Mitochondrial GRIM19 Loss Induces Liver Fibrosis through NLRP3/IL33 Activation via Reactive Oxygen Species/NF-кB Signaling.

Background and Aims: Hepatic fibrosis (HF) is a critical step in the progression of hepatocellular carcinoma (HCC). Gene associated with retinoid-IFN-induced mortality 19 (GRIM19), an essential component of mitochondrial respiratory chain complex I, is frequently attenuated in various human cancers, including HCC. Here, we aimed to investigate the potential relationship and underlying mechanism between GRIM19 loss and HF pathogenesis. Methods: GRIM19 expression was evaluated in normal liver tissues, hepatitis, hepatic cirrhosis, and HCC using human liver disease spectrum tissue microarrays. We studied hepatocyte-specific GRIM19 knockout mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) lentivirus-mediated GRIM19 gene-editing in murine hepatocyte AML12 cells in vitro and in vivo. We performed flow cytometry, immunofluorescence, immunohistochemistry, western blotting, and pharmacological intervention to uncover the potential mechanisms underlying GRIM19 loss-induced HF. Results: Mitochondrial GRIM19 was progressively downregulated in chronic liver disease tissues, including hepatitis, cirrhosis, and HCC tissues. Hepatocyte-specific GRIM19 heterozygous deletion induced spontaneous hepatitis and subsequent liver fibrogenesis in mice. In addition, GRIM19 loss caused chronic liver injury through reactive oxygen species (ROS)-mediated oxidative stress, resulting in aberrant NF-кB activation via an IKK/IкB partner in hepatocytes. Furthermore, GRIM19 loss activated NLRP3-mediated IL33 signaling via the ROS/NF-кB pathway in hepatocytes. Intraperitoneal administration of the NLRP3 inhibitor MCC950 dramatically alleviated GRIM19 loss-driven HF in vivo. Conclusions: The mitochondrial GRIM19 loss facilitates liver fibrosis through NLRP3/IL33 activation via ROS/NF-кB signaling, providing potential therapeutic approaches for earlier HF prevention.

Meniscal Allograft versus Synthetic Graft in Treatment Outcomes of Meniscus Repair: A Mini-review and Meta-analysis.

Meniscal injuries are highly correlated with osteoarthritis (OA) onset and progression. Although meniscal allograft transplantation (MAT) is a therapeutic option to restore meniscal anatomy, a shortage of donor material and the donor-derived infectious risk may be concerns in clinics. This review summarizes the literature reporting meniscus repair status in preclinical models and clinical practice using allografts or synthetic grafts. The advantages and limitations of biodegradable polymer-based meniscal scaffolds, applied in preclinical studies, are discussed. Then, the long-term treatment outcomes of patients with allografts or commercial synthetic scaffolds are compared. A total of 47 studies are included in our network meta-analysis. Compared with the meniscal allografts, the commercial synthetic products significantly improved clinical treatment outcomes in terms of the Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analog Scale (VAS) scores, and Lysholm scores. In addition, development strategies for the next generation of novel synthetic scaffolds are proposed through optimization of structural design and fabrication, and selection of cell sources, external stimuli, and active ingredients. This review may inspire researchers and surgeons to design and fabricate clinic-orientated grafts with improved treatment outcomes.

Identification of Angiogenesis-Related Genes and Molecular Subtypes for Psoriasis Based on Random Forest Algorithm.

Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithms. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis (PCA). A diagnostic model was developed using random forest algorithm (ntree=400) and validated by ROC curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by qRT-PCR. We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P<0.0001) and interleukins pathway (R=0.79, P<0.0001). Furtherer, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes.

The impact of frailty on clinical outcomes among older adults with diabetes: A systematic review and meta-analysis.

