The effect of fine grits and fine debris concentrations on the MLVSS/MLSS ratio of an activated sludge system.

This study embarks on an explorative investigation into the effects of typical concentrations and varying particle sizes of fine grits (FG, the involatile portion of suspended solids) and fine debris (FD, the volatile yet unbiodegradable fraction of suspended solids) within the influent on the mixed liquor volatile suspended solids (MLVSS)/mixed liquor suspended solids (MLSS) ratio of an activated sludge system. Through meticulous experimentation, it was discerned that the addition of FG or FD, the particle size of FG, and the concentration of FD bore no substantial impact on the pollutant removal efficiency (denoted by the removal rate of COD and ammonia nitrogen) under constant operational conditions. However, a notable decrease in the MLVSS/MLSS ratio was observed with a typical FG concentration of 20 mg/L, with smaller FG particle sizes exacerbating this reduction. Additionally, variations in FD concentrations influenced both MLSS and MLVSS/MLSS ratios; a higher FD concentration led to an increased MLSS and a reduced MLVSS/MLSS ratio, indicating FD accumulation in the system. A predictive model for MLVSS/MLSS was constructed based on quality balance calculations, offering a tool for foreseeing the MLVSS/MLSS ratio under stable long-term influent conditions of FG and FD. This model, validated using data from the BXH wastewater treatment plant (WWTP), showcased remarkable accuracy.

Anti-Agrobacterium tumefactions sesquiterpene derivatives from the marine-derived fungus Trichoderma effusum.

Agrobacterium tumefaciens can harm various fruit trees, leading to significant economic losses in agricultural production. It is urgent to develop new pesticides to effectively treat this bacterial disease. In this study, four new sesquiterpene derivatives, trichoderenes A-D (1-4), along with six known compounds (5-10), were obtained from the marine-derived fungus Trichoderma effusum. The structures of 1-4 were elucidated by extensive spectroscopic analyses, and the calculated ECD, ORD, and NMR methods. Structurally, the hydrogen bond formed between the 1-OH group and the methoxy group enabled 1 to adopt a structure resembling that of resorcylic acid lactones, thereby producing the ECD cotton effect. Compound 3 represents the first example of C12 nor-sesquiterpene skeleton. Compounds 1-10 were tested for their antimicrobial activity against A. tumefactions. Among them, compounds 1-3 and 8-10 exhibited inhibitory activity against A. tumefactions with MIC values of 3.1, 12.5, 12.5, 6.2, 25.0, and 12.5 µg/mL, respectively.

Degree of joint risk factor control and incident chronic kidney disease among individuals with obesity.

AIM: To investigate the extent to which joint risk factor control might attenuate the excess risk of chronic kidney disease (CKD) in participants with obesity. PATIENTS AND METHODS: We included a total of 97 538 participants who were obese at baseline and matched 97 538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on six major CKD risk factors, including blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, albuminuria, smoking and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD, following participants from their baseline assessment until the occurrence of CKD, death, or the end of the follow-up period. RESULTS: Among participants with obesity, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (hazard ratio: 0.89; 95% confidence interval: 0.86-0.91) reduced risk of CKD among participants with obesity, with the optimal controlling of all six risk factors associated with a 49% (hazard ratio: 0.51; 95% confidence interval: 0.43-0.61) decrease in risk of CKD. Furthermore, in individuals with obesity who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared with normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared with women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to non-users (pinteraction = 0.017, 0.033 and 0.014, respectively). CONCLUSION: The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among individuals with obesity. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity.

Frailty Status, Sedentary Behaviors, and Risk of Incident Bone Fractures.

BACKGROUND: The associations of physical pre-frailty and frailty with bone fractures and the modified effect of sedentary lifestyle remain uncertain. This study was performed to explore the association of physical pre-frailty and frailty with risk of incident bone fractures, and test the modification effects of sedentary lifestyle and other risk factors. METHODS: This cohort study included 413 630 participants without bone fractures at baseline in the UK Biobank study between 2006 and 2010 and followed up to 2021. The mean age of the participants was 56.5 years. A total of 224 351 (54.2%) enrolled participants were female and 376 053 (90.9%) included participants were White. Three Cox regression models were constructed to analyze the association of pre-frailty and frailty with total fractures, hip fractures, vertebrae fractures, and other fractures. RESULTS: As compared with the physical nonfrailty group, the multivariate-adjusted hazard ratios were 1.17 (95% confidence interval [CI]: 1.14-1.21) and 1.63 (95% CI: 1.53-1.74) for the physical pre-frailty group and frailty group, respectively (p-trend < .001). In addition, we found that sedentary behavior time significantly accentuated the associations of physical pre-frailty and frailty with total fractures (p-interaction <.001), hip fractures (p-interaction = .013), and other fractures (p-interaction <.001). CONCLUSIONS: Our results indicate that physical pre-frailty and frailty are related to higher risks of bone fractures; such association was more pronounced among those with longer sedentary behavior time.

