A new holistic perspective to assess the ecological risk of microplastics: A case study in Baiyangdian Basin, China.

By integrating probabilistic ecological risk assessment with the overall risk index method, which considers the multidimensional characteristics of the microplastome, the ecological risks of microplastic pollution were assessed more comprehensively. This study took the Baiyangdian Basin as an example to address the limitations of current risk assessment methods that rely on concentration data or the individual risk of microplastics. Using an exponential regression model, the acute and chronic ecological risk thresholds for the overall risk index method were determined to be 0.43 and 0.30, respectively. The acute and chronic ecological risks of the microplastome occupied 61 % and 79 % of the Baiyangdian Wetland and 0 % and 14 % of the Fu River, while the Xiaoyi River did not exhibit risk during the rainy season. Results indicated that intense human activities, poor hydrodynamics, low settling velocity and high levels of environmental chemical pollutants jointly contributed to the high risk of the microplastome in water bodies. Compared with the probabilistic ecological risk assessment method (risk characterization ratio), there was a significant difference in the area of acute and chronic ecological risks caused by the microplastome in the Baiyangdian Basin when using the overall risk index method. This proved that considering only concentration cannot truly reflect the toxicity of microplastics to aquatic organisms.

The role of artificial intelligence in the development of anticancer therapeutics from natural polyphenols: Current advances and future prospects.

Natural polyphenols, abundant in the human diet, are derived from a wide variety of sources. Numerous preclinical studies have demonstrated their significant anticancer properties against various malignancies, making them valuable resources for drug development. However, traditional experimental methods for developing anticancer therapies from natural polyphenols are time-consuming and labor-intensive. Recently, artificial intelligence has shown promising advancements in drug discovery. Integrating AI technologies into the development process for natural polyphenols can substantially reduce development time and enhance efficiency. In this study, we review the crucial roles of natural polyphenols in anticancer treatment and explore the potential of AI technologies to aid in drug development. Specifically, we discuss the application of AI in key stages such as drug structure prediction, virtual drug screening, prediction of biological activity, and drug-target protein interaction, highlighting the potential to revolutionize the development of natural polyphenol-based anticancer therapies.

High-quality chromosome-level genomic insights into molecular adaptation to low-temperature stress in Madhuca longifolia in southern subtropical China.

BACKGROUND: Madhuca longifolia, the energy-producing and medicinal tropical tree originally from southern India, faces difficulties in adapting to the low temperatures of late autumn and early winter in subtropical southern China, impacting its usability. Therefore, understanding the molecular mechanisms controlling the ability of this species to adapt to environmental challenges is essential for optimising horticulture efforts. Accordingly, this study aimed to elucidate the molecular responses of M. longifolia to low-temperature stress through genomic and transcriptomic analyses to inform strategies for its effective cultivation and utilisation in colder climates. RESULTS: Herein, the high-quality reference genome and genomic assembly for M. longifolia are presented for the first time. Using Illumina sequencing, Hi-C technology, and PacBio HiFi sequencing, we assembled a chromosome-level genome approximately 737.92 Mb in size, investigated its genomic features, and conducted an evolutionary analysis of the genus Madhuca. Additionally, using transcriptome sequencing, we identified 17,941 differentially expressed genes related to low-temperature response. Through bioinformatics analysis of the WRKY gene family, 15 genes crucial for M. longifolia low-temperature resistance were identified. CONCLUSIONS: This research not only lays the groundwork for the successful ecological adaptation and cultivation of M. longifolia in China's southern subtropical regions but also offers valuable insights for the genetic enhancement of cold tolerance in tropical species, contributing to their sustainable horticulture and broader industrial, medicinal, and agricultural use.

An in situ ratiometric fluorescence immunosensor via Mn2+-triggered aggregation-induced emission transformation of levodopa fluorescent copolymer nanoparticles.

Herein, a direct in situ alkaline phosphatase (ALP)-labeled luminescent nanoimmunoassay platform was constructed using Mn2+-triggered aggregation-induced emission transformation of levodopa fluorescent copolymer (LFC) nanoparticles. Using cardiac troponin I (cTn I) as the model antigen, the proposed nanoimmunosensor has been applied to detect cTn I in clinical samples with satisfactory results.

