Natural ventilation cooling effectiveness classification for building design addressing climate characteristics.

The evaluation of natural ventilation potential for effective sustainable options and innovative green building design strategies is of great interest to architects, researchers and governments. From a retrospective review, we found that the potential evaluation of natural ventilation (NV) cooling effectiveness in the same category based on similar meteorological uncertainty, research objectives and objects showed significant differences. Uncertainties added and uncertainty propagation (both model form uncertainties and parameter uncertainties) could result in large discrepancies between simulation outcomes and real scenarios, especially in the design performance modeling (DPM) phase. In this conceptual design stage, a few parameters are available and therefore decisive. It is necessary to review and identify the key performance indicators and explore the extent to which deviations are caused by inconsistencies or biases in model information. As a basis for more concrete research, we propose statistical tests based on quantitative evaluations to explore the rule of natural ventilation potential volatility and identify whether there is a significant potential improvement resulting from the critical parameter enhancement with the optimal relationship. The showcase is applied in China, where there has been a significant amount of criticism regarding the current building climate zoning due to the perceived coarseness of the system and where there has been an active exploration into the possibility of redefining building climate zoning with a view toward improving its accuracy and effectiveness.

Metabolic health and genetic predisposition in inflammatory bowel disease: Insights from a prospective cohort study.

BACKGROUND: Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic predisposition, and the risk of inflammatory bowel disease (IBD), and to explore the potential benefits of maintaining ideal metabolic status for individuals with a predetermined genetic risk of IBD. METHOD: This population-based prospective study included 385,820 unrelated European descent participants from the UK Biobank. Using multivariable Cox regression, we assessed the relationship of metabolic phenotypes with risk of IBD and its subtypes. We also developed a polygenic risk score to examine how metabolic health status interacted with genetic risk in relation to IBD risk. RESULTS: During the follow-up period of 4,328,895 person-years, 2,044 newly-diagnosed IBD cases were identified. Higher genetic risk and an increasing number of abnormal metabolic phenotypes were associated with elevated IBD risk (p-trend <0.001). Individuals with high genetic risk and poor metabolic health had a significantly higher risk of IBD (HR=4.56, 95 % CI=3.27-6.36) compared to those with low genetic risk and ideal metabolic health. These results remained consistent for IBD subtypes. Maintaining ideal metabolic status reduced IBD risk within each genetic risk category and jointly decreased subsequent risk by 40 % in high genetic risk individuals. CONCLUSION: Our study reveals a combined impact of poor metabolic health and genetic risk on IBD incidence. Those with low genetic risk and optimal metabolic health exhibit the lowest IBD risk, offering insights into potential management strategies for individuals at predefined genetic risk.

Genetic variation mining of the Chinese mitten crab (Eriocheir sinensis) based on transcriptome data from public databases.

At present, public databases house an extensive repository of transcriptome data, with the volume continuing to grow at an accelerated pace. Utilizing these data effectively is a shared interest within the scientific community. In this study, we introduced a novel strategy that harnesses SNPs and InDels identified from transcriptome data, combined with sample metadata from databases, to effectively screen for molecular markers correlated with traits. We utilized 228 transcriptome datasets of Eriocheir sinensis from the NCBI database and employed the Genome Analysis Toolkit software to identify 96 388 SNPs and 20 645 InDels. Employing the genome-wide association study analysis, in conjunction with the gender information from databases, we identified 3456 sex-biased SNPs and 639 sex-biased InDels. The KOG and KEGG annotations of the sex-biased SNPs and InDels revealed that these genes were primarily involved in the metabolic processes of E. sinensis. Combined with SnpEff annotation and PCR experimental validation, a highly sex-biased SNP located in the Kelch domain containing 4 (Klhdc4) gene, CHR67-6415071, was found to alter the splicing sites of Klhdc4, generating two splice variants, Klhdc4_a and Klhdc4_b. Additionally, Klhdc4 exhibited robust expression across the ovaries, testes, and accessory glands. The sex-biased SNPs and InDels identified in this study are conducive to the development of unisexual cultivation methods for E. sinensis, and the alternative splicing event caused by the sex-biased SNP in Klhdc4 may serve as a potential mechanism for sex regulation in E. sinensis. The analysis strategy employed in this study represents a new direction for the rational exploitation and utilization of transcriptome data in public databases.

In Vitro Ciclopirox Glucuronidation in Liver Microsomes from Humans and Various Experimental Animals.