Sulfonic Acid-Functionalized Graphdiyne for Effective Li-S Battery Separators.

Lithium-sulfur (Li-S) batteries enable a promising high-energy-storage system while facing practical challenges regarding lithium dendrites and lithium polysulfides (LiPSs) shuttling. Herein, a fascinating SO3H-functionalized graphdiyne (SOGDY) was developed by grafting SO3H onto GDY to modify the separator in Li-S batteries. It realizes structure-retained material transformation, that is, SOGDY retains the crystalline all-carbon network and uniform subnanopores from the initial GDY. The abundant SO3H and uniform pores create a rapid Li+ transport relay station, benefit rapid Li+ transport and even lithium deposition, and prevent lithium dendrite growth. The spatial obstruction and strong polar adsorption sites from SO3H effectively inhibit LiPS shuttling. Additionally, SOGDY establishes a fast electron-transfer pathway to facilitate the LiPS conversion. The SOGDY/PP separator exhibited steady cycling at 1 mA cm-2 over 3500 h in the Li∥Li symmetric battery and achieved outstanding low-temperature and high-rate performance in the Li-S battery with a high initial specific capacity of 804.5 mA h g-1 and a final capacity of 504.9 mA h g-1 after 500 cycles at 3 C and -10 °C. This work demonstrates that introducing a stable all-carbon network and uniform functionalized nanopores is an effective strategy to modify the Li-S battery separator.

Polarization-insensitive multimode interference coupler on an x-cut thin-film lithium niobate platform.

Thin-film lithium niobate (TFLN) is a promising integrated photonics platform but currently lacks a polarization-insensitive multimode interference (MMI) coupler, a crucial component for polarization-related optical communication applications such as polarization management, polarization-division multiplexing, and polarization-insensitive modulation systems. This paper presents a novel, to the best of our knowledge, approach by rotating the MMI structure on an anisotropic x-cut TFLN at specific angles to compensate for the difference in the beat length between the two polarizations. A polarization-insensitive 1 × 2 MMI coupler is experimentally achieved with measured transmittances of -2.5 to -4 dB for both output ports and polarization modes in the wavelength range of 1520-1580 nm.

The effect of Mankai plant consumption on postprandial glycaemic response among patients with type 2 diabetes: A randomized crossover trial.

AIM: To explore the effect of Mankai, a cultivated aquatic duckweed green plant, on postprandial glucose (PG) excursions in type 2 diabetes (T2D). METHODS: In a 4-week, randomized crossover-controlled trial, we enrolled 45 adults with T2D (HbA1c range: 6.5%-8.5%) from two sites in Israel. Participants were randomized to drink Mankai (200 mL of raw-fresh-aquatic plant + 100 mL of water, 40 kcal, ~10 g of dry matter equivalent) or water (300 mL) following dinner, for 2 weeks each, with a 4-day washout interval, without dietary, physical activity or pharmacotherapy alterations. We used continuous glucose monitoring (CGM) devices. RESULTS: Forty patients (adherence rate = 88.5%; 743 person-intervention-days, 68.9% men, age = 64 years, HbA1c = 6.8%) completed the study with a consistent diet and complete CGM reads. Only two-thirds of the individuals responded beneficially to Mankai. Overall, Mankai significantly lowered the PG peak by 19.3% (∆peak = 24.3 ± 16.8 vs. 30.1 ± 18.5 mg/dL; P < .001) and delayed the time-to-peak by 20.0% (112.5 [interquartile range: 75-135] vs. 90 [60-105] min; P < .001) compared with water. The PG incline and decline slopes were shallower following postdinner Mankai (incline slope: 16.8 vs. water: 29.9 mg/[dL h]; P < .001; decline slope: -6.1 vs. water: -7.9 mg/[dL h]; P < .01). Mean postprandial net incremental area-under-the-glucose-curve was lowered by 20.1% with Mankai compared with water (P = .03). Results were consistent across several sensitivity and subgroup analyses, including across antidiabetic pharmacotherapy treatment groups. Within 2 weeks, the triglycerides/high-density lipoprotein cholesterol ratio in the Mankai group (-0.5 ± 1.3) decreased versus water (+0.3 ± 1.5, P = .05). CONCLUSIONS: Mankai consumption may mitigate the PG response in people with T2D with an ~20% improvement in glycaemic values. These findings provide case-study evidence for plant-based treatments in T2D to complement a healthy lifestyle and pharmacotherapy.

The mediating role of self-esteem in the relationship between hope and life satisfaction among university students during a global health crisis.

Background and Aims: The worldwide health emergency sparked by the COVID-19 pandemic has deeply shaken educational environments, posing unprecedented challenges to university students' well-being. While individual links between self-esteem, hope, and well-being are established, their combined impacts during crises remain underexplored. Our study addresses this gap by investigating the interplay among hope, self-esteem, and life satisfaction within the context of university students navigating the challenges posed by the pandemic. Methods: Conducting an online cross-sectional self-administered survey during Hong Kong's third pandemic wave, we measured hope, self-esteem, and life satisfaction using validated scales. Three hundred and fifteen university students (211 females; mean age = 22.08; SD = 2.74) participated. Results: Through multiple regression and mediation analyses, our findings indicate that university students with elevated hope and self-esteem scored higher on life satisfaction measures. Specifically, our analysis revealed that self-esteem may serve as a partial mediator in the relationship between hope and life satisfaction, highlighting how heightened hope indirectly enhances life satisfaction by strengthening self-esteem. Conclusion: This study reveals intricate relationships among hope, self-esteem, and life satisfaction in university students, particularly during external adversities like the COVID-19 pandemic. The implications extend to mental health interventions, emphasizing the potential benefits of cultivating hope and self-esteem to enhance life satisfaction among university students confronting formidable challenges.

Exploring the Mediating Role of Self-Regulation in Bullying Victimization and Depressive Symptoms among Adolescents: A Cross-Regional and Gender Analysis.

This study explores the mediating role of self-regulation in the relationship between bullying victimization and depressive symptoms among adolescents, considering the moderating effects of gender and region. A cross-sectional analysis was conducted with 3984 adolescents aged 12-18 from the United Kingdom, Hong Kong, Taiwan, and the Netherlands. Data were collected via an online survey administered through Qualtrics. The survey included validated measures such as the Illinois Bullying Scale (IBS) to measure bullying victimization, the Adolescent Self-Regulatory Inventory (ASRI) to measure self-regulation, and the Patient Health Questionnaire (PHQ) to measure depression. The SPSS macro PROCESS was employed for data analysis, with model 4 used for testing the mediating effects of self-regulation and model 1 for assessing the moderating effects of gender and region. The results demonstrated significant associations between bullying victimization, self-regulation, and depressive symptoms. Self-regulation mediated the positive association between bullying victimization and depression, with notable variations across genders and regions. Specifically, male students in Hong Kong exhibited an increased susceptibility to depression when subjected to bullying. These findings underscore the protective role of self-regulation in mitigating the adverse effects of bullying victimization on adolescent mental health. Implications for interventions and prevention strategies targeting adolescent depression are discussed.

Sex differences in circulating metabolites across glycemic status and risk of coronary heart disease.

Background: Women with type 2 diabetes (T2D) have a 50% excess risk of coronary heart disease (CHD) than men with T2D. We compared circulating metabolites and their associations with CHD in men and women across glycemic status. Methods: We used metabolomic data (lipoproteins, fatty acids, amino acids, glycolysis, ketones, inflammation, and fluid balance) for 87,326 CHD-free UK Biobank participants. We used linear regressions to examine the association of sex and metabolites (log) in newly diagnosed T2D (diagnosis<2 yrs from baseline), prediabetes (A1c 5.7-6.5%), and euglycemia, accounting for age, race, Deprivation Index, income, smoking, alcohol drinking, obesity, physical activity, medications for hypertension, hyperlipidemia, and diabetes. We used Cox models to evaluate the association of metabolites and CHD risk by sex, adjusting the same covariates and menopausal status (women). All analyses were FDR-adjusted. Findings: We included 1250 individuals with new T2D, 12,706 with prediabetes, and 83,315 with euglycemia. In adjusted linear regressions, women showed a progressive increase in atherogenic lipid and lipoprotein markers and inflammatory marker, glycoprotein acetyls, compared to men as their glycemic status advanced. However, women had lower levels of albumin during this transition. Menopausal status did not alter these sex differences. In a 10-year follow-up, an SD higher total TG, TG in VLDL, LDL, and HDL, saturated fatty acids (SFA) were positively associated with a higher risk of CHD in women with T2D but not in men (p-interactions 0.03-0.15). Interpretation: With advancing glycemic status, women exhibited higher levels of atherogenic lipids and lipoproteins, as well as inflammatory markers, but lower circulating albumin. Women with T2D appear to be at a higher risk of CHD associated with TG, VLDL-TG, LDL-TG, and HDL-TG, and SFA than men with T2D.