ELOVL1 is upregulated and promotes tumor growth in hepatocellular carcinoma through regulating PI3K-AKT-mTOR signaling.

Background: The functions of the ELOVLs are mainly involved in the elongation of saturated and polyunsaturated fatty acids, thus influencing the metabolism of fatty acids. Abnormal lipid metabolism may result in NAFLD and NASH, which may lead to cirrhosis and liver cancer. These results suggest that ELOVLs-mediated metabolism might be involved in the development of HCC. The purpose of this study was to study the expression and function of ELOVL1 in human liver cancer. Method: Using TCGA, GEPIA and other databases, we analyzed the relationship between the expression of ELOVL1 and liver cancer. The expression of ELOVL1 was detected by immunohistochemical method and Western blot method in hepatic carcinoma and hepatic carcinoma cells. Then, the effects of ELOVL1 on proliferation, apoptosis and invasion in vitro and in vivo were investigated by means of different methods. Result: Our results indicate that ELOVL1 is more highly expressed in liver cancer than in normal tissues. Survival analysis showed that OS and DSS were shorter in patients with high ELOVL1 expression than in those with low expression. Multivariate Cox analysis further demonstrated that over-expression of ELOVL1 was an independent risk factor for overall survival in HCC. The results of ROC also confirmed the value of ELOVL1 in the diagnosis of liver cancer. The results of KEGG enrichment and GSEA indicate that ELOVL1 is associated with lipid metabolism and NAFLD, as well as PPAR, PI3K-AKT-mTOR. Compared with the control group, it was found that silencing ELOVL1 in Huh7 and HepG2 cells could inhibit the growth of cells, promote the apoptosis and decrease the metastasis and invasion. Changes in ELOVL1 induced cell proliferation and metastasis may be related to PI3K/AKT/mTOR. Low expression of ELOVL1 inhibited the growth of xenograft tumors in hepatocellular carcinoma xenograft model. Conclusion: Our data indicate that the activation of PI3K/AKT/mTOR pathway in HCC may contribute to the promotion of cancer. Thus, ELOVL1 may be a promising therapeutic target for HCC.

Controlled Synthesis of 2D Ferromagnetic/Antiferromagnetic Cr7Te8/MnTe Vertical Heterostructures for High-Tunable Coercivity.

Two-dimensional ferromagnetic/antiferromagnetic (2D-FM/AFM) heterostructures are of great significance to realize the application of spintronic devices such as miniaturization, low power consumption, and high-density information storage. However, traditional mechanical stacking can easily damage the crystal quality or cause chemical contamination residues for 2D materials, which can result in weak interface coupling and difficulty in device regulation. Chemical vapor deposition (CVD) is an effective way to achieve a high-quality heterostructure interface. Herein, high-quality interface 2D-FM/AFM Cr7Te8/MnTe vertical heterostructures were successfully synthesized via a one-pot CVD method. Moreover, the atomic-scale structural scanning transmission electron microscope (STEM) characterization shows that the interface of the vertical heterostructure is clear and flat without an excess interface layer. Compared to the parent Cr7Te8, the coercivity (HC) of the high-quality interface Cr7Te8/MnTe heterostructure is significantly reduced as the thickness of MnTe increases, with a maximum decrease of 74.5% when the thickness of the MnTe nanosheet is around 30 nm. Additionally, the HC of the Cr7Te8/MnTe heterostructure can also be regulated by applying a gate voltage, and the HC increases or decreases with increasing positive or negative gate voltages. Thus, the effective regulation of HC is essential to improving the performance of advanced spintronic devices (e.g., MRAM and magnetic sensors). Our work will provide ideas for spin controlling and device application of 2D-FM/AFM heterostructures.

Assessing the impact of vaccination and medical resource allocation on infectious disease outbreak management: a case study of COVID-19 in Taiyuan City.

