Proteomic and metabolomic profiling of plasma predicts immune-related adverse events in older patients with advanced non-small cell lung cancer.

The clinical success of immune checkpoint inhibitors is compromised by the fact of immune-related adverse events (irAEs), especially for older patients. To identify predictive biomarkers for older patients with irAEs, we used multiplex immunoassay and flow cytometry and liquid chromatography-tandem mass spectrometry to test immune factors and plasma protein and metabolites levels in non-small cell lung cancer (NSCLC) patients. The results showed that older patients with irAEs displayed lower CD28, CD4+ T cell, and B cell and higher interleukin (IL)-10 and CCL2 levels at baseline. Besides, lower aldolase, fructose-bisphosphate B (ALDOB), higher ST6GAL1, and lower lactate/pyruvate ratio at baseline were found in older patients with irAEs. Based on metabolomic markers, predictive models were developed to distinguish patients with grade 2-4 irAEs from grade 0-1 (Area under curve, AUC = 0.831) and to distinguish patients with grade 3-4 irAEs from grade 2 (AUC = 1). Our results confirmed the predictive value of plasma metabolites for irAEs in older patients with NSCLC.

Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

BACKGROUND: The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. METHODS: In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. RESULTS: Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. CONCLUSION: Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Advancements of the Fluidized Bed Fenton (FBF) Technology for wastewater treatment: Mechanism, mass and heat transfer.

Fluidized Bed Fenton (FBF) technology, a fusion of the Fenton method and fluidized bed reactor, has emerged as a superior alternative to conventional Fenton technology for treating organic industrial wastewater. This innovative approach has garnered significant attention from researchers in recent years. While earlier studies primarily focused on pollutant degradation in simulated wastewater and catalyst development, there has been a growing interest in examining the alterations in mass or heat transfer performance attributed to fluidized beds. This paper explores the factors that contribute to the effectiveness of Fluidized Bed Fenton technology in efficiently degrading various challenging organic pollutants, while also reducing iron sludge production and expanding the applicable pH range, through an analysis of reaction kinetics. Meanwhile, combined with the related work of fluid dynamics, the research related to mass and heat transfer inside the reactor of Fluidized Bed Fenton technology is summarized, and it is proposed that the use of computers to establish a suitable model of Fluidized Bed Fenton and solve it with the assistance of computational fluid dynamics (CFD) and other software will help to further explore the process of mass and heat transfer inside the fluidized bed, which will provide the basis for the future of the Fluidized Bed Fenton from the laboratory to the actual industrial application.

Lab-on-a-chip: an advanced technology for the modernization of traditional Chinese medicine.

Benefiting from the complex system composed of various constituents, medicament portions, species, and places of origin, traditional Chinese medicine (TCM) possesses numerous customizable and adaptable efficacies in clinical practice guided by its theories. However, these unique features are also present challenges in areas such as quality control, screening active ingredients, studying cell and organ pharmacology, and characterizing the compatibility between different Chinese medicines. Drawing inspiration from the holistic concept, an integrated strategy and pattern more aligned with TCM research emerges, necessitating the integration of novel technology into TCM modernization. The microfluidic chip serves as a powerful platform for integrating technologies in chemistry, biology, and biophysics. Microfluidics has given rise to innovative patterns like lab-on-a-chip and organoids-on-a-chip, effectively challenging the conventional research paradigms of TCM. This review provides a systematic summary of the nature and advanced utilization of microfluidic chips in TCM, focusing on quality control, active ingredient screening/separation, pharmaceutical analysis, and pharmacological/toxicological assays. Drawing on these remarkable references, the challenges, opportunities, and future trends of microfluidic chips in TCM are also comprehensively discussed, providing valuable insights into the development of TCM.

Polyethyleneimine-mediated assembly of DNA nanotubes for KRAS siRNA delivery in lung adenocarcinoma therapy.