Associations of the EAT-Lancet reference diet with metabolic dysfunction-associated steatotic liver disease and its severity: a multi-cohort study.

BACKGROUND AIMS: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and risk of MASLD and its severity. APPROACH RESULTS: This prospective multi-cohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1,137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. Additionally, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3,010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6,454 person-years of follow-up, and the UK Biobank 1,350 developed MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR=0.87, 95% CI: 0.78, 0.96; GNHS: HR=0.79, 95% CI: 0.64, 0.98; UK Biobank: HR=0.73, 95% CI: 0.63, 0.85). Moreover, liver controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (ß=-5.895; 95% CI: -10.014, -1.775). CONCLUSIONS: Adherence to the EAT-Lancet reference diet was inversely associated with risk of MASLD as well as its severity.

Reference Twice: A Simple and Unified Baseline for Few-Shot Instance Segmentation.

Few-Shot Instance Segmentation (FSIS) requires detecting and segmenting novel classes with limited support examples. Existing methods based on Region Proposal Networks (RPNs) face two issues: 1) Overfitting suppresses novel class objects; 2) Dual-branch models require complex spatial correlation strategies to prevent spatial information loss when generating class prototypes. We introduce a unified framework, Reference Twice (RefT), to exploit the relationship between support and query features for FSIS and related tasks. Our three main contributions are: 1) A novel transformer-based baseline that avoids overfitting, offering a new direction for FSIS; 2) Demonstrating that support object queries encode key factors after base training, allowing query features to be enhanced twice at both feature and query levels using simple cross-attention, thus avoiding complex spatial correlation interaction; 3) Introducing a class-enhanced base knowledge distillation loss to address the issue of DETR-like models struggling with incremental settings due to the input projection layer, enabling easy extension to incremental FSIS. Extensive experimental evaluations on the COCO dataset under three FSIS settings demonstrate that our method performs favorably against existing approaches across different shots, e.g., +8.2/ + 9.4 performance gain over state-of-the-art methods with 10/30-shots. Source code and models will be available at this github site.

Is There an Ideal Diet? Some Insights from the POUNDS Lost Study.

Diets for weight loss have a long history but an ideal one has not yet been clearly identified. To compare low-fat and lower carbohydrate diets, we designed The Preventing Overweight by Novel Dietary Strategies (POUNDS) Lost study. This is a 2 × 2 factorial study with diets of 20% or 40% fat and 15% or 25% protein with a graded carbohydrate intake of 35, 45, 55 and 65%. Weight loss, overall, was modest at nearly 6% with all four diets, and no significant dietary difference. The variability in weight loss in each diet group was significant, ranging from greater than 20% to a small weight gain. Studies of genetic variations in relation to weight loss showed that the diet that was selected could significantly affect weight loss, emphasizing that there is no ideal diet and more than one diet can be used to treat obesity. Weight loss was also influenced by the level of baseline triiodothyronine or thyroxine, and baseline carbohydrate and insulin resistance. Achieving a stable Health Eating Food Diversity Index, eating more protein, eating more fiber, engaging in more physical activity, sleeping better and eating less ultra-processed foods were beneficial strategies for weight loss in this trial. Although there is no "ideal diet", both the DASH diet and the Mediterranean diet have clinical trials showing their significant benefit for cardiovascular risk factors. Finally, the lesson of the "Last Chance Diet", which recommended a diet with protein from gelatin, proved that some diets could be hazardous.

Increased microgastropoda sampling give new insights into the phylogenetic relationships of Littorinoidea (Littorinimorpha).

