Differential effects on natural killer cell production by membrane‐bound cytokine stimulations

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A Surface-Scattering-Based Composite Optical Waveguide Sensor for Aerosol Deposition Detection

Aerosol is a suspension of fine chemical or biological particles in the air, and it is harmful, easily causing air pollution, respiratory diseases, infrastructure corrosion, and poor visibility. Therefore, the development of advanced optical sensors for real-time detection of aerosol deposition is of great significance. In this work, a prism-coupled composite optical waveguide (COWG) sensor for aerosol deposition detection based on surface scattering is proposed and demonstrated theoretically and experimentally. The COWG consists of a single-mode slab glass waveguide locally covered with a tapered thin film of high-index metal oxide. The tapered film can greatly enhance the evanescent field through the adiabatic transition of the fundamental transverse electric (TE0) mode between the uncovered and film-covered regions, thereby enabling the COWG to serve as a simple yet highly sensitive evanescent-wave scattering sensor for sensitive detection of aerosol deposition. The COWG with a tapered layer of Ta2O5 was prepared by masked sputtering, aerosol salt particle deposition on the COWG was successfully detected, and the influence of surface water droplets on the COWG sensor performance was analyzed. The experimental results indicate that the sensitivity of the COWG is 30 times higher than that of the bare glass waveguide

An In-Vitro Study of the Expansion and Transcriptomics of CD4+ and CD8+ Naïve and Memory T Cells Stimulated by IL-2, IL-7 and IL-15

The growth of T cells ex vivo for the purpose of T cell therapies is a rate-limiting step in the overall process for cancer patients to achieve remission. Growing T cells is a fiscally-, time-, and resource-intensive process. Cytokines have been shown to accelerate the growth of T cells, specifically IL-2, IL-7, and IL-15. Here a design of experiments was conducted to optimize the growth rate of different naïve and memory T cell subsets using combinations of cytokines. Mathematical models were developed to study the impact of IL-2, IL-7, and IL-15 on the growth of T cells. The results show that CD4+ and CD8+ naïve T cells grew effectively using moderate IL-2 and IL-7 in combination, and IL-7, respectively. CD4+ and CD8+ memory cells favored moderate IL-2 and IL-15 in combination and moderate IL-7 and IL-15 in combination, respectively. A statistically significant interaction was observed between IL-2 and IL-7 in the growth data of CD4+ naïve T cells, while the interaction between IL-7 and IL-15 was found for CD8+ naïve T cells. The important genes and related signaling pathways and metabolic reactions were identified from the RNA sequencing data for each of the four subsets stimulated by each of the three cytokines. This systematic investigation lays the groundwork for studying other T cell subsets

Identification and Functional Characterization of CYP4D2 Putatively Associated with β-Cypermethrin Detoxification in <i>Phortica okadai</i>

Phortica okadai, a polyphagous pest, serves as a vector for Thelazia callipaeda in China. Currently, there are no effective control strategies for this vector. Agricultural pest control may cause P. okadai to become a threat due to the development of pesticide resistance. Cytochrome P450s (CYP450) plays a significant role in detoxifying xenobiotics in insects. In this study, we performed RNA sequencing of P. okadai exposed to β-cypermethrin for 0 and 1 h and then gene cloning of the five up-regulated CYP450 genes. Three CYP450 genes were successfully cloned, and their expression patterns in different developmental stages and in different tissues were analyzed by RT-qPCR. Pocyp4d2 was observed to have the highest expression in the midgut (fold change 2.82 for Pocyp4d2, 2.62 for Pocyp49a1, and 1.77 for Pocyp28d2). Functional analysis was carried out according to overexpression in S2 cells from the pfastbac1 vector and RNAi with siRNA. The results of the CCK8 assay indicated that the overexpression of the recombinant protein PoCYP4D2 suppressed the decrease in S2 cell viability due to β-cypermethrin. The expression levels of PoCYP4D2 decreased significantly, and the mortality rates increased from 6.25% to 15.0% at 3 h and from 15.0% to 27.5% at 6 h after Pocyp4d2-siRNA injection. These results suggest that Pocyp4d2 may be an essential key gene in the metabolism of β-cypermethrin in P. okadai. This study constitutes a foundation to explore further the functions of P. okadai CYP450 genes in insecticide metabolism

Functional Characterization and Whole-Genome Analysis of an Aflatoxin-Degrading <i>Rhodococcus pyridinivorans</i> Strain

Aflatoxin B1 (AFB1) is one of the most toxic, naturally occurring carcinogen compounds and is produced by specific strains of fungi. Crop contamination with AFB1 can cause huge economic losses and serious health problems. Many studies have examined the microbiological degradation of AFB1, especially the use of efficient AFB1-degrading microorganisms, to control AFB1 contamination. Here, we reported the identification of a new Rhodococcus pyridinivorans strain (4-4) that can efficiently degrade AFB1 (degradation rate 84.9%). The extracellular component of this strain showed the strongest capacity to degrade AFB1 (degradation rate 83.7%). The effects of proteinase K, SDS, temperature, pH, incubation time, and AFB1 concentration on the AFB1 degradation ability of the extracellular component were investigated. We sequenced the complete genome of this strain, encoding 5246 protein-coding genes and 169 RNA genes on a circular chromosome and two plasmids. Comparative genomic analysis revealed high homology with other Rhodococcus strains with high AFB1-degradation ability. Further proteomic analyses of this strain identified a total of 723 proteins in the extracellular component, including multiple potential AFB1-degrading enzymes, along with enzymes that are reported to response to AFB1 treatment. Overall, the results demonstrate that R. pyridinivorans 4-4 would be an excellent candidate for the biodegradation and detoxification of AFB1 contamination

Non‐invasive omics analysis delineates molecular changes in water‐only fasting and its sex‐discriminating features in metabolic syndrome patients

Abstract Fasting has been grown in popularity with multiple potential benefits. However, very few studies dynamically monitor physiological and pathological changes during long‐term fasting using noninvasive methods. In the present study, we recruited 37 individuals with metabolic syndrome to engage in a 5‐day water‐only fasting regimen, and simultaneously captured the molecular alterations through urinary proteomics and metabolomics. Our findings reveal that water‐only fasting significantly mitigated metabolic syndrome‐related risk markers, such as body weight, body mass index, abdominal circumference, blood pressure, and fasting blood glucose levels in metabolic syndrome patients. Indicators of liver and renal function remained within the normal range, with the exception of uric acid. Notably, inflammatory response was inhibited during the water‐only fasting period, as evidenced by a decrease in the human monocyte differentiation antigen CD14. Intriguingly, glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation underwent a sex‐dependent reprogramming throughout the fasting period, whereby males exhibited a greater upregulation of carbohydrate metabolism‐related enzymes than females. This disparity may be attributed to evolutionary pressures. Collectively, our study sheds light on the beneficial physiological effects and novel dynamic molecular features associated with fasting in individuals with metabolic syndrome using noninvasive methods

Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-naïve or anti-TNF-exposed Crohn's disease: a multicenter cohort studyResearch in context

Summary: Background: Ustekinumab and vedolizumab are both effective for treating Crohn’s disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi). Methods: Patients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score–weighted cohort. Findings: A total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423). Interpretation: Ustekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients. Funding: National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline