appears downstream from the activation of the inflammasome. Clear evidence of enhanced pyroptosis-related proteins activity in common NDs has coincided with abnormal aggregation of pathological proteins (such as Aβ, tau, α-synuclein et al.), making pyroptosis an attractive direction for the recent study of NDs. The purpose of this review is to provide an overview of the molecular mechanisms driving pyroptosis, the mechanistic links between pyroptosis and NDs, and emerging therapeutic strategies in Traditional Chinese Medicine (TCM) to inhibit pyroptosis for the treatment of NDs.

Gastric cancer (GC) is a malignant cancer that reduces life expectancy worldwide. Although treatment strategies have improved, patients with GC still have poor prognoses. Hence, it is necessary to understand the molecular mechanisms of GC and to find new therapeutic targets. Mitochondrial dynamics and mitochondrial dysfunction are associated with cancer cell growth and progression. Numerous studies have reported that non-coding RNAs (ncRNAs) can participate in the occurrence and development of GC by regulating mitochondrial dynamics. Elucidating the crosstalk between ncRNAs and mitochondria would be helpful in preventing and treating GC. Herein, we review and summarize the functions of oncogenes and tumor suppressors in suppressing ncRNAs and regulating mitochondrial dynamics in GC tumor growth, proliferation, invasion and metastasis. This review provides new insights into the pathogenesis of and intervention for GC.

Preeclampsia (PE) is a severe placenta-related pregnancy disease that has been associated with maternal systemic inflammation and immune system disorders. However, the distribution and functional changes in immune cells of the maternal–placental interface have not been well characterized. Herein, cytometry by time-of-flight mass spectrometry (CyTOF) was used to investigate the immune atlas at the decidua, which was obtained from four PE patients and four healthy controls. Six superclusters were identified, namely, T cells, B cells, natural killer (NK) cells, monocytes, granulocytes, and others. B cells were significantly decreased in the PE group, among which the reduction in CD27+CD38+ regulatory B cell (Breg)-like cells may stimulate immune activation in PE. The significantly increased migration of B cells could be linked to the significantly overexpressed chemokine C-X-C receptor 5 (CXCR5) in the PE group, which may result in the production of excessive autoantibodies and the pathogenesis of PE. A subset of T cells, CD11c+CD8+ T cells, was significantly decreased in PE and might lead to sustained immune activation in PE patients. NK cells were ultimately separated into four subsets. The significant reduction in a novel subset of NK cells (CD56-CD49a-CD38+) in PE might have led to the failure to suppress inflammation at the maternal–fetal interface during PE progression. Moreover, the expression levels of functional markers were significantly altered in the PE group, which also inferred that shifts in the decidual immune state contributed to the development of PE and might serve as potential treatment targets. This is a worthy attempt to elaborate the differences in the phenotype and function of CD45+ immune cells in the decidua between PE and healthy pregnancies by CyTOF, which contributes to understand the pathogenesis of PE, and the altered cell subsets and markers may inspire the immune modulatory therapy for PE.

Abstract Background Cardiotocography (CTG) interpretation plays a critical role in prenatal fetal monitoring. However, the interpretation of fetal status assessment using CTG is mainly confined to clinical research. To the best of our knowledge, there is no study on data analysis of CTG records to explore the causal relationships between the important CTG features and fetal status evaluation. Methods For analyses, 2126 cardiotocograms were automatically processed and the respective diagnostic features measured by the Sisporto program. In this paper, we aim to explore the causal relationships between the important CTG features and fetal status evaluation. First, we utilized data visualization and Spearman correlation analysis to explore the relationship among CTG features and their importance on fetal status assessment. Second, we proposed a forward-stepwise-selection association rule analysis (ARA) to supplement the fetal status assessment rules based on sparse pathological cases. Third, we established structural equation models (SEMs) to investigate the latent causal factors and their causal coefficients to fetal status assessment. Results Data visualization and the Spearman correlation analysis found that thirteen CTG features were relevant to the fetal state evaluation. The forward-stepwise-selection ARA further validated and complemented the CTG interpretation rules in the fetal monitoring guidelines. The measurement models validated the five latent variables, which were baseline category (BCat), variability category (VCat), acceleration category (ACat), deceleration category (DCat) and uterine contraction category (UCat) based on fetal monitoring knowledge and the above analyses. Furthermore, the interpretable models discovered the cause factors of fetal status assessment and their causal coefficients to fetal status assessment. For instance, VCat could predict BCat, and UCat could predict DCat as well. ACat, BCat and DCat directly affected fetal status assessment, where ACat was the important causal factor. Conclusions The analyses revealed the interpretation rules and discovered the causal factors and their causal coefficients for fetal status assessment. Moreover, the results are consistent with the computerized fetal monitoring and clinical knowledge. Our approaches are conducive to evidence-based medical research and realizing intelligent fetal monitoring.