Littorinoidea is one of the most diverse radiations and the most successful group that evolutionary transitions from marine to terrestrial within Littorinimorpha. With such an unmatched diversity, few phylogenetic investigations have attempted to understand their evolutionary relationships, and existing research has primarily focused on typical intertidal species. To address this gap, we conducted the first phylogenomic analysis of the Littorinoidea, leveraging 35 transcriptomes to investigate their internal relationships. Our analyses revealed significant revisions necessary within the Littorinoidea: 1) Pomatias appears distantly related to Littorinidae, suggesting a potential ancestral origin outside of Littorinoidea, challenging traditional classification. The homology of penial innervation within Littorinoidea warrants reevaluation. 2) Lacuna's placement indicates a close relationship with Naticidae, prompting consideration for its removal from Littorinidae. 3) Based on the current phylogenetic research, Peasiella may belong to a distinct family separate from Littorinidae. 4) Our findings support revising the placement of Pteropods within the Littorinimorpha, which is situated phylogenetically between the families Littorinoidea and Naticoidea. Additionally, we highlight the impact of site heterogeneity and evolutionary rate variation on phylogenetic inference. Our study provides a robust phylogenomic framework for the Littorinoidea, emphasizing the importance of including microgastropoda taxa in molecular phylogenetic reconstructions of gastropod subgroups.

Enhanced wastewater treatment with an AnF-AAO system for improved internal carbon source utilization.

The main challenge in removing nutrients from municipal wastewater in China is the lack of available carbon sources. While hydrolysis acidification tanks can improve wastewater biodegradability by effectively utilizing internal carbon sources, high sludge concentrations are difficult to control in traditional tank variants. In this study, an innovative anaerobic filter (AnF) hydrolysis acidification reactor composed of a continuously stirred tank reactor (CSTR) and cloth media filter was designed to regulate and maintain high sludge concentrations in the hydrolysis acidifier. The reactor was used as a pretreatment unit for the anaerobic/anoxic/oxic (AAO) units and combined into an AnF-AAO system to explore the effectiveness of internal carbon source utilization in wastewater. The results indicate that as the sludge concentration in the hydrolysis acidifier increased, the hydrolysis and acidification processes became more efficient. The optimal sludge concentration was 40 g/L, which significantly increased the production of soluble chemical oxygen demand and volatile fatty acids. Above this concentration, the efficiency decreased. Compared to traditional AAO processes, the AnF-AAO system achieved superior total nitrogen and phosphorus removal with shorter hydraulic retention times and reduced sludge production by a significant amount of 35%. Due to its capacity for enhancing internal carbon source utilization, the AnF-AAO system constitutes a promising approach for sustainable urban wastewater treatment.

Investigation of the causal relationship between breast cancer and thyroid cancer: a set of two-sample bidirectional Mendelian randomization study.

PURPOSE: A potential association between breast (BC) and thyroid cancer (TC) has been observed. We investigated if the relationship between BC and TC is causal using bidirectional Mendelian randomization (MR) in Asian and European populations. METHODS: BC-linked single nucleotide polymorphisms (SNPs) were acquired from a genome-wide association study (GWAS) conducted by the Breast Cancer Association Consortium and Biobank Japan. The most recent TC GWAS data were obtained from the FinnGen Project and National Biobank of Korea. We assessed the potential causal relationship between BC and TC using various MR methods, including inverse-variance-weighting (IVW). Sensitivity, heterogeneity, and pleiotropic tests were performed to assess reliability. RESULTS: We found a bidirectional causal association between BC and TC within Europeans (IVW, TC on BC: odds ratio [OR] 1.090, 95% confidence interval [CI]: 1.012-1.173, P = 0.023; BC on TC: OR 1.265, 95% CI: 1.158-1.381, P < 0.001). A one-way causal relationship between BC susceptibility and TC risk was found in Asians (IVW BC on TC: OR 2.274, 95% CI: 2.089-2.475, P < 0.001). Subsequently, we identified a noteworthy bidirectional causal relationship between estrogen receptor (ER)-positive BC and TC (IVW, TC on ER-positive BC: OR 1.104, 95% CI: 1.001-1.212, P = 0.038; ER-positive BC on TC: OR 1.223, 95%CI: 1.072-1.395, P = 0.003), but not ER-negative BC and TC in Europeans. CONCLUSION: We revealed a reciprocal causal association between ER-positive BC and TC. These findings establish a theoretical framework for the simultaneous surveillance and treatment of BC and TC.

Gut-Microbiota-Related Metabolite Phenylacetylglutamine and Risk of Incident Coronary Heart Disease among Women.

