Pseudomonas aeruginosa Mediates Host Necroptosis through Rhl-Pqs Quorum Sensing Interaction.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that can cause serious infections in immunocompromised patients. Quorum sensing (QS), a communication system evolved by P. aeruginosa to survey its density, is well acknowledged to be involved in various activities during bacterial infection. Recent studies have revealed the link between P. aeruginosa QS and host innate immune response. Previous evidence suggests that programmed cell death exists in response to P. aeruginosa infection. However, it remains unclear whether QS plays a role in the host programmed cell death process during the infection. In this study, we found that the deficiency of one of QS subsystems, rhl, markedly increased mouse bone marrow macrophage cell death induced by P. aeruginosa, which was accompanied by elevated phosphorylation of RIPK3 and MLKL. This highly increased necroptosis activation was caused by the upregulation of another QS subsystem, pqs, because the deletion of pqs in rhl-deficient P. aeruginosa abolished macrophage necroptosis in vitro and in vivo. In sum, our data highlight the cross-talk between P. aeruginosa QS and host necroptosis, which is executed through the rhl-pqs axis.

Changes in enzyme activity, structure and growth strategies of the rhizosphere microbiome influenced by elevated temperature and CO2.

The impacts of global warming and increased CO2 levels on soil processes and crop growth are concerning. Soil enzymes in the rhizosphere, produced mainly by microbes, play a vital role in nutrients mobilization for plants. Nevertheless, a comprehensive understanding of how microbial communities in the rhizosphere respond to increased temperatures and CO2 levels, particularly in relation to nutrient acquisition, is still lacking. Addressing this problem, we grew soybeans under elevated temperature (ET, +2 °C) and CO2 levels (eCO2, +300 ppm), both individually and in combination (eCO2 + eT), in rhizobox mesocosms. Enzyme activity and microbial communities in soybean rhizospheres were investigated using soil zymography. eCO2 increased enzyme activity by 2.5 % to 8.7 %, while eT expanded the hotspot area from 1.8 % to 3.3 %. The combined factors amplified both the hotspot area by 5.3 % to 10.1 % and enzyme activity by 35.4 % to 67.3 %. Compared to ambient conditions, rhizosphere communities under eCO2 were predominantly comprised of r-strategist keystone taxa, including Acidobacteria, Proteobacteria, and Ascomycota. On the contrary, eT induced a shift in the microbial community towards K-selected taxa, characterized by an increased relative abundance of Basidiomycota and Actinobacteria. Furthermore, the combination of eCO2 and eT led to an increase in the relative abundance of key bacterial species (Acidobacteria, Proteobacteria, and Actinobacteria) as well as fungi (Ascomycota and Basidiomycota). These findings indicate the potential significance of enzyme hotspots in modulating responses to climate change. Changes in enzyme activity and hotspot area could indicate the alteration in microbial growth strategies. The treatments exhibited distinct changes in the composition of microbial communities, in network organization, and in the proportion of species designated as r or K-strategists. Overall, these findings highlight the combined effects of global change factors on bacterial and fungal communities, providing insights into their growth strategies and nutrient mobilization under climate change scenarios.

Regio-, stereo-, and enantioselective ipso- and migratory defluorinative olefin cross-coupling to access highly functionalized monofluoroalkenes.

Monofluoroalkenes serve as nonhydrolyzable mimetics of amides and are frequently encountered in drug candidates. Herein we report a regio-, enantio-, and stereoselective NiH-catalyzed ipso- and migratory defluorinative olefin cross-coupling employing readily available olefins and gem-difluoroalkenes under mild conditions. This approach enables the efficient synthesis of a broad array of structurally diverse monofluoroalkenes bearing a tertiary allylic stereogenic center. Mechanistically, the challenging migratory defluorinative olefin cross-coupling process is successfully realized through a ligand relay catalytic strategy, enabling the formal C(sp3)-H/C(sp2)-F activation with high levels of regio-, stereo-, and enantiocontrol.

Ontology-based inference decision support system for emergency response in tunnel vehicle accidents.

