Long-Term Disinfection in Operating Rooms Affects Skin Microbiota and Metabolites of Medical Personnel.

INTRODUCTION: Disinfectants play a critical role in reducing healthcare-associated infections by eliminating microorganisms on surfaces. However, prolonged use of disinfectants may adversely affect the skin microflora, essential for skin health and infection prevention. This study investigates the impact of disinfection on the skin microbiota and metabolites of medical personnel in operating rooms, aiming to provide a scientific foundation for safeguarding their skin health. METHODS: We conducted 16S sequencing and metabolomic analysis to assess the effects of disinfection on the skin microbiota and metabolites of medical personnel. Samples were collected from operating room personnel after disinfectant exposure to identify changes in microbial communities and metabolite profiles. RESULTS: Our analysis revealed that prolonged use of disinfectants led to alterations in skin microbial communities and microbial metabolites. These alterations included the production of harmful metabolites that could potentially promote skin infections and other health issues among medical personnel. CONCLUSION: The findings underscore the importance of minimizing disruptions to skin microbiota and metabolites caused by long-term disinfectant use to preserve the overall health of medical personnel. This study provides valuable insights into the relationship between disinfectant use, skin microbiota, and metabolites, highlighting the necessity for further research in this area.

Initiating PeriCBD to probe perinatal influences on neurodevelopment during 3-10 years in China.

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.

The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment.

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.

Three-Component Construction of Mesoporous Metal-Organic Frameworks and Their Incorporation into Solid Polymer Electrolytes for Li-Ion Conduction.

Solid electrolytes with high ionic conductivity and satisfactory electrochemical stability are essential for the development of solid-state batteries. However, current strategies, including polymer (and polymer-based composite) electrolytes, still face challenges in meeting the bar set by real operations. We seek to improve the Li-ion conduction of the electrolytes by incorporating mesoporous metal-organic frameworks (MOFs) into the polymer matrix. Specifically, MOFs with pores larger than 3.0 nm are constructed by three-component reactions that involve the construction of both coordinative and dynamic imine linkages. The MOFs allow polymer penetration and amorphization and efficient lithium salt dissociation in the confined channels. Numerous metal sites and organic functionalities in the MOF backbone further assist the ion migration by providing strong interactions with the fluorinated polymer and the Li+. Remarkable ionic conductivity (0.95 mS cm-1) and a large lithium transference number (0.64) are achieved. Overall, the study fully utilizes both the MOF structural units with atomic precision and the encompassed space at the mesoscale for solid-state electrolyte development.

MicroRNAs as Key Regulators in RA and SLE: Insights into Biological Functions.

MicroRNAs (miRNAs) are non-coding RNA molecules that bind to mRNAs to regulate gene expression. Since changes in miRNA expression levels have been found in a variety of autoimmune illnesses, miRNAs are important in autoimmune diseases. MiRNAs serve not only as pathogenic factors and biomarkers for autoimmune diseases but also as important targets for disease therapeutics. Although miRNA-based treatments are still in the research stage, in-depth investigations into the biological functions of miRNAs have significantly enhanced our understanding of their mechanisms in autoimmune diseases. The purpose of this review is to summarize the biological functions of miRNAs, their roles in rheumatoid arthritis and systemic lupus erythematosus, therapeutic strategies, and challenges.

KRAS depletion suppresses ferroptosis and affects Hippo pathway in cataract.

Cataract, a painless and progressive disorder is manifested as the opacification of the lens that represents the most significant cause of blindness worldwide. The objective of this study is to unveil the function of Kirsten rat sarcoma (KRAS) and potential action mechanisms against cataract. The ferroptosis-associated differentially expressed genes (DEGs) and pivot genes were extracted through the comprehensive bioinformatics methods. Erastin was applied for inducing ferroptosis in hydrogen peroxide (H2O2)-treated SRA01/04 cells, and validated by detecting content of intracellular iron, glutathione (GSH), malondialdehyde (MDA). Additionally, the effects of KRAS deficiency on ferroptosis were determined by functional assays. The proteins expression related to ferroptosis and Hippo pathway were determined by Western blotting. A total of 73 ferroptosis-related DEGs were discovered, and 6 critical core genes were confirmed upregulation in cataract cell model. The H2O2-treated SRA01/04 cells exhibited decrease of cell viability and proliferation, iron accumulation, MDA increase, GSH consumption, rise of COX2 and decline of GPX4, with further aggravated under erastin treatment, while the phenomena were improved by KRAS knockdown. Additionally, KRAS deficiency was involved in the Hippo signalling pathway activation. Downregulation of KRAS might restrain ferroptosis and affect Hippo pathway in cataract.