CONTEXT: Phenylacetylglutamine (PAGln) is a novel metabolite derived from gut microbial metabolism of dietary proteins, specifically phenylalanine, which may be linked to risks of adverse cardiovascular events. OBJECTIVE: We investigated whether higher plasma levels of PAGln were associated with a greater risk of incident coronary heart disease (CHD) and tested whether adherence to a plant-based diet, which characterizes habitual dietary patterns of animal and plant food intake, modified the associations. METHODS: We examined associations between plasma PAGln and risk of incident CHD over 11-16 years in a nested case-control study of 1520 women (760 incident cases and 760 controls) from the Nurses' Health Study. Separately, we analyzed relations between PAGln and dietary intakes measured through dietary records in the Women's Lifestyle Validation Study (n=725). RESULTS: Higher PAGln levels were related to a greater risk of CHD (p <0.05 for dose-response relationship). Higher PAGln was associated with greater red/processed meat intake and lower vegetable intake (p <0.05 for all). We found a significant interaction between PAGln and adherence to plant-based diet index (PDI) on CHD (Pinteraction=0.008); higher PAGln levels were associated with an increased risk of CHD (relative risk per 1 SD: 1.22 [95% CI: 1.05, 1.41]) among women with low PDI but not among those with high PDI. CONCLUSION: Higher PAGln was associated with higher risk of CHD, particularly in women with dietary patterns of eating more animal foods and fewer plant-based foods. Adherence to plant-based diets might attenuate unfavorable associations between a novel microbial metabolite and CHD risk.

Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer.

Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) presses for a comprehensive understanding of treatment responsiveness. Here, we analyze multiple sequential single-cell samples from 22 patients undergoing PD-1 blockade to map the evolution of local and systemic immunity of CRC patients. In tumors, we identify coordinated cellular programs exhibiting distinct response associations. Specifically, exhausted T (Tex) or tumor-reactive-like CD8+ T (Ttr-like) cells are closely related to treatment efficacy, and Tex cells show correlated proportion changes with multiple other tumor-enriched cell types following PD-1 blockade. In addition, we reveal the less-exhausted phenotype of blood-associated Ttr-like cells in tumors and find that their higher abundance suggests better treatment outcomes. Finally, a higher major histocompatibility complex (MHC) II-related signature in circulating CD8+ T cells at baseline is linked to superior responses. Our study provides insights into the spatiotemporal cellular dynamics following neoadjuvant PD-1 blockade in CRC.

Effectiveness of cloth media filters on mitigating membrane fouling in anaerobic filter membrane bioreactors.

Membrane fouling is a persistent challenge that has impeded the broader application of anaerobic membrane bioreactors (AnMBRs). To mitigate membrane fouling, between the outlet of the UASB anaerobic bioreactor and the PVDF membrane to form the anaerobic filter membrane bioreactor (AnFMBR) system. Through comprehensive experiments, the optimal pore size for cloth filters was determined to be 50 µm. A comprehensive assessment over 140 days of operation shows that the novel AnFMBR had significantly greater resistance to membrane pollution than the traditional AnMBR. The AnFMBR system membrane tank exhibited lower mixed liquor suspended solid and mixed liquor volatile suspended solid concentrations, smaller sludge particle sizes, increased hydrophilicity of sludge flocs, and optimized microbial community distribution compared to those of conventional AnMBRs. The total solids foulant accumulation rate in the AnMBR was 5.1 g/m2/day, while in the AnFMBR, the rate was 2.4 g/m2/day, marking a 53.7 % decrease in fouling rate for the AnFMBR compared with the AnMBR. This decrease indicates that integrating the filtration assembly significantly lowered the rate of solid foulant accumulation on the membrane surface, primarily by controlling the buildup of solid foulants in the cake layer, thereby alleviating membrane fouling. AnFMBR compared to AnMBR, the membrane fouling rate halved, effectively doubled the interval between membrane cleaning from seven days, as observed in the AnMBR system, to fourteen days. These findings underscore the potential of integrating cloth media filters into AnMBRs to improve operational efficiency, economic viability, and sustainability.

Effects of genetically proxied lipid-lowering drugs on acute myocardial infarction: a drug-target mendelian randomization study.

OBJECTIVE: High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. METHODS: Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. RESULTS: Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004-1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002-1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995-0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994-0.999 and 0.986, 0.975-0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993-0.996). CONCLUSIONS: The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.