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Abstract Recent studies have implicated the phenazine biosynthesis-like domain-containing protein (PBLD) in the negative regulation of the development and progression of various cancers. However, its function in viral infection remains unknown. In this study, we found that PBLD plays important roles in multiple virus infections including BPIV3, SeV, VSV, and HSV-1. Our study revealed that PBLD enhances the expression of type I interferon (IFN-I) and ISGs through interferon regulatory factor 3 (IRF3). Further study indicated that PBLD promotes transcriptional phosphorylation of IRF3 (S385/386), thereby facilitating virus-induced IFN-I production. Interestingly, PBLD mediates virus-triggered mitochondrial apoptosis through its dependence on IRF3 (K313/315). Mechanistically, PBLD facilitated virus-induced apoptosis by recruiting the Puma protein to the mitochondria via IRF3. Additionally, we performed mutational analyses of IRF3, showing that its loss of either transcriptional or apoptotic function markedly increased viral replication. Moreover, macrophages with PBLD deficiency during viral infection exhibited decreased the IFN-I and ISGs expression, exacerbating viral infection. Importantly, mice deficient in PBLD exhibited increased viral replication and susceptibility to SeV infection, leading to decreased survival. Notably, Cedrelone, a chemical activator of PBLD, has the ability to reduce SeV replication. Collectively, we first discovered the new function of PBLD in viral infection, broadening our understanding of potential therapeutic targets and offering new insights for antiviral drug development.

The objective of this paper was to analyze the difference of composition between hybrid sorghum and conventional sorghum in southwest China, and to establish the method of variety identification. The basic physical and chemical components of 29 sorghum samples were determined, and the metabolite composition of 29 sorghum samples was determined by ultra high performance liquid chromatography coupled with Q Exactive HF-X mass spectrometry. The marker component screening and construction of variety identification model were carried out using stoichiometry, which included principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), cluster analysis and receiver operating characteristic (ROC) curve analysis. The model was based on the basic physicochemical composition and all metabolites. The results showed that the contents of amylopectin and tannin of the conventional varieties form southwest China were higher than that of hybrid varieties, while the contents of amylose and 1000-grain weight were lower. By analyzing the physicochemical properties, it was possible to identify certain samples. The OPLS-DA model was constructed with all 1048 compounds variables, and 46 of the differential metabolites that had a significant impact on the model identification were screened out. A novel OPLS-DA identification model was developed for sorghum varieties, achieving a 100% accuracy in identification. The conventional varieties from southwest China exhibited a relatively high concentration of phenolic compounds. Furthermore, after conducting receiver operating characteristic (ROC) curve analysis and assessing the relative standard deviation (RSD) of quality control sample (QC), 20 feature components that exhibited both high diagnostic accuracy and good reproducibility were identified. Among them, syringetin 3-glucoside and 6"-o-acetyldaidzein had higher expression abundance in conventional sorghum varieties, while D-glucarate, putsutrine, N-acetylputsutrine and L-glutamine had higher content in hybrid sorghum varieties. This study unveiled the disparity in metabolites between hybrid sorghum and conventional sorghum. The study successfully developed a scientifically rigorous and precise untargeted metabolomics approach using UHPLC-Q Exactive HF-X-MS. This method can be effectively utilized for the identification of sorghum varieties, offering a novel strategy for sorghum variety identification.

As the Industrial Internet of Things rapidly evolves, enterprises are increasingly using a wide variety of web containers. However, this growing usage also magnifies the complexities associated with managing these assets, leading to a rise in network security risks and vulnerabilities. This trend not only highlights a shift in industrial practices but also underscores the urgent need for proactive measures to strengthen network security. In response to this complex challenge, this paper presents a cutting-edge approach for detecting and identifying web containers through proactive probing. During the detection phase, we meticulously construct web container probes, laying the groundwork for their central role in the identification process. During this stage, the probe leverages a payload-based identification method for web containers, achieving an exceptional level of accuracy by implementing advanced protocol decoding techniques. The integration of these innovative techniques not only enhances the precision of web container identification but also demonstrates our commitment to providing a comprehensive solution to the challenges posed by web container management. This pioneering methodology reflects the ongoing evolution of detection strategies and our dedication to pushing technological boundaries for an improved understanding of web containers. By seamlessly integrating these two advanced identification methods, we have successfully identified four different types of web containers. Importantly, we have made significant progress in precision and accurately differentiating between various versions of these web containers, with a total of ten versions correctly identified. This groundbreaking method is not only crucial for addressing the current complexities in web container asset management but also provides enterprises with a more effective means of network security defense. Through the use of this advanced proactive probing method, enterprises can better understand and manage their web container assets, reducing network security risks and ensuring system stability and security. Our contribution plays a pivotal role in the ongoing development of the Industrial Internet of Things and lays a strong foundation for future research and applications in network security. The innovative approach presented here serves as a catalyst for the positive advancement of the current Industrial Internet of Things landscape and lays a solid groundwork for future exploration and application in network security.

Sugars will eventually be exported transporter (SWEET) is a novel class of sugars transporter families which mainly mediate either sucrose or hexose translocation bidirectional across the cellular membranesfollowinga concentrating gradient with a passive diffusion patten. In higher plants, SWEET proteins commonly have seven transmembrane domains that form a pore in the membrane to allow the passage of sugars, containing two MtN3/Saliva domains. Phylogenetically, plant SWEETs are divided into four clades. SWEET transporters play important roles in diverse physiological and biochemical processes including phloem loading, plant hormone transportand vegetative growth. In this review, based on the current advance of the plant SWEET transporters, we summarized their discovery, structure characteristicsand biological functions, and pointed out current research problems. Finally,put forward several better future research directions and potential solutions for SWEET sugar transporters in plant from the following three aspects: 1) exploring the molecular mechanism of substrate recognition and selectivity of SWEET proteins; 2) mining and utilizing of key SWEET genes increasing crop yield and improving quality; 3) using gene editing technology and phosphorylation of SWEET transporters to engineer high-yielding and high-quality crops.

Detecting and removing pesticide and veterinary drug residues in agricultural products are important for ensuring food safety. Current methods for detecting pesticide residues are mainly relied on sophisticated instruments, which require long detection time and skilled operators, limiting their accessibility. Metal-Organic Frameworks (MOFs) are a hybrid material composed of metal ions/clusters and organic ligands. MOFs possess multiple functions such as adsorption enrichment, catalytic degradation, and fluorescent and electrochemical signal generation. Therefore, MOFs have great potential in rapidly detecting and removing pesticide and veterinary drug residues. This review introduces functionalities of MOFs: Enrichment and removal, catalytic degradation, fluorescence sensing, and electrochemical sensing, and then summarizes their applications for rapid detecting and removing pesticide and veterinary drug residues. Additionally, this article comprehensively analyzes the advantages and disadvantages about combining RGB analysis and portable monitoring devices with MOFs. Also, the challenges of applying MOFs to detecting and removing pesticide and veterinary drug residue are discussed. Overall, this paper provides a reference for developing techniques to rapidly detect and remove containments in agricultural products.

Abstract Climate deterioration, water shortages, and abiotic stress are the main threats worldwide that seriously affect cotton growth, yield, and fiber quality. Therefore, research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance. The NAC proteins are crucial and plant-specific transcription factors (TFs) that are involved in cotton growth, development, and stress responses. The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible. Based on cotton genomic data, genome-wide identification and analyses have revealed potential functions of cotton NAC genes. Here, we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought, salt, and Verticillium wilt-related stresses, as well as leaf senescence and the development of fibers, xylem, and glands. The detailed regulatory network of NAC proteins in cotton is also elucidated. Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation, participate in several biological processes by interacting with related proteins, and regulate the expression of downstream genes. Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance. This review elucidates the latest findings on the functions and regulation of cotton NAC proteins, broadens our understanding of cotton NAC TFs, and lays a fundamental foundation for further molecular breeding research in cotton.