Candida albicans is the most frequent fungal species responsible for vulvovaginal candidiasis (VVC), which exhibits distinct genetic diversity that is linked with the clinical phenotype. This study aimed to assess the genotypes and clinical characteristics of different C. albicans isolates from VVC patients. Based on multilocus sequence typing (MLST), clade 1 was identified as the largest C. albicans group, which appeared most frequently in recurrent VVC and treatment failure cases. Further study of antifungal susceptibility demonstrated that MLST clade 1 strains presented significantly higher drug resistance ability than non-clade 1 strains, which result from the overexpression of MDR1. The mRNA and protein expression levels of virulence-related genes were also significantly higher in clade 1 isolates than in non-clade 1 isolates. Proteomic analysis indicated that the protein stabilization pathway was significantly enriched in clade 1 strains and that RPS4 was a central regulator of proteins involved in stress resistance, adherence, and DNA repair, which all contribute to the resistance and virulence of MLST clade 1 strains. This study was the first attempt to compare the correlation mechanisms between C. albicans MLST clade 1 and non-clade 1 strains and the clinical phenotype, which is of great significance for VVC classification and treatment.

Abstract Background Pneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model. Methods The network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP-induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (ribavirin or ceftriaxone sodium injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin staining (HE) staining. Proteins expression was quantified by western blotting. Results The network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway. Conclusion Our findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.

Objectives: Fine particulate matter (PM2.5) is the principal air pollutant and poses a serious threat to public health. This study explored the effects of PM2.5 on the action spectrum of ultraviolet radiation for vitamin D production (UVvitD) received by manikin surfaces. Methods: Multi-inclination angle ultraviolet radiation monitoring was conducted with different concentrations of PM2.5. Combining monitoring data with the PM2.5 concentration, solar elevation angle (SEA), and inclination angle, a UVvitD exposure model for human body multi-inclined surfaces was constructed through a multiple linear regression analysis. A 3D manikin model was used to examine the PM2.5 effects on UVvitD received by the manikin surface. Results: When PM2.5 concentrations ranged from 35 μg/m3 to 100 μg/m3 (average concentration of PM2.5 in this range: 62 μg/m3), the UVvitD received by the whole body was reduced by approximately 8.45% to 19.82% compared with the UVvitD received when PM2.5 concentrations ranged from 6 μg/m3 to 35 μg/m3 (average concentration of PM2.5 in this range: 17 μg/m3) with SEAs between 30° and 50°. Moreover, the UVvitD dose was reduced by 11.82% in the above comparisons. When further comparing PM2.5 concentrations from 100 μg/m3 to 161 μg/m3 (average concentration of PM2.5 in this range: 132 μg/m3) with those from 6 μg/m3 to 35 μg/m3 (average concentration of PM2.5 in this range: 17 μg/m3), the UVvitD received by the whole body was reduced by approximately 21.6% to 50.64% at SEAs between 30° and 50°. The UVvitD dose was reduced by 30.2%. Conclusions: The occurrence of PM2.5 obviously reduced the UVvitD received by the manikin surface.