BACKGROUND AND OBJECTIVE: Ciclopirox is a widely used antifungal drug, redisposition of which has drawn increasing attentions due to multiple promising activities. The drug undergoes extensive glucuronidation, which acts as a major obstacle in the ongoing novel application and still remains poorly understood. The current study aims to phenotype ciclopirox glucuronidation pathway and as well to decipher the related species differences. METHODS: Ciclopirox glucuronidation was investigated in liver microsomes from humans (HLM) and various experimental animals. Assays with recombinant uridine diphosphate glucuronosyltransferases (UGTs), enzyme kinetic analyses and selective inhibitors were used to determine the role of individual UGTs in ciclopirox glucuronidation. RESULTS: HLM is highly active in ciclopirox glucuronidation with Michaelis-Menten constant (Km), maximum velocity (Vmax), and intrinsic clearance (CLint) values of 139 µM, 7.89 nmol/min/mg, and 56 µL/min/mg, respectively. UGT1A9 displays by far the highest activity, whereas several other isoforms (UGT1A6, UGT1A7, and UGT1A8) catalyze formation of traced glucuronides. Further kinetic analysis demonstrates that UGT1A9 has a closed Km value (167 µM) to HLM. UGT1A9 selective inhibitor (magnolol) can potently inhibit ciclopirox glucuronidation in HLM with the IC50 value of 0.12 µM. The reaction displays remarkable differences across liver microsomes from mice, rats, cynomolgus monkey, minipig, and beagle dog, with the CLint values in the range of 26-369 µL/min/mg. In addition, ciclopirox glucuronidation activities of experimental animals' liver microsomes were less sensitive to magnolol than that of HLM. CONCLUSIONS: Ciclopirox glucuronidation displays remarkable species differences with UGT1A9 as a dominant contributor in humans. It is suggested that the pharmacological or toxicological effects of ciclopirox may be UGT1A9 and species dependent.

Psychosocial Factors Associated With Long-Term Cognitive Impairment Among COVID-19 Survivors: A Cross-Sectional Study.

ABSTRACT: COVID-19 survivors complained of the experience of cognitive impairments, which also called "brain fog" even recovered. The study aimed to describe long-term cognitive change and determine psychosocial factors in COVID-19 survivors. A cross-sectional study was recruited 285 participants from February 2020 to April 2020 in 17 hospitals in Sichuan Province. Cognitive function, variables indicative of the virus infection itself, and psychosocial variables were collected by telephone interview. Univariate logistic regression and Lasso logistic regression models were used for variable selection which plugged into a multiple logistics model. Overall prevalence of moderate or severe cognitive impairment was 6.3%. Logistic regression showed that sex, religion, smoking status, occupation, self-perceived severity of illness, sleep quality, perceived mental distress after COVID-19, perceived discrimination from relatives and friends, and suffered abuse were associated with cognitive impairment. The long-term consequences of cognitive function are related to multiple domains, in which psychosocial factors should be taken into consideration.

Integrating Multiple Bacterial Phenotypes and Bayesian Network for Analyzing Health Risks of Pathogens in Plastisphere.

Plastic pollution represents a critical threat to soil ecosystems and even humans, as plastics can serve as a habitat for breeding and refuging pathogenic microorganisms against stresses. However, evaluating the health risk of plastispheres is difficult due to the lack of risk factors and quantification model. Here, DNA sequencing, single-cell Raman-D2O labeling, and transformation assay were used to quantify key risk factors of plastisphere, including pathogen abundance, phenotypic resistance to various stresses (antibiotic and pesticide), and ability to acquire antibiotic resistance genes. A Bayesian network model was newly introduced to integrate these three factors and infer their causal relationships. Using this model, the risk of pathogen in the plastisphere is found to be nearly 3 magnitudes higher than that in free-living state. Furthermore, this model exhibits robustness for risk prediction, even in the absence of one factor. Our framework offers a novel and practical approach to assessing the health risk of plastispheres, contributing to the management of plastic-related threats to human health.

Expanding the targeting scope of CRISPR/Cas9-mediated genome editing by Cas9 variants in Brassica.

CRISPR/Cas9, presently the most widely used genome editing technology, has provided great potential for functional studies and plant breeding. However, the strict requirement for a protospacer adjacent motif (PAM) has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is limited. Recently, the engineered variants Cas9-NG, SpG, and SpRY, which recognize non-canonical PAMs, have been successfully tested in plants (mainly in rice, a monocot). In this study, we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables, Chinese cabbage (Brassica rapa spp. pekinensis) and cabbage (Brassica oleracea var. capitata). Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs, while SpG outperformed Cas9-NG at NGC and NGT PAMs. SpRY achieved efficient editing at almost all PAMs (NRN > NYN), albeit with some self-targeting activity at transfer (T)-DNA sequences. And SpRY-induced mutants were detected in cabbage plants in a PAM-less fashion. Moreover, an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical PAMs. Together, the toolboxes developed here induced successful genome editing in Chinese cabbage and cabbage. Our work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00155-7.

Technical considerations and strategies for generating and optimizing humanized mouse tumor models in immuno-oncology research.

The field of cancer immunotherapy has experienced significant progress, resulting in the emergence of numerous biological drug candidates requiring in vivo efficacy testing and a better understanding of their mechanism of action (MOA). Humanized immune system (HIS) models are valuable tools in this regard. However, there is a lack of systematic guidance on HIS modeling. To address this issue, the present study aimed to establish and optimize a variety of HIS models for immune-oncology (IO) study, including genetically engineered mouse models and HIS models with human immune components reconstituted in severely immunocompromised mice. The efficacy and utility of these models were tested with several marketed or investigational IO drugs according to their MOA, followed by immunophenotypic analysis and efficacy evaluation. The results of the present study demonstrated that the HIS models responded to various IO drugs as expected and that each model had unique niches, utilities and limitations. Researchers should carefully choose the appropriate models based on the MOA and the targeted immune cell populations of the investigational drug. The present study provides valuable methodologies and actionable technical guidance on designing, generating or utilizing appropriate HIS models to address specific questions in translational IO.

Salinity affects microbial function genes related to nutrient cycling in arid regions.

Introduction: Salinization damages soil system health and influences microbial communities structure and function. The response of microbial functions involved in the nutrient cycle to soil salinization is a valuable scientific question. However, our knowledge of the microbial metabolism functions in salinized soil and their response to salinity in arid desert environments is inadequate. Methods: Here, we applied metagenomics technology to investigate the response of microbial carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) cycling and the key genes to salinity, and discuss the effects of edaphic variables on microbial functions. Results: We found that carbon fixation dominated the carbon cycle. Nitrogen fixation, denitrification, assimilatory nitrate reduction (ANRA), and nitrogen degradation were commonly identified as the most abundant processes in the nitrogen cycle. Organic phosphorus dissolution and phosphorus absorption/transport were the most enriched P metabolic functions, while sulfur metabolism was dominated by assimilatory sulfate reduction (ASR), organic sulfur transformation, and linkages between inorganic and organic sulfur transformation. Increasing salinity inhibited carbon degradation, nitrogen fixation, nitrogen degradation, anammox, ANRA, phosphorus absorption and transport, and the majority of processes in sulfur metabolism. However, some of the metabolic pathway and key genes showed a positive response to salinization, such as carbon fixation (facA, pccA, korAB), denitrification (narG, nirK, norBC, nosZ), ANRA (nasA, nirA), and organic phosphorus dissolution processes (pstABCS, phnCD, ugpAB). High salinity reduced the network complexity in the soil communities. Even so, the saline microbial community presented highly cooperative interactions. The soil water content had significantly correlations with C metabolic genes. The SOC, N, and P contents were significantly correlated with C, N, P, and S network complexity and functional genes. AP, NH4+, and NO3- directly promote carbon fixation, denitrification, nitrogen degradation, organic P solubilization and mineralization, P uptake and transport, ASR, and organic sulfur transformation processes. Conclusion: Soil salinity in arid region inhibited multiple metabolic functions, but prompted the function of carbon fixation, denitrification, ANRA, and organic phosphorus dissolution. Soil salinity was the most important factor driving microbial functions, and nutrient availability also played important roles in regulating nutrient cycling.

Impaired embryo development potential associated with thyroid autoimmunity in euthyroid infertile women with diminished ovarian reserve.

Purpose: The aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR). Methods: This retrospective cohort study involved 1,172 euthyroid women aged 20-40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study's subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (≥7) and high FR (>60%). Results: For the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI (P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group (P < 0.001 for both). Furthermore, negative associations were observed between log10(TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos (P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos (P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007]. Conclusions: TAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR.

Nordihydroguaiaretic Acid-Cross-Linked Phenylboronic Acid-Functionalized Polyplex Micelles for Anti-angiogenic Gene Therapy of Orthotopic and Metastatic Tumors.

