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Dongmei Lu,1 Maidina Abudouaini,1,2 Munire Kerimu,2 Qiuping Leng,1 Hongtao Wu,1 Amar Aynazar,1,2 Zhiwei Zhong1,2 1Center of Pulmonary and Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 2Department of Public Health, Xinjiang Medical University, Urumqi, People’s Republic of ChinaCorrespondence: Dongmei Lu, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China, Tel +18997982968, Email dongmeilu2009@sina.comPurpose: Severe community-acquired pneumonia (SCAP) is the leading cause of death among patients with infectious diseases worldwide. This study aimed to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) through detecting pathogens in bronchoalveolar lavage fluid (BALF) and identifying risk factors for recovery in SCAP patients.Patients and Methods: This prospective study recruited 158 SCAP patients admitted to respiratory intensive care unit that were randomly divided into control and study groups, with receiving conventional tests and the same conventional tests plus mNGS, respectively. The diagnostic efficiency of mNGS was evaluated by comparing with conventional tests. Furthermore, univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for recovery in SCAP patients, and a nomogram prediction model was established based on these factors.Results: Within the study group, the pathogen detection rate was significantly higher with mNGS than that with conventional tests (84.81% vs 45.57%, P < 0.001), with a positive coincidence rate of 94.44%. Acinetobacter baumannii (21.52%, 17/79), Candida albicans (17.72%, 14/79), and Klebsiella pneumonia (15.19%, 12/79) were the top three common pathogens detected by mNGS. Of note, the improvement rate of patients in the study group was significantly higher than that in the control group. The further analysis revealed that the increased levels of interleukin-6, blood urea nitrogen, procalcitonin, the longer length of hospital stay, and bacterial infection were independent risk factors for recovery of SCAP patients, while mNGS detection status was a protective factor. The predictive model showed a good performance for the modeling and validation sets.Conclusion: Early mNGS exhibited a superior diagnostic efficiency to conventional tests in SCAP patients, which can reduce the risk of death in SCAP patients. Moreover, the clinical factors could also be used for the management and prognosis prediction of SCAP patients.Keywords: severe community-acquired pneumonia, metagenomic next-generation sequencing, pathogen, risk factor

Background The magnitude of the thermal stress in the first wall system is one of the key factors affecting the safe operation of the fusion reactor. Purpose This study aims to investigate the effect of a rough substrate on the thermal stress in the W/316L stainless steel first wall system. Method The finite-element analysis software Ansys Workbench was employ to analyze the distribution of thermal stree in a W/316L stainless steel first wall system with a rough substrate. Depth analysis was conducted on factors such as the temperature, coating thickness, and substrate thickness that affect the magnitude of thermal stress. Meanwhile, starting from the interface shear stress in the system, the influence of rough substrate on the bonding strength of coatings was simultaneously investigated. Results The simulation results indicate that the thermal stress in the rough substrate system increases with the the increase of temperature and substrate thickness, but decreases with the increase of coating thickness. The maximum thermal stress and the adhesive strength between the coating and the substrate are raised by the introduction of the rough substrate. Conclusions Results of this study can provide reference for the development of high-adhesive strength first wall coating systems.

Oral tolerance is essential for intestinal homeostasis and systemic immune function. However, our understanding of how oral tolerance is maintained is inadequate. Here we report that food-derived nucleic acids promote oral tolerance through innate sensing pathways. We find that dietary nucleic acids, but not microbiota, expand the natural intraepithelial lymphocyte (IEL) pool, specifically in the small intestine. TGF-β1, produced by natural IELs, then promotes activation of gut CD103 + dendritic cells to support the induction of antigen-specific Treg cells in a mouse model of OVA-induced oral tolerance. Mechanistically, MAVS and STING are redundantly required for sensing dietary RNAs and DNAs to activate downstream TBK1 signalling to induce IL-15 production, which results in the accumulation of natural IELs. Thus, our study demonstrates a key role of food-triggered innate sensing pathways in the maintenance of natural IELs and oral tolerance., (© 2024. The Author(s).)

Traditional reduction or oxidation processes generating one-component free radicals face challenges in deep dechlorination and mineralization of chlorophenols from wastewater. Herein, an efficient electrocatalytic process has been developed, which couples atomic H* reduction with reactive oxidation species ( • OH and 1 O 2 ) oxidation on a bifunctional cathode for 4 -chlorophenol (4 -CP) removal. The N - doped carbon nanotubes encapsulated manganese nanoparticles was fabricated as cathode, which could generate atomic H* , initiating nucleophilic hydrodechlorination in presence of confined MnO sites. Subsequently, electrophilic oxidation by generating mainly 1 O 2 on confined Mn 7 C 3 sites and • OH on confined MnO sites, facilitating the oxidative processes. Experimental results and theory calculations demonstrated that reductive dechlorination and oxidative mineralization processes could mutually promote each other, resulting in an enhancement factor of 2.90. At pH 7, this process achieved 100 % removal for 4 -CP, 84 % dechlorination, 76 % total organic carbon (TOC) removal and low energy consumption (0.76 kWh g -1 TOC ) within 120 min. Notably, TOC for chlorophenols containing Cl substituents at different positions and real lake water containing 4 -CP could be almost completely removed. This research establishes confined non-noble bifunctional active sites that synergistically enhance reductive dechlorination and oxidative degradation processes, holding significant treatment potential for application in deep mineralization of organochlorine from water/wastewater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The lipid-lowering simvastatin (SIM) has been shown to be an effective inhibitor of keloid proliferation. However, due to its low water solubility and short half-life, simvastatin aggregates to the liver and does not reach the skin lesions after oral administration, which restricts its widespread clinical use. The development of nanomedicine provides the possibility for us to break through this bottleneck problem clinically. The objective of this study was to investigate the feasibility of using complex nanocontrolled delivery system (CNDS), simvastatin-loaded polyethylene glycol-poly lactic-co-glycolic acid (PEG-PLGA), in the treatment of keloids., Methods: In the in vitro study, the release of simvastatin in fibroblasts by CNDS@Simvastatin and its effect on inhibition of the proliferation of fibroblasts, Col Ι, and CTGF by the slow release of simvastatin were assessed. The efficacy of CNDS@Simvastatin in improving keloids and the biocompatibility and safety of CNDS@Simvastatin were examined in vivo by establishing a murine ear keloid model., Results: CNDS@Simvastatin showed sustained and uniform inhibition of the proliferation of fibroblasts, Col Ι, and CTGF via the gradual release of simvastatin over 72 h. It was efficient in the treatment of the murine ear keloid with no observable toxic side effects on various organs., Conclusion: Simvastatin-loaded copolymer acid-sensitive nanocarriers, CNDS@Simvastatin nanospheres, were successfully developed in this study, and these were characterized by favorable physicochemical properties and biocompatibility., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Esophageal cancer (EC) is one of the most fatal cancers all over the world. Sensitive detection modalities for early-stage EC and efficient treatment methods are urgently needed for the improvement of the prognosis of EC. Exosomes are small vesicles for intercellular communication, mediating many biological responses including cancer progression, which are not only promising biomarkers for diagnosis and prognosis but also therapeutic tools for EC. This review provides an overview of the relationships between exosomes and EC progression, as well as the application of exosomes in the diagnosis, prognosis, and treatment of EC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2024 Wiley Periodicals LLC.)