Emergency response plans for tunnel vehicle accidents are crucial to ensure human safety, protect critical infrastructure, and maintain the smooth operation of transportation networks. However, many decision-support systems for emergency responses still rely significantly on predefined response strategies, which may not be sufficiently flexible to manage unexpected or complex incidents. Moreover, existing systems may lack the ability to effectively respond effectively to the impact different emergency scenarios and responses. In this study, semantic web technologies were used to construct a digital decision-support system for emergency responses to tunnel vehicle accidents. A basic digital framework was developed by analysing the knowledge system of the tunnel emergency response, examining its critical elements and intrinsic relationships, and mapping it to the ontology. In addition, the strategies of previous pre-plans are summarised and transformed into semantic rules. Finally, different accident scenarios were modelled to validate the effectiveness of the developed emergency response system.

Key microbial taxa play essential roles in maintaining soil muti-nutrient cycling following an extreme drought event in ecological buffer zones along the Yangtze River.

Climatic extremes, especially extreme droughts, are occurring more frequently and profoundly impacting biogeochemical processes. However, the relative importance of microbial communities on soil nutrient cycling and community maintenance under natural extreme drought events remains elusive. During a record-breaking drought in the Yangtze River Basin (YRB) in the summer of 2022, we collected ambient soils and drought-affected bare and vegetated soils in ecological buffer zones from two sites with similar soil and vegetation characteristics along the YRB, and examined the relative contribution of soil bacterial communities in supporting multi-nutrient cycling index (MNCI) involving carbon-, nitrate- and phosphorus-cycling and their associations with microbial network. Extreme drought decreased (p < 0.05) bacterial α-diversity but increased MNCI in vegetated soils at both sites, while both remained unchanged (p > 0.05) in bare soils, possibly as a result of vegetation releasing rhizodeposits under drought which selectively recruited bacterial communities. Bacterial community compositions were shifted (p < 0.05) only in vegetated soils, and they exerted more influence than α-diversity on soil MNCI. Notably, the Anaerolineae, identified as a biomarker enriched in vegetated soils, had close associations with enzyme activities and soil MNCI at both sites, suggesting their potential recruitment by vegetation to withstand drought. Furthermore, key ecological clusters (Module 1) in bacterial co-occurrence networks at both sites supported (p < 0.05) higher MNCI, despite no substantial variation in network structure due to drought. Specifically, the most important taxa within Module 1 for predicting soil MNCI revealed by random forest modeling analysis (R2 = 0.44 - 0.63, p < 0.001), such as B1-7BS, SBR1031 and Nocardioides, could be deeply involved in soil nitrogen-cycling, suggesting an essential role of specialized interactions of bacterial communities in maintaining soil multifunctionality. Overall, this study demonstrates that changes in biomarkers and functional taxa under extreme drought may better reflect the biological mechanisms involved in microbial communities impacting ecosystem function, which may aid in forecasting the ecological consequences of ongoing climate change in the ecological buffer zones along the YRB.

Clinical and pathogen features of COVID-19-associated infections during an Omicron strain outbreak in Guangzhou, China.

Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens. IMPORTANCE: Our study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

Multi-dimensional signals coupling of simultaneous acquisition stripping current with laser-induced breakdown spectroscopy for accurate analysis of Cd(II) in coexisting Cu(II).

BACKGROUND: Despite significant advancements in detecting Cd(II) using nanomaterials-modified sensitive interfaces, most detection methods rely solely on a single electrochemical stripping current to indicate concentration. This approach often overlooks potential inaccuracies caused by interference from coexisting ions. Therefore, establishing multi-dimensional signals that accurately reflect Cd(II) concentration in solution is crucial. RESULTS: In this study, we developed a system integrating concentration, electrochemical stripping current, and laser-induced breakdown spectroscopy (LIBS) characteristic peak intensity through in-situ laser-induced breakdown spectroscopy and electrochemical integrated devices. By simultaneously acquiring multi-dimensional signals to dynamically track the electrochemical deposition and stripping processes, we observed that replacement reactions occur between Cu(II) and Cd(II) on the surface of Ru-doped MoS2 modified carbon paper electrodes (Ru-MoS2/CP). These reactions facilitate the oxidation of Cd(0) to Cd(II) during the stripping process, significantly increasing the currents of Cd(II). Remarkably, the ingenious design of the Ru-MoS2 sensitive interface allowed for the undisturbed deposition of Cu(II) and Cd(II) during the electrochemical deposition process. Consequently, our in-situ integrated device achieved accurate detection of Cd(II) in complex environments, boasting a detection sensitivity of 8606.5 counts µM⁻1. SIGNIFICANCE: By coupling multi-dimensional signals from stripping current and LIBS spectra, we revealed the interference process between Cu(II) and Cd(II), providing valuable insights for accurate electrochemical analysis of heavy metal ions in complex water environments.