Abstract To explore the hub comorbidity genes and potential pathogenic mechanisms of hypopharyngeal carcinoma with esophageal carcinoma, and evaluate their diagnostic value for hypopharyngeal carcinoma with co-morbid esophageal carcinoma. We performed gene sequencing on tumor tissues from 6 patients with hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma (hereafter referred to as “group A”) and 6 patients with pure hypopharyngeal squamous cell carcinoma (hereafter referred to as “group B”). We analyzed the mechanism of hub genes in the development and progression of hypopharyngeal squamous cell carcinoma with esophageal squamous cell carcinoma through bioinformatics, and constructed an ROC curve and Nomogram prediction model to analyze the value of hub genes in clinical diagnosis and treatment. 44,876 genes were sequenced in 6 patients with group A and 6 patients with group B. Among them, 76 genes showed significant statistical differences between the group A and the group B.47 genes were expressed lower in the group A than in the group B, and 29 genes were expressed higher. The top five hub genes were GABRG2, CACNA1A, CNTNAP2, NOS1, and SCN4B. GABRG2, CNTNAP2, and SCN4B in the hub genes have high diagnostic value in determining whether hypopharyngeal carcinoma patients have combined esophageal carcinoma (AUC: 0.944, 0.944, 0.972). These genes could possibly be used as potential molecular markers for assessing the risk of co-morbidity of hypopharyngeal carcinoma combined with esophageal carcinoma.

Objectives: Intrinsic capacity impairment results in poor outcomes among older adults. Here we tested handgrip strength as a screening tool for IC impairment in community-dwelling older adults in Xinjiang, China. We assessed the diagnostic accuracy and established optimal cut-off points for handgrip strength in the detection of intrinsic capacity impairment. Methods: In total, 1072 participants were included using a multilevel random sampling method. Intrinsic capacity was constructed according to the definition of the Integrated Care for Older People screening tool proposed by the WHO. Results: Altogether, 73.4 % (787/1072) participants had intrinsic capacity impairment. The prevalence of intrinsic capacity impairment for hearing, vision, mobility, cognition, psychological, and vitality domains was 8.6 %, 4.8 %, 39.6 %, 47.3 %, 12.0 %, and 18.8 %, respectively. The adjusted odds ratios [95 % confidence interval) for handgrip strength was 0.935 [0.914–0.956]. The area under the curve of the receiver operating characteristic curve for handgrip strength of older men, and handgrip strength of older women with intrinsic capacity impairment were 0.7278, and 0.7534, respectively. The handgrip strength cut-off points were 28.47 kg (60–69 years), 25.76 kg (70–79 years), and 24.45 kg (≥80 years) for men, and 20.75 kg (60–69 years), 19.90 kg (70–79 years), and 16.17 kg (≥80 years) for women. Conclusions: Handgrip strength can be used as a convenient tool for evaluating intrinsic capacity. Weak handgrip strength and low education level were associated with intrinsic capacity impairment in community-dwelling older adults in Xinjiang. Using the cut-off points of handgrip strength for different age groups and genders, older adults with impaired intrinsic capacity can be identified, which may reduce the occurrence of adverse outcomes.

Abstract Objectives This study systematically evaluated the relationship between tertiary lymphoid structures (TLS) and clinical pathological features as well as immune infiltrating cells in gastrointestinal cancers. Methods We searched Web of science, Pubmed, Embase, and Cochrane Library for studies that met the requirements as of July 1, 2023, and the odds ratio, the corresponding 95% confidence interval or mean and standard deviation, were included in the analysis. Findings We eventually included 20 studies, involving a total of 4856 patients. TLS were found to be significantly associated with T stage, N stage, TNM stage, and tumor size. Moreover, patients with positive TLS showed significantly elevated expression of T‐cell related markers, including CD3, CD4, CD8, CD45RO; B‐cell related markers, such as CD11c and CD20; and dendritic cell‐related marker CD103. On the other hand, positive TLS correlated significantly with low expression of FOXP3 and CD68. Additionally, there was a significant positive association between TLS and overall infiltration of tumor‐infiltrating lymphocytes. Conclusion The presence of TLS is significantly correlated with the infiltration of various immune cells in gastrointestinal cancers. To determine the ideal balance between the presence of mature TLS and appropriate immune cell infiltration, further high‐quality and multicenter clinical studies need to be conducted.

Karst is widely researched in the field of carbonate reservoirs. This study proposes a new formation mechanism and development model, specifically epigenetic karst, and asserts that high-quality reservoirs can be developed in the karst highlands and karst slopes of ancient landforms under the epigenetic karst with facies-controlled characteristics. The results indicate that there are three stages of karst in the study area. The first period is syngenetic karst, characterized by molds, intragranular dissolution pores, and micritization. Isotopic data reveal that the range of variation of carbonate rock 13C and 18O is similar to that of cement. The second period is epigenetic karst, the most significant karst in the study area. It undergoes a prolonged development time and features non-selective fabric dissolution. Oxygen and carbon isotopes exhibit negative values (18O ranges from −10.033‰ to −13.767‰ and 13C ranges from −2.56‰ to −0.52‰), which are significantly altered by atmospheric precipitation. The third period is buried karst, characterized by suture structure and asphaltene filling. The negative value of 18O in calcite veins is significantly

ObjectivesTo describe the carriage rate, serotype distribution, and antimicrobial susceptibility patterns of Streptococcus pneumoniae (S. pneumoniae) nasopharyngeal (NP) isolates among healthy children aged 30 days to

Purpose: This study explored whether a free-breathing mean heart dose (FB-MHD) of 4 Gy is a reliable dose threshold for selecting left breast cancer patients after modified radical mastectomy suitable for deep inspiration breath-hold (DIBH) and developed anatomical indicators to predict FB-MHD for rapid selection. Materials and methods: Twenty-three patients with left breast cancer treated with DIBH were included to compare FB and DIBH plans. The patients were divided into the high-risk (FB-MHD ≥ 4 Gy) and low-risk (FB-MHD

Sarcopenia is prevalent among the elderly.The incidence of this condition rises with advancing age,posing danger and lacking effective therapeutic options.Hence,timely detection is crucial.Enhancing the ability to identify biomarkers with high sensitivity and specificity may enhance the early diagnosis and prognosis of sarcopenia.This article examines recent advancements in the investigation of the correlation between biomarkers,including inflammatory variables,hormones,oxidative stress,circulatory mediators,and sarcopenia.It offers novel concepts and techniques for the identification,management,and prediction of sarcopenia.

Abstract Understanding water saturation levels in tight gas carbonate reservoirs is vital for optimizing hydrocarbon production and mitigating challenges such as reduced permeability due to water saturation (Sw) and pore throat blockages, given its critical role in managing capillary pressure in water drive mechanisms reservoirs. Traditional sediment characterization methods such as core analysis, are often costly, invasive, and lack comprehensive spatial information. In recent years, several classical machine learning models have been developed to address these shortcomings. Traditional machine learning methods utilized in reservoir characterization encounter various challenges, including the ability to capture intricate relationships, potential overfitting, and handling extensive, multi-dimensional datasets. Moreover, these methods often face difficulties in dealing with temporal dependencies and subtle patterns within geological formations, particularly evident in heterogeneous carbonate reservoirs. Consequently, despite technological advancements, enhancing the reliability, interpretability, and applicability of predictive models remains imperative for effectively characterizing tight gas carbonate reservoirs. This study employs a novel data-driven strategy to prediction of water saturation in tight gas reservoir powered by three recurrent neural network type deep/shallow learning algorithms—Gated Recurrent Unit (GRU), Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), Support Vector Machine (SVM), K-nearest neighbor (KNN) and Decision tree (DT)—customized to accurately forecast sequential sedimentary structure data. These models, optimized using Adam's optimizer algorithm, demonstrated impressive performance in predicting water saturation levels using conventional petrophysical data. Particularly, the GRU model stood out, achieving remarkable accuracy (an R-squared value of 0.9973) with minimal errors (RMSE of 0.0198) compared to LSTM, RNN, SVM, KNN and, DT algorithms, thus showcasing its proficiency in processing extensive datasets and effectively identifying patterns. By achieving unprecedented accuracy levels, this study not only enhances the understanding of sediment properties and fluid saturation dynamics but also offers practical implications for reservoir management and hydrocarbon exploration in complex geological settings. These insights pave the way for more reliable and efficient decision-making processes, thereby advancing the forefront of reservoir engineering and petroleum geoscience.

Tumor-associated macrophage (TAM) play a crucial role in the immune microenvironment of lung cancer. Through changes in their phenotype and phagocytic functions, TAM contribute to the initiation and progression of lung cancer. By promoting the formation of an immune-suppressive microenvironment and accelerating the growth of abnormal tumor vasculature, TAM facilitate the invasion and metastasis of lung cancer. Macrophages can polarize into different subtypes with distinct functions and characteristics in response to various stimuli, categorized as anti-tumor M1 and pro-tumor M2 types. In tumor tissues, TAM typically polarize into the alternatively activated M2 phenotype, exhibiting inhibitory effects on tumor immunity. This article reviews the role of anti-angiogenic drugs in modulating TAM phenotypes, highlighting their potential to reprogram M2-type TAM into an anti-tumor M1 phenotype. Additionally, the functional alterations of TAM play a significant role in anti-angiogenic therapy and immunotherapy strategies. In summary, the regulation of TAM polarization and function opens up new avenues for lung cancer treatment and may serve as a novel target for modulating the immune microenvironment of tumors.

ABSTRACT: Objectives: This study aimed to evaluate the molecular epidemiology and antimicrobial resistance of invasive pneumococcal isolates from children in Shenzhen, China, in the early stage of the pneumococcal 13-valent conjugated vaccine (PCV-13) era from 2018 to 2020. Methods: Invasive pneumococcal strains were isolated from hospitalized children with invasive pneumococcal diseases (IPDs) from January 2018 to December 2020. The serotype identification, multilocus sequence typing (MLST), and antibiotic susceptibility tests were performed on all culture-confirmed strains. Results: Sixty-four invasive strains were isolated mainly from blood (70.3%). Prevalent serotypes were 23F (28.1%), 14 (18.8%), 19F (15.6%), 6A/B (14.1%), and 19A (12.5%), with a serotype coverage rate of 96.9% for PCV13. The most common sequence types (STs) were ST876 (17.1%), ST271 (10.9%), and ST320 (7.8%). Half of the strains were grouped in clonal complexes (CCs): CC271 (21.9%), CC876 (20.3%), and CC90 (14.1%). Meningitis isolates showed a higher resistance rate (90.9% and 45.5%) to penicillin and ceftriaxone than the rate (3.8% and 9.4%) of non-meningitis isolates. The resistance rates for penicillin (oral), cefuroxime, and erythromycin were 53.13%, 73.4%, and 96.9%, respectively. The dual ermB and mefA genotype was found in 81.3% of erythromycin-resistant strains. The elevated minimum inhibitory concentration (MIC) of β-lactam antibiotics and dual-genotype macrolide resistance were related mainly to three major serotype-CC combinations: 19F-CC271, 19A-CC271, and 14-CC876. Conclusion: Invasive pneumococcus with elevated MICs of β-lactams and increased dual ermB and mefA genotype macrolide resistance were alarming. Expanded PCV13 vaccination is expected to reduce the burden of paediatric IPD and to combat antibiotic-resistant pneumococcus in Shenzhen.

Abstract Objective Postoperative fasting following thoracoscopic surgery can cause intense thirst and oral discomfort. However, there is currently no research on ultraearly oral hydration (UEOH) in middle-aged or elderly patients after thoracoscopic surgery. The aim of this study was to investigate the effectiveness and safety of UEOH for improving oral discomfort after thoracoscopic surgery. Methods This single-center prospective double-blind randomized controlled trial was conducted from April 2022 to November 2023. A total of 64 middle-aged and elderly patients who underwent the first thoracoscopic surgery on the day were enrolled at our institution. Postoperatively, in the Postanesthesia Care Unit (PACU), patients were randomly assigned at a 1:1 ratio to either the UEOH group or the standard care (SC) group. The primary outcome was the patient’s thirst score at 6 h after surgery. Secondary outcomes included the incidence of postoperative oral discomfort; pain scores; the occurrence of adverse reactions such as nausea, vomiting, regurgitation and aspiration; anxiety scores on the first postoperative day; the time to first flatus; and recovery satisfaction scores. Results The demographic and surgical characteristics were similar between the two groups. Patients in the UEOH group had lower thirst scores 6 h after surgery than did those in the SC group(16.1 ± 6.70 vs. 78.4 ± 8.42, P 0.05). Conclusion For middle-aged and elderly patients undergoing thoracoscopic surgery, the use of a modified UEOH protocol postoperatively can improve thirst and promote gastrointestinal recovery without increasing complications. Trial registration This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 07/12/2023 with the registration number ChiCTR2300078425.

Abstract Background Healthcare accessibility and utilization are important social determinants of health. Lack of access to healthcare, including missed or no-show appointments, can have negative health effects and be costly to patients and providers. Various office-based approaches and community partnerships can address patient access barriers. Objectives (1) To understand provider perceptions of patient barriers; (2) to describe the policies and practices used to address late or missed appointments, and (3) to evaluate access to patient support services, both in-clinic and with community partners. Methods Mailed cross-sectional survey with online response option, sent to all Nebraska primary care clinics (n = 577) conducted April 2020 and January through April 2021. Chi-square tests compared rural-urban differences; logistic regression of clinical factors associated with policies and support services computed odds ratios (OR) and 95% confidence intervals (CI). Results Response rate was 20.3% (n = 117), with 49 returns in 2020. Perceived patient barriers included finances, higher among rural versus urban clinics (81.6% vs. 56.1%, p =.009), and time (overall 52.3%). Welcoming environment (95.5%), telephone appointment reminders (74.8%) and streamlined admissions (69.4%) were the top three clinic practices to reduce missed appointments. Telehealth was the most commonly available patient support service in rural (79.6%) and urban (81.8%, p =.90) clinics. Number of providers was positively associated with having a patient navigator/care coordinator (OR = 1.20, CI = 1.02–1.40). For each percent increase in the number of privately insured patients, the odds of providing legal aid decreased by 4% (OR = 0.96, CI = 0.92-1.00). Urban clinics were less likely than rural clinics to provide social work services (OR = 0.16, CI = 0.04–0.67) or assist with applications for government aid (OR = 0.22, CI = 0.06–0.90). Conclusions Practices to reduce missed appointments included a variety of reminders. Although finances and inability to take time off work were the most frequently reported perceived barriers for patients’ access to timely healthcare, most clinics did not directly address them. Rural clinics appeared to have more community partnerships to address underlying social determinants of health, such as transportation and assistance applying for government aid. Taking such a wholistic partnership approach is an area for future study to improve patient access.

Abstract Background Neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) are closely related to the prognosis of patients with non‐small cell lung cancer, but their effect on extensive‐stage small cell lung cancer (ES‐SCLC) remains uncertain. Methods This retrospective study was conducted in ES‐SCLC patients treated with first‐line atezolizumab or durvalumab and platinum‐etoposide. Clinical data from three hospitals were analyzed. Significant risk factors for survival were identified using descriptive statistics and Cox regression. Homogeneity was assessed using t‐tests or nonparametric tests. Kaplan‐Meier analysis revealed an association between high NLR level and median PFS and OS. Results A total of 300 ES‐SCLC patients were included in the study. Cox regression analysis revealed that an elevated NLR level after the second treatment cycle (defined as NLRT2) was an independent prognostic factor for survival. Stratifying patients based on median NLRT2 showed significant differences in both PFS (HR: 1.863, 95% CI: 1.62–2.12, p

Introduction Gingivitis is a prevalent complication in adolescents undergoing fixed orthodontic treatments. However, changes in the supragingival microbiome associated with gingivitis and the impact of Candida albicans remain elusive. Therefore, we investigated supragingival microbiome discrepancy and C. albicans colonization in adolescent orthodontic patients with gingivitis.Methods Dental plaques were collected from 30 gingivitis patients and 24 healthy adolescents, all undergoing fixed orthodontic treatment. The supragingival microbiome composition was analyzed using 16S rRNA sequencing. C. albicans colonization was determined using fungal culture and real-time quantitative polymerase chain reaction.Results Our analysis revealed significantly heightened microbial diversity in the Gingivitis group. Notably, patients with gingivitis exhibited an enrichment of periodontal pathogens, such as Saccharibacteria (TM7) [G-1], Selenomonas, Actinomyces dentalis, and Selenomonas sputigena. Additionally, 33% of the gingivitis patients tested positive for C. albicans, exhibiting significantly elevated levels of absolute abundance, while all healthy patients tested negative. Significant differences in microbial composition were also noted between C. albicans-positive and -negative samples in the Gingivitis group.Conclusion Significant disparities were observed in the supragingival microbiome of adolescent orthodontic patients with and without gingivitis. The presence of C. albicans in the supragingival plaque may alter the microbiome composition and potentially contribute to gingivitis pathogenesis.

ABSTRACTBovine viral diarrhoea-mucosal disease caused by bovine viral diarrhoea virus (BVDV) is a major infectious disease that affects the cattle industry. The nonstructural protein Npro of BVDV antagonizes the type I interferon (IFN-I) pathway, thereby escaping the host immune response. The exact mechanism by which Npro uses host proteins to inhibit IFN-I production is unclear. The host protein CALCOCO2 was identified as a binding partner of Npro using a yeast two-hybrid screen. The interaction between Npro and CALCOCO2 was confirmed by yeast co-transformation, co-immunoprecipitation assays, and GST pull-down assays. The stable overexpression of CALCOCO2 markedly promoted BVDV propagation, while the knockdown of CALCOCO2 significantly inhibited BVDV replication in MDBK cells. Interestingly, CALCOCO2 inhibited IFN-I and IFN-stimulated gene production in BVDV-infected cells. Ectopic expression of CALCOCO2 effectively reduced IRF3 protein levels via the proteasome pathway. CALCOCO2 was found to promote Npro-mediated ubiquitination degradation of IRF3 by interacting with IRF3. Our results demonstrate the molecular mechanism by which Npro recruits the CALCOCO2 protein to regulate IRF3 degradation to inhibit IFN-I production.

Abstract Background Organising pneumonia (OP) is one of the most common and lethal diseases in the category of interstitial pneumonia, along with lung cancer. Reprogramming of lipid metabolism is a newly recognized hallmark of many diseases including cancer, cardiovascular disorders, as well as liver fibrosis and sclerosis. Increased levels of ceramides composed of sphingosine and fatty acid, are implicated in the development of both acute and chronic lung diseases. However, their pathophysiological significance in OP is unclear. The aim of this study was to investigate the role of lipid metabolism reprogramming in OP, focusing on inflammation and fibrosis. Methods Comprehensive multi‐omics profiling approaches, including single‐cell RNA sequencing, Visium CytAssist spatial transcriptomics, proteomics, metabolomics and mass spectrometry, were employed to analyze the tissues. OP mice model was utilized and molecular mechanisms were investigated in macrophages. Results The results revealed a significant association between OP and lipid metabolism reprogramming, characterized by an abnormal expression of several genes related to lipid metabolism, including CD36, SCD1, and CES1 mainly in macrophages. CD36 deficiency in alveolar macrophages, led to an increased expression of C16/24 ceramides that accumulated in mitochondria, resulting in mitophagy or mitochondrial dysfunction. The number of alveolar macrophages in OP was significantly reduced, which was probably due to the ferroptosis signaling pathway involving GSH/SLC3A2/GPX4 through CD36 downregulation in OP. Furthermore, macrophage secretion of DPP7 and FABP4 influenced epithelial cell fibrosis. Conclusions CD36 inhibited the ferroptosis pathway involving SLC3A2/GPX4 in alveolar macrophages of OP tissue by regulating lipid metabolism, thus representing a new anti‐ferroptosis and anti‐fibrosis effect of CD36 mediated, at least in part, by ceramides. Highlights Our findings reveal a significant association between organising pneumonia and lipid metabolism reprogramming and will make a substantial contribution to the understanding of the mechanism of organising pneumonia in patients.

With a significant increase in the obesity epidemic in China, addressing adolescent obesity should be highlighted as a priority. The current qualitative study aims to explore the perspectives of key stakeholders regarding adolescent obesity, providing guidance for developing effective obesity interventions for Chinese adolescents. A total of 12 focus group discussions were convened with a range of representative stakeholders including adolescents (n = 37), parents (n = 28), and school staff (n = 21) from sample schools. Semi-structured topic guides were used for data collection. All data were transcribed verbatim and analyzed thematically. From multiple stakeholder perspectives, we finally identified 3 overarching themes ( Understanding adolescent obesity, Key healthy lifestyles, and Barriers to obesity prevention practices ) and 8 sub-themes. While participants had mixed perceptions of status and prevalence of adolescent obesity, all acknowledged the serious health consequences associated with it. As significant modifiable risk factors, unhealthy diet and physical activity were identified to be prevalent among Chinese teenagers and lead to excessive weight gain. However, a variety of individual, environmental and sociocultural factors hindered the implementation of healthy lifestyles, affecting adolescent obesity prevention and control. Given adolescent obesity is a complex, multifactorial and multilevel public issue, comprehensive lifestyle interventions are recommended that synergistically engage multiple stakeholders across key communities to fight the ongoing obesity epidemic.

Alternatives to fish meal (FM) in fish feed are urgently required in aquaculture. We therefore examined the effect of replacing FM with a complex protein source (CPS) comprising soybean meal, peanut meal, corn protein meal, feather meal, and yeast protein, on carp (Cyprinus carpio) growth, body composition, lipidomics, and flesh quality. Lipidomics analysis was conducted to reveal the impact of dietary changes on fish lipid composition and metabolism, which is closely related to flesh quality and nutritional value. Over an eight-week growth trial, fish meal was replaced with CPS at 0 % (FM only), 20 %, 40 %, 60 %, 80 %, or 100 %. Weight gain and other growth parameters did not differ significantly among the treatments. Lipid deposition (LD) was positively correlated, and protein deposition negatively correlated, with CPS levels. LD and fillet ether extract were significantly elevated at 100 % CPS, whereas superoxidase dismutase expression, claudin-1 expression, and lipase activity were significantly reduced. The n-3 PUFA level and n-3/n-6 PUFA ratio were significantly lower following CPS feeding, reducing flesh quality. These findings indicate that CPS successfully replaced 60–80 % of dietary FM in carp diets, while the 100 % replacement group provided insights into the comprehensive effects of total substitution. Future studies will further optimize formulations based on these results to resemble practical production more closely. CPS with nutrient supplementation may therefore present a viable and safe partial replacement for dietary FM.

IntroductionOutcome-based education (OBE) leads to revolutionary change in medical education, but each medical school is acknowledged to develop suited framework based on specific positioning, educational philosophy and expected outcomes.MethodsBased on the graduate outcomes of basic medical education in China released by Working Committee for the Accreditation of Medical Education (WCAME) which officially recognized by World Federation for Medical Education (WFME), Taizhou University re-documented the overall organization of the curriculum and classified the courses as “Crucial, Supporting and Associated (CSA)” categories to connect the graduate outcomes and course objectives.ResultsWe redefined the standard for graduates in Taizhou University Medical School including 34 items in four domains and redesigned the curriculum with 76 courses classified as CSA. Empirical data reveals a substantial improvement in students’ performance on Standardized Competence Test for Clinical Medicine Undergraduates in China (SCTCMU) by implementing the CSA system between 2022 and 2023. Notably, in 2023, Taizhou University’s students achieved pass rates more than 20 percentage points higher than the national average, demonstrating a profound and unprecedented impact.ConclusionThe CSA classification system provides a notably clear and structured framework for categorizing courses based on their direct or indirect relevance to educational objectives, which provides clarity to educators and empowers students with a more purposeful approach to their studies.

Off-targeting toxicity and immunosuppressive tumor microenvironment still restrict the therapeutic requirement of photodynamic therapy (PDT). The development of metal ion-coordination-based nanoparticles (NPs) for cancer therapy has advantages, such as precious nanostructure and potent therapeutic effect as well as great safety. In this study, we prepared calcium ions (Ca2+)-coordination photosensitizer NPs, based on Ca2+-pyrochloric acid (PPA)-coordination as the new photosensitive nanoamplifiers, and microneedles (MNs) as the personalized apparatus, and investigated the nanoamplifiers for treating the melanoma via transdermal administration. This nanoamplifiers was synthesized via a simple coordination of Ca2+ and PPA with the addition of bovine serum albumin (BSA), and further fabricated into MNs (nanoamplifiers@MNs). Following inserted into the tumor, the released nanoamplifiers from the tips and back layer exhibited great photodynamic activity under irradiation, inducing cancer cell death. Meanwhile, Ca2+ acted as the second messenger, promoting M1 polarization of macrophages and maturation of dendritic cells (DCs), thereby enhancing the immune activation effect in the tumor microenvironment. As a result, such nanoamplifiers effectively achieved significant efficacy against malignant melanoma tumors by synergistically tumor killing and potent anti-tumor immune activation without obviously side effect. This work demonstrated the potential of MNs-mediated metal ion-coordination-based nanoamplifier as a novel photodynamic therapeutic platform for the efficient and safe treatment of cancer.

BackgroundMacrophages play a pivotal role in the research landscape of non-small cell lung cancer (NSCLC), contributing significantly to understanding tumor progression, treatment resistance, and immunotherapy efficacy. In this study, we utilized bibliometric techniques to analyze shifts in research hotspots and trends within the field, while also forecasting future research directions. These insights aim to offer guidance for both clinical therapeutic interventions and foundational scientific inquiries.MethodsAll publications were released between 1993 and 2023 and focus on research pertaining to macrophages in the field of NSCLC. The articles were identified from the Web of Science Core Collection and analyzed using VOSviewer 1.6.19, CiteSpace 6.2.R2, and Scimago Graphica 1.0.35.ResultA total of 361 articles authored by 3,072 researchers from 48 countries were included in the analysis. TAMs have gained increasing attention for their role in NSCLC development and as potential therapeutic targets. Modulating TAM behavior may offer avenues to suppress tumor growth and drug resistance, improving patient outcomes. International collaboration, particularly between China and the United States, accelerates progress in NSCLC research, benefiting patients worldwide. The research hotspot revolves around understanding the role of macrophages in immunotherapy, focusing on their contribution to tumor progression, therapeutic resistance, and potential as therapeutic targets in NSCLC.ConclusionsThe therapeutic significance of macrophages in the field of NSCLC is gaining increasing attention and recognition, highlighting their potential as key players in the development of novel treatment strategies. Future research will focus on understanding TAM molecular mechanisms, interactions with immune cells, and exploring novel therapies, with the aim of improving NSCLC treatment outcomes.

Abstract Background Pancreatic adenocarcinoma (PAAD), a member of highly lethal malignant tumors, has a poor outcome and extremely poor prognosis. The transient receptor potential (TRP) superfamily, a group of nonselective cation channels, is capable of influencing cellular functions by regulating calcium homeostasis. In addition, it has been shown that TRP channels can also affect various cellular phenotypes by regulating gene transcription levels and are involved in the development of a variety of malignant tumors. Aims In order to find new therapeutic targets and biomarkers to improve the clinical prognosis of pancreatic cancer, we performed genetic and immunological characterization of TRP channels in PAAD, as well as related functional and prognostic analyses. Methods and Results We investigated the expression, genetic alterations, methylation levels, and immune infiltration levels of TRP channels in PAAD, and further also analyzed the function of TRP channels in PAAD and their prognostic value for PAAD patients. Our results suggest that TRPM8 may contribute to tumor proliferation by controlling the PI3K‐AKT–mTOR signaling pathway in PAAD. Conclusion After careful evaluation of the accumulated data, we concluded that TRPM8 has potential as a prognostic indicator and prospective therapeutic target in PAAD.

Abstract Apoptosis plays a pivotal role in pathogen elimination and maintaining homeostasis. However, viruses have evolved strategies to evade apoptosis, enabling their persistence within the host. Z-DNA binding protein 1 (ZBP1) is a potent innate immune sensor that detects cytoplasmic nucleic acids and activates the innate immune response to clear pathogens. When apoptosis is inhibited by viral invasion, ZBP1 can be activated to compensate for the effect of apoptosis by triggering an innate immune response. This review examined the mechanisms of apoptosis inhibition and ZBP1 activation during viral invasion. The authors outlined the mechanisms of ZBP1-induced type I interferon, pyroptosis and necroptosis, as well as the crosstalk between ZBP1 and the cGAS-STING signalling pathway. Furthermore, ZBP1 can reverse the suppression of apoptotic signals induced by viruses. Intriguingly, a positive feedback loop exists in the ZBP1 signalling pathway, which intensifies the innate immune response while triggering a cytokine storm, leading to tissue and organ damage. The prudent use of ZBP1, which is a double-edged sword, has significant clinical implications for treating infections and inflammation.

Objective To establish a highly sensitive detection method of platelet HPA-3 and HPA-15 genotyping by droplet digital PCR (ddPCR), and to explore the feasibility of applying it to the detection of human platelet antigen (HPA) compatibility in maternal peripheral blood fetal free DNA. Methods For SNP mutation sites of HPA-3 and HPA-15, specific primers and MGB probes were designed, and amplification conditions such as annealing temperature and primer concentration of ddPCR were optimized to establish the optimal reaction system and clarify the test procedures. The methodological performance of the assay was evaluated, including specificity, sensitivity, repeatability and stability. ddPCR was used to detect 67 clinical blood samples, and the allele typing results were compared with the gene sequencing results. The fetal free DNA HPA antigen of 52 maternal peripheral blood samples was detected. Results The ddPCR method for detecting platelet HPA-3 and HPA-15 showed good specificity of primers and probes. The optimal annealing temperatures for HPA-3 and HPA-15 were 61.6℃ and 60.2℃, respectively. The optimal concentrations of primers were 900 nM and 700 nM respectively. The final concentration of the probe was 250 nM. The quantitative detection range of copy number was 2 to 20 000 copies, with lower limit of detection of 0.1 copies/μL, and the linearity is good. In low copy number samples, the intra - and inter batch coefficient of variation (CV) of actual detection values for HPA-3 and HPA-15 were both lower than 5%. The detection results of HPA-3 and HPA-15 genotypes of 67 blood samples were consistent with the gene sequencing results, and its application in fetomaternal platelet HPA-3, HPA-15 genotype detection met expectations. Conclusion The HPA-3 and HPA-15 ddPCR detection system constructed in this study has high accuracy, good repeatability, stability and sensitivity, and can be applied to the establishment of platelet HPA-3 and HPA-15 genotype donor pool, gene matching and fetomaternal platelet compatibility detection.

Objective To investigate the frequency of platelet antibodies in voluntary blood donors and patients in Zhongshan, Guangdong Province, and to study the specificity and cross-matching of platelet antibodies. Methods Platelet antibodies of blood donors and patients were screened by solid-phase immunoadsorption (SPIA), rechecked by flow cytometry (FCM), and antibody specificity was identified by PakPlus enzyme immunoassay, and platelet cross-matching was simulated by SPIA. Results A total of 1 049 blood donor samples and 598 patient samples were tested, with 6 (0.57%) and 49 (8.19%) samples positive for SPIA,respectively(P

The atmospheric infrared ultraspectral sounder (AIUS) is China's first infrared occultation spectrometer onboard the GaoFen-5 satellite. This instrument provides measurements in the near-infrared and mid-infrared spectral regions with a spectral resolution of 0.02 cm$^{-1}$, monitoring key greenhouse gases like methane (CH$_{4}$). In this study, we have developed a physics-based retrieval algorithm for accurately deriving CH$_{4}$ mole fraction profiles from infrared absorption spectra. The retrieval algorithm is applied to the AIUS and successfully obtains CH$_{4}$ mole fraction profiles from January to December 2019 over Antarctic. The validation results show that the retrieval algorithm has a satisfactory performance using AIUS measurements, with average relative standard deviation of the differences less than 7.2% throughout the altitude range of 10–70 km.

Abstract MP-HJ-1b is a novel microtubule inhibitor that we designed and reported previously. Ferroptosis is a newly identified type of nonapoptotic cell death induced by ferrous catalysis and lipid peroxidation. Here, transcriptomics, proteomics, and molecular docking analyses were combined to explore the novel effects of MP-HJ-1b on tumors. Both omics analyses suggested that MP-HJ-1b affects ribosomes, and we confirmed that it inhibits the ribosomal component proteins RPL35 and MRPL28. Colchicine was used as an analog, and the results showed that MP-HJ-1b and colchicine increased reactive oxygen species and malondialdehyde levels and decreased reduced glutathione levels, suggesting that they promoted ferroptosis in HeLa cells. Specifically, MP-HJ-1b downregulated SLC7A11 and GPX4 to enhance the classical pathway of ferroptosis, while colchicine upregulated LC3A/B-II and enhanced autophagy. Clinically, the serum concentrations of ferrous ions, reduced glutathione, and Hcy were higher in cervical cancer patients than in healthy individuals. ALT, AST, Cho, HDL-C, and LDL-C levels were decreased in the serum of patients. Our study expands understanding of the way MP-HJ-1b promotes cell death and enriches research on microtubule inhibitors in the ferroptosis field.

Community pharmacies have unparalleled potential to increase access to pre-exposure prophylaxis medications (PrEP) for HIV prevention; however, only 17 out of 50 states in the United States have statewide authority for pharmacists to provide PrEP at community pharmacies. Few studies have reported on how pharmacists overcome the legislative barrier and provide PrEP services in restrictive pharmacy prescription states. The objective of this article is to identify the existing primary literature describing pharmacist PrEP services in the community in states with restrictive prescription authority. Methods: A systemic literature review was conducted to identify the primary literature that involved community pharmacy service and PrEP conducted in states that do not have expanded pharmacist prescriptive authority between 2000 to 2024. Results: Ten publications were identified, describing nine studies, including four interview and survey studies, three intervention reports, and two ongoing clinical trials. None of these studies have a control group. Most pharmacists provide PrEP services in the community through a collaborative practice agreement with a primary care provider. Conclusions: Future clinical studies with randomized controlled designs are required to test novel strategies in the education and implementation of pharmacy-led PrEP services in a community pharmacy setting to increase PrEP access.

Subsurface karst caves provide unique opportunities to study the deep biosphere, shedding light on microbial contribution to elemental cycling. Although ammonia oxidation driven by both ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) is well explored in soil and marine environments, our understanding in the subsurface biosphere still remained limited to date. To address this gap, weathered rock and sediment samples were collected from the Xincuntun Cave in Guilin City, an alkaline karst cave, and subjected to high-throughput sequencing and quantification of bacterial and archaeal amoA, along with determination of the potential nitrification rates (PNR). Results revealed that AOA dominated in ammonia oxidation, contributing 48–100% to the PNR, and AOA amoA gene copies outnumbered AOB by 2 to 6 orders. Nitrososphaera dominated in AOA communities, while Nitrosopira dominated AOB communities. AOA demonstrated significantly larger niche breadth than AOB. The development of AOA communities was influenced by deterministic processes (50.71%), while AOB communities were predominantly influenced by stochastic processes. TOC, NH4+, and Cl− played crucial roles in shaping the compositions of ammonia oxidizers at the OTU level. Cross-domain co-occurrence networks highlighted the dominance of AOA nodes in the networks and positive associations between AOA and AOB, especially in the inner zone, suggesting collaborative effort to thrive in extreme environments. Their high gene copies, dominance in the interaction with ammonia oxidizing bacteria, expansive niche breadth and substantial contribution to PNR collectively confirmed that AOA better adapted to alkaline, oligotrophic karst caves environments, and thus play a fundamental role in nitrogen cycling in subsurface biosphere.

Background: Sarcopenia is a harmful condition common among older adults for which no treatment is available. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (FN14) are known to play important roles in the pathogenesis of sarcopenia. This study investigated alterations in methylation in TWEAK and Fn14 to identify potential targets for the managing sarcopenia. Materials and methods: Through an epidemiological investigation, we detected methylation of CpG islands (CpGs) in TWEAK and Fn14 in community-dwelling older adult of Xinjiang by bisulfite sequencing. Significant CpGs associated with sarcopenia were selected for detection in 152 older individuals by pyrosequencing. Associations between CpG methylation, plasma inflammatory marker levels, and sarcopenia were analyzed. Results: Of 38 CpGs in TWEAK and 30 CpGs in Fn14 detected in 60 individuals, 6 CpGs showed lower methylation in sarcopenia patients compared with control individuals. In 152 older adults, covariance analysis with adjustment for age, gender, triglyceride level, obesity, diabetes, and hypertension showed that the methylation levels of 6 CpGs (CpG8, CpG12, CpG13, CpG20 and CpG21of TWEAK, and CpG24 of Fn14) were significantly lower in sarcopenia patients than in control individuals. With adjustment for additional confounding factors, covariate variance analysis showed that plasma TWEAK, TNF-α and IL-10 levels in the sarcopenia group were significant higher than those in the control group (P = 0.007, P

Purpose: This study aimed to investigate the diagnostic and prognostic values of neuropilin-1 (NRP-1) in triple-negative breast cancer (TNBC) and analyze its immune function in the tumor microenvironment. Methods: Based on The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, Genotype Tissue Expression, Immune Cell Abundance Identifier (ImmuCellAI), Reactome, and Genomics of Drug Sensitivity in Cancer databases, the cancer tissues from 50 patients with TNBC and corresponding adjacent noncancerous tissues from 10 patients (tissue microarrays were purchased from Shanghai Xinchao Biotechnology Co., Ltd.) were collected for validation. Bioinformatics combined with immunohistochemistry was used to analyze the relationship among NRP-1 expression, prognosis, tumor immune cell infiltration, immune genes, and drug resistance so as to investigate the role of NRP-1 in the development of TNBC. Results: A significant difference in NRP-1 gene expression was found between the cancerous and noncancerous tissues (p-value < 0.05); NRP-1 expression was high in carcinoma. No significant correlation was found between NRP-1 protein expression levels and each stage in the TCGA database. Prognostic expression survival analysis showed that the survival probability of patients with high NRP-1 expression was significantly lower than that of patients with low NRP-1 expression (p-value < 0.05), suggesting that the gene might be a pro-oncogene. The data from 50 clinical samples also confirmed that the NRP-1 expression was significantly higher in triple-negative breast cancer (TNBC) tissues than in adjacent noncancerous tissues. The NRP-1 expression significantly correlated with the tumor diameter and pathological grade (p-value < 0.05), but not with age, stage, and ki67 (p-value > 0.05). The Kaplan–Meier survival curves suggested that the median overall survival was significantly shorter in patients with high NRP-1 expression than in those with low NRP-1 expression (13.6 months vs 15.2 months, p-value < 0.05). The 300 genes most significantly positively associated with this gene were selected for Gene Ontology (including Biological Process, Molecular Function, and Cellular Component groups) and Kyoto Encyclopedia of Genes and Genomics enrichment analysis. The findings showed that NRP-1 was involved in immune regulation in TNBC. In addition, the NRP-1 expression in TNBC positively correlated with a variety of immune cells and checkpoints. Conclusion: NRP-1 can be used as a potential biomarker and therapeutic target in TNBC.

Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-β1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.

Abstract Chronic stress is a known risk factor for breast cancer, yet the underlying mechanisms are unclear. This study explores the potential involvement of microbial and metabolic signals in chronic stress-promoted breast cancer progression, revealing that reduced abundances of Blautia and its metabolite acetate may contribute to this process. Treatment with Blautia and acetate increases antitumor responses of CD8+ T cells and reverses stress-promoted breast cancer progression in female mice. Patients with depression exhibit lower abundances of Blautia and acetate, and breast cancer female patients with depression display lower abundances of acetate, decreased numbers of tumor-infiltrating CD8+ T cells, and an increased risk of metastasis. These results suggest that Blautia-derived acetate plays a crucial role in modulating the immune response to breast cancer, and its reduction may contribute to chronic stress-promoted cancer progression. Our findings advance the understanding of microbial and metabolic signals implicated in cancer in patients with depression and may provide therapeutic options for female patients with breast cancer and depression.

Abstract Allicin exhibits various pharmacological activities and has been suggested to be beneficial in the treatment of stroke. However, the underlying mechanisms are largely unknown. Here, we confirmed that allicin protected the brain from cerebral injury, which could be ascribed to its anti‑apoptotic and anti‑inflammatory effects, as well as the regulation of lipid metabolism, using proteomics and metabolomics analysis. Our results suggested that allicin could significantly ameliorate behavioral characteristics, cerebral infarct area, cell apoptosis, inflammatory factors, and lipid metabolic-related factors (arachidonic acid, 15-hydroperoxy-eicosatetraenoic acid (15S-HPETE), palmitoylcarnitine, and acylcarnitine) by recalibrating astrocyte homeostasis in mice with photothrombotic stroke (PT). In astrocytes, allicin significantly increased glutathione peroxidase 1 (GPX1) levels and inhibited the arachidonic acid-related pathway, which was also observed in the brains of mice with PT. Allicin was proven to inhibit hypoxia-induced astrocyte apoptosis by increasing GPX1 expression, activating proto-oncogene tyrosine-protein kinase Src (Src)- protein kinase B (AKT)-extracellular signal-regulated kinase (ERK) phosphorylation, and decreasing lipid peroxidation. Thus, we concluded that allicin significantly prevented and ameliorated ischemic stroke by increasing GPX1 levels to complete the complex physiological process.

Abstract Zika virus (ZIKV) infection during pregnancy threatens pregnancy and fetal health. However, the infectivity and pathological effects of ZIKV on placental trophoblast progenitor cells in early human embryos remain largely unknown. Here, using human trophoblast stem cells (hTSCs), we demonstrated that hTSCs were permissive to ZIKV infection, and resistance to ZIKV increased with hTSC differentiation. Combining gene knockout and transcriptome analysis, we demonstrated that the intrinsic expression of AXL and TIM-1, and the absence of potent interferon (IFN)-stimulated genes (ISGs) and IFNs contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived trophoblast organoid (hTSC-organoid), we demonstrated that ZIKV infection disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Single-cell RNA sequencing (scRNA-seq) further demonstrated that ZIKV infection of hTSC-organoids disrupted the stemness of hTSCs and the proliferation of cytotrophoblast cells (CTBs) and probably led to a preeclampsia (PE) phenotype. Overall, our results clearly demonstrate that hTSCs represent the major target cells of ZIKV, and a reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepen our understanding of the characteristics and consequences of ZIKV infection of hTSCs in early human embryos.

Background: Adjuvant chemotherapy (AC) is an important, effective treatment for breast cancer. This study evaluates the effectiveness of post-mastectomy AC in treating patients with prognostic stage IB breast cancer. Method: We conducted a retrospective cohort-based study using Surveillance, Epidemiology, and End-Results database. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated using the Kaplan–Meier method. Multivariate Cox risk models were used to identify the impact of AC. Stratified analysis was performed according to molecular subtypes, anatomic stages, and other risk factors to evaluate the effect of AC on survival. Results: 28,825 women diagnosed with prognostic stage IB breast cancer were included. The 5-year OS was significantly higher in AC group than in non-adjuvant chemotherapy (NAC) group (P 0.05). Meanwhile, AC is not an independent prognostic factor for OS and BCSS in patients with lymph node micrometastases. Conclusion: Our study demonstrates that patients with prognostic stage IB do not fully benefit from AC. Individualized treatment management is required for patients with pT1a-1b/N0-1 tumors, lymph node micrometastases, or HR(+)/HER2(−) subtypes.

It is important to develop effective strategies for enhancing the removal capacity of aromatic volatile organic compounds (VOCs) by modifying conventional porous adsorbents. In this study, a novel HZSM-5 zeolite-supported sulfonic acid (ZSM−OSO3H) was prepared through ClSO3H modification in dichloromethane and employed for the elimination of gaseous o-xylene. The ClSO3H modification enables the bonding of −OSO3H groups onto the HZSM-5 support, achieving a loading of 8.25 mmol·g−1 and leading to a degradation in both crystallinity and textural structure. Within an active temperature range of 110–145 °C, ZSM−OSO3H can efficiently remove o-xylene through a novel reactive adsorption mechanism, exhibiting a removal rate exceeding 98% and reaching a maximum breakthrough adsorption capacity of 264.7 mg. The adsorbed o-xylene derivative is identified as 3,4-dimethylbenzenesulfonic acid. ZSM−OSO3H demonstrates superior adsorption performance for o-xylene along with excellent recyclability. These findings suggest that ClSO3H sulfonation offers a promising approach for modifying various types of zeolites to enhance both the elimination and resource conversion of aromatic VOCs.

Cotton is one of the world’s most important economic crops. Verticillium wilt is a devastating cotton disease caused by Verticillium dahliae, significantly impacting cotton yield and quality. E3 ubiquitin ligases are essential components of the ubiquitin-mediated 26S proteasome system, responsible for recognizing ubiquitinated target proteins and promoting their degradation, which play a crucial regulatory role in plant immune responses. In this study, on the basis of the confirmation of differential expression of GhDIRP1, a RING-type E3 ubiquitin ligase encoding gene, in two cotton varieties resistant (Zhongzhimian 2) or susceptible (Jimian 11) to V. dahliae, we demonstrated that GhDIRP1 is a negative regulator of V. dahliae resistance because silencing GhDIRP1 in cotton and heterogeneously overexpressing the gene in Arabidopsis enhanced and compromised resistance to V. dahliae, respectively. The GhDIRP1-mediated immune response seemed to be realized through multiple physiological pathways, including hormone signaling, reactive oxygen species, and lignin biosynthesis. Based on the sequences of GhDIRP1 isolated from Zhongzhimian 2 and Jimian 11, we found that GhDIRP1 had identical coding but different promoter sequences in the two varieties, with the promoter of Zhongzhimian 2 being more active than that of Jimian 11 because the former drove a stronger expression of GUS and LUC reporter genes. The results link the ubiquitination pathway to multiple physiological pathways acting in the cotton immune response and provide a candidate gene for breeding cotton varieties resistant to V. dahliae.

Based on the field survey data for 1216 apple growers in three provinces from China’s Loess Plateau Region, this paper adopted Multivariate Probit (MVP) model and intermediary effect model to analyze the influence mechanisms of digital technology adoption (DTA) on farmers’ choices of Fertilizer-reduction and Efficiency-improving Technologies (FETs) from the perspective of farmers’ cognition (FC). The correlation effects of three typical FETs of soil testing and formula fertilization, integrated water-fertilizer fertilization and slow/controlled release fertilizer, were tested empirically. The results showed that DTA could significantly affect the adoption of FETs by apple growers, and FC played a partial mediating role, and there were complementary effects among the three typical FETs. The results were further confirmed by the propensity score matching (PSM) robustness test and the instrumental variable (IV) endogeneity test conducted in the conditional mixed-process (CMP). The results of our heterogeneity analysis showed that the promotion effect of DTA on FETs in the group with junior high school education or below was more significant than that in the group with higher education, and the promotion effect was more significant in the group with large operation scale. Therefore, the improvement in Internet penetration should not be taken as the ultimate goal, but more attention should be paid to farmers’ mastery and effective use of DTA, promote the improvement in farmers’ cognitive level, and implement the “bundled” publicity and guidance strategy of FETs adoption, so as to help in the green transformation of agriculture.

Mealy peaches are dry and flavorless, which reduces their consumer acceptance. A deeper understanding of the mechanism underlying mealiness is crucial to enhancing peach fruit quality. In this study, comparative profiling was conducted on CP13, CP14, CM, and RM peaches. Sensory evaluation indicated that CP13 and CM are non-mealy clingstone and freestone peaches, respectively, and CP14 and RM are mealy freestone peaches. Both CP13 and CP14, identified as stony hard (SH) peaches, exhibited minimal ethylene release, whereas CM and RM, identified as melting flesh (MF) peaches, released high amounts of ethylene during the ripening process. Scanning electron microscopy (SEM) microstructure observation indicated that cells in the flesh tissue of mealy peaches, CP14 (SH) and RM (MF), were intact and separated, with large intercellular spaces and irregular arrangements. The main factor that promotes mealiness is differences in pectin metabolism, which impact cell wall composition. The fluctuations in polygalacturonase (PG) and pectin methylesterase (PME) activity between mealy and non-mealy peaches were the main factor contributing to mealiness. However, the changes in cell wall metabolism that caused these fluctuations did not have a clear direction. Using transcriptome analysis and weighted gene co-expression network analysis (WGCNA), we were able to identify forty differentially expressed genes (DEGs) that are associated with mealy patterns. Among these DEGs, genes encoding PG were significantly upregulated in mealy peaches (CP14 and RM) compared to non-mealy peaches (CP13 and CM). PpPG1 was the main effector gene for mealiness, while PpPG2, PpEGase2, PpEXP1, PpEXP3, PpAGP2, PpIAA4, and PpABA2 were identified as candidate genes regulating peach mealiness. These findings provide a solid experimental basis for understanding the textual distinctions between mealy and non-mealy peaches.

Abstract Background Collision and composite carcinomas of the thyroid are extremely rare, and their clinical and biological characteristics are poorly understood. Case presentation The first case was a 41-year-old female patient with a right thyroid nodule. Pathological diagnosis was papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma composite carcinoma. Surgical treatment was right thyroid lobectomy + left partial thyroidectomy + right central neck lymph node dissection. The second case was a 60-year-old female with bilateral thyroid nodules. Total thyroidectomy was performed, and the pathological diagnosis was thyroid collision carcinoma involving follicular thyroid carcinoma on the left side and PTC on the right side. Summary The clinical, histological and gene changes of collision and composite carcinomas of the thyroid are poorly described. With different biological invasion characteristics, the ideal treatment and the prognosis is currently unknown and individualized treatment is necessary. Conclusions It is recommended that in composite carcinoma, each cancer is evaluated and treated according to the most severe tumor. Collision carcinoma should be treated as two separate synchronous primary tumors. For both collision and composite carcinomas of the thyroid, the follow-up after treatment should be extensive.

Abstract Background Cotton is extremely affected by severe natural stresses. Drought is one of the most serious abiotic stress that adversely influences cotton growth, productivity, and fiber quality. Previous studies indicate that basic leucine-zipper (bZIP) transcription factors are involved in the response of plants to various stresses. However, the molecular function and regulatory mechanism of GhVIP1 in response to drought stress are still unknown. Results In this research, GhVIP1 was cloned from a drought-tolerant variety. Expression of GhVIP1 was up-regulated in response to multiple abiotic stresses, especially under drought stress. And GhVIP1 was highly expressed in the root, stem, and 10 days post-anthesis ovule. Inhibiting the expression of GhVIP1 in cotton using the virus-induced gene silencing method resulted in higher electrical conductivity in leaves, but lower water content under drought stress compared with the WT plant. Overexpression of GhVIP1 in Arabidopsis enhanced plant drought tolerance through increasing the seed germination rate and improving the development of root. The exogenous expression of GhVIP1 up-regulated the transcription of genes associated with drought response and proline biosynthesis during drought stress in Arabidopsis. Conclusion In summary, these results indicated that GhVIP1 played a positive role in plants' response to drought stress. The use of GhVIP1 via modern biotechnology might facilitate the improvement of drought tolerance in cotton cultivars.

Abstract Background Multiple chronic conditions (MCC) refer to the presence of two or more chronic diseases. The incidence of MCC is higher in older people, and increases with age. Studies have shown an association between MCC and increased adverse outcome, as well as the higher mortality, decline of physical function, and poor quality of life in older populations. Herein, for the first time we provide the data of ethnic and geographic variations in the prevalence of MCC among community-dwelling older people in Xinjiang, China. Methods A multilevel random sampling method was employed to perform an epidemiological survey in community-dwelling older adults in southern, northern, and eastern Xinjiang between January 2019 to December 2019. In total, 87,000 participants volunteered, with a response rate of 96.67%; 490 participants with incomplete data were excluded and data from 86,510 participants were analyzed. Results Our analysis demonstrated that hypertension (51.5%), obesity (27.0%), diabetes (16.9%), heart disease (8.2%), and anxiety/depression (4.5%) were the five main chronic diseases in Xinjiang. The prevalence of MCC in the population surveyed was 33.4% (95%CI, 33.1–33.7). The prevalence in females was 36.6% (95%CI, 36.1–37), which was higher than that in male (30%,95%CI, 29.5–30.4). The prevalence of MCC in older people aged 60–69, 70–79, 80–89, and ≥ 90 years was 32.7% (95%CI, 32.2–33.3), 34.3% (95%CI, 33.9–34.7), 32.5% (95% CI, 31.7–33.3), and 25.9% (95% CI, 23.5–28.3) respectively. As far as the ethnic group was concerned, the prevalence of MCC in Uygur, Han, Kazak, Hui, and Mongolian was 31.3% (95%CI, 30.9–31.7), 34.4% (95%CI, 33.9–35), 40.4% (95%CI, 39.1–41.8), 40.8% (95%CI, 38.9–42.7), 44.4% (95%CI, 38.1–50.6), respectively. The prevalence of MCC was 32.8% (95%CI, 32.1–33.5), 31.7% (95%CI, 31.2–32.1), 36.0% (95%CI, 35.3–36.7) and 39.2% (95%CI, 38.1–40.3) among uneducated, educated for 1–6, 7–9, and more than 10 years. After adjusting for age, sex, smoking, alcohol consumption, and education by level, the binary logistic analysis showed that, compared with eastern Xinjiang, the risk of MCC in the southern area was increased (odds ratio [OR], 1.418; 95% confidence interval [CI], 1.367–1.471), and it was relatively higher in northern Xinjiang (OR, 2.021; 95% CI, 1.944–2.102). Compared with Uygur, Han, Kazakh, Hui and Mongolian had an increased risk of MCC, which was (OR, 1.075; 95% CI, 1.040–1.111), (OR, 1.414; 95% CI, 1.332–1.501), (OR, 1.515; 95% CI, 1.396–1.644), (OR, 1.566; 95% CI, 1.216–2.017), respectively. Conclusions There are ethnic and geographic variations in multiple chronic conditions among community-dwelling older people in Xinjiang. The older adults living in northern and southern Xinjiang and Han, Kazakh, Mongolian and Hui older adults have a higher risk of MCC.

Aiming at the current bottleneck of constructing a fine geomagnetic fingerprint library that required a lot of labor costs, two generative models called the conditional variational autoencoder and the conditional confrontational generative network were proposed, which could collect a small number of data samples for a given location, and generate pseudo-label fingerprints.At the same time, in order to solve the problem of low positioning accuracy of single-point geomagnetic fingerprints, a geomagnetic sequence positioning algorithm based on attention mechanism of convolutional neural network-gated recurrent unit was designed, which could effectively use the spatial and temporal characteristics of fingerprints to achieve precise positioning.In addition, a real-time, portable mobile terminal data collection and positioning system was also designed and built.The actual test shows that the proposed model can effectively construct the available geomagnetic fingerprint database, and the average error of the proposed algorithm can reach 0.16 m.