Introduction: Amidst an emerging infectious disease outbreak, the rational allocation of vaccines and medical resources is crucial for controlling the epidemic's progression. Method: Analysing COVID-19 data in Taiyuan City from December 2022 to January 2023, this study constructed a S V 1 V 2 V 3 E I Q H R dynamics model to assess the impact of COVID-19 vaccination and resource allocation on epidemic trends. Results: Vaccination significantly reduces infection rates, hospitalisations, and severe cases, while also curtailing strain on medical resources by reducing congestion periods. An early and sufficient reserve of medical resources can delay the onset of medical congestion, and with increased maximum capacity of medical resources, the congestion's end can be accelerated. Stronger resource allocation capabilities lead to earlier congestion resolution within a fixed total resource pool. Discussion: Integrating vaccination and medical resource allocation can effectively reduce medical congestion duration and alleviate the epidemic's strain on medical resource capacity (CCMR).

Characteristics and performance of algal-bacterial granular sludge in photo-sequencing batch reactors under various substrate loading rates.

The algae-bacterial granular sludge (ABGS) technology has garnered significant attention due to its remarkable attributes of low carbon emissions. To investigate the performance of the ABGS system under various substrate loading rates, the parallel photo-sequencing batch reactors (P1 and P2) were set up. The results indicated that chlorophyll-a content and extracellular polymeric substance content were measured at 10.7 ± 0.3 mg/L and 61.4 ± 0.7 mg/g SS in P1 under relatively low substrate loading rate (0.9 kg COD/m3/d and 0.09 kg N/m3/d). Moreover, kinetic study revealed that the maximal specific P uptake rate for P1 reached 0.21 mg P/g SS/h under light conditions, and it achieved 0.078 mg P/g SS/h under dark conditions, highlighting the significant role on phosphorus removal played by algae in the ABGS system. The microbial analysis and scanning electron microscopy confirmed that filamentous algae predominantly colonize the surface in P1, whereas spherical bacteria dominate the surface of granular sludge in P2. Additionally, a diverse array of microorganisms including bacteria, algae, and metazoa such as Rotifers and Nematodes were observed in both systems, providing evidence for the establishment of a symbiotic system. This study not only confirmed the ability of ABGS for efficient N and P removal under different substrate loading conditions but also highlighted its potential to enhance the ecological diversity of the reaction system.

Comparison of blended learning and traditional lecture method on learning outcomes in the evidence-based medicine course: a comparative study.

BACKGROUND: Blended learning comprised with flipped classroom (FC) and "internet plus" is a new learning strategy that reverses the position of teacher and students in class, and provides abundant learning resources before and after class. This study aimed to assess the impact of blended learning on learning outcomes in evidence-based medicine course, and compare with traditional learning method. METHODS: The participants of the two groups were from two difference cohorts in Air force medical university in China. The two groups toke the same pre-test before class and then were given the teaching of same chapters of evidence-based medicine with two different learning strategy. In the blended learning group, the participants were required to create a debriefing slide about their learning outcomes and the answers of questions given in advance after study the learning material sent by teacher a week before class, and the teacher gave a detailed summary based on the common problems, and distributed multimedia resources for review. After the experiment was carried out, learning outcomes including mastering knowledge, learning satisfaction, and self-evaluation were compared. RESULTS: 37 and 39 participants were enrolled to blended learning and traditional learning groups, respectively, and no statistically significant difference were found in baseline information and pre-test grades. Statistically significant differences were found in learning outcomes including post-test score (t = 2.90, p = 0.005), changes of scores between pre-test and post-test (t = 2.49, p = 0.022), learning satisfaction (t = 12.41, p = 0.001), and self-evaluation of the two groups (t = 7.82, p = 0.001). Especially, the changes of scores between pre-test and post-test of blended learning and traditional learning groups were 4.05 (4.26), and 2.00 (2.85), respectively. CONCLUSIONS: This study showed that compared with traditional learning strategy, blended learning can effectively enhanced participants' acquisition of knowledge, learning satisfaction, and self-evaluation in evidence-based medicine. Using blended learning method including "internet plus" and flipped classroom is recommended in the teaching of evidence-based medicine course.

Identified γ-glutamyl cyclotransferase (GGCT) as a novel regulator in the progression and immunotherapy of pancreatic ductal adenocarcinoma through multi-omics analysis and experiments.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is renowned for its formidable and lethal nature, earning it a notorious reputation among malignant tumors. Due to its challenging early diagnosis, high malignancy, and resistance to chemotherapy drugs, the treatment of pancreatic cancer has long been exceedingly difficult in the realm of oncology. γ-Glutamyl cyclotransferase (GGCT), a vital enzyme in glutathione metabolism, has been implicated in the proliferation and progression of several tumor types, while the biological function of GGCT in pancreatic ductal adenocarcinoma remains unknown. METHODS: The expression profile of GGCT was validated through western blotting, immunohistochemistry, and RT-qPCR in both pancreatic cancer tissue samples and cell lines. Functional enrichment analyses including GSVA, ssGSEA, GO, and KEGG were conducted to explore the biological role of GGCT. Additionally, CCK8, Edu, colony formation, migration, and invasion assays were employed to evaluate the impact of GGCT on the proliferation and migration abilities of pancreatic cancer cells. Furthermore, the LASSO machine learning algorithm was utilized to develop a prognostic model associated with GGCT. RESULTS: Our study revealed heightened expression of GGCT in pancreatic cancer tissues and cells, suggesting an association with poorer patient prognosis. Additionally, we explored the immunomodulatory effects of GGCT in both pan-cancer and pancreatic cancer contexts, found that GGCT may be associated with immunosuppressive regulation in various types of tumors. Specifically, in patients with high expression of GGCT in pancreatic cancer, there is a reduction in the infiltration of various immune cells, leading to poorer responsiveness to immunotherapy and worse survival rates. In vivo and in vitro assays indicate that downregulation of GGCT markedly suppresses the proliferation and metastasis of pancreatic cancer cells. Moreover, this inhibitory effect appears to be linked to the regulation of GGCT on c-Myc. A prognostic model was constructed based on genes derived from GGCT, demonstrating robust predictive ability for favorable survival prognosis and response to immunotherapy.

Insurance Disparities in Quality of Care Among Patients With Head and Neck Cancer.

Importance: Significant insurance status disparities have been demonstrated in head and neck cancer (HNC) outcomes. The effects of insurance status on HNC outcomes may be explained by differential access to high-quality care. Objective: To evaluate the association of insurance status with the quality of the treating hospital and receipt of guideline-compliant care among patients with HNC. Design, Setting, and Participants: This retrospective cohort study of data from the California Cancer Registry dataset linked with discharge records and hospital characteristics from the California Department of Health Care Access and Information included adult patients with HNC diagnosed between January 1, 2010, and December 31, 2019. Data were analyzed from May 10, 2023, to March 25, 2024. Exposures: Insurance status: commercial, Medicare, Medicaid, uninsured, other, or unknown. Main Outcomes and Measures: Quality of the treating hospital (tertiles), receipt of National Comprehensive Cancer Network guideline-compliant care, and overall survival. Results: A total of 23 933 patients (mean [SD] age, 64.8 [12.3] years; 75.3% male) met the inclusion criteria. Treatment in top-tertile hospitals (hazard ratio, 0.87; 95% CI, 0.79-0.95) was associated with improved overall survival compared with treatment in bottom-tertile hospitals. Medicare (odds ratio [OR], 0.78; 95% CI, 0.73-0.84), Medicaid (OR, 0.60; 95% CI, 0.54-0.66), and uninsured (OR, 0.38; 95% CI, 0.29-0.49) status were associated with lower likelihood of treatment in high-quality hospitals compared with commercial insurance. Among patients with advanced disease, Medicaid (OR, 0.72; 95% CI, 0.62-0.83) and uninsured (OR, 0.64; 95% CI, 0.44-0.93) patients were less likely to receive dual-modality therapy. Among patients with surgically resected advanced disease, Medicaid coverage (OR, 0.73; 95% CI, 0.58-0.93) was associated with lower likelihood of receiving adjuvant radiotherapy. Conclusions and Relevance: This study found significant insurance disparities in quality of care among patients with HNC. These findings highlight the need for continued health insurance reform in the US to improve the quality of insurance coverage, in addition to expanding access to health insurance.

HIV-Associated Heart Failure: Phenotypes and Clinical Outcomes in a Safety-Net Setting.