Current efforts for the prevention of malaria have resulted in notable reductions in the global malaria burden; however, they are not enough. Good hygiene is universally considered one of the most efficacious and straightforward measures to prevent disease transmission. This work analyzed whether improved drinking water and sanitation (WS) conditions were associated with a decreased risk of malaria infection. Data were acquired through surveys published between 2006 and 2018 from the Demographic and Health Program in sub-Saharan Africa (SSA). Multiple logistic regression was used for each national survey to identify the associations between WS conditions and malaria infection diagnosed by microscopy or a malaria rapid diagnostic test (RDT) among children (0–59 months), with adjustments for age, gender, indoor residual spraying (IRS), insecticide-treated net (ITN) use, house quality, and the mother’s highest educational level. Individual nationally representative survey odds ratios (ORs) were combined to obtain a summary OR using a random-effects meta-analysis. Among the 247,440 included children, 18.8% and 24.2% were positive for malaria infection based on microscopy and RDT results, respectively. Across all surveys, both unprotected water and no facility users were associated with increased malaria risks (unprotected water: aOR 1.17, 95% CI 1.07–1.27, P = 0.001; no facilities: aOR 1.35, 95% CI 1.24–1.47, P

Maternal rectovaginal colonization with Group B Streptococcus (GBS) during labor is a prerequisite for neonatal early-onset GBS disease. Intrapartum antibiotic prophylaxis (IAP) has been proven to prevent GBS perinatal infection, while there are few studies on the evaluation of the effectiveness of different antibiotic prophylaxis regimens. This study aimed to assess the maternal rectovaginal GBS colonization status after IAP, antimicrobial susceptibility and maternal and neonatal outcomes among women administered different antibiotic prophylaxis regimens. A prospective study was conducted between June 2018 and June 2022. GBS carriers identified at 35–37 weeks of gestation were provided IAP (penicillin, cefazolin or clindamycin) at delivery based on the local protocol for GBS prevention. Rectovaginal samples were obtained from participants again after delivery. Antimicrobial susceptibility testing in GBS isolates was performed using the broth microdilution method. A total of 295 cases were included in this study. In the postpartum re-examination for GBS, the overall negative rectovaginal culture rate was 90.8% (268/295). Women who received cefazolin prophylaxis had the highest negative culture rate (95.2%, 197/207), which was followed by those who received penicillin (80.7%, 67/83) and clindamycin (80.0%, 4/5) (p = 0.001). All GBS isolates achieved sensitivity to penicillin and cefazolin, whereas resistance to clindamycin was shown in 21.4% of the strains. There were no significant differences in maternal and neonatal outcomes among the IAP groups. The use of IAP is highly effective in reducing the maternal rectovaginal GBS colonization. Cefazolin may offer equivalent efficacy and safety compared to standard penicillin prophylaxis.

The purpose of this study was to evaluate the effectiveness of metronidazole and oral probiotics adjunct to metronidazole in the treatment of bacterial vaginosis (BV). One hundred and twenty-six Chinese women with BV were enrolled in this parallel, controlled trial, and were randomly assigned into two study arms: the metronidazole group, which was prescribed metronidazole vaginal suppositories for 7 days, and the adjunctive probiotic group, which received Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 orally for 30 days as an adjunct to metronidazole. Clinical symptoms and Nugent scores at the initial visit, 30 days and 90 days were compared. There was no significant difference of the 30-day total cure rate between the adjunctive probiotic group (57.69%) and the metronidazole group (59.57%), with an odds ratio (OR) of 0.97 (95% confidence interval (CI), 0.70 to 1.35, p-value = 0.04), or of the 90-day total cure rate (36.54% vs. 48.94%, OR, 0.75; 95% CI, 0.47 to 1.19; p-value = 0.213). Also, no significant difference of the vaginal and faecal microbial diversity and structure between the two groups at 0, 30 or 90 days were shown based on 16S rRNA sequences. The probiotic species were rarely detected in either the vaginal microbiota or the faecal microbiota after administration which may revealed the cause of noneffective of oral probiotics. No serious adverse effects were reported in the trial. The study indicated that oral probiotic adjunctive treatment did not increase the cure rate of Chinese BV patients compared to metronidazole.