Polyplexes are required to be equipped with multiple functionalities to accomplish adequate structure stability and gene transfection efficacy for gene therapy. Herein, a 4-carboxy-3-fluorophenylboronic acid (FPBA)-functionalized block copolymer of PEG-b-PAsp(DET/FBA) and PAsp(DET/FBA) (abbreviated as PB and HB) was synthesized and applied for engineering functional polyplex micelles (PMs) through ionic complexation with pDNA followed by strategic cross-linking with nordihydroguaiaretic acid (NDGA) in respect to the potential linkage of polyphenol and FPBA moieties. In relation to polyplex micelles void of cross-linking, the engineered multifunctional polyplex micelles (PBHBN-PMs) were determined to possess improved structural tolerability against the exchange reaction with charged species. Besides, the FPBA/NDGA cross-linking appeared to be selectively cleaved in the acidic endosomal compartments but not the neutral milieu. Furthermore, the PBHB-PMs with the optimal FPBA/NDGA cross-linking degree were identified to possess appreciable cellular uptake and endosomal escape activities, eliciting a significantly high level of gene expression relative to P-PMs and PB-PMs. Eventually, in vivo antitumor therapy by our proposed multifunctional PMs appeared to be capable of facilitating expression of the antiangiogenic genomic payloads (sFlt-1 pDNA) via systemic administration. The enriched antiangiogenic sFlt-1 in the tumors could silence the activities of angiogenic cytokines for the inhibited neo-vasculature and the suppressed growth of orthotopic 4T1 tumors. Of note, the persistent expression of the antiangiogenic sFlt-1 is also presumed to migrate into the blood circulation, thereby accounting for an overall antiangiogenic environment in preventing the potential pulmonary metastasis. Hence, our elaborated multifaceted PMs inspired fascinating potential as an intriguing gene delivery system for the treatment of clinical solid tumors and metastasis.

Clinical application of dual-layer spectral CT multi-parameter feature to predict microvascular invasion in hepatocellular carcinoma.

OBJECTIVE: This study aimed to investigate the feasibility of using dual-layer spectral CT multi-parameter feature to predict microvascular invasion of hepatocellular carcinoma. METHODS: This retrospective study enrolled 50 HCC patients who underwent multiphase contrast-enhanced spectral CT studies preoperatively. Combined clinical data, radiological features with spectral CT quantitative parameter were constructed to predict MVI. ROC was applied to identify potential predictors of MVI. The CT values obtained by simulating the conventional CT scans with 70 keV images were compared with those obtained with 40 keV images. RESULTS: 50 hepatocellular carcinomas were detected with 30 lesions (Group A) with microvascular invasion and 20 (Group B) without. There were significant differences in AFP,tumer size, IC, NIC,slope and effective atomic number in AP and ICrr in VP between Group A ((1000(10.875,1000),4.360±0.3105, 1.7750 (1.5350,1.8825) mg/ml, 0.1785 (0.1621,0.2124), 2.0362±0.2108,8.0960±0.1043,0.2830±0.0777) and Group B (4.750(3.325,20.425),3.190±0.2979,1.4700 (1.4500,1.5775) mg/ml, 0.1441 (0.1373,0.1490),1.8601±0.1595, 7.8105±0.7830 and 0.2228±0.0612) (all p < 0.05). Using 0.1586 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.875 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.625 with CT value at 70 keV and improved to 0.843 at 40 keV. CONCLUSION: Dual-layer spectral CT provides additional quantitative parameters than conventional CT to enhance the differentiation between hepatocellular carcinoma with and without microvascular invasion. Especially, the normalized iodine concentration (NIC) in arterial phase has the greatest potential application value in determining whether microvascular invasion exists, and can offer an important reference for clinical treatment plan and prognosis assessment.

Analysis of radiologic parameters and clinical outcomes in supramalleolar osteotomy for varus ankle osteoarthritis: A novel method for evaluating ankle alignment.

BACKGROUND: Solely relying on the tibial ankle surface (TAS) angle for determining the mechanical ankle axis might be insufficient. We introduce a novel method to determine the distance from the center of the talus to the tibial axis (TTD). This study aimed to investigate the association between clinical outcomes and radiological changes before and after supramalleolar osteotomy (SMO), including TAS angle, talar tilt (TT) angle, tibiotalar surface (TTS) angle and TTD. METHODS: Seventy patients who received SMO were enrolled. Radiological changes were measured using weight-bearing anteroposterior imaging. The percentage of talar center displacement (TTDP) was calculated as the difference between postoperative and preoperative TTD, divided by talar width (TW). Clinical assessments were performed using the American Orthopedic Foot and Ankle Society ankle-hindfoot (AOFAS) scale. Differences in the aforementioned indicators before and after the operation were analyzed. We defined ΔAOFAS, ΔTAS, ΔTT and ΔTTS as the difference between postoperative and preoperative values. RESULTS: ΔTTS correlated with ΔAOFAS (r = 0.40, p = 0.008), as did TTDP (r = 0.32, p = 0.035). No correlation was observed between ΔAOFAS and ΔTAS. In the comparison between groups, patients with a TTDP greater than 26.19 exhibited a significantly greater ΔAOFAS. The high intraclass correlation coefficient indicated good reliability of the novel method. CONCLUSION: Solely relying on the TAS angle for tibial correction was insufficient. We found TTD as a novel method to evaluate mechanical ankle joint axis. TTDP and ΔTTS both positively correlated with ΔAOFAS, indicating the usefulness of these radiologic parameters.

Fluorescence molecular tomography based on an online maximum a posteriori estimation algorithm.

Fluorescence molecular tomography (FMT) is a non-invasive, radiation-free, and highly sensitive optical molecular imaging technique for early tumor detection. However, inadequate measurement information along with significant scattering of near-infrared light within the tissue leads to high ill-posedness in the inverse problem of FMT. To improve the quality and efficiency of FMT reconstruction, we build a reconstruction model based on log-sum regularization and introduce an online maximum a posteriori estimation (OPE) algorithm to solve the non-convex optimization problem. The OPE algorithm approximates a stationary point by evaluating the gradient of the objective function at each iteration, and its notable strength lies in the remarkable speed of convergence. The results of simulations and experiments demonstrate that the OPE algorithm ensures good reconstruction quality and exhibits outstanding performance in terms of reconstruction efficiency.

Bifunctional interfacial engineering enabled efficient and stable carbon-based CsPbIBr2 perovskite solar cells.

Carbon-based inorganic CsPbIBr2 perovskite solar cells (C-IPSC) have attracted widespread attention due to their low cost and excellent thermal stability. Unfortunately, due to the soft ion crystal nature of perovskite, inherent bulk defects and energy level mismatch at the CsPbIBr2/carbon interface limit the performance of the device. In this study, we introduced aromatic benzyltrimethylammonium chloride (BTACl) as a passivation layer to passivate the surface and grain boundaries of the CsPbIBr2 film. Due to the reduction of perovskite defects and better energy level arrangement, carrier recombination is effectively suppressed and hole extraction is improved. The champion device achieves a maximum power conversion efficiency (PCE) of 11.30% with reduces hysteresis and open circuit voltage loss. In addition, unencapsulated equipment exhibits excellent stability in ambient air.

Superimposed Electric Field Enhanced Electrospray for High-Throughput and Consistent Cell Encapsulation.

Cell encapsulation technology, crucial for advanced biomedical applications, faces challenges in existing microfluidic and electrospray methods. Microfluidic techniques, while precise, can damage vulnerable cells, and conventional electrospray methods often encounter instability and capsule breakage during high-throughput encapsulation. Inspired by the transformation of the working state from unstable dripping to stable jetting triggered by local electric potential, this study introduces a superimposed electric field (SEF)-enhanced electrospray method for cell encapsulation, with improved stability and biocompatibility. Utilizing stiffness theory, we quantitatively analyze the stability of the electrospray, whose stiffness is five times stronger under conical confinement. The SEF technique enabled rapid, continuous production of ∼300 core-shell capsules per second in an aqueous environment, significantly improving cell encapsulation efficiency. Our method demonstrated remarkable potential as exemplified in two key applications: 1) a 92-fold increase in human-derived induced pluripotent stem cells (iPSCs) expansion over 10 days, outperforming traditional 2D cultures in both growth rate and pluripotency maintenance, and 2) the development of liver capsules for steatosis modeling, exhibiting normal function and biomimetic lipid accumulation. The SEF-enhanced electrospray method presents a significant advancement in cell encapsulation technology. It offers a more efficient, stable, and biocompatible approach, opening new possibilities in clinical transplantation, drug screening, and cell therapy. This article is protected by copyright. All rights reserved.

LDHA contributes to nicotine induced cardiac fibrosis through autophagy flux impairment.