Background: Human immunodeficiency virus (HIV) is associated with increased risk of heart failure (HF) but data regarding phenotypes of heart failure and outcomes after HF diagnosis, especially within the safety-net which is where half of people with HIV in the United States receive care, are less clear. Methods: Using an electronic health record cohort of all individuals with HF within a municipal safety-net system from 2001-2019 linked to the National Death Index Plus, we compared HF phenotypes, all-cause mortality, HF hospitalization, and cause of death for individuals with and without HIV. Results: Among people with HF (n=14,829), 697 individuals had HIV (4.7%). Persons with HIV (PWH) were diagnosed with HF ten years younger on average. A higher proportion of PWH had a reduced ejection fraction at diagnosis (37.9% vs 32.7%). Adjusted for age, sex, and risk factors, coronary artery disease on angiography was similar by HIV status. HIV was associated with 55% higher risk of all-cause mortality (HR 1.55; 95% CI 1.37-1.76; P<0.001) and lower odds of HF hospitalization (OR 0.51; 95% CI 0.39-0.66; P<0.001). Among PWH with HF, cause of death was less often attributed to cardiovascular disease (22.5% vs 54.6% uninfected; P<0.001) and more to substance use (17.9% vs 9.3%; P<0.001), consistent with autopsy findings in a subset (n=81). Conclusions: Among people with HF who receive care within a municipal safety-net system, HIV infection is associated with higher mortality, despite lower odds of HF hospitalization, attributable to non-cardiovascular causes including substance-related and HIV-related mortality.

Earthworm-Inspired Ultra-Durable Sliding Triboelectric Nanogenerator with Bionic Self-Replenishing Lubricating Property for Wind Energy Harvesting and Self-Powered Intelligent Sports Monitoring.

Triboelectric nanogenerators (TENGs), a promising strategy for harvesting distributed low-quality power sources, face inevitable bottlenecks regarding long-term abrasion and poor durability. Herein, both issues are addressed by selecting an earthworm-inspired self-replenishing bionic film (ERB) as the tribo-material of sliding-freestanding TENGs (SF-TENGs), it consists of an interconnected 3D porous network structure capable of storing and releasing lubricant under cyclic mechanical stimuli. Thanks to the superiority of self-replenishing property, there is no need for periodic replenishment and accurate content control of lubricant over the interfacial-lubricating SF-TENGs based on dense tribo-layers. Additionally, an SF-TENG based on ERB film (ERB-TENG) demonstrates remarkable output stability with only a slight attenuation of 1% after continuous operation for 100 000 cycles. Moreover, the ERB-TENG displays a distinguished anti-wear property, exhibiting no distinct abrasion with an ultra-low coefficient of friction (0.077) and maintaining output stability over a prolonged period of 35 days. Furthermore, integration with an energy management circuit enables the ERB-TENG to achieve a 39-fold boost in charging speed. This work proposes a creative approach to enhance the durability and extend the lifespan of TENG devices, which is also successfully applied to wind energy harvesting and intelligent sports monitoring.

Cerebral 18F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment.

Our aim was to investigate probable biomarkers specific to immune-related central nervous system toxicity (CNST) in cancer patients treated with immune checkpoint inhibitors (ICI) by analysis of 18F-FDG PET/CT images. Methods: Cancer patients receiving ICI treatment were enrolled in a multicenter observational study that analyzed regional metabolic changes before and during CNST onset from January 2020 to February 2022. In 1:1 propensity score-matched pairs, the regional SUVmean of each bilateral brain lobe of CNST patients (CNST+) was compared with that of patients who had central nervous system infections (CNSIs) and patients without CNST or CNSI (CNST-). In a validation cohort, patients were recruited from February 2022 to July 2023 and followed up for 24 wk after the start of ICI. Early changes in regional SUVmean at 5-6 wk after therapy initiation were evaluated for ability to predict later CNST onset. Results: Of 6,395 ICI-treated patients, 2,387 underwent prognostic 18F-FDG PET/CT and 125 of the scanned patients had CNST (median time from ICI treatment to onset, 9 wk; quartile range, 2-23 wk). Regional 18F-FDG PET/CT SUVmean changes were higher in CNST+ than in CNST- patients (117 patient pairs) but were lower than in CNSI patients (50 pairs). Differentiating analysis reached an area under the curve (AUC) of 0.83 (95% CI, 0.78-0.88) for CNST+ versus CNST- and of 0.80 (95% CI, 0.72-0.89) for CNST+ versus CNSI. Changes in SUVmean were also higher before CNST onset than for CNST- (60 pairs; AUC, 0.74; 95% CI, 0.66-0.83). In a validation cohort of 2,878 patients, preonset changes in SUVmean reached an AUC of 0.86 (95% CI, 0.79-0.94) in predicting later CNST incidence. Conclusion: Brain regional hypermetabolism could be detected during and before CNST clinical onset. CNST may be a distinct pathologic entity versus brain infections defined by 18F-FDG PET/CT brain scans. Regional SUV differences may be translated into early diagnostic tools based on moderate differentiating accuracy in our study.

