Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells.

BACKGROUND: Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive. METHODS: Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion. RESULTS: Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells. CONCLUSIONS: Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.

Defibrillation strategies for patients with refractory ventricular fibrillation: A systematic review and meta-analysis.

AIM: The aim of this study was to summarize the existing evidence about the effectiveness of double defibrillation (DD) in comparison to standard defibrillation for patients with refractory ventricular fibrillation (RVF). DD encompasses double "sequential" external defibrillation (DSeq-D) and double "simultaneous" defibrillation (DSim-D), with the study also shedding light on the respective effects of DSeq-D and DSim-D. METHODS: Investigators systematically searched PubMed, EMBASE and Cochrane Central databases for randomized controlled trials (RCTs) and cohort studies from their inception until June 06, 2024. The rate of survival to hospital discharge was the primary outcome, while the incidence of return of spontaneous circulation (ROSC), termination of ventricular fibrillation (VF), survival to hospital admission and good neurologic outcome were secondary outcomes. Relative ratios (RR) and 95% confidence intervals (CIs) were calculated for each outcome. Heterogeneity was assessed using I square value. RESULTS: A total of 6 trials, comprising 1360 patients, were included. One was an RCT, and five were observational cohort studies. The RCT showed that, compared to standard defibrillation, DSeq-D was associated with higher incidences of survival to hospital discharge, termination of VF, ROSC and good neurologic outcome. However, the pooled results of cohort studies found no benefit of DD over standard defibrillation in survival to hospital discharge (RR, 0.91; 95% CI, 0.46-1.78), nor in secondary outcomes. Furthermore, subgroup analysis suggested DSim-D was linked with lower ROSC rate compared to standard defibrillation (RR, 0.65; 95% CI, 0.49-0.86), while there was no significance between DSeq-D and standard defibrillation (RR, 1.00; 95% CI, 0.70-1.42). CONCLUSIONS: The benefit of DSeq-D in survival to hospital discharge for RVF patients was found in the RCT, but not in cohort studies. Additionally, DSim-D should be applied with greater caution for RVF patients. Further validation is needed through larger-scale and higher-quality trials. TRIAL REGISTRY: INPLASY; Registration number: INPLASY202340015; URL: https://inplasy.com/.

Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.

Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD.

Liver injury in paraquat poisoning: A retrospective cohort study.

BACKGROUND AND AIMS: Liver injury is one of the common complications of paraquat (PQ) poisoning, but whether the degree of liver injury is related to patient prognosis is still controversial. This study aimed to investigate whether liver injury was a risk factor for death in PQ-poisoned patients. METHODS: We conducted a retrospective cohort study of PQ-poisoned patients from the past 10 years (2011-2020) from a large tertiary academic medical centre in China. PQ-poisoned patients were divided into a normal liver function group (n = 580) and a liver injury group (n = 60). Propensity score matching (PSM) analysis was then performed. RESULTS: A total of 640 patients with PQ poisoning were included in this study. To reduce the impact of bias, dose of PQ, urinary PQ concentration and time from poisoning to hospital admission were matched between the two groups. A 3:1 PSM analysis was performed, ultimately including 240 patients. Compared with the normal liver function group, patients in the liver injury group were older, had a higher R value ([ALT/ULN]/[ALP/ULN]) (p < .001) and had a higher mortality rate. Cox regression analysis showed that there was no significant association between alanine aminotransferase, alkaline phosphatase, total bilirubin levels and hazard of death, but age, PQ dose, creatine kinase isoenzyme, creatine kinase, white blood cell count, neutrophil percentage and lymphocyte percentage were associated with mortality in patients with PQ poisoning. CONCLUSIONS: The occurrence of liver injury within 48 h after PQ poisoning was a risk factor for mortality, and such liver injury was likely of a hepatocellular nature. Age, PQ dose, creatine kinase isoenzyme and white blood cell count were positively correlated with mortality, while creatine kinase, percentage of neutrophils and lymphocytes were inversely correlated.

Progress and challenges in nitrous oxide decomposition and valorization.