Cornuside ameliorates cognitive impairments via RAGE/TXNIP/NF-κB signaling in Aß1-42 induced Alzheimer's disease mice.

Cornuside has been discovered to improve learning and memory in AD mice, however, its underlying mechanism was not fully understood. In the present study, we established an AD mice model by intracerebroventricular injection of Aß1-42, which were treated with cornuside (3, 10, 30 mg/kg) for 2 weeks. Cornuside significantly ameliorated cognitive function of AD mice in series of behavioral tests, including Morris water maze test, nest building test, novel object recognition test and step-down test. Additionally, cornuside could attenuate neuronal injury, and promote cholinergic synaptic transmission by restoring the level of acetylcholine (ACh) via inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as facilitating choline acetyltransferase (ChAT). Furthermore, cornuside inhibited oxidative stress levels amplified as decreased malondialdehyde (MDA), by inhibiting TXNIP expression, improving total anti-oxidative capacity (TAOC), raising activities of superoxide dismutase (SOD) and catalase (CAT). Cornuside also reduced the activation of microglia and astrocytes, decreased the level of proinflammatory factors TNF-α, IL-6, IL-1ß, iNOS and COX2 via interfering RAGE-mediated IKK-IκB-NF-κB phosphorylation. Similar anti-oxidative and anti-inflammatory effects were also found in LPS-stimulated BV2 cells via hampering RAGE-mediated TXNIP activation and NF-κB nuclear translocation. Virtual docking revealed that cornuside could interact with the active pocket of RAGE V domain directly. In conclusion, cornuside could bind to the RAGE directly impeding the interaction of Aß and RAGE, and cut down the expression of TXNIP inhibiting ROS production and oxidative stress, as well as hamper NF-κB p65 mediated the inflammation.

Whispers in the Neck: Unmasking Cystic Metastases From Hidden Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma is the most common thyroid malignancy and it frequently causes lymph node metastases. Approximately 50% of patients with papillary thyroid carcinoma have cervical lymph node metastases at the time of their initial presentation. Here we report a case of a young female who presented with a benign-appearing cystic neck mass, which was revealed to be metastases from occult papillary thyroid carcinoma. Completion thyroidectomy and neck dissection were done after the diagnosis of papillary thyroid carcinoma.

Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

Linkage-Mediated Electronic Structure Modulation in Multicomponent Covalent Organic Frameworks for Dramatically Promoted Photocatalytic Hydrogen Evolution.

Linkage chemistry is an essential aspect to covalent organic framework (COF) applications; it is highly desirable to precisely modulate electronic structure mediated directly by linkage for efficient COF-based photocatalytic hydrogen evolution, which however, remains substantially challenging. Herein, as a proof of concept, a collection of robust multicomponent pyrene-based COFs with abundant donor-acceptor (D-A) interactions has been judiciously designed and synthesized through molecularly engineering linkage for photogeneration of hydrogen. Controlled locking and conversion of linkage critically contribute to continuously regulating COFs' electronic structures further to optimize photocatalytic activities. Remarkably, the well-modulated optoelectronic properties turn on the average hydrogen evolution rate from zero to 15.67 mmol g-1 h-1 by the protonated quinoline-linked COF decorated with the trifluoromethyl group (TT-PQCOF-CF3). Using diversified spectroscopy and theoretical calculations, we show that multiple modifications toward linkage synergistically lead to the redistribution of charge on COFs with extended π-conjugation and reinforced D-A effect, making TT-PQCOF-CF3 a promising material with significantly boosted carrier separation and migration. This study provides important guidance for the design of high-performance COF photocatalysts based on the strategy of linkage-mediated electronic structure modulation in COFs.

mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models.

Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4-binding site of the HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle-encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as a soluble self-assembling nanoparticle in mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation without exclusionary competition. Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.

Comprehensive analysis of metal(loid)s and associated metal(loid) resistance genes in atmospheric particulate matter.

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.

An Investigation of the Anisotropic Mechanical Properties of Additive-Manufactured 316L SS with SLM.

Selective laser melting (SLM) forms specimens that often exhibit anisotropic mechanical properties. Most existing research only explains that the mechanical properties of specimens perpendicular to the build direction are superior to those parallel to the build direction. In this paper, the mechanical properties of SLM 316L SS specimens with different surfaces and different directions are compared. Finally, it was found that the mechanical properties of specimens on Face 3 are stronger than those on Face 1 and Face 2, while the mechanical properties of specimens on Face 1 and Face 2 are similar. For specimens in different directions on the same surface, the mechanical properties of Face 1 and Face 2 exhibit clear anisotropy, while the mechanical properties of Face 3 tend to be isotropic. In this paper, the EBSD technique was used to analyze the specimens. It was found that the anisotropy of the mechanical properties of Face 1 and Face 2 are attributed to the presence of texture and columnar crystals in the sample. This paper can provide accurate and reliable material performance data for the practical application of SLM 316L SS, thereby guiding the optimization of engineering design and manufacturing processes.

Study of Anisotropic Behavior in Sheet Metal Forming.

Since sheet metal exhibits significant anisotropy in processing and forming, which has a significant impact on its performance during processing, forming, and use, we explore the anisotropic behavior of materials in the forming process of sheet metal. The ability of the Yld2000-2d criterion to describe anisotropic behavior is analyzed, and its accuracy for characterization of the anisotropic behavior of metal plates is improved, based on which anisotropic behavior is predicted in three-dimensional space. Theoretical and experimental results on the anisotropy of sheet metal are compared, and two materials, 5754O aluminum alloy and DP980 steel plate, are tested and analyzed, and the anisotropic behaviors, such as three-point bending and cylindrical deep-drawing, are well predicted.

The association between humidex and tuberculosis: a two-stage modelling nationwide study in China.

BACKGROUND: Under a changing climate, the joint effects of temperature and relative humidity on tuberculosis (TB) are poorly understood. To address this research gap, we conducted a time-series study to explore the joint effects of temperature and relative humidity on TB incidence in China, considering potential modifiers. METHODS: Weekly data on TB cases and meteorological factors in 22 cities across mainland China between 2011 and 2020 were collected. The proxy indicator for the combined exposure levels of temperature and relative humidity, Humidex, was calculated. First, a quasi-Poisson regression with the distributed lag non-linear model (DLNM) was constructed to examine the city-specific associations between humidex and TB incidence. Second, a multivariate meta-regression model was used to pool the city-specific effect estimates, and to explore the potential effect modifiers. RESULTS: A total of 849,676 TB cases occurred in the 22 cities between 2011 and 2020. Overall, a conspicuous J-shaped relationship between humidex and TB incidence was discerned. Specifically, a decrease in humidex was positively correlated with an increased risk of TB incidence, with a maximum relative risk (RR) of 1.40 (95% CI: 1.11-1.76). The elevated RR of TB incidence associated with low humidex (5th humidex) appeared on week 3 and could persist until week 13, with a peak at approximately week 5 (RR: 1.03, 95% CI: 1.01-1.05). The effects of low humidex on TB incidence vary by Natural Growth Rate (NGR) levels. CONCLUSION: A J-shaped exposure-response association existed between humidex and TB incidence in China. Humidex may act as a better predictor to forecast TB incidence compared to temperature and relative humidity alone, especially in regions with higher NGRs.

Neoadjuvant immunotherapy improves outcomes for resectable gastroesophageal junction cancer: A systematic review and meta-analysis.