BACKGROUND: Frailty has been identified as a risk factor for adverse outcomes in older adults with diabetes. This study aimed to investigate the impact of frailty on the prognosis of older adults with diabetes through a systematic review and meta-analysis, with the goal of offering insights for clinical decision-making. METHODS: PubMed, Web of Science, Embase, Cochrane were systematically searched from inception to September 10th, 2023. Reviewers independently selected studies, extracted data and evaluated the quality of studies. Stata 15.1 Software was used to perform the meta-analysis. The primary outcomes of this study were mortality, hospitalization and disability, and the secondary outcomes were diabetes complications (including nephropathy, microvascular complications, macroangiopathy, cardiovascular events, hypoglycemia) and urolithiasis. RESULTS: A total of 14 studies were included in this study, with low risk of bias and moderate to good quality. The results showed that frailty increased the risk of mortality (HR 1.91, 95% CI 1.55-2.35, P < .001), hospitalization (HR 2.19, 95% CI 1.53-3.13, P < .001), and disability in older adults with diabetes (HR 3.84, 95% CI 2.35-6.28, P < .001). In addition, frailty was associated with diabetes complications (including nephropathy, microvascular complications, macroangiopathy, cardiovascular events, hypoglycemia), urolithiasis. CONCLUSIONS: Frailty is an important predictor of adverse outcomes, such as mortality, hospitalization, and disability in older adults with diabetes. Accurate assessment of the frailty in older adults with diabetes can help improve the adverse outcomes of patients.

Efficacy of Baclofen as Add-on Therapy for Refractory Gastroesophageal Reflux Disease: A Meta-analysis.

OBJECTIVES: As a GABAB receptor agonist, baclofen has demonstrated efficacy in alleviating symptoms of refractory gastroesophageal reflux disease (r-GERD). This meta-analysis aims to evaluate the safety and effectiveness of baclofen as an add-on therapy for this condition. METHOD: We conducted a comprehensive search of the PubMed, Embase, and Web of Science databases for studies published up until October 2023. Subsequently, we performed a meta-analysis encompassing all eligible trials. RESULTS: From 719 records, 10 studies were included, most of these studies were moderate risk. The findings demonstrated that the addition of baclofen as a supplementary treatment effectively improves symptoms (GERD Q score) in r-GERD (standardized mean difference=-0.78, 95% CI: -1.06 to -0.51, I2=0%). The addition of this treatment also resulted in a decrease in the frequency of nonacidic reflux episodes (standardized mean difference=-0.93, 95% CI: -1.49 to -0.37, I2=63%) and an improvement in DeMeester scores (standardized mean difference=-0.82, 95% CI: -1.61 to -0.04, I2=81%) among patients with r-GERD when compared with the use of proton pump inhibitor (PPI) drugs alone. However, no significant disparity was observed in terms of reducing acid reflux episodes (standardized mean difference=-0.12, 95% CI: -0.49 to 0.19, I2=0%) and proximal reflux (standardized mean difference=-0.47, 95% CI: -1.08 to 0.14, I2=60%). CONCLUSION: Baclofen as an add-on treatment can effectively improve the symptoms of patients with r-GERD and reduce the incidence of nonacidic reflux and improve DeMeester score. However, long-term use of baclofen leads to an increased incidence of side effects and is not effective in reducing the occurrence of acid reflux.

Structural and electronic properties of clathrate-like hydride: MH6 and MH9 (M = Sc, Y, La).

CONTEXT: The addition of central metal atoms to hydrogen clathrate structures is thought to provide a certain amount of "internal chemical pressure" to offset some of the external physical pressure required for compound stability. The size and valence of the central atoms significantly affect the minimum pressure required for the stabilization of hydrogen-rich compounds and their superconducting transition temperature. In recent years, many studies have calculated the minimum stable pressure and superconducting transition temperature of compounds with H24, H29, and H32 hydrogen clathrates, with centrally occupied metal atoms. In order to investigate the stability and physical properties of compounds with H cages in which the central atoms change in the same third group B, herein, based on first-principles calculations, we systematically investigated the lattice parameters, crystal volume, band structures, density of states, Mulliken analysis, charge density, charge density difference, and electronic localization function in I m 3 ¯ m -MH6 and P63/mmc-MH9 systems with different centered rare earth atoms M (M = Sc, Y, La) under a series of pressures. We find that for MH9, the pressure mainly changes the crystal lattice parameters along the c-axis, and the contributions of the different H atoms in MH9 to the Fermi level are H3 > H1 > H2. The density of states at the Fermi level of MH6 is mainly provided by H 1 s. Moreover, the size of the central atom M is particularly important for the stability of the crystal. By observing a series of properties of the structures with H24 and H29 cages wrapping the same family of central atoms under a series of pressures, our theoretical study is helpful for further understanding the formation mechanism of high-temperature superconductors and provides a reference for future research and design of high-temperature superconductors. METHODS: The first principles based on the density functional theory and density functional perturbation theory were employed to execute all calculations by using the CASTEP code in this work.

Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence.

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy owing to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from patients with AD. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and ROS production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

Combination therapy using Cel-CSO/Taxol NPs for reversing drug resistance in breast cancer through inhibiting PI3K/AKT/NF-κB/HIF-1α pathway.

The resistance of malignant tumors to multiple drugs is a significant obstacle in cancer treatment and prognosis. Accordingly, we synthesized a celastrol (Cel) prodrug (Cel-CSO) by conjugating chitosan oligosaccharides (CSO) to Cel for reversing Taxol resistance in chemotherapy, followed by self-assembly with Taxol into a novel nanoplatform of Cel-CSO/Taxol nanoparticles (termed NPs). NPs showed a suitable size (about 153 nm), excellent stability and prolonged release of Cel and Taxol in a manner that depended on both pH and time. NPs effectively inhibited the overexpression of multidrug resistance-related protein P-gp, hypoxia inducible factor-1α (HIF-1α), and triggered the MCF-7/Taxol cell apoptosis through inhibiting the PI3K/AKT/NF-κB/HIF-1α pathway. In tumor-bearing mice, NPs exhibited significant curative effects in inducing apoptosis of MCF-7/Taxol tumors which showed a low expression level of P-gp, microtubule-related proteins TUBB3 and Tau. The results indicated that NPs may be a promising strategy to overcome drug resistance caused by P-gp, which improve the antitumor effects in drug-resistant breast cancer.

Insights Into Preaggregation Control of Y-Series Nonfullerene Acceptors in Liquid State for Highly Efficient Binary Organic Solar Cells.

Leveraging breakthroughs in Y-series nonfullerene acceptors (NFAs), organic solar cells (OSCs) have achieved impressive power conversion efficiencies (PCEs) exceeding 19%. However, progress in advancing OSCs has decelerated due to constraints in realizing the full potential of the Y-series NFAs. Herein, a simple yet effective solid additive-induced preaggregation control method employing 2-chloro-5-iodopyridine (PDCI) is reported to unlock the full potential of the Y-series NFAs. Specifically, PDCI interacts predominantly with Y-series NFAs enabling enhanced and ordered phase-aggregation in solution. This method leads to a notable improvement and a redshifted absorption of the acceptor phase during film formation, along with improved crystallinity. Moreover, the PDCI-induced preaggregation of NFAs in the solution enables ordered molecule packing during the film-formation process through delicate intermediate states transition. Consequently, the PDCI-induced preaggregated significantly improves the PCE of PM6:Y6 OSCs from 16.12% to 18.12%, among the best values reported for PM6:Y6 OSCs. Importantly, this approach is universally applicable to other Y-series NFA-based OSCs, achieving a champion PCE of 19.02% for the PM6:BTP-eC9 system. Thus, the preaggregation control strategy further unlocks the potential of Y-series NFAs, offering a promising avenue for enhancing the photovoltaic performance of Y-series NFA-based OSCs.

Hydronidone induces apoptosis in activated hepatic stellate cells through endoplasmic reticulum stress-associated mitochondrial apoptotic pathway.

BACKGROUND AND AIM: Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals and humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed to investigate whether HDD exerts its anti-fibrotic effect by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the endoplasmic reticulum stress (ERS)-associated mitochondrial apoptotic pathway. METHODS: The carbon tetrachloride (CCl4)- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis models were used for in vivo studies. In vitro studies were conducted using the human hepatic stellate cell line LX-2. The apoptotic effect of HDD on aHSCs was examined using TUNEL and flow cytometry assays. The small interfering RNA (siRNA) technique was employed to downregulate the expression of interest genes. RESULTS: HDD treatment significantly promoted apoptosis in aHSCs in both the CCl4- and DDC-induced liver fibrosis in mice and LX-2 cells. Mechanistic studies revealed that HDD triggered ERS and subsequently activated the IRE1α-ASK1-JNK pathway. Furthermore, the influx of cytochrome c from the mitochondria into the cytoplasm was increased, leading to mitochondrial dysfunction and ultimately triggering apoptosis in aHSCs. Notably, inhibition of IRE1α or ASK1 by siRNA partially abrogated the pro-apoptotic effect of HDD in aHSCs. CONCLUSIONS: The findings of both in vivo and in vitro studies suggest that HDD induces apoptosis in aHSCs via the ERS-associated mitochondrial apoptotic pathway, potentially contributing to the amelioration of liver fibrosis.