Cardiac fibrosis is a typical feature of cardiac pathological remodeling, which is associated with adverse clinical outcomes and has no effective therapy. Nicotine is an important risk factor for cardiac fibrosis, yet its underlying molecular mechanism remains poorly understood. This study aimed to identify its potential molecular mechanism in nicotine-induced cardiac fibrosis. Our results showed nicotine exposure led to the proliferation and transformation of cardiac fibroblasts (CFs) into myofibroblasts (MFs) by impairing autophagy flux. Through the use of drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) technology, it was discovered that nicotine directly increased the stability and protein levels of lactate dehydrogenase A (LDHA) by binding to it. Nicotine treatment impaired autophagy flux by regulating the AMPK/mTOR signaling pathway, impeding the nuclear translocation of transcription factor EB (TFEB), and reducing the activity of cathepsin B (CTSB). In vivo, nicotine treatment exacerbated cardiac fibrosis induced in spontaneously hypertensive rats (SHR) and worsened cardiac function. Interestingly, the absence of LDHA reversed these effects both in vitro and in vivo. Our study identified LDHA as a novel nicotine-binding protein that plays a crucial role in mediating cardiac fibrosis by blocking autophagy flux. The findings suggest that LDHA could potentially serve as a promising target for the treatment of cardiac fibrosis.

Analysis of factors influencing onset and survival of patients with severe acute pancreatitis: A clinical study.

OBJECTIVES: Acute pancreatitis (AP) is an inflammatory disease of the pancreas, and the prognosis of severe AP (SAP) is poor. The study aimed to identify promising biomarkers for predicting the occurrence and survival outcome of SAP patients. MATERIALS AND METHODS: Two hundred and forty AP patients were retrospectively recruited, in which 72 cases with SAP. Blood test was done for collection of laboratory indicators. After treatment, the mortality of patients was recorded. RESULTS: Patients in the SAP group had higher intensive care unit admissions and longer hospital stays (p < .001). Among laboratory parameters, significantly high values of C-reactive protein (CRP), triglycerides and glucose (TyG) index, Von willebrand factor antigen (vWF:Ag) and D-dimer were found in SAP groups relative to non-SAP ones. Receiver operating characteristic curve indicated the good performance of CRP, TyG index, vWF:Ag and D-dimer in SAP diagnosis. Among all SAP cases, 51 survived while 21 died. TyG index (odds ratio [OR] = 6.914, 95% confidence interval [CI] = 1.193-40.068, p = .028), vWF:Ag (OR = 7.441, 95% CI = 1.236-244.815, p = .028), and D-dimer (OR = 7.987, 95% CI = 1.251-50.997, p = .028) were significantly related to survival outcome of SAP patients by multiple logistic regression analysis. Both TyG index and vWF showed favorable efficiency in predicting overall prognosis. The area under the curve for the multivariate model (PRE = -35.908 + 2.764 × TyG + 0.021 × vWF:Ag) was 0.909 which was greater than 0.9, indicating its excellent performance in prognosis prediction. CONCLUSION: CRP, TyG index, vWF:Ag, and D-dimer values on admission may be potential clinical predictors of the development of SAP. Moreover, TyG index and vWF:Ag may be helpful to predict survival outcome.

Sewage Sludge Promotes the Accumulation of Antibiotic Resistance Genes in Tomato Xylem.

Xylem serves as a conduit linking soil to the aboveground plant parts and facilitating the upward movement of microbes into leaves and fruits. Despite this potential, the composition of the xylem microbiome and its associated risks, including antibiotic resistance, are understudied. Here, we cultivated tomatoes and analyzed their xylem sap to assess the microbiome and antibiotic resistance profiles following treatment with sewage sludge. Our findings show that xylem microbes primarily originate from soil, albeit with reduced diversity in comparison to those of their soil microbiomes. Using single-cell Raman spectroscopy coupled with D2O labeling, we detected significantly higher metabolic activity in xylem microbes than in rhizosphere soil, with 87% of xylem microbes active compared to just 36% in the soil. Additionally, xylem was pinpointed as a reservoir for antibiotic resistance genes (ARGs), with their abundance being 2.4-6.9 times higher than in rhizosphere soil. Sludge addition dramatically increased the abundance of ARGs in xylem and also increased their mobility and host pathogenicity. Xylem represents a distinct ecological niche for microbes and is a significant reservoir for ARGs. These results could be used to manage the resistome in crops and improve food safety.