The growth-promoting effects of protein hydrolysates and their derived peptides on probiotics: structure-activity relationships, mechanisms and future perspectives.

Lactic acid bacteria (LAB) are the main probiotics currently available in the markets and are essential for maintaining gut health. To guarantee probiotic function, it is imperative to boost the culture yield of probiotic organisms, ensure the sufficient viable cells in commercial products, or develop effective prebiotics. Recent studies have shown that protein hydrolysates and their derived peptides promote the proliferation of probiotic in vitro and the abundance of gut flora. This article comprehensively reviews different sources of protein hydrolysates and their derived peptides as growth-promoting factors for probiotics including Lactobacillus, Bifidobacterium, and Saccharomyces. We also provide a preliminary analysis of the characteristics of LAB proteolytic systems focusing on the correlation between their elements and growth-promoting activities. The structure-activity relationship and underlying mechanisms of growth-promoting peptides and their research perspectives are thoroughly discussed. Overall, this review provides valuable insights into growth-promoting protein hydrolysates and their derived peptides for proliferating probiotics in vivo or in vitro, which may inspire researchers to explore new options for industrial probiotics proliferation, dairy products fermentation, and novel prebiotics development in the future.

Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro.

BACKGROUND: Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis. METHODOLOGYS/PRINCIPAL FINDINGS: In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms. CONCLUSIONS: Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.

Low-intensity pulsed ultrasound modulates disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord, and there are no effective drug treatments. Low-intensity pulsed ultrasound (LIPUS) has garnered attention as a promising noninvasive neuromodulation method. In this study, we investigate its effects on the motor cortex and underlying mechanisms using the SOD1G93A mouse model of ALS. Our results show that LIPUS treatment delays disease onset and prolongs lifespan in ALS mice. LIPUS significantly increases cerebral blood flow in the motor cortex by preserving vascular endothelial cell integrity and increasing microvascular density, which may be mediated via the ion channel TRPV4. RNA sequencing analysis reveals that LIPUS substantially reduces the expression of genes associated with neuroinflammation. These findings suggest that LIPUS applied to the motor cortex may represent a potentially effective therapeutic tool for the treatment of ALS.

Monoacylglycerol lipase blockades the senescence-associated secretory phenotype by interfering with NF-κB activation and promotes docetaxel efficacy in prostate cancer.

Metabolic reprogramming and cellular senescence greatly contribute to cancer relapse and recurrence. In aging and treated prostate, persistent accumulating senescence-associated secretory phenotype (SASP) of cancer cells often limits the overall survival of patients. Novel strategic therapy with monoacylglycerol lipase (MGLL) upregulation that counters the cellular and docetaxel induced SASP might overcome this clinical challenge in prostate cancer (PCa). With primary comparative expression and survival analysis screening of fatty acid (FA) metabolism signature genes in the TCGA PCa dataset and our single center cohort, MGLL was detected to be downregulated in malignancy prostate tissues and its low expression predicted worse progression-free and overall survival. Functionally, overexpression of MGLL mainly suppresses NF-κB-driven SASP (N-SASP) which mostly restricts the cancer cell paracrine and autocrine tumorigenic manners and the corresponding cellular senescence. Further investigating metabolites, we determined that MGLL constitutive expression prevents lipid accumulation, decreases metabolites preferably, and consequently downregulates ATP levels. Overexpressed MGLL inhibited IκBα phosphorylation, NF-κB p65 phosphorylation, and NF-κB nuclear translocation to deactivate NF-κB transcriptional activities, and be responsible for the repressed N-SASP, partially through reducing ATP levels. Preclinically, combinational treatment with MGLL overexpression and docetaxel chemotherapy dramatically delays tumor progression in mouse models. Taken together, our findings identify MGLL as a switch for lipase-related N-SASP suppression and provide a potential drug candidate for promoting docetaxel efficacy in PCa.