Effect of non-enzymatic browning on oysters during hot air drying process: Color and chemical changes and insights into mechanisms.

Hot air drying (HAD) is an extensive method used on oysters and it causes the most intuitive change, a color change. However, the mechanism of color change remains unclear. This study showed that oysters underwent browning during the HAD process. The colorimetric parameter L* decreased while a* and b* increased, all of which were well described by the first-order color kinetic model. Mechanistically, the HDA process induced the oxidative browning of phenols and the generation of Maillard reaction products (5-hydroxymethylfurfural and hydrophilic pyrrole). Meanwhile, the HAD process caused lipid oxidation, leading to the reduction of phosphatidylethanolamine and the generation of reactive carbonyl compounds (aldehydes and α-dicarbonyl compounds). Moreover, the accumulation of hydrophobic pyrroles, a lipid-induced Maillard-like reaction product, was observed. These results suggest that, in addition to phenolic oxidation, sugar- and amino acid-mediated non-enzymatic browning reactions, lipid-mediated Maillard-like reactions play important roles in oyster darkening during the HAD process.

Exploring the role of autophagy in psoriasis pathogenesis: Insights into sustained inflammation and dysfunctional keratinocyte differentiation.

Psoriasis is a common and prevalent chronic papulosquamous cutaneous disorder characterized by sustained inflammation, uncontrolled keratinocyte proliferation, dysfunctional differentiation, and angiogenesis. Autophagy, an intracellular catabolic process, can be induced in response to nutrient stress. It entails the degradation of cellular constituents through the lysosomal machinery, and its association with psoriasis has been well-documented. Nevertheless, there remains a notable dearth of research concerning the involvement of autophagy in the pathogenesis of psoriasis within human skin. This review provides a comprehensive overview of autophagy in psoriasis pathogenesis, focusing on its involvement in two key pathological manifestations: sustained inflammation and uncontrolled keratinocyte proliferation and differentiation. Additionally, it discusses potential avenues for disease management.

The impact of fear of cancer recurrence on the quality of life of breast cancer patients: A longitudinal study of the mediation effect of cortisol and hope.

OBJECTIVE: This longitudinal study sought to explore the impact of cortisol and hope levels on Fear of Cancer Recurrence (FCR) and Quality of Life (QOL) in a cohort of 552 breast cancer patients from three centers in Wuhan City. METHOD: A longitudinal study involving 552 breast cancer patients from three centers in Wuhan City utilized Chinese versions of the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the Herth Hope Index (HHI), and the Functional Assessment of Cancer Therapy-Breast (FACT-B) scale. Cortisol levels were measured thrice daily, and data was collected longitudinally three times. Data analysis was conducted using SPSS 26.0 and Mplus 8.3, employing a longitudinal path model constructed via the cross-lagged method. RESULTS: The results showed there were significant correlations between FCR, cortisol levels, and QOL at different time points. A significant mediating model was found with outcomes related to hope levels. Specifically, FCR predicted a decrease in hope levels (ß = -0.163, p < 0.001), which in turn led to a decrease in overall QOL (ß = -0.078, p < 0.001), with a mediation effect accounting for 10.34%. Although there were correlations between FCR, cortisol levels, and QOL at different time points, further analysis revealed that cortisol levels did not exhibit a mediating effect between the two (95% confidence interval: -0.002 to 0.001). CONCLUSION: This study demonstrated there were significant correlations among FCR, QOL, and hope levels. Considering hope as a crucial mediator between FCR and QOL, potential intervention strategies for optimizing the QOL of breast cancer patients are proposed.

The immune landscape of sepsis and using immune clusters for identifying sepsis endotypes.

Background: The dysregulated immune response to sepsis still remains unclear. Stratification of sepsis patients into endotypes based on immune indicators is important for the future development of personalized therapies. We aimed to evaluate the immune landscape of sepsis and the use of immune clusters for identifying sepsis endotypes. Methods: The indicators involved in innate, cellular, and humoral immune cells, inhibitory immune cells, and cytokines were simultaneously assessed in 90 sepsis patients and 40 healthy controls. Unsupervised k-means cluster analysis of immune indicator data were used to identify patient clusters, and a random forest approach was used to build a prediction model for classifying sepsis endotypes. Results: We depicted that the impairment of innate and adaptive immunity accompanying increased inflammation was the most prominent feature in patients with sepsis. However, using immune indicators for distinguishing sepsis from bacteremia was difficult, most likely due to the considerable heterogeneity in sepsis patients. Cluster analysis of sepsis patients identified three immune clusters with different survival rates. Cluster 1 (36.7%) could be distinguished from the other clusters as being an "effector-type" cluster, whereas cluster 2 (34.4%) was a "potential-type" cluster, and cluster 3 (28.9%) was a "dysregulation-type" cluster, which showed the lowest survival rate. In addition, we established a prediction model based on immune indicator data, which accurately classified sepsis patients into three immune endotypes. Conclusion: We depicted the immune landscape of patients with sepsis and identified three distinct immune endotypes with different survival rates. Cluster membership could be predicted with a model based on immune data.

Expression of 10 circulating cytokines/chemokines in HBV-related liver disease.

BACKGROUND: Cytokines/chemokines play essential roles in the occurrence and progression of hepatitis B virus (HBV) infection. This study aimed to observe the expression patterns of 10 related cytokines/chemokines in the serum of healthy individuals, self-limited patients and HBV-infected patients at different stages of disease (chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular dysplastic nodules (DNs) and hepatocellular carcinoma (HCC)) and to analyze the relationships of these cytokines/chemokines with disease progression. METHODS: The levels of six cytokines (FGF-2, IFN-α2, IL-4, IL-6, IL-10 and VEGF-A) and four chemokines (GRO-α, IL-8, IP-10 and MCP-1) were quantified using Luminex multiplex technology. RESULTS: There were no significant differences in the expression of the 10 cytokines/chemokines between healthy individuals and self-limited patients. The levels of IL-4, IL-6, and IL-8 increased significantly in the CHB and LC groups. IL-10 was highly expressed in the HCC group. The level of IP-10 was significantly greater in all liver disease groups (CHB, LC, DN and HCC) than in the HI and SL-HBV groups, while the level of GRO was significantly lower in all liver disease groups than in the HI and SL-HBV groups. The levels of the 10 cytokines/chemokines were not significantly different between the preoperative group and the two-day postoperative group. Significant increases in the levels of IL-4, VEGF-A and IL-8 and significant decreases in those of IL-10 and GRO-α were observed 3 months after surgery. Correlation analysis revealed that most of the cytokines/chemokines with significant correlation differences were positively correlated before and after HCC surgery. CONCLUSION: Our results highlight the fluctuating status of specific cytokines in HBV infection-related disease progression. It is speculated that these cytokines may be used as serum markers to monitor dynamic changes during the progression of HBV-related liver disease and to predict patient prognosis.

Bioremoval of Co(II) by a novel halotolerant microalgae Dunaliella sp. FACHB-558 from saltwater.

Cobalt pollution is harmful to both the aquatic ecosystem and human health. As the primary producer of aquatic ecosystems in hypersaline environments, unicellular planktonic Dunaliella microalgae is considered to be a low-energy and eco-friendly biosorbent that removes excess cobalt and enhances the vitality of coastal and marine ecosystems. In this study, we found that the halotolerant microalga named Dunaliella sp. FACHB-558 could grow under a salinity condition with 0.5-4.5 M NaCl. A phylogenetic analysis based on the rbcL gene revealed that Dunaliella sp. FACHB-558 is a close relative of Dunaliella primolecta TS-3. At lab-scale culture, Dunaliella sp. FACHB-558 exhibited high tolerance to heavy metal stresses, including cobalt, nickel, and cadmium. Treatment with 60 µM cobalt delayed its stationary phase but ultimately led to a higher population density. Furthermore, Dunaliella sp. FACHB-558 has the ability to adsorb the cobalt ions in the aquatic environment, which was evidenced by the decreased amount of cobalt in the culture medium. In addition, the tolerance of Dunaliella sp. FACHB-558 to cobalt stress was correlated with enhanced nitric oxide content and peroxidase activity. The autophagy inhibitor 3-MA enhanced nitric oxide burst, increased peroxidase activity, and accelerated the bioremoval of cobalt, suggesting that the autophagy pathway played a negative role in response to cobalt stress in Dunaliella sp. FACHB-558. In summary, our study identified a novel microalga possessing high cobalt tolerance and provided a promising natural biosorbent for the research and application of heavy metal bioremediation technology.

Ecological implications and drivers of emerging contaminants in Dongting Lake of Yangtze River Basin, China: A multi-substance risk analysis.

Emerging contaminants (ECs) are increasingly recognized as a global threat to biodiversity and ecosystem health. However, the cumulative risks posed by ECs to aquatic organisms and ecosystems, as well as the influence of anthropogenic activities and natural factors on these risks, remain poorly understood. This study assessed the mixed risks of ECs in Dongting Lake, a Ramsar Convention-classified Typically Changing Wetland, to elucidate the major EC classes, key risk drivers, and magnitude of anthropogenic and natural impacts. Results revealed that ECs pose non-negligible acute (30% probability) and chronic (70% probability) mixed risks to aquatic organisms in the freshwater lake ecosystem, with imidacloprid identified as the primary pollutant stressor. Redundancy analysis (RDA) and structural equation modeling (SEM) indicated that cropland and precipitation were major drivers of EC contamination levels and ecological risk. Cropland was positively associated with EC concentrations, while precipitation exhibited a dilution effect. These findings provide critical insights into the ecological risk status and key risk drivers in a typical freshwater lake ecosystem, offering data-driven support for the control and management of ECs in China.

Epidemiology of malignant tumors in patients with pemphigus: an analysis of trends from 1955 to 2021.

BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.

Novel use of structural equation modeling to examine the development of a framework of patient-centered two-way referral systems for building digital subjective well-being healthcare: A cross-sectional survey in Central China.

Background: Digital health technologies are progressively assuming significant roles in aspects encompassing in-hospital management, patient-centered design, and tiered referral systems. Nevertheless, current studies do not involve exploration into the potential value and mechanisms of digital health in a patient-centered context. This study aimed to explore the development of a framework of comprehensive, evidence-based digital health technologies for the construction of welfare-oriented healthcare. Methods: From March to June 2023, a cross-sectional online study was performed, involving 335 respondents with prior referral experiences hailing from the Central China region. Data on welfare-oriented healthcare factors (clinical pathway management, medical structure configuration, healthcare service accessibility, two-way referrals) underwent factor analysis in advance, and correlation between these factors and their association with two-way referrals was evaluated by testing for direct and indirect (mediating) effects. Results: Firstly, there existed a significant positive correlation between integrative medical indicators and welfare-centered healthcare (ß = 0.02-0.16, p < 0.05). Furthermore, two-way referral had an direct association with integrative medical parameters and the welfare healthcare service system (ß = 0.15-0.31, p < 0.05), but exerted a partial mediatory function in the welfare healthcare service system (ß = 0.005-0.021, α < 0.05). Two-way referrals partially mediate the integrated medical indicators, mainly through direct effects, while also providing complementary support. Clinical pathways, medical structure, and accessibility are closely linked to welfare healthcare and significantly influence healthcare quality. Thus, improving these factors should be prioritized. Conclusion: This study proposes a method combining integrated evaluation indicators with pathway mechanism design. This pathway mechanism design includes key steps such as patient registration, information extraction, hospital allocation or referral, diagnosis and treatment, rehabilitation plan monitoring, service feedback, and demand resolution. This design aims to change patients' intentions in seeking healthcare, thereby increasing their acceptance of bidirectional referrals, and ultimately enhancing the effectiveness and realization of welfare healthcare.

Structure of the SigF1-dependent pilA1 gene promoter and characterization of the light-activated response in the cyanobacterium Synechococcus elongatus PCC 7942.

In cyanobacteria that perform oxygenic photosynthesis, alternative sigma factors can play critical roles in environmental acclimation at the transcriptional initiation step. Here, we found in Synechococcus elongatus PCC 7942 that transcription of the pilA1 gene, encoding the type IV pilin, is dependent on one of the group 3 sigma factors, SigF1. We analyzed the promoter sequence determinants and proposed herein that the -10 and -35 boxes upstream of the transcriptional start site are critical for transcription. Interestingly, while the pilA1 promoter is activated by illumination, RNA polymerase containing SigF1 is already located on the promoter region under dark conditions, prior to illumination. This strongly suggests that promoter activation by light follows the recruitment of RNA polymerase during transcriptional initiation.