Thyroid Cancer Incidence Among Korean Individuals: A Comparison of South Korea and the United States.

OBJECTIVE: To compare thyroid cancer incidence rates and trends between Korean, non-Korean Asian, and non-Hispanic White populations in the United States, and between the US Korean population and the South Korean population. METHOD: Population-based analysis of cancer incidence data. Cases of thyroid cancer diagnosed during 1999-2014 from the Korean Central Cancer Registry (KCCR) and the Surveillance, Epidemiology, and End Results (SEER) 9 detailed Asian/Pacific Islander subgroup incidence and population dataset were included. Incidence rates were obtained from the datasets, and annual percent change (APC) of the incidence rates was calculated using Joinpoint regression analysis. RESULTS: Thyroid cancer incidence rate for 1999-2014 was significantly higher for South Korea (48.05 [95% CI 47.89-48.22] per 100,000 person-years) than for the US Korean population (11.12 [95% CI 10.49-11.78] per 100,000 person-years), which was slightly higher than the Non-Korean Asian population (10.23 [95% CI 10.02-10.43] per 100,000 person-years), and slightly lower than the Non-Hispanic White population (12.78 [95% CI 12.69-12.87] per 100,000 person-years). Incidence rates in South Korea increased dramatically (average APC 17.9, 95% CI 16.0-19.9), significantly higher than the US Korean population (average APC 5.0, 95% CI 3.1-6.8), which was similar to the non-Korean Asian (average APC 2.5, 95% CI 0.9-4.2) and the non-Hispanic White (average APC 5.1, 95% CI 4.7-5.6) populations. CONCLUSIONS: South Korea's high thyroid cancer incidence rates cannot be attributed to genetic factors, but are likely due to health care system factors. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:4156-4160, 2024.

Association Between Coronary Assessment in Heart Failure and Clinical Outcomes Within a Safety-Net Setting Using a Target Trial Emulation Observational Design.

BACKGROUND: Ischemic cardiomyopathy is the leading cause of heart failure (HF). Most patients do not undergo coronary assessment after HF diagnosis. There are no randomized clinical trials of coronary assessment after HF diagnosis. METHODS: Using an electronic health record cohort of all individuals with HF within the San Francisco Health Network from 2001 to 2019, we identified factors associated with coronary assessment. Then, we studied the association of coronary assessment within 30 days of HF diagnosis with all-cause mortality and a composite of mortality and emergent angiography using a target trial emulation observational comparative-effectiveness approach. Target trial emulation is an approach to causal inference based on creating a hypothetical randomized clinical trial protocol and using observational data to emulate the protocol. We used propensity scores for covariate adjustment. We used national death records to improve the ascertainment of mortality and included falsification end points for the cause of death. RESULTS: Among 14 829 individuals with HF (median, 62 years old; 5855 [40%] women), 3987 (26.9%) ever completed coronary assessment, with 2467/13 301 (18.5%) with unknown coronary artery disease status at HF diagnosis assessed. Women, older individuals, and people without stable housing were less likely to complete coronary assessment. Among 5972 eligible persons of whom 627 underwent early elective coronary assessment, coronary assessment was associated with lower mortality (hazard ratio, 0.84 [95% CI, 0.72-0.97]; P=0.025), reduced risk of the composite outcome (hazard ratio, 0.86 [95% CI, 0.73-1.00]), higher rates of revascularization (odds ratio, 7.6 [95% CI, 5.4-10.6]), and higher use of medical therapy (odds ratio, 2.5 [95% CI, 1.7-3.6]), but not the falsification end points. CONCLUSIONS: In a safety-net population, disparities in coronary assessment after HF diagnosis are not fully explained by coronary artery disease risk factors. Early coronary assessment is associated with improved HF outcomes possibly related to higher rates of revascularization and guideline-directed medical therapy but with low certainty that this finding is not attributable to unmeasured confounding.