Genetic Influence of Oily Fish Intake on Age-Related Macular Degeneration Risk: A Two-Sample Mendelian Randomization Analysis.

Purpose: Emerging research indicates a link between the intake of fatty fish and age-related macular degeneration (AMD). However, observational studies fall short in establishing a direct causal link between oily fish intake and AMD. We wanted to determine whether causal association lies between oily fish intake and age-related macular degeneration (AMD) risk in human beings. Methods: This two-sample mendelian randomization (MR) study used the MR method to probe the genetic causality in the relationship between oily fish intake and AMD. The genome-wide association study (GWAS) data for AMD were acquired from a Finnish database, whereas the data on fish oil intake came from the UK Biobank. The analysis used several approaches such as inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode MR. In addition, the Cochran's Q test was used to evaluate heterogeneity in the MR data. The MR-Egger intercept and MR-pleiotropy residual sum and outlier (MR-PRESSO) tests were used to assess the presence of horizontal pleiotropy. A leave-one-out sensitivity analysis was conducted to determine the reliability of the association. Results: The IVW method revealed that the intake of oily fish is an independent risk factor for AMD (P = 0.034). It also suggested a minimal likelihood of horizontal pleiotropy affecting the causality (P > 0.05), with no substantial heterogeneity detected in the genetic variants (P > 0.05). The leave-one-out analysis confirmed the reliability and stability of this correlation. Conclusions: This research used a two-sample MR analysis to provide evidence of a genetic causal relationship between the eating of oily fish and AMD. This discovery held potential significance in AMD prevention.

Comparative Analysis of Woody Biomass Fly Ash and Class F Fly Ash as Supplementary Cementitious Materials in Mortar.

Biomass fly ash is a sustainable, eco-friendly cement substitute with economic and performance benefits, being renewable compared to coal fly ash. This study examines using biomass fly ash (BFA) as a sustainable cement substitute, comparing it with Class F fly ash (CFA). With a water-binder ratio of 0.5 and replacement rates of 10%, 15%, 20%, 25%, and 30% (by mass), the research highlights BFA's promising applications. BFA and CFA were mixed into cement paste/mortar to analyze their reactivity and properties, with hydration products CH and C-S-H evaluated at 7, 28, and 91 days. Compressive strength, micro-pore structure, and drying shrinkage (assessed from 7 to 182 days) were tested. Results showed BFA had similar pozzolanic reactions to CFA at later stages. While compressive strength decreased with higher BFA replacement rates, early-stage performance matched CFA; growth was CFA-10 (18 MPa) and BFA-10 (17.6 MPa). BFA mortars exhibited slightly better deformation properties. BFA-30 cement had superior performance, with a lower drying shrinkage rate of 65.7% from 14 to 56 days compared to CFA-10's 73.4% and a more stable shrinkage growth rate decrease to 8.4% versus CFA-10's 6.4% after 56 days. This study concluded that BFA, usable without preprocessing, performed best at a 10-15% replacement rate.

Bioinspired Total Synthesis of 3-epi-Junipercedrol.

A bioinspired total synthesis of 3-epi-junipercedrol, which contains a strained tricyclo[5.2.2.03,7]undecane allo-cedrane framework and five stereocenters, was accomplished via an effective anionic semipinacol rearrangement of a tricyclic cedrane mesylate. The corresponding cedrane precursor was synthesized efficiently by employing the reductive oxy-Nazarov cyclization and an intramolecular aldol condensation as the key steps. This synthetic approach provided a further evidence for the biogenetic relationship between the typical cedrane and allo-cedrane sesquiterpenoids.

Global burden of childhood nutritional deficiencies, 1990-2019.

OBJECTIVES: The aim of this study was to estimate the global burden, trends and health inequality of childhood nutritional deficiencies (CND) from 1990 to 2019. STUDY DESIGN: This was an epidemiological study. METHODS: Data were extracted from the 2019 Global Burden of Disease study. Estimates and 95% uncertainty intervals (UIs) for the rates and numbers were used to evaluate the global burden of CND. Temporal trends in the burden of CND were examined using Joinpoint analysis and average annual percentage changes. To assess health inequality, the slope index was used. RESULTS: In 2019, 52 million new cases of CND and 105,000 deaths related to CND were recorded. Additionally, 435 million prevalence cases and 26 million disability-adjusted life years (DALYs) were recorded in the same year. From 1990 to 2019, the incidence rate of CND generally increased globally, except for the years 2010-2017; conversely, the prevalence, death and DALY rates exhibited decreasing trends over the study period. Half of the analysed regions and countries/territories demonstrated decreasing trends in the incidence, prevalence, death and DALY rates associated with CND. The incidence and prevalence of CND remained high in low-middle sociodemographic index (SDI) and low-SDI regions; however, they exhibited decreasing trends over the 30-year study period. The slope indexes showed that there were no significant changes in SDI-related inequality over 30 years. CONCLUSIONS: Despite decreasing trends in the prevalence, death and DALY rates associated with CND over the three decades, the degree of inequality related to SDI in the burden of nutritional deficiencies has not shown a significant decline. In summary, CND remain a major public health burden in middle-SDI and low-SDI countries.

Association between nutritional literacy and nutrition label use in Chinese community residents.

Introduction: Nutritional literacy (NL) has a critical influence on food choices. The objective of the present study was to examine the association of NL with nutrition label use. Methods: A cross-sectional study was conducted in Bengbu, China. In total, 955 adults were interviewed using a questionnaire designed for the present study to collect information on demographics, lifestyle, nutrition label use, and NL. Binary logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for nutrition label use and its predictive variables. Results: In total, 40.4% of the participants reported looking at nutrition label when purchasing prepackaged foods. NL was significantly positively associated with nutrition label use and specifically with checking nutrition facts table, purported nutrition benefits and purported health benefits. In terms of specific facets of NL, nutrition knowledge, applying skills, and critical skills were associated with nutrition label use. After stratification by monthly income and education, the association between NL and nutrition label use was discovered only in individuals with low monthly income. Additionally, nutrition knowledge was associated with nutrition label use only in adults with high education level, whereas applying skills were associated with nutrition label use only in those with low education level. Conclusion: The use of nutrition label remains low among Chinese community residents, especially the purported nutritional benefits and purported health benefits. NL is positively associated with nutrition label use, especially with respect to functional and critical NL, with differences based on socioeconomic status. The findings highlight the need for NL interventions targeting individuals with different levels of education and income to encourage use of nutrition label in China.

Causality of genetically determined blood metabolites on inflammatory bowel disease: a two-sample Mendelian randomization study.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease of the gastrointestinal tract, including two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Metabolic disorders are important factors in the development of IBD. However, the evidence for the causal relationship between blood metabolites and IBD remains limited. A two-sample MR analysis was applied to evaluate relationships between 486 blood metabolites and IBD. The inverse variance weighted method was chosen as the primary MR analysis method. False discovery rate correction was used to control for false positives in multiple testing. Following complementary and sensitivity analyses were conducted using methods such as weight median, MR-egger, weighted mode, simple mode, Cochran Q test, and MR-PRESSO. Moreover, we performed replication, meta-analysis, Steiger test, and linkage disequilibrium score regression to enhance the robustness of the results. Additionally, we performed metabolic pathway analysis to identify potential metabolic pathways. As a result, we identified four significant causal associations between four blood metabolites and two IBD subtypes. Specifically, one metabolite was identified as being associated with the development of CD (mannose: odds ratio (OR) = 0.19, 95% confidence interval (CI) 0.08-0.43, P = 8.54 × 10-5). Three metabolites were identified as being associated with the development of UC (arachidonate (20:4n6): OR = 0.18, 95% CI 0.11-0.30, P = 2.09 × 10-11; 1, 5-anhydroglucitol: OR = 2.21, 95% CI 1.47-3.34, P = 1.50 × 10-4; 2-stearoylglycerophosphocholine: OR = 2.66, 95% CI 1.53-4.63, P = 5.30 × 10-4). The findings of our study suggested that the identified metabolites and metabolic pathways can be considered as useful circulating metabolic biomarkers for the screening and prevention of IBD in clinical practice, as well as candidate molecules for future mechanism exploration and drug target selection.

Lenvatinib targets STAT-1 to enhance the M1 polarization of TAMs during hepatocellular carcinoma progression.

Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.

Association between drinking water sources and cognitive functioning in Chinese older adults residing in rural areas.

OBJECTIVES: To explore the association between drinking water sources and cognitive functioning among older adults residing in rural China. METHODS: Data were extracted from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey. Drinking water sources were categorized according to whether purification measures were employed. The Chinese version of the Mini-Mental State Examination was used for cognitive functioning assessment, and the score of <24 was considered as having cognitive dysfunction. Cox regression analyses were conducted to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the effects of various drinking water sources, changes in such sources, and its interaction with exercise on cognition dysfunction. RESULTS: We included 2304 respondents aged 79.67 ± 10.02 years; of them, 1084 (44.49%) were men. Our adjusted model revealed that respondents consistently drinking tap water were 21% less likely to experience cognitive dysfunction compared with those drinking untreated water (HR = 0.79, 95% CI: 0.70-0.90). Respondents transitioning from natural to tap water showed were 33% less likely to experience cognitive dysfunction (HR = 0.67, 95% CI: 0.58-0.78). Moreover, the HR (95% CI) for the interaction between drinking tap water and exercising was 0.86 (0.75-1.00) when compared with that between drinking untreated water and not exercising. All results adjusted for age, occupation, exercise, and body mass index. CONCLUSIONS: Prolonged tap water consumption and switching from untreated water to tap water were associated with a decreased risk of cognitive dysfunction in older individuals. Additionally, exercising and drinking tap water was synergistically associated with the low incidence of cognitive dysfunction. These findings demonstrate the importance of prioritizing drinking water health in rural areas, indicating that purified tap water can enhance cognitive function among older adults.

Impact of major hepatectomy on recurrence after resection of hepatocellular carcinoma at CNLC Ib stage: a propensity score matching study.

OBJECTIVE: Patients with hepatocellular carcinoma (HCC) who undergo curative hepatectomy may experience varying remnant liver volumes. Our study aimed to evaluate whether the extent of liver resection has an effect on postoperative recurrence in HCC patients at China Liver Cancer Staging (CNLC) Ib stage. METHODS: A retrospective analysis was conducted on 197 patients who underwent hepatectomy for a solitary HCC lesion measuring ≥5 cm (CNLC Ιb stage) between January 2019 and June 2022. Patients were divided into major hepatectomy (MAH) group (n=70) and minor hepatectomy (MIH) group (n=127) based on the extent of liver resection. Recurrence-free survival (RFS) was compared between the two groups. Propensity score matching (PSM) was employed to minimize bias in the retrospective analysis. RESULTS: Patients who underwent MAH had a greater total complication rate than did those who underwent MIH (35.7% vs. 11.8%, P<0.001). The median RFS was 14.6 months (95% CI: 11.1-18.1) for MAH group and 24.1 months (95% CI 21.2-27.1) for MIH group (P<0.001). After PSM, patients who underwent MAH still had a greater total complication rate than those who underwent MIH (36.7% vs. 16.3%, P=0.037). The median RFS was 13.2 months (95% CI: 15.1-21.7) for MAH group and 22.3 months (95% CI 18.1-26.5) for MIH group (P=0.0013). The Cox regression model identified MAH as an independent poor predictor for HCC recurrence (hazard ratios of 1.826 and 2.062 before and after PSM, respectively; both P<0.05). CONCLUSION: MIH can be performed with fewer postoperative complications and contributes to improved RFS in patients with HCC at CNLC Ιb stage compared to MAH. Parenchyma-sparing resection should be considered the first choice for these HCCs.