Association Between the Improvement of Knowledge, Attitude and Practice of Hypertension Prevention and Blood Pressure Control-A Cluster Randomized Controlled Study.

BACKGROUND: Hypertension-related knowledge, attitude and practice (KAP) of hypertensive patients can affect the awareness, treatment and control of hypertension. However, little attention has been paid to the association between the change of hypertension preventive KAP and blood pressure (BP) control in occupational population using longitudinal data. We assess the effectiveness of a workplace-based multicomponent hypertension intervention program on improving the level of KAP of hypertension prevention, and the association between improvement in KAP and BP control during intervention. METHODS: From January 2013 to December 2014, workplaces across 20 urban regions in China were randomized to either the intervention group (n = 40) or control group (n = 20) using a cluster randomized control method. All employees in each workplace were asked to complete a cross-sectional survey to screen for hypertension patients. Hypertension patients in the intervention group were given a 2-year workplace-based multicomponent hypertension intervention for BP control. The level of hypertension prevention KAP and BP were assessed before and after intervention in the two groups. RESULTS: Overall, 3331 participants (2658 in the intervention group and 673 in the control group) were included (mean [standard deviation] age, 46.2 [7.7] years; 2723 men [81.7%]). After 2-year intervention, the KAP qualified rate was 63.2% in the intervention groups and 50.1% in the control groups (odds ratio = 1.65, 95% CI, 1.36∼2.00, P < .001). Compared with the control group decreased in the qualified rate of each item of hypertension preventive KAP questionnaire, all the items in the intervention group increased to different degrees. The increase of KAP score was associated with the decrease of BP level after intervention. For 1 point increase in KAP score, systolic blood pressure (SBP) decreased by .28 mmHg and diastolic blood pressure (DBP) decreased by .14 mmHg [SBP: ß = -.28, 95%CI: -.48∼-.09, P = .004; DBP: ß = -.14, 95%CI: -.26∼-.02, P = .024]. SBP and DBP was significantly in manual labor workers (SBP: ß = -.34, 95%CI: -.59∼-.09, P = .008; DBP: ß = -.23, 95%CI: -.38∼-.08, P = .003), workers from private enterprise, state-owned enterprise (SOE) (SBP: ß = -.40, 95%CI: -.64∼-.16, P = .001; DBP: ß = -.21, 95%CI: -.36∼-.06, P = .005) and a workplace with an affiliated hospital (SBP: ß = -.31, 95%CI: -.52∼-.11, P = .003; DBP: ß = -.16, 95%CI: -.28∼-.03, P = .016). The improvement of knowledge (SBP: ß = -.29, 95%CI: -.56∼-.02, P = .038; DBP: ß = -.12, 95%CI: -.29∼.05, P = .160), as well as attitude (SBP: ß = -.71, 95%CI: -1.25∼-.18, P = .009; DBP: ß = .18, 95%CI: -.23∼.59, P = .385) and behavior (SBP: ß = -.73, 95%CI: -1.22∼-.23, P = .004; DBP: ß = -.65, 95%CI: -.97∼-.33, P < .001) was gradually strengthened in relation to BP control. CONCLUSION: This study found that workplace-based multicomponent hypertension intervention can effectively improve the level of hypertension preventive KAP among employees, and the improvement of KAP levels were significantly associated with BP control. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR-ECS-14004641.

Selective degradation of PL2L60 by metabolic stresses­induced autophagy suppresses multi­cancer growth.