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) is considered a crucial step for boosted immunotherapy. Here, a high-lactate-metabolizing photosynthetic bacteria (LAB-1) is selectively screened for TIM reprogramming, which then improves the efficacy of tumor immunotherapy. The culture medium for LAB-1 screening is initially developed through an orthogonal experiment, simulating the tumor microenvironment (TME) and utilizing lactate as the sole organic carbon source. As demonstrated in a murine 4T1 model, LAB-1 colonizes the TME selectively, resulting in a significant reduction in lactate levels and a subsequent increase in pH values within the tumor tissue. Furthermore, single-cell RNA sequencing analysis reveals that LAB-1 effectively reprograms the TIM, thereby enhancing the effectiveness of antitumor immune therapy. This approach of utilizing lactate-consuming bacteria represents a potent tool for augmenting tumor immunotherapy efficiency., (© 2024 Wiley‐VCH GmbH.)

Cationic polymers that bind with the plasmids to form polyplexes protect the DNA from enzymatic degradation and improve cellular and tissue uptake. Complete or near complete gel retardation of the polyplex is an important assay to determine the optimal polymer: plasmid ratio for in vitro and in vivo studies. Nevertheless, despite minimal to moderate gel retardation of histidine-lysine (HK) polyplexes formed with low peptide: plasmid DNA ratios (1:2 and 1:4; w:w), the polyplexes effectively targeted the tumor in vivo. To understand the lack of predictability of the initial gel mobility shift assays, we revisited the retardation and stability of polyplexes with these electrophoresis assays. Because the histidine component with a pKa of about 6.0 will have a greater positive charge and may bind plasmids with a higher affinity at lower pHs, we compared the retardation of the two HK polyplexes when the pH of the running buffer of the gel mobility shift assay was altered. Both HK polyplexes were retarded significantly more when the running buffer had a pH of 7.3 instead of the standard pH of 8.3. Indeed, the HK polyplexes formed at the 1:2 ratio showed complete retardation at pH 7.3. Consequently, while both HK polyplexes formed at these low ratios targeted the tumor, the polyplex formed with the 1:2 ratio had reduced tumor gene expression variability and lower lung and liver values. Thus, the selection of the optimal ratios for the linear HK and plasmid for transfection studies in vivo was improved with a running buffer pH of 7.3., Competing Interests: Declaration of competing interest The authors of this manuscript declare that there are no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The influence of Open Access (OA) on the citation impact of scholarly articles remains a topic of considerable debate. This study aims to elucidate the relationship between OA publication and citation metrics, as well as article visibility, within the context of the Postgraduate Medical Journal (PMJ)., Methods: We conducted a retrospective analysis of 373 articles published in PMJ between 2020 and 2021. Data on OA status, citations, page views, PDF downloads, and other relevant variables were extracted from Journal Citation Reports and PMJ's official website. Multivariable linear regression and other statistical analyses were used to assess the impact of OA on these metrics., Results: OA articles (n = 78) demonstrated significantly higher citation counts, page views, and PDF downloads compared with subscription-based articles (n = 295). Specifically, OA articles showed a significant increase in citation frequency with a β coefficient of 25.08 and a 95% CI of 17.168-32.992 (P < .001). Similarly, OA status was independently associated with increases in page views [β = 288.636, 95%CI: 177.749-399.524, P < .001] and PDF downloads [β = 118.966, 95%CI: 86.357-151.575, P < .001]. Strong correlations among total citations, page views, and PDF downloads were observed in both OA and subscription articles., Conclusion: The study highlights a significant and independent association of OA publishing with increased citation counts, page views, and PDF downloads in PMJ, suggesting that OA articles have broader reach and greater visibility. Further research, including randomized controlled studies across various journals, is needed to confirm these findings and explore the full impact of OA publishing., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The study employed meta-analysis to provide a comprehensive synthesis of evidence regarding the association between the prothrombin A19911G polymorphism and the risk of venous thromboembolism (VTE)., Method: The databases were searched to identify studies investigating the association between the prothrombin A19911G polymorphism and the risk of VTE. Meta-analysis was conducted using Stata 14.0 software., Results: A total of five literature studies were included, involving 14,001 participants. Meta-analysis demonstrated that prothrombin A19911G polymorphism increased the risk of VTE (G vs A: OR = 1.17, 95% CI = 1.11-1.22, p < .00001; GG + AG vs AA: OR = 1.22, 95% CI = 1.13-1.31, p < .00001; GG vs AG + AA: OR = 1.23, 95% CI = 1.14-1.33, p < .00001; AG vs AA: OR = 1.15, 95% CI = 1.06-1.25, p = .0006; GG vs AA: OR = 1.34, 95% CI = 1.22-1.48, p < .00001)., Conclusion: The polymorphism of prothrombin A19911G enhances the susceptibility to VTE., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.

Enterococcus faecalis is a prevalent opportunistic pathogen associated with chicken embryonic and neonatal chick mortality, posing a significant challenge in poultry farming. In the current study, E. faecalis strain EF6, isolated from a recent hatchery outbreak, served as the host bacterium for the isolation of a novel phage EFP6, capable of lysing E. faecalis . Transmission electron microscopy revealed a hexagonal head and a short tail, classifying EFP6 as a member of the Autographiviridae family. EFP6 showed sensitivity to ultraviolet radiation and resistance to chloroform. The lytic cycle duration of EFP6 was determined to be 50 min, highlighting its efficacy in host eradication. With an optimal multiplicity of infection of 0.001, EFP6 exhibited a narrow lysis spectrum and strong specificity towards host strains. Additionally, EFP6 demonstrated optimal growth conditions at 40 °C and pH 8.0. Whole genome sequencing unveiled a genome length of 18,147 bp, characterized by a GC concentration of 33.21% and comprising 25 open reading frames. Comparative genomic assessment underscored its collinearity with related phages, notably devoid of lysogenic genes, thus ensuring genetic stability. This in-depth characterization forms the basis for understanding the biological attributes of EFP6 and its potential utilization in phage therapy, offering promising prospects for mitigating E. faecalis -associated poultry infections.

Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated with a considerably worse prognosis. Approximately one-third of patients are diagnosed with metastatic disease, with liver metastases being the most prevalent. Diagnosis relies on histopathological alterations including squamous vesicles, positive staining for CK8/CK18/CK19, and nuclear displacement of β-catenin. Additionally, liver metastases demonstrate substantial enhancement during the arterial phase of a contrast-enhanced computed tomography (CT) scan. Surgical resection serves as the principal therapeutic approach for addressing primary lesions and liver metastatic PB. In instances where surgical intervention is not viable, patients may derive benefits from systemic therapy and radiotherapy. This particular case report presents the clinical details of a 27-year-old female patient diagnosed with PB, who subsequently developed multiple liver metastases following a pancreaticoduodenectomy. Genomic examinations revealed the presence of ERBB2 amplification, RAD54L deletion, low TMB-L, and MSS in the patient. Despite the patient undergoing chemotherapy and Her-2 targeted therapy in conjunction with immunotherapy, no reduction in lesion size was observed until the administration of surufatinib. Subsequently, a notable outcome ensued, where the metastatic lesions were effectively excised via surgical intervention. Surufatinib has demonstrated a progression-free survival (PFS) of no less than 14 months, and the patient's survival has endured for a duration of 33 months. This indicates the potential efficacy of surufatinib as a viable therapeutic alternative for adult patients afflicted with PB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Leng, Lv, Yang, Li, Wang, Cheng, Chang and Cao.)

The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development. Additionally, we provide an in-depth analysis of pivotal phase 2 and 3 clinical trials evaluating the performance and safety of FGFR inhibitors in oncology, thereby shedding light on the current state of clinical research in this field. Then, we highlight four drugs that have been approved for marketing by the FDA, offering insights into their molecular mechanisms and clinical achievements. Our discussion encompasses the intricate landscape of FGFR-driven tumorigenesis, current techniques for pinpointing FGFR anomalies, and clinical experiences with FGFR inhibitor regimens. Furthermore, we discuss the inherent challenges of targeting the FGFR pathway, encompassing resistance mechanisms such as activation by gatekeeper mutations, alternative pathways, and potential adverse reactions. By synthesizing the current evidence, we underscore the potential of FGFR-centric therapies to enhance patient prognosis, while emphasizing the imperative need for continued research to surmount resistance and optimize treatment modalities., (© 2024. The Author(s).)

Herbicide resistance is a worldwide concern for weed control. Cucumis melo L. var. agrestis Naud. (C. melo) is an annual trailing vine weed that is commonly controlled by nicosulfuron, acetolactate synthase (ALS)-inhibiting herbicides. However, long-term use of this herbicide has led to the emergence of resistance and several nicosulfuron resistant populations of C. melo have been found. Here we identified a resistant (R) C. melo population exhibiting 7.31-fold resistance to nicosulfuron compared with a reference sensitive (S) population. ALS gene sequencing of the target site revealed no amino acid substitution in R plants, and no difference in enzyme activity, as shown by ALS activity assays in vitro. ALS gene expression was not significantly different before and after the application of nicosulfuron. Pretreatment with the cytochrome P450 monooxygenase (P450) inhibitor malathion reduced nicosulfuron resistance in the R population. RNA-Seq transcriptome analysis was used to identify candidate genes that may confer metabolic resistance to nicosulfuron. We selected genes with annotations related to detoxification functions. A total of 20 candidate genes (7 P450 genes, 1 glutathione S-transferase (GST) gene, 2 ATP-binding cassette (ABC) transporters, and 10 glycosyltransferase (GT)) were identified; 12 of them (7 P450s, 1 GST, 2 ABC transporters, and 2 GTs) were demonstrated significantly differential expression between R and S by quantitative real-time RT-PCR (qRT-PCR). Our findings revealed that the resistance mechanism in C. melo was nontarget-site based. Our results also provide a valuable resource for studying the molecular mechanisms of weed resistance., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

In plants, the rapid accumulation of proline is a common response to combat abiotic stress 1-7 . Delta-1-pyrroline-5-carboxylate synthase (P5CS) is a rate-limiting enzyme in proline synthesis, catalysing the initial two-step conversion from glutamate to proline 8 . Here we determine the first structure of plant P5CS. Our results show that Arabidopsis thaliana P5CS1 (AtP5CS1) and P5CS2 (AtP5CS2) can form enzymatic filaments in a substrate-sensitive manner. The destruction of AtP5CS filaments by mutagenesis leads to a significant reduction in enzymatic activity. Furthermore, separate activity tests on two domains reveal that filament-based substrate channelling is essential for maintaining the high catalytic efficiency of AtP5CS. Our study demonstrates the unique mechanism for the efficient catalysis of AtP5CS, shedding light on the intricate mechanisms underlying plant proline metabolism and stress response., (© 2024. The Author(s).)

Introduction: In order to enhance the effectiveness of resource allocation, regions must tailor their responses to their specific epidemiological and economic situations., Methods: Utilizing Spectrum software, we projected the cost-effectiveness of 10 chosen HIV interventions in six cities in eastern China from 2019 to 2028. We assessed three scenarios - Base, Achievable, and Idealized - for each city. The analysis included the projected number of HIV infections and deaths averted, as well as the incremental cost-effectiveness ratios for each intervention in the six cities., Results: In Shijiazhuang, Wuxi, Yantai, and Zhenjiang, cities with initially low antiretroviral therapy (ART) coverage, ART showed significant effectiveness, especially for males. Conversely, in Foshan and Ningbo, where ART coverage was notably high, oral pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) proved effective in the Idealized scenario. MSM outreach, ART for males, and ART for females demonstrated cost-effectiveness across all six cities in both Achievable and Idealized scenarios at the predefined thresholds for each city., Discussion: Maintaining an appropriate coverage rate for outreach to MSM can lead to cost-effectiveness. In cities with low ART coverage, scaling up ART remains a crucial intervention. In regions with high ART coverage, consideration may be given to the utilization of oral PrEP for MSM individuals, requiring budget allocation., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Klebsiella pneumoniae ( K. pneumoniae ) is recognized as a zoonotic pathogen with an increasing threat to livestock and poultry. However, research on K. pneumoniae of animal origin remains limited. To address the gap, a comprehensive investigation was carried out by collecting a total of 311 samples from the farms of four animal species (dairy cow, chicken, sheep, and pig) in selected areas of Xinjiang, China. Isolates were identified by khe gene amplification and 16S rRNA gene sequencing. Genotyping of K. pneumonia isolates was performed using wzi typing and multilocus sequence typing (MLST). PCR was employed to identify virulence and resistance genes. An antibiotic susceptibility test was conducted using the Kirby-Bauer method. The findings revealed an isolation of 62 K. pneumoniae strains, with an average isolation rate of 19.94%, with the highest proportion originating from cattle sources (33.33%). Over 85.00% of these isolates harbored six virulence genes ( wabG, uge, fimH, markD, entB, and ureA ); while more than 75.00% of isolates possessed four resistance genes ( bla TEM , bla SHV , oqxA , and gyrA ). All isolates exhibited complete resistance to ampicillin and demonstrated substantial resistance to sulfisoxazole, amoxicillin/clavulanic acid, and enrofloxacin, with an antibiotic resistance rate of more than 50%. Furthermore, 48.39% (30/62) of isolates were classified as multidrug-resistant (MDR) strains, with a significantly higher isolation rate observed in the swine farms (66.67%) compared to other farms. Genetic characterization revealed the classification of the 62 isolates into 30 distinct wzi allele types or 35 different sequence types (STs). Notably, we identified K. pneumoniae strains of dairy and swine origin belonging to the same ST42 and wzi33-KL64 types, as well as strains of dairy and chicken origin belonging to the same wzi31-KL31-K31 type. These findings emphasize the widespread occurrence of drug-resistant K. pneumoniae across diverse animal sources in Xinjiang, underscoring the high prevalence of multidrug resistance. Additionally, our results suggest the potential for animal-to-animal transmission of K. pneumoniae and there was a correlation between virulence genes and antibiotic resistance genes. Moreover, the current study provides valuable data on the prevalence, antibiotic resistance, and genetic diversity of K. pneumoniae originating from diverse animal sources in Xinjiang, China.

The present study aimed to conduct a comprehensive meta-analysis to assess the diagnostic value of fluorometric assays and tandem mass spectrometry (MS/MS) for hyperphenylalaninemia (HPA) and its subtypes. The PubMed, Embase and Cochrane Library databases were searched from inception to October 2023. The present study included studies that reported the newborn screening and genetic features of patients with HPA and excluded duplicate publications, studies without full text, studies with incomplete information, studies from which it was not possible to extract data, animal experiments, reviews and systematic reviews. STATA 15.1 was used to analyze the data. The pooled results revealed that 0.04% [95% confidence interval (CI): 0.019-0.069] of neonatal HPA fluorometric assays and MS/MS. The positive predictive value (PPV) of neonatal HPA screening using fluorometric assays and tandem mass spectrometry was 31.7% (95% CI: 19.6-45.2). Notably, the PPV of neonatal HPA screening using fluorometric assays was 8.3% (95% CI: 7.1-9.6), while the PPV of neonatal HPA screening using tandem mass spectrometry was 31.8% (95% CI: 16.4-49.4). Additionally, the pooled results showed that the incidence of tetrahydrobiopterin deficiency (BH4D) in HPA patients was 12.43% (95% CI: 3.28-25.75) and the incidence of phenylalanine hydroxylase deficiency (PAHD) in HPA patients was 88.65% (95% CI: 78.84-95.86). Newborn screening is an effective method for the early detection of HPA and MS/MS has a greater PPA than fluorometric assays for diagnosing HPA. In addition, in the screening of HPA, the proportion of HPA patients with PAHD was significantly higher than that of patients with BH4D., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Shang et al.)

The worldwide incidence of cognitive impairment is escalating, yet no effective solutions for these afflictions have been discovered. Consequently, the importance of early identification and immediate intervention is heightened. Advanced eye movements-a form of voluntary eye movements that includes anti-saccades, memory-guided saccades, predictive saccades, pro-saccades and gap/overlap saccades, mediated by the cerebral cortex and subcortical pathways reflect cognitive levels and functions across different domains. In view of their objectivity, reproducibility, and non-invasive characteristics, advanced eye movement examination possesses significant prospective utility across a wide range of cognitive impairment. This paper extensively reviews various models associated with advanced eye movement examinations and their current applications in cognitive impairment such as Alzheimer's disease, Lewy body dementia and frontotemporal dementia. Advanced eye movement examination can serve as a biomarker for early screening diagnosis and research on cognitive impairment. In the future, combining advanced eye movement examination with neuropsychological scale assessment and other diagnostic methods may contribute to further early identification of these types of diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Leng, Deng and Ju.)

Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs.

Chronic rejection is the primary cause of late allograft failure, however, the current treatments for chronic rejection have not yielded desirable therapeutic effects. B cell activation and donor-specific antibody (DSA) production are the primary factors leading to chronic rejection. Bruton's tyrosine kinase (BTK) plays a key role in the activation and differentiation of B cells and in antibody production. This study investigated the efficacy of blocking BTK signalling in the prevention of chronic rejection. BTK signalling was blocked using the BTK inhibitor ibrutinib and gene knockout. In vitro assays were conducted to examine the consequences and underlying mechanisms of BTK blockade in regards to B cell activation, differentiation, and antibody secretion. Additionally, we established a cardiac transplantation mouse model of chronic rejection to explore the preventive effects and mechanisms of BTK ablation on chronic rejection. Ablating BTK signalling in vitro resulted in the inhibition of B cell activation, differentiation, and antibody production. In vivo experiments provided evidence that ablating BTK signalling alleviated chronic rejection, leading to reduced damage in myocardial tissue, neointimal hyperplasia, interstitial fibrosis, inflammatory cell infiltration, and C4d deposition. Allograft survival was prolonged, and B cell responses and DSA production were inhibited as a result. We confirmed that ablation of BTK signalling inhibited B cell response by blocking downstream PLCγ2 phosphorylation and inhibiting the NF-κB, NFAT, and ERK pathways. Our findings demonstrated that ablation of BTK signalling inhibited B cell activation and differentiation, reduced DSA production, and effectively prevented chronic rejection., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although Warburg discovered pH discrepancies between tumor and normal tissues nearly 100 years ago, developing therapies to take advantage of this concept was relatively slow for the first 70 years. During the last 30 years, there has been an exponential increase in the use of pH-dependent strategies for both low molecular weight drugs and nanoparticles. Two frequently discussed approaches are the chemotherapy's release from pH-sensitive covalent linkages of macromolecules or from pH-dependent disruption of charged polymeric nanoparticles. In contrast, pH-dependent non-covalent bonds between the chemotherapy agent and macromolecules have rarely been discussed, yet this underappreciated strategy has great potential. These non-covalent interactions are primarily ionic or hydrogen bonds with supporting roles from hydrophobic bonds. In addition to the facile coupling of the drug with the carrier, these non-covalent interactions may show marked pH dependence. Consistent with pH dependence, many of these drug-loaded carriers showed significant in vitro and, in some cases, striking in vivo activity. In this review, we will focus on pH-sensitive non-covalent bonds, highlighting the release of drugs from diverse carriers such as tetrahedron DNA structures, cyclodextrin, polymeric carriers, and carbon-based quantum particles.

In the 21st century, the development of medical science has entered the era of big data, and machine learning has become an essential tool for mining medical big data. The establishment of the SEER database has provided a wealth of epidemiological data for cancer clinical research, and the number of studies based on SEER and machine learning has been growing in recent years. This article reviews recent research based on SEER and machine learning and finds that the current focus of such studies is primarily on the development and validation of models using machine learning algorithms, with the main directions being lymph node metastasis prediction, distant metastasis prediction, and prognosis-related research. Compared to traditional models, machine learning algorithms have the advantage of stronger adaptability, but also suffer from disadvantages such as overfitting and poor interpretability, which need to be weighed in practical applications. At present, machine learning algorithms, as the foundation of artificial intelligence, have just begun to emerge in the field of cancer clinical research. The future development of oncology will enter a more precise era of cancer research, characterized by larger data, higher dimensions, and more frequent information exchange. Machine learning is bound to shine brightly in this field., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction. Salmonella Typhimurium (STM) is a food-borne Gram-negative bacterium, which can infect humans and a wide range of livestock and poultry, causing a variety of diseases such as septicaemia, enteritis and abortion. Hypothesis/Gap Statement. We will decipher the impacts of sRNA STnc1280 on STM virulence and provide a theoretical basis to reveal the regulatory role and molecular mechanism of STnc1280 . Aim. The main objective of this study was to clarify whether sRNA STnc1280 exerts regulatory roles on STM pathogenicity. Methodology. The STnc1280 gene was amplified and its molecular characteristics were analysed in this study. Then, STnc1280 gene deletion strain (STM- ΔSTnc1280 ) and the complementary strain ( ΔSTnc1280/STnc1280 ) were constructed by λ-Red homologous recombination method, respectively, to analyse of adhesion and invasive ability and pathogenicity of different strains. Subsequently, the potential target gene regulated by STnc1280 was predicted using target RNA2 software, followed by the verification of the interaction between STnc1280 and target mRNA using the dual plasmid reporter system (DPRS). Furthermore, the mRNA and protein level of target gene was determined using qRT-PCR and Western blot, respectively. Results. The results revealed that the cell adhesion and invasive ability and pathogenicity of STM- ΔSTnc1280 were significantly reduced compared to STM-SL1344 strain, indicating that the deficiency of STnc1280 gene significantly influenced STM pathogenicity. The DPRS results showed that STnc1280 can interact with the mRNA of target gene gldA , thus suppressing the expression of lacZ gene. Furthermore, the level of gldA mRNA was not influenced in STM- ΔSTnc1280 , but the expression of GldA protein decreased significantly. Conclusion. Combining the bioinformatic analysis, these findings suggested that STnc1280 may bind to the SD sequence of gldA mRNA, hindering the binding of ribosomes to gldA mRNA, thereby inhibiting the expression of GldA protein to modulate the virulence of STM.

Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5' untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. Mice received three injections in 21 d intervals. IgG antibodies, neutralizing antibodies, cellular immunity, and gene expression from peripheral blood mononuclear cells were evaluated. Significant differences in levels of IgG antibodies were not observed in groups with adjuvant but were observed in groups without adjuvant. The vaccine without adjuvant induced the highest antibody titers after intramuscular injection. The vaccine elicited a potent antiviral immune response characterized by antiviral clusters of differentiation CD8 + T cells. VP7-mRNA induced interferon-γ secretion to mediate cellular immune responses. Chemokine-mediated signaling pathways and immune response were activated by VP7-mRNA vaccine injection. The mRNA LNP vaccine will require testing for protective efficacy, and it is an option for preventing rotavirus infection.

Lung cancer is the leading cause of cancer-related deaths among both men and women. African Americans (AAs) experience disproportionately higher incidence and mortality compared to other ethnic groups. Cytokines play multifaceted and crucial roles in the initiation, progression, and spread of cancer. Our aim was to identify cytokine biomarkers for the early detection of lung cancer in AAs. We examined eight key cytokines (Interleukin-1, IL-6, IL-8, IL-10, IL-12p70, monocyte chemotactic protein-1 (MCP-1), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)) in the plasma of 104 lung cancer patients and 48 cancer-free individuals using the FirePlex Immunoassay. These findings were subsequently validated in a separate cohort of 58 cases and 58 controls. IL-8, IFN-γ, and TNF-α exhibited elevated levels in both AA and White American (WA) lung cancer cases. Notably, IL-10 and MCP-1 displayed significant increases specifically in AA lung cancer patients, with MCP-1 levels associated with lung adenocarcinoma cases. Conversely, WA lung cancer patients showed heightened IL-6 levels, particularly linked to lung adenocarcinoma. The combined use of specific cytokines showed promise in lung cancer diagnosis, with IL-8, IL-10, and MCP-1 achieving 76% sensitivity and 79% specificity in AAs and IL-6 and IL-8 combined offering 76% sensitivity and 74% specificity in WAs. These diagnostic biomarkers were validated in the independent cohort. The ethnicity-related cytokine biomarkers hold promise for diagnosing lung cancer in AAs and WAs, potentially addressing the observed racial disparity.

Transfection with mRNA has been considered superior to that with plasmids since the mRNA can be translated to a protein in the cytosol without entering the nucleus. One disadvantage of using mRNA is its susceptibility to enzymatic biodegradability, and consequently, significant research has occurred to determine nonviral carriers that will sufficiently stabilize this nucleic acid for cellular transport. Histidine-lysine peptides (HK) are one such class of mRNA carriers, which we think serves as a model for other peptides and polymeric carrier systems. When the HK peptide and mRNA are mixed and interact through ionic and nonionic bonds, mRNA polyplexes are formed, which can transfect cells. In contrast to linear HK peptides, branched HK peptides protected and efficiently transfected mRNA into cells. After describing the preparation and biophysical characterization of these polyplexes, we will provide protocols for in vitro and in vivo transfection for these mRNA polyplexes., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Anthurium andraeanum Linden is a prominent ornamental plant belonging to the family Araceae and is cultivated worldwide. The morphology characteristics are crucial because they significantly impact ornamental values, commercial properties, and the efficiency of space utilization in production. However, only a few related investigations have been conducted in anthurium to date. In this study, an F 1 genetic segregation population containing 160 progenies was generated through hybridization between potted and cut anthurium varieties. Fifteen morphological traits were assessed and revealed substantial levels of genetic variation and widespread positive correlation. Based on specific length amplified fragment (SLAF) sequencing technology, 8171 single nucleotide polymorphism (SNP) markers were developed, and the high-density linkage map of 2202.27 cM in length distributed on 15 linkage groups was constructed successfully, with an average distance of 0.30 cM. Using the inclusive composite interval mapping (ICIM) method, 59 QTLs related to 15 key morphological traits were successfully identified, which explained phenotypic variance (PVE) ranging from 6.21% to 17.74%. Thirty-three of those associated with 13 traits were designated as major QTLs with PVE > 10%. These findings offer valuable insights into the genetic basis of quantitative traits and are beneficial for molecular marker-assisted selection (MAS) in anthurium breeding.

Background: Adipose fibrosis is a major factor of adipose dysfunction, which causes metabolic dysfunction during obesity, but its molecular mechanisms are poorly understood. This study investigated the role and potential mechanisms of mTORC1 in obesity-induced adipose fibrosis., Methods: ob/ob mice were injected with rapamycin or the same volume of normal saline. The level of fibrosis in epididymal adipose tissue (EAT) was detected by observing aberrant deposition of extracellular matrix. Expression of fibrotic related genes was analysed using RNA-seq. 3T3-L1 preadipocytes were treated with cobalt chloride (CoCl 2 ) and TGF-β1 to induce preadipocyte fibrosis. The fibrosis-related gene expression and protein levels were determined by RT-PCR, WB, and immunofluorescence in two types of fibrotic preadipocytes with or without rapamycin., Results: Compared with vehicle treatment, EAT fibrosis-related aberrant deposition of extracellular matrix proteins and fibrotic gene expression were reduced in ob/ob mice treated with rapamycin. Both CoCl 2 -induced hypoxia and TGF-β1 successfully promoted adipocyte fibrosis, and the upregulated fibrosis-related genes expression was inhibited after the mTORC1 pathway was inhibited by rapamycin., Conclusion: Inhibition of the mTORC1 pathway ameliorates adipose fibrosis by suppressing fibrosis-related genes in hypoxia- and TGF-β-induced fibrotic preadipocytes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Neoadjuvant immune-checkpoint blockade therapy only benefits a limited fraction of patients with glioblastoma multiforme (GBM). Thus, targeting other immunomodulators on myeloid cells is an attractive therapeutic option. Here, we performed single-cell RNA sequencing and spatial transcriptomics of patients with GBM treated with neoadjuvant anti-PD-1 therapy. We identified unique monocyte-derived tumor-associated macrophage subpopulations with functional plasticity that highly expressed the immunosuppressive SIGLEC9 gene and preferentially accumulated in the nonresponders to anti-PD-1 treatment. Deletion of Siglece (murine homolog) resulted in dramatically restrained tumor development and prolonged survival in mouse models. Mechanistically, targeting Siglece directly activated both CD4 + T cells and CD8 + T cells through antigen presentation, secreted chemokines and co-stimulatory factor interactions. Furthermore, Siglece deletion synergized with anti-PD-1/PD-L1 treatment to improve antitumor efficacy. Our data demonstrated that Siglec-9 is an immune-checkpoint molecule on macrophages that can be targeted to enhance anti-PD-1/PD-L1 therapeutic efficacy for GBM treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Here, a novel molecularly imprinted photopolymer was prepared using CsPbBr 3 quantum dots as the fluorescence source, TpPa-2 as substrate for selective solid fluorescence detection of patulin (PAT). TpPa-2 can promote efficient recognition of PAT due to its unique structure and significantly improve the fluorescence stability and sensitivity. The test results showed that the photopolymer exhibited large adsorption capacity (131.75 mg/g), fast adsorption ability (12 mins), superior reusability and high selectivity. The sensor proposed had good linearity for PAT in the range of 0.2-20 ng/mL and was applied to the analysis of PAT in apple juice and apple jam with a limit of detection as low as 0.027 ng/mL. Therefore it maybe a promising method for solid fluorescence detection of trace PAT in food analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To compare the differences in clinical symptoms and the time required for diagnosis of benign paroxysmal positional vertigo (BPPV) between older patients and young and middle-aged patients in the structured inquiry of dizziness history. Methods: The medical records of 6 807 patients diagnosed with BPPV from the Vertigo Database of Vertigo Clinical Diagnosis, Treatment, and Research Center of Beijing Tiantan Hospital, Capital Medical University, between January 2019 and October 2021 were retrospectively analyzed. The data included basic demographic information, clinical symptoms in a structured medical history questionnaire, and the time interval from the appearance of BPPV symptoms to diagnosis consultation. The patients were divided into the young and middle-aged group (<65 years old) and the older group (≥65 years old). The differences in clinical symptoms and consultation time were compared between these two groups. Categorical variables were represented by numbers (%), and compared using Chi-squared tests or Fisher's exact probability test for analysis; whereas, continuous variables conforming to normal distribution were represented by mean±standard deviation. Both data groups were compared and analyzed by Student's t -test. Results: The mean age of the older group was 65-92 (71±5) years, while the mean age of the middle-aged group was 18-64 (49±12) years. The incidence of vertigo (42.5% vs. 49.1%, χ 2 =23.69, P <0.001); vertigo triggered by changes in position of the head or body (52.4% vs. 58.7%, χ 2 =22.31, P <0.001); and autonomic symptoms (10.1% vs. 12.4%, χ 2 =7.09, P =0.008) were lower, but hearing loss (11.8% vs. 7.8%, χ 2 =27.36, P <0.001) and sleep disorders (18.5% vs. 15.2%, χ 2 =11.13, P =0.001) were higher in the older group than in the young and middle-aged group. The time from the appearance of dizziness to diagnosis was commonly longer in the older patient group than the other group (55.0% vs. 38.5%, χ 2 =55.95, P <0.001). Conclusions: Older patients with BPPV have more atypical symptoms and complex concomitant symptoms than young and middle-aged patients. For older patients with dizziness, positional testing is needed to confirm the possibility of BPPV even if the clinical symptoms are atypical.

This research study investigates the extent of heavy metal pollution and pollution trends in agricultural soil in mining areas during different time periods. A total of 125 soil samples were collected from two mining areas in China, the Chengchao iron mine and Tonglushan ancient copper mine. The samples were analyzed for various potentially toxic elements (PTEs). The index of geoaccumulation (Igeo), pollution index (Pi), potential ecological risk index (Eri), and hazard index (HI) were calculated to evaluate the pollution status of PTEs in the farmland around the two mining areas. The sources of PTEs were inferred by pollution distribution, and the pollution conditions of the two mining areas were compared. The results showed that the pollution of ancient copper mines was relatively severe. The main pollution elements were Cu, Cd, and As, and their average Pi values were 3.76, 4.12, and 1.84, respectively. These PTEs mainly came from mining and transportation. There are no particularly polluted elements in the Chengchao iron mine and the average Pi of all PTEs were classified as light pollution and had a wide range of sources. The findings suggest that the ancient copper mine, due to outdated mining techniques and insufficient mine restoration efforts, resulted in the spread and accumulation of PTEs in the soil over an extended period, making the farmland soil around the ancient copper mine more polluted compared to the Chengchao iron mine. In the two mining areas, there is no risk of cancer for adults and children. However, the RI values of Cr in adults and children are higher than 10 -4 , which indicates that the carcinogenic risk of Cr in these soils is very high. The non-carcinogenic effects of PTEs on the human body in the soil of ancient copper mine are also higher than that of the Chengchao iron mine.

Programmed cell death ligand 1 (PD-L1) is an immune checkpoint protein frequently expressed in human cancers that contributes to immune evasion through its binding to PD-1 on activated T cells. Unveiling the mechanisms underlying PD-L1 expression is essential for understanding the impact of the immunosuppressive microenvironment and is also crucial for the purpose of reboosting antitumor immunity. However, how PD-L1 is regulated, particularly at translational levels, remains largely unknown. Here, we discovered that a long noncoding RNA (lncRNA), HIF-1α inhibitor at translation level (HITT), was transactivated by E2F transcription factor 1 (E2F1) under IFN-γ stimulation. It coordinated with regulator of G protein signaling 2 (RGS2) in binding to the 5' UTR of PD-L1, resulting in reduced PD-L1 translation. HITT expression enhanced T cell-mediated cytotoxicity both in vitro and in vivo in a PD-L1-dependent manner. The clinical correlation between HITT/PD-L1 and RGS2/PD-L1 expression was also detected in breast cancer tissues. Together, these findings demonstrate the role of HITT in antitumor T cell immunity, highlighting activation of HITT as a potential therapeutic strategy for enhancing cancer immunotherapy.

With less than one percent of systemically injected nanoparticles accumulating in tumors, several novel approaches have been spurred to direct and release the therapy in or near tumors. One such approach depends on the acidic pH of the extracellular matrix and endosomes of the tumor. With an average pH of 6.8, the extracellular tumor matrix provides a gradient for pH-responsive particles to accumulate, enabling greater specificity. Upon uptake by tumor cells, nanoparticles are further exposed to lower pHs, reaching a pH of 5 in late endosomes. Based on these two acidic environments in the tumor, various pH-dependent targeting strategies have been employed to release chemotherapy or the combination of chemotherapy and nucleic acids from macromolecules such as the keratin protein or polymeric nanoparticles. We will review these release strategies, including pH-sensitive linkages between the carrier and hydrophobic chemotherapy agent, the protonation and disruption of polymeric nanoparticles, an amalgam of these first two approaches, and the release of polymers shielding drug-loaded nanoparticles. While several pH-sensitive strategies have demonstrated marked antitumor efficacy in preclinical trials, many studies are early in their development with several obstacles that may limit their clinical use.

Background: New strategies are needed to improve the treatment of patients with breast cancer (BC). Oncolytic virotherapy is a promising new tool for cancer treatment but still has a limited overall durable antitumor response. A novel replicable recombinant oncolytic herpes simplex virus type 1 called VG161 has been developed and has demonstrated antitumor effects in several cancers. Here, we explored the efficacy and the antitumor immune response of VG161 cotreatment with paclitaxel (PTX) which as a novel oncolytic viral immunotherapy for BC., Methods: The antitumor effect of VG161 and PTX was confirmed in a BC xenograft mouse model. The immunostimulatory pathways were tested by RNA-seq and the remodeling of tumor microenvironment was detected by Flow cytometry analysis or Immunohistochemistry. Pulmonary lesions were analyzed by the EMT6-Luc BC model., Results: In this report, we demonstrate that VG161 can significantly represses BC growth and elicit a robust antitumor immune response in a mouse model. The effect is amplified when combined with PTX treatment. The antitumor effect is associated with the infiltration of lymphoid cells, including CD4 + T cells, CD8 + T cells, and NK cells (expressing TNF and IFN-γ), and myeloid cells, including macrophages, myeloid-derived suppressor cells, and dendritic cell cells. Additionally, VG161 cotreatment with PTX showed a significant reduction in BC lung metastasis, which may result from the enhanced CD4 + and CD8 + T cell-mediated responses., Conclusions: The combination of PTX and VG161 is effective for repressing BC growth by inducing proinflammatory changes in the tumor microenvironment and reducing BC pulmonary metastasis. These data will provide a new strategy and valuable insight for oncolytic virus therapy applications in primary solid or metastatic BC tumors., (© 2023 Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Objective: Anxiety and depression in patients with systemic lupus erythematosus (SLE) complicate clinical treatment and can seriously affect prognosis. The present study aims to investigate the effects of the anti-ribosomal P protein antibody (anti-RibP) in the peripheral blood and insomnia on the severity of anxiety and depression in case of SLE. The study compared both the results of the investigation on the objective perceptions of physicians concerning mood changes in patients with SLE and the results of self-rating scales that were completed by the enrolled patients. The conclusion of the comparation is used to determine the probability of the accurate detection of anxiety and depression by physicians. The study aims to assist in the early detection in clinical practice of abnormal emotions in patients with SLE and to summarize common clinical interventions for anxiety and depression., Method: The relationship between anxiety and depression was evaluated by the Zung self-rating anxiety/depression scale (SAS/SDS). Basic information (e.g., blood type, smoking history, drinking history, educational background, duration of illness), the insomnia severity index (ISI) results, and anti-RibP in the peripheral blood, were investigated in 107 patients with SLE in northeastern China to further analyze the correlation between the severity of depression and anti-RibP, together with the consistency between results of the questionnaire for physicians and the self-rating scale for patients., Results: Gender, smoking history, drinking history, educational background, and duration of illness were correlated with the SAS/SDS scores (P < 0.05). Family history had a significant effect on the SAS score (P = 0.031), while the SDS score was significantly correlated with blood type (P = 0.021). The ISI score was significantly and positively correlated with the SAS/SDS score (P < 0.001). The titer of anti-RibP showed a correlation with the SDS score (P < 0.05) but not with the SAS score (P = 0.198). The titer of anti-RibP was significantly higher in patients with major depression compared with those with no depression, patients with mild depression, and those with moderate depression (P < 0.001)., Conclusion: Anxiety and depression in patients with SLE were correlated with sleeping, educational background, blood type, smoking history, and alcohol consumption. Although anti-RibP was not significantly correlated with anxiety, it indicated a significant correlation with major depression. Clinicians were more accurate in assessing anxiety compared with depression., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Background: Evaluation of the therapeutic effects of cerclage on preterm birth (PTB) caused by cervical incompetence remains challenging. The vaginal microbiome is associated with preterm births. Thus, this study aimed to analyse the vaginal microbiota of patients with cervical incompetence, explore the relationship between the composition of the vaginal microbiota before cervical cerclage and at term delivery, and assess the effect of cervical cerclage on the vaginal microbiota., Methods: Patients (n = 30) underwent cerclage performed by the same surgical team. Vaginal swabs were obtained pre-surgery and seven days post-surgery. A gestational age-matched cohort of healthy pregnant women (n = 20) (no particular abnormality during pregnancy, delivery at term) was used as the control group and sampled during a comparable pregnancy. All collected vaginal swabs were analysed by 16S rRNA gene sequencing., Results: When comparing the healthy control and cervical cerclage groups, the enriched microorganism in the healthy controls was G. Scardovia , and the enriched microorganism of the cerclage was G. Streptococcus . α diversity was significantly increased in patients who received cerclage with preterm delivery compared with those with full-term delivery, and the enriched microorganism was F. Enterococcus . A comparison before and after nonemergency cerclage suggested that the enriched microorganisms were G. Lactobacillus and F. Lactobacillaceae before surgery. After nonemergency cerclage, the enriched microorganisms were F. Enterobacteriaceae and C. Gammaproteobacteria . Vaginal microbiota diversity significantly increased, and the proportion of women with Lactobacillus spp.-depleted microbiomes increased after emergency cerclage. Significant differences in β diversity were found between the groups. Before the emergency cerclage, the enriched microorganisms were G. Lactobacillus , O. Alteromonadales , and P. Firmicutes . After emergency cerclage, the enriched microorganisms were P. Actinobacteria , C. Actinobacteria , P. Proteobacteria , F. Bifidobacteriaceae , O. Bifidobacteriales , G. Gardnerella , and G. Veillonella ., Conclusion: Cerclage (particularly emergency cerclage) may alter the vaginal microbiota by increasing microbiota diversity, decreasing vaginal Lactobacillus abundance, and increasing the abundance of pathogenic bacteria that are not conducive to pregnancy maintenance, thereby affecting surgical efficacy. Therefore, the role of the vaginal microbiome should be considered when developing treatment strategies for pregnant women with cervical incompetence., Clinical Trial Registration: https://www.chictr.org.cn, identifier ChiCTR2100046305., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xiao, Huang, Yu, Ni, Lu, Wu, Leng, Yang, Ni, Xie and Zhang.)

Post-stroke depression (PSD) is a common complication of stroke that can damage patients' brains. More and more studies have been conducted on PSD in recent years, but the exact mechanism is still not understood. Currently, animal models provide an alternative approach to better understand the pathophysiology of PSD and may also pave the way for the discovery of new treatments for depression. This study investigated the therapeutic effect and mechanism of aloe-emodin (AE) on PSD rats. Previous studies have shown that AE positively affects PSD in rats by improving depression, increasing their activities and curiosities, enhancing the number of neurons, and ameliorating damage to brain tissue. Meanwhile, AE could up-regulate the expression of brain-derived neurotrophic factor (BDNF) and neurotrophic 3 (NTF3), but it could also down-regulate the expression of aquaporins (AQP3, AQP4, and AQP5), glial fibrillary acidic protein (GFAP), and transient receptor potential vanilloid 4 (TRPV4), which is helpful in maintaining homeostasis and alleviating encephaledema. AE may be a prospective solution in the future for the treatment of PSD patients.

Efficient electrode materials are essential to convert salinity gradient energy into oxidative degradation energy and electrical energy by reverse electrodialysis reactor (REDR). In this context, comparative experiments of REDR using different anodes (Ti/IrO 2 -RuO 2 , Ti/PbO 2 and Ti/Ti 4 O 7 ) were conducted. The effects of output current and electrode rinse solution (ERS) flowrate on mineralization efficiency and energy output were discussed. Results demonstrated that the COD removal rate(η COD ) rose almost linearly with output current and ERS flowrate when using Ti/Ti 4 O 7 anode, but excessive operating conditions caused a slow increase or even decrease of η COD when using Ti/IrO 2 -RuO 2 or Ti/PbO 2 anodes. The order of electrode system potential loss (E ele ) for the three anodes was Ti/Ti 4 O 7 > Ti/PbO 2 > Ti/IrO 2 -RuO 2 . High E ele was beneficial to η COD but had a negative effect on the net output power (P net ) of REDR. Regardless of the applied anodes, increasing the current and decreasing the ERS flowrate was detrimental to P net due to higher E ele . Based on these findings, four energy efficiency parameters were defined to evaluate energy recovery from multiple perspectives by linking energy output with mineralization capacity. They were electrode efficiency (η ele ), energy efficiency (EE), general current efficiency (GCE) and energy consumption (EC), respectively. Results showed that REDR with Ti/Ti 4 O 7 anodes and suitable operating conditions achieved the optimal energy indicators and mineralization efficiency, which provided an efficient and economical option for wastewater treatment and energy recovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Lung cancer is a leading cause of cancer deaths and early diagnosis can significantly improve outcomes. Pathogenic bacteria have been shown to play a role in tumorigenesis and its analysis provides a new approach for cancer diagnosis. To evaluate the potential of bacteria as plasma biomarkers for early lung cancer detection, we analyzed eight lung-cancer-related bacterial genera in 58 lung cancer patients and 58 controls using ddPCR. Our results showed that five genera had higher DNA abundance in lung tumor tissues compared with normal tissues. Three of these genera ( Selenomonas , Streptococcus , and Veillonella ) displayed consistent changes in plasma, with higher DNA abundance in lung cancer patients compared with controls. When used as a panel, these three bacterial genera had a sensitivity of 75% and specificity of 78% for lung cancer detection, regardless of stage or histology. The performance of this biomarker panel was confirmed in an independent cohort of 93 lung cancer cases and 93 controls. Thus, circulating bacterial DNA has the potential to be used as plasma biomarkers for early lung cancer detection.

Berberine (BBR), which is a compound derived from the Chinese medicinal plant Coptis chinensis, promotes weight loss, but the molecular mechanisms are not well understood. Here, we show that BBR increases the serum level of growth differentiation factor 15 (GDF15), which is a stress response cytokine that can reduce food intake and lower body weight in diet-induced obese (DIO) mice. The body weight and food intake of DIO mice were decreased after BBR treatment, and the weight change was negatively correlated with the serum GDF15 level. Further studies show that BBR induced GDF15 mRNA expression and secretion in the brown adipose tissue (BAT) of DIO mice and primary mouse brown adipocytes. In addition, we found that BBR upregulates GDF15 mRNA expression and secretion by activating the integrated stress response (ISR) in primary mouse brown adipocytes. Overall, our findings show that BBR lowers body weight by inducing GDF15 secretion via the activation of the ISR in BAT., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)