BACKGROUND: In recent years, neoadjuvant immunotherapy (NAIT) has developed rapidly in patients with gastroesophageal junction cancer (GEJC). The suggested neoadjuvant treatment regimens for patients with GEJC may vary in light of the efficacy and safety results. METHODS: A search of the Cochrane Library, PubMed, Embase, and Web of Science was completed to locate studies examining the safety and effectiveness of NAIT for resectable GEJC. We analyzed the effect sizes (ES) and 95% confidence intervals (CI) in addition to subgroups and heterogeneity. Meta-analyses were performed using Stata BE17 software. RESULTS: For these meta-analyses, 753 patients were chosen from 21 studies. The effectiveness of NAIT was assessed using the pathological complete response (pCR), major pathological response (MPR), and nodal downstage to ypN0 rate. The MPR, pCR, and nodal downstage to ypN0 rate values in NAIT were noticeably higher (MPR: ES = 0.45; 95% CI: 0.36-0.54; pCR: ES = 0.26; 95% CI: 0.21-0.32; nodal downstage to ypN0 rate: ES = 0.60; 95% CI: 0.48-0.72) than those of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) (MPR < 30%; pCR: ES = 3%-17%; nodal downstage to ypN0 rate: ES = 21%-29%). Safety was assessed using the treatment-related adverse events (trAEs) incidence rate, surgical delay rate, surgical complications incidence rate, and surgical resection rate. In conclusion, the incidence of trAEs, incidence of surgical complications, and surgical delay rate had ES values of 0.66, 0.48, and 0.09, respectively. These rates were comparable to those from nCT or nCRT (95% CI: 0.60-0.70; 0.15-0.51; and 0, respectively). The reported resection rates of 85%-95% with nCT or nCRT were comparable to the mean surgical resection rate of 90%. CONCLUSION: NAIT is an effective treatment for resectable GEJC; additionally, the level of NAIT toxicity is acceptable. The long-term effects of NAIT require further study.

Topology Prediction of Gas-Separating Metal-Organic Frameworks with Low Symmetry Vertices.

Topology serves as a blueprint for the construction of reticular structures such as metal-organic frameworks, especially for those based on building blocks with highly symmetrical shapes. However, it remains a challenge to predict the topology of the frameworks from less symmetrical units, because their corresponding vertex figures are largely deformed from the perfect geometries with no "default" net embedding. Furthermore, vertices involving flexible units may have multiple shape choices, and the competition among their designated topologies makes the structure prediction in large uncertainty. Herein, the deformation index is proposed to characterize the symmetry loss of the vertex figure by comparing it with its ideal geometry. The mathematical index is employed to predict the shapes of two in situ formed Co-based metalloligands (pseudo-tetrahedron and pseudo-square), which further dictate the framework topology (flu and scu) when they are joined with the [Zr6O8]-based cuboid units. The two frameworks with very similar constituents provide an ideal platform to investigate how the pore shapes and interconnectivity influence the gas separation. The net with cylindrical channels outperforms the other with discreate cages in C3H8/C2H6/CH4 separation, benefiting from the facile accessibility of its interaction sites to the guests imposed by the specific framework topology.

Empirical Study on Hospitalist System: A Value Creation Perspective.

This study investigates the impact of hospitalist system awareness, motivation, and behavior on value creation within the healthcare context of Taiwan. As population aging and the prevalence of chronic diseases continue to rise, accompanied by increased medical resource consumption, the Taiwan Ministry of Health and Welfare introduced the hospitalist system. Despite its implementation, the number of participating hospitals remains low. Using a questionnaire survey conducted from October 2021 to March 2022, data were collected from medical teams involved in the hospitalist system. A total of 324 valid questionnaires were analyzed. The results reveal that hospitalist awareness positively influences participation motivation (ß = 0.846, p < 0.001), which subsequently impacts participation behavior positively (ß = 0.888, p < 0.001). Moreover, participation behavior significantly contributes to value creation (ß = 0.869, p < 0.001), along with the direct effect of awareness (ß = 0.782, p < 0.001) on value creation. In conclusion, the successful promotion and implementation of the hospitalist system rely heavily on the support and active participation of medical staff. Effective interactions and comprehensive information dissemination are essential for maximizing healthcare value creation.