It has been reported that PL2L60 proteins, a product of PIWIL2 gene which might be activated by an intragenic promoter, could mediate a common pathway specifically for tumorigenesis. In the present study, it was further identified by using western blot assay that the PL2L60 proteins could be degraded in cancer cells through a mechanism of selective autophagy in response to oxidative stress. The PL2L60 was downregulated in various types of cancer cells under the hypoxic condition independently of HIF­1α, resulting in apoptosis of cancer cells. Inhibition of autophagy by small interfering RNA targeting of either Beclin­1 (BECN1) or Atg5 resulted in restoration of PL2L60 expression in hypoxic cancer cell. The hypoxic degradation of PL2L60 was also blocked by the attenuation of the autophagosome membrane protein Atg8/microtubule­associated protein 1 light chain 3 (LC3) or autophagy cargo protein p62 expression. Surprisingly, Immunofluorescence analysis demonstrated that LC3 could be directly bound to PL2L60 and was required for the transport of PL2L60 from the nucleus to the cytoplasm for lysosomal flux under basal or activated autophagy in cancer cells. Moreover, flow cytometric analysis displayed that knocking down of PL2L60 mRNA but not PIWIL2 mRNA effectively inhibited cancer cell proliferation and promoted apoptosis of cancer cells. The similar results were obtained from in vivo tumorigenic experiment, in which PL2L60 downregulation in necroptosis areas was confirmed by immunohistochemistry. These results suggested that various cancer could be suppressed by promoting autophagy. The present study revealed a key role of autophagic degradation of PL2L60 in hypoxia­induced cancer cell death, which could be used as a novel therapeutic target of cancer.

Candidate Gene Identification and Transcriptome Analysis of Tomato male sterile-30 and Functional Marker Development for ms-30 and Its Alleles, ms-33, 7B-1, and stamenless-2.

Male sterility is a valuable trait for hybrid seed production in tomato (Solanum lycopersicum). The mutants male sterile-30 (ms-30) and ms-33 of tomato exhibit twisted stamens, exposed stigmas, and complete male sterility, thus holding potential for application in hybrid seed production. In this study, the ms-30 and ms-33 loci were fine-mapped to 53.3 kb and 111.2 kb intervals, respectively. Tomato PISTILLATA (TPI, syn. SlGLO2), a B-class MADS-box transcription factor gene, was identified as the most likely candidate gene for both loci. TPI is also the candidate gene of tomato male sterile mutant 7B-1 and sl-2. Allelism tests revealed that ms-30, ms-33, 7B-1, and sl-2 were allelic. Sequencing analysis showed sequence alterations in the TPI gene in all these mutants, with ms-30 exhibiting a transversion (G to T) that resulted in a missense mutation (S to I); ms-33 showing a transition (A to T) that led to alternative splicing, resulting in a loss of 46 amino acids in protein; and 7B-1 and sl-2 mutants showing the insertion of an approximately 4.8 kb retrotransposon. On the basis of these sequence alterations, a Kompetitive Allele Specific PCR marker, a sequencing marker, and an Insertion/Deletion marker were developed. Phenotypic analysis of the TPI gene-edited mutants and allelism tests indicated that the gene TPI is responsible for ms-30 and its alleles. Transcriptome analysis of ms-30 and quantitative RT-PCR revealed some differentially expressed genes associated with stamen and carpel development. These findings will aid in the marker-assisted selection for ms-30 and its alleles in tomato breeding and support the functional analysis of the TPI gene.

Single Droplet Tweezer Revealing the Reaction Mechanism of Mn(II)-Catalyzed SO2 Oxidation.

Sulfate aerosol is one of the major components of secondary fine particulate matter in urban haze that has crucial impacts on the social economy and public health. Among the atmospheric sulfate sources, Mn(II)-catalyzed SO2 oxidation on aerosol surfaces has been regarded as a dominating one. In this work, we measured the reaction kinetics of Mn(II)-catalyzed SO2 oxidation in single droplets using an aerosol optical tweezer. We show that the SO2 oxidation occurs at the Mn(II)-active sites on the aerosol surface, per a piecewise kinetic formulation, one that is characterized by a threshold surface Mn(II) concentration and gaseous SO2 concentration. When the surface Mn(II) concentration is lower than the threshold value, the reaction rate is first order with respect to both Mn(II) and SO2, agreeing with our traditional knowledge. But when surface Mn(II) concentration is above the threshold, the reaction rate becomes independent of Mn(II) concentration, and the reaction order with respect to SO2 becomes greater than unity. The measured reaction rate can serve as a tool to estimate sulfate formation based on field observation, and our established parametrization corrects these calculations. This framework for reaction kinetics and parametrization holds promising potential for generalization to various heterogeneous reaction pathways.