Nitrous oxide (N2O) decomposition is increasingly acknowledged as a viable strategy for mitigating greenhouse gas emissions and addressing ozone depletion, aligning significantly with the UN's sustainable development goals (SDGs) and carbon neutrality objectives. To enhance efficiency in treatment and explore potential valorization, recent developments have introduced novel N2O reduction catalysts and pathways. Despite these advancements, a comprehensive and comparative review is absent. In this review, we undertake a thorough evaluation of N2O treatment technologies from a holistic perspective. First, we summarize and update the recent progress in thermal decomposition, direct catalytic decomposition (deN2O), and selective catalytic reduction of N2O. The scope extends to the catalytic activity of emerging catalysts, including nanostructured materials and single-atom catalysts. Furthermore, we present a detailed account of the mechanisms and applications of room-temperature techniques characterized by low energy consumption and sustainable merits, including photocatalytic and electrocatalytic N2O reduction. This article also underscores the extensive and effective utilization of N2O resources in chemical synthesis scenarios, providing potential avenues for future resource reuse. This review provides an accessible theoretical foundation and a panoramic vision for practical N2O emission controls.

Invited review: Application of biosensors and biomimetic sensors in dairy product testing.

This article summarizes the applications of biosensors and biomimetic sensors in the detection of residues in dairy products. Biosensors use biological molecules, such as enzymes or antibodies, to detect residual substances in dairy products, demonstrating high specificity and sensitivity. Biomimetic sensors, inspired by biosensors, use synthetic materials to mimic biological sensing mechanisms, enhancing stability and reproducibility. Both sensor types have achieved notable success in detecting pesticide residues, veterinary drugs, bacteria, and other contaminants in dairy products. The applications of biological and biomimetic sensors not only improve the efficiency of residue detection in dairy products but also have the potential to reduce the time and cost of traditional methods. Their specificity and high sensitivity make them powerful tools in the dairy industry, thus contributing to ensuring the quality and safety of dairy products and meeting the growing consumer demands for health and food safety.

CT data analysis of catheter morphology and displacement in peritoneal dialysis: an exploratory study.

PURPOSE: Catheter displacement is a common complication of peritoneal dialysis. The aim of this study was to explore the correlation between catheter morphology and displacement by analyzing CT data, providing a scientific basis for optimizing catheter morphology within abdominal wall layers. METHODS: We retrospectively analyzed the clinical data of 94 patients. The parameters for analyzing catheter morphology were defined based on six key points identified from CT images. The covariates considered in the analysis included demographics, primary disease, body size, peritoneal dialysis method, and total weekly urea clearance index. RESULTS: During a mean follow-up period of 1056 ± 480 days, only the angle of the intramuscular part (IM angle) of the catheter significantly correlated with the time to first catheter displacement according to the multivariate analysis (hazard ratio [HR]: 1.039, 95% confidence interval [CI] 1.02-1.058, p < 0.01). When the cut-off value of IM angle was 39.4 ∘ , the area under receiver-operating characteristic (ROC) curve for predicting catheter displacement was 0.791 (95% CI 0.701-0.881, p < 0.01), with a sensitivity and specificity of 82.9% and 66.0%, respectively. Kaplan-Meier survival curves showed that the catheter survival rate was significantly higher in the group with an IM angle < 39.4 ∘ than in the group with an IM angle > 39.4 ∘ (log-rank χ 2 =19.479, p < 0.01). None of the catheter morphology parameters were significantly correlated with technique survival in the multivariate analysis. CONCLUSION: There is a correlation between catheter morphology and catheter displacement. An IM angle > 39.4 ∘ is an independent risk factor for catheter displacement, while the position and angle of the subcutaneous part are not correlated with catheter displacement.

Generation of rat forebrain tissues in mice.

Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.

Epidemiological and etiological characteristics of 1266 patients with severe acute respiratory infection in central China, 2018-2020: a retrospective survey.

BACKGROUND: Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. METHODS: Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. RESULTS: The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. DISCUSSION: In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.

Dynamic changes of Bacterial Microbiomes in Oropharynx during Infection and Recovery of COVID-19 Omicron Variant.

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.

Optimizing dietary rumen-degradable starch to rumen-degradable protein ratio improves lactation performance and nitrogen utilization efficiency in mid-lactating Holstein dairy cows.

The dietary rumen-degradable starch (RDS) to rumen-degradable protein (RDP) ratio, denoted as the RDS-to-RDP ratio (SPR), has been proven to enhance in vitro rumen fermentation. However, the effects of dietary SPR in vivo remain largely unexplored. This study was conducted to investigate the effect of dietary SPR on lactation performance, nutrient digestibility, rumen fermentation patterns, blood indicators, and nitrogen (N) partitioning in mid-lactating Holstein cows. Seventy-two Holstein dairy cows were randomly assigned to three groups (24 head/group), balanced for (mean ± standard deviation) days in milk (116 ± 21.5), parity (2.1 ± 0.8), milk production (42 ± 2.1 kg/d), and body weight (705 ± 52.5 kg). The cows were fed diets with low (2.1, control), medium (2.3), or high (2.5) SPR, formulated to be isoenergetic, isonitrogenous, and iso-starch. The study consisted of a one-week adaptation phase followed by an eight-week experimental period. The results indicated that the high SPR group had a lower dry matter intake compared to the other groups (p < 0.05). A quadratic increase in milk yield and feed efficiency was observed with increasing dietary SPR (p < 0.05), peaking in the medium SPR group. The medium SPR group exhibited a lower milk somatic cell count and a higher blood total antioxidant capacity compared to other groups (p < 0.05). With increasing dietary SPR, there was a quadratic improvement (p < 0.05) in the total tract apparent digestibility of crude protein, ether extract, starch, neutral detergent fiber, and acid detergent fiber. Although no treatment effect was observed in rumen pH, the rumen total volatile fatty acids concentration and microbial crude protein synthesis increased quadratically (p < 0.05) as dietary SPR increased. The molar proportion of propionate linearly increased (p = 0.01), while branched-chain volatile fatty acids linearly decreased (p = 0.01) with increasing dietary SPR. The low SPR group (control) exhibited higher concentration of milk urea N, rumen ammonia N, and blood urea N than other groups (p < 0.05). Despite a linear decrease (p < 0.05) in the proportion of urinary N to N intake, increasing dietary SPR led to a quadratic increase (p = 0.01) in N utilization efficiency and a quadratic decrease (p < 0.05) in the proportion of fecal N to N intake. In conclusion, optimizing dietary SPR has the potential to enhance lactation performance and N utilization efficiency. Based on our findings, a medium dietary SPR (with SPR = 2.3) is recommended for mid-lactating Holstein dairy cows. Nevertheless, further research on rumen microbial composition and metabolites is warranted to elucidate the underlying mechanisms of the observed effects.

Widespread occurrence of two typical N, N'-substituted p-phenylenediamines and their quinones in humans: Association with oxidative stress and liver damage.

While N, N'-substituted p-phenylenediamines (PPDs) and their quinone derivatives (PPDQs) have been widely detected in the environment, there is currently limited data on their occurrence in humans. In this study, we conducted the first serum analysis of two PPDs and PPDQs in the healthy and secondary nonalcoholic fatty liver disease (S-NAFLD) cohorts in South China. The concentrations of four oxidative stress biomarkers (OSBs), namely, 8-iso-prostaglandin F2α (8-PGF2α), 11ß-prostaglandin F2α (11-PGF2α), 15(R)-prostaglandin F2α (15-PGF2α), and 8-hydroxy-2'-deoxyguanosine in serum samples were also measured. Results showed that N-(1,3-dimethybutyl)-N'-phenyl-p-phenylenediamine (6PPD) quinone was the predominant target analytes both in the healthy and S-NAFLD cohorts, with the median concentrations of 0.13 and 0.20 ng/mL, respectively. Significant (p < 0.05) and positive correlations were found between 6PPD concentration and 8-PGF2α, 11-PGF2α, and 15-PGF2α in both the healthy and S-NAFLD cohorts, indicating that 6PPD may be associated with lipid oxidative damage. In addition, concentrations of 6PPD in serum were associated significantly linked with total bilirubin (ß = 0.180 µmol/L, 95%CI: 0.036-0.396) and direct bilirubin (DBIL, ß = 0.321 µmol/L, 95%CI: 0.035-0.677) related to hepatotoxicity. Furthermore, 8-PGF2α, 11-PGF2α, and 15-PGF2α mediated 17.1%, 24.5%, and 16.6% of 6PPD-associated DBIL elevations, respectively. Conclusively, this study provides novel insights into human exposure to and hepatotoxicity assessment of PPDs and PPDQs.

Effects of dietary palmitic acid and oleic acid ratio on milk production, nutrient digestibility, blood metabolites, and milk fatty acid profile of lactating dairy cows.

Adequate energy supply is a crucial factor for maintaining the production performance in cows during the early lactation period. Adding fatty acids (FA) to diets can improve energy supply, and the effect could be related to the chain length and degree of saturation of those FA. This study was conducted to evaluate the effect of different ratios of palmitic acid (C16:0) to oleic acid (cis-9 C18:1) on the production performance, nutrient digestibility, blood metabolites, and milk FA profile in early lactation dairy cows. Seventy-two multiparous Holstein cows (63.5 ± 2.61 days in milk) blocked by parity (2.39 ± 0.20), body weight (668.3 ± 20.1 kg), body condition score (3.29 ± 0.06), and milk yield (47.9 ± 1.63 kg) were used in a completely randomized design. Cows were divided into 3 groups with 24 cows in each group. Cows in the 3 treatment groups were provided iso-energy and iso-nitrogen diets, but the C16:0 to cis-9 C18:1 ratios were different: (1) 90.9% C16:0 + 9.1% cis-9 C18:1 (90.9:9.1); (2) 79.5% C16:0 + 20.5% cis-9 C18:1 (79.5:20.5); and (3) 72.7% C16:0 + 27.3% cis-9 C18:1 (72.7:27.3). Fatty acids were added at 1.3% on a dry matter basis. Although the dry matter intake fat-corrected milk yield and energy-corrected milk yield were not affected, the milk yield, milk protein yield, and feed efficiency increased linearly with increasing cis-9 C18:1 ratio. The milk protein percentage and milk fat yield did not differ among treatments, whereas the milk fat percentage tended to decrease linearly with the increasing cis-9 C18:1 ratio. The lactose yield increased linearly and lactose percentage tended to increase linearly with increasing cis-9 C18:1 ratio, but the percentage of milk total solids and somatic cell count decreased linearly. Although body condition scores were not affected by treatments, body weight loss decreased linearly with increasing cis-9 C18:1 ratio. The effect of treatment on nutrient digestibility was limited, except for a linear increase in ether extract and neutral detergent fiber digestibility with increasing cis-9 C18:1 ratio. There was a linear increase in the concentration of plasma glucose, but the triglyceride and nonesterified FA concentrations decreased linearly with increasing cis-9 C18:1 ratio. As the cis-9 C18:1 ratio increased, the concentration of de novo FA decreased quadratically, but the mixed and preformed fatty acids increased linearly. In conclusion, increasing cis-9 C18:1 ratio could increase production performance and decrease body weight loss by increasing nutrient digestibility, and the ratio that had the most powerful beneficial effect on early lactation cows was 72.7:27.3 (C16:0 to cis-9 C18:1).

Early microbial intervention reshapes phenotypes of newborn Bos taurus through metabolic regulations.

BACKGROUND: The rumen of neonatal calves has limited functionality, and establishing intestinal microbiota may play a crucial role in their health and performance. Thus, we aim to explore the temporal colonization of the gut microbiome and the benefits of early microbial transplantation (MT) in newborn calves. RESULTS: We followed 36 newborn calves for 2 months and found that the composition and ecological interactions of their gut microbiomes likely reached maturity 1 month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction of Bacteroides species, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion and antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. CONCLUSIONS: Our study provides a metagenomic and metabolomic atlas of the temporal development of the gut microbiome in newborn calves. MT can alter the gut microbiome of newborns, leading to improved physiological status and later milk production. The data may help develop strategies to manipulate the gut microbiota during early life, which may be relevant to the health and production of newborn calves.

A review of sources, pathways, and toxic effects of human exposure to benzophenone ultraviolet light filters.

Benzophenone ultraviolet light filters (BPs) are high-production-volume chemicals extensively used in personal care products, leading to widespread human exposure. Given their estrogenic properties, the potential health risks associated with exposure to BPs have become a public health concern. This review aims to summarize sources and pathways of exposure to BPs and associated health risks. Dermal exposure, primarily through the use of sunscreens, constitutes a major pathway for BP exposure. At a recommended application rate, dermal exposure of BP-3 via the application of sunscreens may reach or exceed the suggested reference dose. Other exposure pathways to BPs, such as drinking water, seafood, and packaged foods, contribute minimal to the overall dose. Inhalation is a minor pathway of exposure; however, its contribution cannot be ignored. Human exposure to BPs is an order of magnitude higher in North America than in Asia and Europe. Studies conducted on laboratory animals and cells have consistently demonstrated the toxic effects of BP exposure. BPs are estrogenic and elicit reproductive and developmental toxicities. Furthermore, neurotoxicity, hepatotoxicity, nephrotoxicity, and carcinogenicity have been reported from chronic BP exposure. In addition to animal and cell studies, epidemiological investigations have identified associations between BPs and couples' fecundity and other reproductive disorders, as well as adverse birth outcomes. Further studies are urgently needed to understand the risks posed by BPs on human health.

Quantitative identification of the co-exposure effects of e-waste pollutants on human oxidative stress by explainable machine learning.

Global electronic waste (e-waste) generation continues to grow. The various pollutants released during precarious e-waste disposal activities can contribute to human oxidative stress. This study encompassed 129 individuals residing near e-waste dismantling sites in China, with elevated urinary concentrations of e-waste-related pollutants including heavy metals, polycyclic aromatic hydrocarbons (PAHs), organophosphorus flame retardants (OPFRs), bisphenols (BPs), and phthalate esters (PAEs). Utilizing an explainable machine learning framework, the study quantified the co-exposure effects of these pollutants, finding that approximately 23% and 18% of the variance in oxidative DNA damage and lipid peroxidation, respectively, was attributable to these substances. Heavy metals emerged as the most critical factor in inducing oxidative stress, followed by PAHs and PAEs for oxidative DNA damage, and BPs, OPFRs, and PAEs for lipid peroxidation. The interactions between different pollutant classes were found to be weak, attributable to their disparate biological pathways. In contrast, the interactions among congeneric pollutants were strong, stemming from their shared pathways and resultant synergistic or additive effects on oxidative stress. An intelligent analysis system for e-waste pollutants was also developed, which enables more efficient processing of large-scale and dynamic datasets in evolving environments. This study offered an enticing peek into the intricacies of co-exposure effect of e-waste pollutants.

The association between levosimendan and mortality in patients with sepsis or septic shock: a systematic review and meta-analysis.

BACKGROUND: Levosimendan is increasingly being used in patients with sepsis or septic shock because of its potential to improve organ function and reduce mortality. We aimed to determine if levosimendan can reduce mortality in patients with sepsis or septic shock via meta-analysis. EVIDENCE SOURCES AND STUDY SELECTION: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception through 1 October 2022. Literature evaluating the efficacy of levosimendan in patients with sepsis or septic shock was included. DATA EXTRACTION AND OUTCOME MEASUREMENTS: Two reviewers extracted data and assessed study quality. A meta-analysis was performed to calculate an odds ratio (OR), 95% confidence intervals (CI), and P -values for 28-day mortality (primary outcome). Secondary outcomes included changes in indexes reflecting cardiac function before and after treatment, changes in serum lactate levels in the first 24 h of treatment, and the mean SOFA score during the study period. Safety outcomes included rates of tachyarrhythmias and total adverse reactions encountered with levosimendan. RESULTS: Eleven randomized controlled trials were identified, encompassing a total of 1044 patients. After using levosimendan, there was no statistical difference between groups for 28-day mortality (34.9% and 36.2%; OR: 0.93; 95% CI [0.72-1.2]; P  = 0.57; I 2  = 0%; trial sequential analysis-adjusted CI [0.6-1.42]) and sequential organ failure assessment (SOFA) score, and more adverse reactions seemed to occur in the levosimendan group, although the septic shock patient's heart function and serum lactate level improved. CONCLUSION: There was no association between the use of levosimendan and 28-day mortality and SOFA scores in patients with septic shock, though there was statistically significant improvement in cardiac function and serum lactate.