Microbial Translocation and Gut Damage Are Associated With an Elevated Fast Score in Women Living With and Without HIV.

Background: Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Women's Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan-aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis. Methods: Among 883 women with HIV and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut damage (kynurenine and tryptophan ratio, intestinal fatty acid-binding protein, soluble CD14, and soluble CD163) with a log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. Results: HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in women with HIV than women without HIV (P < .001 for each). MT biomarkers mediated 13% to 32% of the association of HIV and FAST score. Conclusions: Biomarkers linked to MT and gut damage are associated with a higher FAST score and mediate the association of HIV with a higher FAST score. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.

The CREB1/WNK1 axis promotes the tumorigenesis of ovarian cancer via regulating HIF-1.

The aim of this study was to explore the functions and molecular mechanisms of the WNK lysine deficient protein kinase 1 (WNK1) in the development of ovarian cancer. Firstly, loss- and gain-of-function assays were carried out and subsequently cell proliferation, apoptosis, invasion and migration were detected. Furthermore, WNK1 action on glucose uptake, lactate production and adenosine triphosphate (ATP) level were assessed. The roles of WNK1 on cisplatin resistance were explored using CCK-8, colony formation, and flow cytometry in vitro. Immunohistochemistry, Western blot and qRT-PCR were conducted to determine the protein and mRNA expression. Additionally, tumor growth in vivo was also monitored. We found that the overexpression of WNK1 predicted a bad prognosis of ovarian cancer patients. WNK1 enhanced the malignant behavior and facilitated glycolysis of ovarian cancer cells. Moreover, WNK1 increased cisplatin resistance in ovarian cancer cells. Mechanistically, we found that WNK1 expression was promoted by CREB1 at the transcriptional level. And CREB1 could facilitate ovarian cancer cells malignant behavior through target upregulating WNK1. Besides, we also showed that WNK1 facilitated the malignant behavior by accelerating HIF-1 expression. In xenograft tumor tissues, the downregulation of WNK1 significantly reduced HIF-1α expression. These data demonstrated that the CREB1/WNK1 axis could promote the tumorigenesis of ovarian cancer via accelerating HIF-1 expression, suggesting that the CREB1/WNK1 axis could be a potential target during the therapy of ovarian cancer.

Integrative chemical and multiomics analyses of tetracycline removal mechanisms in Pseudomonas sp. DX-21.

Tetracycline (TC), widely found in various environments, poses significant risks to ecosystems and human health. While efficient biodegradation removes TC, the mechanisms underlying this process have not been elucidated. This study investigated the molecular mechanisms underlying TC biosorption and transfer within the extracellular polymeric substances (EPS) of strain DX-21 and its biodegradation process using fourier transform infrared spectroscopy, molecular docking, and multiomics. Under TC stress, DX-21 increased TC biosorption by secreting more extracellular polysaccharides and proteins, particularly the latter, mitigating toxicity. Moreover, specialized transporter proteins with increased binding capacity facilitated TC movement from the EPS to the cell membrane and within the cell. Transcriptomic and untargeted metabolomic analyses revealed that the presence of TC led to the differential expression of 306 genes and significant alterations in 37 metabolites. Notably, genes related to key enzymes, such as electron transport, peroxidase, and oxidoreductase, exhibited significant differential expression. DX-21 combated and degraded TC by regulating metabolism, altering cell membrane permeability, enhancing oxidative defense, and enhancing energy availability. Furthermore, integrative omics analyses indicated that DX-21 degrades TC via various enzymes, reallocating resources from other biosynthetic pathways. These results advance the understanding of the metabolic responses and regulatory mechanisms of DX-21 in response to TC.