Comprehensive analysis of vulnerability status and associated affect factors among prehospital emergency patients: a single-center descriptive cross-sectional study.

Background: Prehospital emergency care is a critical but often understudied aspect of healthcare. Patient vulnerability in this setting can significantly impact outcomes. The aim of this study was to investigate the vulnerability status and to determine associated affect factors among prehospital emergency patients in China. Methods: In this cross-sectional study conducted in China, from April 2023 to July 2023, we assessed the vulnerability of prehospital emergency patients using the Safety in Prehospital Emergency Care Index (SPECI) scale. We conducted a detailed questionnaire-based survey to gather demographic and disease-related information. We employed the SPECI scale, consisting of two subscales, to evaluate patient vulnerability. Statistical analyses, including t-tests, ANOVA, and multiple linear regression, were used to identify factors associated with vulnerability. Results: The study included a total of 973 prehospital emergency patients, with a response rate of 81.9%. These patients exhibited a low-to-moderate level of vulnerability, with an average SPECI score of 14.46 out of 40. Vulnerability was significantly associated with age (particularly those aged 60 and above), disease severity (severe conditions increased vulnerability), disease type (circulatory diseases correlated with higher vulnerability), alterations in consciousness, and chronic diseases. Unexpectedly, digestive system diseases were negatively correlated with vulnerability. Conclusion: Addressing patient vulnerability in prehospital care is essential. Tailored interventions, EMS provider training, and interdisciplinary collaboration can mitigate vulnerability, especially in older patients and those with severe conditions.

Turbid Waters and Clearer Standards: Refining Water Quality Criteria for Coastal Environments by Encompassing Metal Bioavailability from Suspended Particles.

Suspended particulate matter (SPM) carries a major fraction of metals in turbid coastal waters, markedly influencing metal bioaccumulation and posing risks to marine life. However, its effects are often overlooked in current water quality criteria for metals, primarily due to challenges in quantifying SPM's contribution. This contribution depends on the SPM concentration, metal distribution coefficients (Kd), and the bioavailability of SPM-bound metals (assimilation efficiency, AE), which can collectively be integrated as a modifying factor (MF). Accordingly, we developed a new stable isotope method to measure metal AE by individual organisms from SPM, employing the widely distributed filter-feeding clam Ruditapes philippinarum as a representative species. Assessing SPM from 23 coastal sites in China, we found average AEs of 42% for Zn, 26% for Cd, 20% for Cu, 8% for Ni, and 6% for Pb. Moreover, using stable isotope methods, we determined metal Kd of SPM from these sites, which can be well predicted by the total organic carbon and iron content (R2 = 0.977). We calculated MFs using a Monte Carlo method. The calculated MFs are in the range 9.9-43 for Pb, 8.5-37 for Zn, 2.9-9.7 for Cu, 1.4-2.7 for Ni, and 1.1-1.6 for Cd, suggesting that dissolved-metal-based criteria values should be divided by MFs to provide adequate protection to aquatic life. This study provides foundational guidelines to refine water quality criteria in turbid waters and protect coastal ecosystems.

Depletion Strategies for Crystallized Layers of Two-Dimensional Nanosheets to Enhance Lithium-Ion Conductivity in Polymer Nanocomposites.

The assembly of long-range aligned structures of two-dimensional nanosheets (2DNSs) in polymer nanocomposites (PNCs) is in urgent need for the design of nanoelectronics and lightweight energy-storage materials of high conductivity for electricity or heat. These 2DNS are thin and exhibit thermal fluctuations, leading to an intricate interplay with polymers in which entropic effects can be exploited to facilitate a range of different assemblies. In molecular dynamics simulations of experimentally studied 2DNSs, we show that the layer-forming crystallization of 2DNSs is programmable by regulating the strengths and ranges of polymer-induced entropic depletion attractions between pairs of 2DNSs, as well as between single 2DNSs and a substrate surface, by exclusively tuning the temperature and size of the 2DNS. Enhancing the temperature supports the 2DNS-substrate depletion rather than crystallization of 2DNSs in the bulk, leading to crystallized layers of 2DNSs on the substrate surfaces. On the other hand, the interaction range of the 2DNS-2DNS depletion attraction extends further than the 2DNS-substrate attraction whenever the 2DNS size is well above the correlation length of the polymers, which results in a nonmonotonic dependence of the crystallization layer on the 2DNS size. It is demonstrated that the depletion-tuned crystallization layers of 2DNSs contribute to a conductive channel in which individual lithium ions (Li ions) migrate efficiently through the PNCs. This work provides statistical and dynamical insights into the balance between the 2DNS-2DNS and 2DNS-substrate depletion interactions in polymer-2DNS composites and highlights the possibilities to exploit depletion strategies in order to engineer crystallization processes of 2DNSs and thus to control electrical conductivity.

Embrittlement Mechanisms of HR3C Pipe Steel at Room Temperature in Ultra-Supercritical Unit.

HR3C steel is an austenitic high-temperature-resistant steel. Because of its good strength and high-temperature performance, it has been widely used in ultra-supercritical power plant boilers. With the increasingly frequent start-up and shutdown of thermal power units, leakages of HR3C steel pipes have occasionally occurred due to the embrittlement of HR3C pipe steel after a long service duration. In this study, the embrittlement mechanisms of HR3C pipe steel are investigated systematically. The mechanical properties of the pipe steel after running for 70,000 h in an ultra-supercritical unit were determined. As a comparison, the pipe steel supplied in the same batch was aged at 700 degrees Celsius for 500 h. The mechanical properties and the micro-precipitation of the aged counterparts were also determined for comparison. The results show that the embrittlement of HR3C pipe steel in service for 70,000 h is obvious. The average impact absorption is only 5.5 J, which is a decrease of 96.7%. It is found that embrittlement of HR3C steel also occurs after 500 h of aging at 700 °C, and the average value of impact absorption energy decreases by 70.4%. The comparison experiment between the in-service pipe steel and the aged pipe steel shows that in the rapid decline stage of the impact toughness of HR3C steel, the M23C6 carbide in the microstructure has a continuous chain distribution in the grain boundary. There were no other precipitated phases observed. The rapid precipitation and aggregation of M23C6 carbides leads to the initial embrittlement of HR3C steel at room temperature. The CRFe-type σ phase was found in the transmission electron microscope (TEM) image of the steel pipe after 70 thousand hours of use. The precipitation of the σ phase further induces the embrittlement of HR3C pipe steel after a long service duration.

Association between short-term daily temperature variability and blood pressure in the Chinese population: From the China hypertension survey.

BACKGROUND: We aimed to evaluate the impacts of short-term daily temperature variability (DTV) on blood pressure (BP) among participants with normotension, prehypertension, and hypertension, respectively, and explore the effects in different climate zones and seasons. METHODS: A representative population sample (n = 397,173) covering the subtropical, temperate continental, and temperate monsoon zones was obtained from the China Hypertension Survey. DTV was calculated as the standard deviation of daily minimum and maximum temperatures during the exposure days. The linear mixed effect regression model was used to estimate the associations between DTV exposure and BP among normotension, prehypertension, and hypertension, respectively, and further stratified analysis was performed by climate zones and seasons. RESULTS: After adjustment for confounders, per interquartile range (IQR) increase in DTV (2.28 °C) at 0-6 days of exposure was associated with an increase of 0.41 mmHg (95 % confidence interval [CI]: 0.07, 0.75) in systolic BP (SBP) and 0.41 mmHg (95 % CI: 0.09, 0.72) in pulse pressure (PP) among hypertensive participants in the subtropical zone. Similarly, DTV exposure was associated with an increase of 0.31 mmHg (95 % CI: 0.06, 0.55) in SBP and 0.59 mmHg (95 % CI: 0.24, 0.94) in PP among prehypertensive participants in the temperate continental zone. Additionally, during the warm season, DTV was positively associated with SBP among populations with prehypertension and hypertension, and with PP among all three populations. CONCLUSION: Short-term DTV exposure was associated with an increase in SBP and PP among hypertensive and prehypertensive participants in the subtropical zone and the temperate continental zone. In addition, positive associations of DTV with SBP and PP were observed among participants with prehypertension and hypertension in the warm season. Comprehensive health education and effective intervention strategies should be implemented to mitigate the effects of temperature variations on BP, particularly among prehypertensive and hypertensive populations.

Efficacy and safety of Ruxolitinib, Crisaborole, and Tapinarof for mild-to-moderate atopic dermatitis: a Bayesian network analysis of RCTs.

Given the lack of head-to-head studies of novel non-steroidal molecule topical therapies in mild-to-moderate atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, we performed a literature search until 01 March 2023 for eligible studies written in English using databases, including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Only double-blind randomized clinical trials (RCTs) with topical Ruxolitinib, Crisaborole, or Tapinarof versus vehicle for patients with mild-to-moderate AD were included. Baseline and follow-up data were extracted. Efficacy was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear," with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA success." For binary outcomes, we analyzed in random-effects Bayesian NMA consistency models to compare the efficacy of these 3 topical therapies by odds ratio (OR) with 95% credibility interval (CrI). Overall, 10 phase 2 or phase 3 RCTs were identified, which included 4010 patients with mild to moderate AD. Compared with the topical vehicle control, all these 3 treatments had higher response rate of "IGA success" at the end of trial (Ruxolitinib 1.5% b.i.d: OR, 11.94; 95%CrI, 6.28-23.15; Crisaborole 2% b.i.d: OR, 2.08; 95%CrI, 1.46-3.52; Tapinarof 1% b.i.d: OR, 2.64; 95%CrI, 0.75-9.70). Notably, Ruxolitinib 1.5% b.i.d. had the highest probability of achieving "IGA success" in ranking analysis (Rank 1, SUCRA = 0.75) and lower risk of AE (Rank 8, SUCRA = 0.22). Besides, there was no difference in treatment-related adverse events between 3 therapies. Heterogeneity was not significant across studies.

Conductive nanofiltration membranes via in situ PEDOT-polymerization for electro-assisted membrane fouling mitigation.

Nanofiltration (NF) membranes play a pivotal role in water treatment; however, the persistent challenge of membrane fouling hampers their stable application. This study introduces a novel approach to address this issue through the creation of a poly(3,4-ethylenedioxythiophene) (PEDOT)-based conductive membrane, achieved by synergistically coupling interfacial polymerization (IP) with in situ self-polymerization of EDOT. During the IP reaction, the concurrent generation of HCl triggers the protonation of EDOT, activating its self-polymerization into PEDOT. This interwoven structure integrates with the polyamide network to establish a stable selective layer, yielding a remarkable 90 % increase in permeability to 20.4 L m-2 h-1 bar-1. Leveraging the conductivity conferred by PEDOT doping, an electro-assisted cleaning strategy is devised, rapidly restoring the flux to 98.3 % within 5 min, outperforming the 30-minute pure water cleaning approach. Through simulations in an 8040 spiral-wound module and the utilization of the permeated salt solution for cleaning, the electro-assisted cleaning strategy emerges as an eco-friendly solution, significantly reducing water consumption and incurring only a marginal electricity cost of 0.055 $ per day. This work presents an innovative avenue for constructing conductive membranes and introduces an efficient and cost-effective electro-assisted cleaning strategy to effectively combat membrane fouling.

A randomized controlled trial investigating the impact of a single flash cupping session on patients with chronic lower back pain using multichannel surface electromyographic assessment.

BACKGROUND: Chronic lower back pain (CLBP) is one of the most common disorders worldwide. Flash cupping has the ability to relieve CLBP; nevertheless, its impact on CLBP and the likely mechanism of action have not been studied. OBJECTIVE: The goal of this study was to assess the impact of a single, brief cupping session on CLBP and low back muscle activity using multichannel surface electromyography (sEMG). METHODS: In this randomized controlled trial, 24 patients with CLBP were enrolled and randomly assigned to the control group (treated by acupuncture) and cupping group (treated by acupuncture and flash cupping). Acupuncture was applied on the shen shu (BL23), dachang shu (BL25), and wei zhong (BL40) acupoints in both the groups. A brief cupping treatment was applied to the shen shu (BL23), qihai shu (BL24), dachang shu (BL25), guanyuan shu (BL26), and xiaochang shu (BL27) acupoints on both sides of the lower back in the cupping group. The numeric rating scale (NRS) was used to assess therapy efficacy for lower back pain (LBP) before and after treatment. Surface EMG data collected during symmetrical trunk flexion-extension movements were utilized to measure lower back muscle activity and the effectiveness of LBP therapy. RESULTS: There was no statistically significant difference (P= 0.63) in pain intensity between the two groups before and after treatment. There was a statistically significant difference (P= 0.04) between the control group and the cupping group in the sEMG topographic map parameter CoGx-To-Midline. CONCLUSION: This study established a connection between the action mechanism of flash cupping and enhanced horizontal synchronization of lower back muscular activity.

Overview of role of survivin in cancer: expression, regulation, functions, and its potential as a therapeutic target.

Survivin holds significant importance as a member of the inhibitor of apoptosis protein (IAP) family due to its predominant expression in tumours rather than normal terminally differentiated adult tissues. The high expression level of survivin in tumours is closely linked to chemotherapy resistance, heightened tumour recurrence, and increased tumour aggressiveness and serves as a negative prognostic factor for cancer patients. Consequently, survivin has emerged as a promising therapeutic target for cancer treatment. In this review, we delve into the various biological characteristics of survivin in cancers and its pivotal role in maintaining immune system homeostasis. Additionally, we explore different therapeutic strategies aimed at targeting survivin.

Solar-driven membrane separation for direct lithium extraction from artificial salt-lake brine.

The demand for lithium extraction from salt-lake brines is increasing to address the lithium supply shortage. Nanofiltration separation technology with high Mg2+/Li+ separation efficiency has shown great potential for lithium extraction. However, it usually requires diluting the brine with a large quantity of freshwater and only yields Li+-enriched solution. Inspired by the process of selective ion uptake and salt secretion in mangroves, we report here the direct extraction of lithium from salt-lake brines by utilizing the synergistic effect of ion separation membrane and solar-driven evaporator. The ion separation membrane-based solar evaporator is a multilayer structure consisting of an upper photothermal layer to evaporate water, a hydrophilic porous membrane in the middle to generate capillary pressure as the driving force for water transport, and an ultrathin ion separation membrane at the bottom to allow Li+ to pass through and block other multivalent ions. This process exhibits excellent lithium extraction capability. When treating artificial salt-lake brine with salt concentration as high as 348.4 g L-1, the Mg2+/Li+ ratio is reduced by 66 times (from 19.8 to 0.3). This research combines ion separation with solar-driven evaporation to directly obtain LiCl powder, providing an efficient and sustainable approach for lithium extraction.

Dose-response association between physical activity and blood pressure among Chinese adults: a nationwide cross-sectional study.

OBJECTIVES: The aim of this study was to examine the dose-response associations of physical activity with blood pressure (BP) and hypertension risk among Chinese adults. METHODS: Derived from the national community-based China Hypertension Survey database during 2012--2015, a total of 203 108 residents aged at least 18 years were included. Individual-level physical activity was evaluated using a standardized questionnaire, and minutes of metabolic equivalent tasks per week (MET-min/week) were calculated, integrating domain, intensity, frequency, and duration. Multivariable linear and logistic regressions were used to estimate associations of physical activity with BP and hypertension risk, and restricted cubic spline regressions were performed for their nonlinear dose-response relationships. RESULTS: Overall, the median total physical activity (TPA) was 3213.0 MET-min/week and the prevalence of physical inactivity was 14.8%. TPA was negatively associated with BP. Increasing TPA levels was related to a steep decrease in systolic BP, up to approximately 2500 MET-min/week, with more modest benefits above that level of TPA. Higher levels of domain-specific and intensity-specific physical activity were found to be associated with lower BP levels and hypertension risk, except for the association between vigorous-intensity physical activity and systolic BP. We found that TPA within the range of 2000--4000 MET-min/week, a higher frequency and shorter duration were inversely associated with diastolic BP levels. CONCLUSION: Total, domain-specific, and intensity-specific physical activity were inversely related to BP levels, respectively, in a dose-response fashion. Of a given amount, higher-frequency, shorter-duration, and lower-intensity physical activity produced more beneficial effects.

A variety of death modes of neutrophils and their role in the etiology of autoimmune diseases.

Neutrophils are important in the context of innate immunity and actively contribute to the progression of diverse autoimmune disorders. Distinct death mechanisms of neutrophils may exhibit specific and pivotal roles in autoimmune diseases and disease pathogenesis through the orchestration of immune homeostasis, the facilitation of autoantibody production, the induction of tissue and organ damage, and the incitement of pathological alterations. In recent years, more studies have provided in-depth examination of various neutrophil death modes, revealing nuances that challenge conventional understanding and underscoring their potential clinical utility in diagnosis and treatment. This review explores the multifaceted processes and characteristics of neutrophil death, with a focus on tailored investigations within various autoimmune diseases. It also highlights the potential interplay between neutrophil death and the landscape of autoimmune disorders. The review encapsulates the pertinent pathways implicated in various neutrophil death mechanisms across diverse autoimmune diseases while also charts possible avenues for future research.

BLK positively regulates TLR/IL-1R signaling by catalyzing TOLLIP phosphorylation.

TLR/IL-1R signaling plays a critical role in sensing various harmful foreign pathogens and mounting efficient innate and adaptive immune responses, and it is tightly controlled by intracellular regulators at multiple levels. In particular, TOLLIP forms a constitutive complex with IRAK1 and sequesters it in the cytosol to maintain the kinase in an inactive conformation under unstimulated conditions. However, the underlying mechanisms by which IRAK1 dissociates from TOLLIP to activate TLR/IL-1R signaling remain obscure. Herein, we show that BLK positively regulates TLR/IL-1R-mediated inflammatory response. BLK-deficient mice produce less inflammatory cytokines and are more resistant to death upon IL-1ß challenge. Mechanistically, BLK is preassociated with IL1R1 and IL1RAcP in resting cells. IL-1ß stimulation induces heterodimerization of IL1R1 and IL1RAcP, which further triggers BLK autophosphorylation at Y309. Activated BLK directly phosphorylates TOLLIP at Y76/86/152 and further promotes TOLLIP dissociation from IRAK1, thereby facilitating TLR/IL-1R-mediated signal transduction. Overall, these findings highlight the importance of BLK as an active regulatory component in TLR/IL-1R signaling.

Lipid metabolism analysis providing insights into nonylphenol multi-toxicity mechanism.

Nonylphenol (NP), a widely recognized endocrine disruptor, exhibits lipophobic properties that drive its accumulation in adipose tissue, leading to various physiological disruptions. Using Caenorhabditis elegans, this study investigated the effects of NP exposure on lipid homeostasis and physiological indicators. NP exposure increased lipid storage, hindered reproduction and growth, and altered phospholipid composition. Transcriptional analysis revealed NP's promotion of lipogenesis and inhibition of lipolysis. Metabolites related to lipid metabolism like citrate, amino acids, and neurotransmitters, along with lipids, collectively influenced physiological processes. This work elucidates the complex link between lipid metabolism disturbances and NP-induced physiological disruptions, enhancing our understanding of NP's multifaceted toxicity.

The Na+ /Ca2+ antiporter slr0681 affects carotenoid production in Synechocystis sp. PCC 6803 under high-light stress.

BACKGROUND: Carotenoids play key roles in photosynthesis and are widely used in foods as natural pigments, antioxidants, and health-promoting compounds. Enhancing carotenoid production in microalgae via biotechnology has become an important area of research. RESULTS: We knocked out the Na+ /Ca2+ antiporter gene slr0681 in Synechocystis sp. PCC 6803 via homologous recombination and evaluated the effects on carotenoid production under normal (NL) and high-light (HL) conditions. On day 7 of NL treatment in calcium ion (Ca2+ )-free medium, the cell density of Δslr0681 decreased by 29% compared to the wild type (WT). After 8 days of HL treatment, the total carotenoid contents decreased by 35% in Δslr0681, and the contents of individual carotenoids were altered: myxoxanthophyll, echinenone, and ß-carotene contents increased by 10%, 50%, and 40%, respectively, while zeaxanthin contents decreased by ~40% in Δslr0681 versus the WT. The expression patterns of carotenoid metabolic pathway genes also differed: ipi expression increased by 1.2- to 8.5-fold, whereas crtO and crtR expression decreased by ~90% and 60%, respectively, in ∆slr0681 versus the WT. In addition, in ∆slr0681, the expression level of psaB (encoding a photosystem I structural protein) doubled, whereas the expression levels of the photosystem II genes psbA2 and psbD decreased by ~53% and 84%, respectively, compared to the WT. CONCLUSION: These findings suggest that slr0681 plays important roles in regulating carotenoid biosynthesis and structuring of the photosystems in Synechocystis sp. This study provides a theoretical basis for the genetic engineering of microalgae photosystems to increase their economic benefits and lays the foundation for developing microalgae germplasm resources with high carotenoid contents. © 2023 Society of Chemical Industry.

Clinical application of amplification-based versus amplification-free metagenomic next-generation sequencing test in infectious diseases.

Background: Recently, metagenomic next-generation sequencing (mNGS) has been used in the diagnosis of infectious diseases (IDs) as an emerging and powerful tool. However, whether the complicated methodological variation in mNGS detections makes a difference in their clinical performance is still unknown. Here we conducted a method study on the clinical application of mNGS tests in the DNA detection of IDs. Methods: We analyzed the effect of several potential factors in the whole process of mNGS for DNA detection on microorganism identification in 98 samples of suspected ID patients by amplification-based mNGS. The amplification-based and amplification-free mNGS tests were successfully performed in 41 samples. Then we compared the clinical application of the two mNGS methods in the DNA detection of IDs. Results: We found that a higher concentration of extracted nucleic acid was more conducive to detecting microorganisms. Other potential factors, such as read depth and proportion of human reads, might not be attributed to microorganism identification. The concordance rate of amplification-based and amplification-free mNGS results was 80.5% (33/41) in the patients with suspected IDs. Amplification-based mNGS showed approximately 16.7% higher sensitivity than amplification-free mNGS. However, 4 cases with causative pathogens only detected by amplification-based mNGS were finally proved false-positive. In addition, empirical antibiotic treatments were adjusted in 18 patients following mNGS testing with unexpected pathogens. Conclusions: Amplification-based and amplification-free mNGS tests showed their specific advantages and disadvantages in the diagnosis of IDs. The clinical application of mNGS still needs more exploration from a methodological perspective. With advanced technology and standardized procedure, mNGS will play a promising role in the diagnosis of IDs and help guide the use of antibiotics.