The prevalence of age-related cataracts is higher in Asians than Caucasians. Ocular ultraviolet (UV) exposure is an important environmental risk factor leading to age-related cataracts. The purpose of this paper is to clarify the effects of facial anatomy on ocular UV exposure between Asians and Europeans. We built optical models with 3D-printed Asian and European manikins that could truly reflect the typical facial features of Asians and Europeans, monitored the ambient and ocular UV exposure using these models in Fuxin (42.00°N, 121.69°E), China, and used 3ds Max software to model the effects of the facial anatomy structures on the light entering the eyes by rendering the resulting shadows. We found that the ocular UV exposure intensity in the Asian manikin was higher than that in the European manikin at a rotation angle of 282° to 354° when the solar elevation angle (SEA) was approximately 30° to 60° and at a rotation angle of 150° toward the sun when the SEA was approximately above 60°. Based on the optical models we built, we conclude that, due to the differences in the superciliary arch and glabella, the risk of high ocular UV exposure is greater in the Asian manikin than in the European manikin. Our findings provide grounds for speculation about whether the blocking effect of the superciliary arch and glabella of the European manikin on ocular UV exposure is one of the reasons for the higher prevalence of age-related cataracts in Asians than in Europeans.

Coriander, Coriandrum Sativum L., is one of the commonest food and medicinal plants in many countries, but its chemical ingredients and pivotal role in anti-inflammatory activity have not been fully explored. The present study aimed to identify new compounds in the fruits of coriander and explore their anti-inflammatory activity. The compounds were isolated by chromatographic seperations and identified using spectroscopic and spectrometric methods. RAW264.7 macrophage cells were used to detect the anti-inflammatory activity of the compounds via Griess assay, western blotting, ELISA, and flow cytometry methods. The study resulted in the discovery of four new compounds, which were identified as: 4α-(furo[2,3-d]pyrimidin-6′-ylmethyl)-9α-propylnonolactone (1), 4-(formyloxy)-4-(6′-methylcyclohex-1-en-1-yl)butanoate(2), (7α,8α)-3α-hydroxyl-12,13α-dimethyl-5(6)-en-bicyclo[5,3,0]caprolactone (3), 7-methoxy-4-methyl-5,6-dihydro-7H-(2-hydroxypropan-2-yl)furo[2,3-f] coumarin (4). Compound 3 showed the highest anti-inflammatory activity with IC50 of 6.25 μM for an inhibitory effect on nitrite oxide (NO) level. In addition, compound 3 decreased the lipopolysaccharides-stimulated generations of ROS and the inflammatory cytokines (IL-6 and TNF-α). Mechanism exploration indicated that compound 3 suppressed inflammatory mediators’ expression, like iNOS and COX-2. Furthermore, the NF-κB and MAPK pathways were involved in the anti-inflammatory process of compound 3.

Acute lung injury (ALI) is an acute inflammatory process in the lung parenchyma. Anemoside B4 (B4) was isolated from Pulsatilla, a plant-based drug against inflammation and commonly applied in traditional Chinese medicine. However, the anti-inflammatory effect and the mechanisms of B4 are not clear. In this study, we explored the potential mechanisms and anti-inflammatory activity of B4 both in vitro and in vivo. The results indicated that B4 suppressed the expression of iNOS, COX-2, NLRP3, caspase-1, and IL-1β. The ELISA assay results showed that B4 significantly restrained the release of inflammatory cytokines like TNF-α, IL-6, and IL-1β in macrophage cells. In addition, B4 rescued mitochondrial membrane potential (MMP) loss in (lipopolysaccharide) LPS plus ATP stimulated macrophage cells. Co-IP and molecular docking results illustrated that B4 disrupted the dimerization of TLR4. For in vivo results, B4 exhibited a protective effect on LPS and bleomycin- (BLM-) induced ALI in mice through suppressing the lesions of lung tissues, the release of inflammatory cytokines, and the levels of white blood cells, neutrophils, and lymphoid cells in the blood. Collectively, B4 has a protective effect on ALI via blocking TLR4 dimerization and NLRP3 inflammasome activation, suggesting that B4 is a potential agent for the treatment of ALI.

Bambusa vulgaris cv. Wamin is an attractive ornamental bamboo species of southern China. It has large swollen internodes and weeping culms, and it has considerable economic importance. In the present study, we sequenced the complete chloroplast genome of B. vulgaris cv. Wamin and reported it for the first time. The genome was 139,528 bp in total length, including a large single-copy (LSC) region of 83,038 bp, a small single-copy (SSC) region of 12,893 bp, and a pair of invert repeats (IR) regions of 21,799 bp. Plastid genome contained 138 genes, 82 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The overall GC content of the genome was 38.9%. The phylogenetic analysis based on the complete chloroplast genome reveals that B. vulgaris cv. Wamin is closely related to Bambusa teres. This research strengthens the genetic information of both the B. vulgaris cv. Wamin and the phylogenetic analyses of Gramineae.

UV-B radiation may be an important risk factor in cataract etiology. After exposure to UV-B radiation, cells show imbalances in the repair of DNA damage, which induce changes in the levels of certain proteins, including alpha-crystallin, which is the most abundant protein in the lens and crucial for the maintenance of lens transparency. Lanosterol synthase (LSS), an essential rate-limiting enzyme in cholesterol biosynthesis, might play significant roles in oxidative stress and in the maintenance of lens transparency. However, the roles of LSS in UV-B-induced apoptosis are not well understood. Therefore, we irradiated female Sprague-Dawley rats with ultraviolet radiation to establish an animal model for exploring the variations in LSS expression during the early stages of UV-B exposure. In addition, we cultured human lens epithelial (HLE) cells that overexpress LSS and exposed them to UV-B radiation to explore the function of increased LSS expression in UV-B-induced apoptosis. The data demonstrated that UV-B exposure induced oxidative stress and apoptosis in rat lens epithelial cells and that irradiance exposure increased the level of lenticular damage. Additionally, UV-B exposure decreased the alpha-crystallin content and increased the expressions of Bax and cleaved caspase-3 compared with the control levels. After exposure to UV-B, the apoptosis-related index of HLE cells overexpressing LSS was lower than that of the control cells. Furthermore, ROS overproduction might activate the sirtuin 1 (Sirt1) pathway, which induced protein expressions of sterol regulatory element-binding transcription factor 2 (SREBF2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and LSS. However, the specific mechanism of the Sirt1 pathway needed to be further studied. In summary, UV-B exposure induced oxidative injury and resulted in crystallin denaturation and apoptosis in lens epithelial cells, and LSS might play a protective role during the early stages of this process and could be an important target in the cataract prevention.

Objective The agranulocytosis-associated perianal infection (PI) rate ranges from 60% to 100% among patients with hematopoietic malignancies. In this study, we assessed the efficacy of a quality control circle (QCC) to minimize the PI rate. Methods Among 274 patients with severe immunodeficiency (agranulocytosis of ≥2 weeks) in our bone marrow transplantation center, the PI rate was 17.20%. A QCC was established following the 10 steps of the plan-do-check-act (PDCA) model; this was scientifically supported by culturing the bacterial colony from patients’ perianal skin to determine the sanitization effect and interval time. Because a warm aqueous solution of potassium permanganate is recommended for sanitization, the bacterial colony culture was also used to determine the proper drug concentration, water temperature, and soaking time. All procedures were standardized. Patients, hospital staff, and medical students were enrolled into the QCC team based on the patient–hospital–student (PHS) win–win concept. Results After establishment of the PDCA model, the PI rate among 253 patients decreased from 17.20% to 5.93% and remained at 5.25% during the following year. The medical expenses and length of hospital stay consequently decreased. Conclusion The QCC and PHS win–win concept can reduce the PI rate and promote medical quality.

ObjectiveA meta-analysis was conducted to investigate the efficacy and safety of three main iron chelators, namely, deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX) for thalassemia major (TM) patients.MethodsRandomized controlled trials comparing mono-therapy DFO, DFP, DFX and combined DFP with DFO therapy in TM patients from January 1990 to December 2012 were searched and selected. Two independent authors assessed data from extracted randomized trials for efficacy and safety in the measurements of serum ferritin (SF), live iron concentration (LIC), myocardial iron content (MIC), left ventricular ejection fraction (LVEF) and adverse events (AEs).ResultsSixteen studies were selected. In the comparison of DFP versus DFO treatment groups, a significant difference was revealed on MIC and LVEF (P=0.01 and P=0.007, respectively) but not on SF or LIC level (P=0.65 and P=0.37, respectively). In comparing combined therapy (DFP plus DFO) versus DFO, a significant difference was shown on MIC and LVEF measurements (PConclusionFindings indicated that the most effective and safe iron chelators remains to be proven, and further large-scale, long-term studies are needed.