Self-assembled DNA nanostructures hold great promise in biosensing, drug delivery and nanomedicine. Nevertheless, challenges like instability and inefficiency in cellular uptake of DNA nanostructures under physiological conditions limit their practical use. To tackle these obstacles, this study proposes a novel approach that integrates the cationic polymer polyethyleneimine (PEI) with DNA self-assembly. The hypothesis is that the positively charged linear PEI can facilitate the self-assembly of DNA nanostructures, safeguard them against harsh conditions and impart them with the cellular penetration characteristic of PEI. As a demonstration, a DNA nanotube (PNT) was successfully synthesized through PEI mediation, and it exhibited significantly enhanced stability and cellular uptake efficiency compared to conventional Mg2+-assembled DNA nanotubes. The internalization mechanism was further found to be both clathrin-mediated and caveolin-mediated endocytosis, influenced by both PEI and DNA. To showcase the applicability of this hybrid nanostructure for biomedical settings, the KRAS siRNA-loaded PNT was efficiently delivered into lung adenocarcinoma cells, leading to excellent anticancer effects in vitro. These findings suggest that the PEI-mediated DNA assembly could become a valuable tool for future biomedical applications.

Association of Family Support With Lower Modifiable Risk Factors for Dementia Among Cognitively Impaired Older Adults.

OBJECTIVES: Cognitive impairment poses considerable challenges among older adults, with the role of family support becoming increasingly crucial. This study examines the association of children's residential proximity and spousal presence with key modifiable risk factors for dementia in cognitively impaired older adults. METHODS: We analyzed 14,600 individuals (35,165 observations) aged 50 and older with cognitive impairment from the Health and Retirement Study (1995-2018). Family support was categorized by spousal presence and children's residential proximity. Modifiable risk factors, including smoking, depressive symptoms, and social isolation, were assessed. Associations between family support and the modifiable risk factors were determined using mixed-effects logistic regressions. RESULTS: A significant proportion of older adults with cognitive impairment lacked access to family support, with either no spouse (46.9%) or all children living over 10 miles away (25.3%). Those with less available family support, characterized by distant-residing children and the absence of a spouse, had a significantly higher percentage of smoking, depressive symptoms, and social isolation. Moreover, we revealed a consistent gradient in the percentage of the risk factors by the degree of family support. Relative to older adults with a spouse and co-resident children, those without a spouse and with all children residing further than 10 miles displayed the highest percentage of the risk factors. These findings were robust to various sensitivity analyses. CONCLUSIONS: Family support from spouses and nearby children serves as a protective factor against modifiable dementia risk factors in cognitively impaired older adults. Policies that strengthen family and social support may benefit this population.

Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis.

Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9+CD55low APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9+CD55low APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.

Immunotoxicity of 2-Acetyl-4-tetrahydroxybutylimidazole in BALB/c mice with different vitamin B6 nutritional statuses.

Caramel color is a widely used food pigment, and 2-Acetyl-4-tetrahydroxybutylimidazole (THI) is a by-products of Class III caramel color. Some studies have shown that THI can reduce the number of peripheral blood lymphocytes. However, the comprehensive mechanism of THI immunotoxicity requires further study. In this study, the effects of THI on lymphocyte count, humoral immunity, cellular immunity and nonspecific immunity were determined and the effect of the nutritional status of VB6 on THI immunotoxicity was evaluated. Female BALB/c mice were divided into 3 groups and fed chow containing different doses of VB6: VB6-normal (6 mg/kg VB6), VB6-deprived (0.5 mg/kg VB6) or VB6-enhanced (12 mg/kg VB6) feed. Each group was further divided into 4 subgroups and treated with THI (0.5, 2.5 or 12.5 mg/kg bw) or the solvent control by gavage for 30 days. The thymic cortical thickness was measured with ViewPoint; the proportions of major immune cells and T cells in peripheral blood and tissues were detected via flow cytometry; the transformation and proliferation abilities of T and B cells were detected via T and B lymphocyte proliferation assays; NK cell activity was assessed via lactate dehydrogenase assays; humoral immune function was assessed via plaque-forming cell assays; and the immune function of T lymphocytes was assessed via delayed type hypersensitivity assays. The results showed that compared with those in the corresponding control group, the white blood cell count and lymphocyte count decreased significantly in all the VB6-deprived groups, in the 2.5 and 12.5 mg/kg VB6 groups, and in the 12.5 mg/kg VB6-enhanced group. With increasing THI dose, the thymic cortical layer became thinner. In the thymus, THI increased the proportions of CD3+ T cells and mature CD8+ T cells and decreased the proportions of immature double-positive, double-negative T cells and CD69-expressing lymphocytes. The proportions of naïve T cells and Tcm (central memory T) cells related to homing decreased. The proportion of mature T cells in the spleen decreased significantly. The proliferation of T cells stimulated by ConA decreased after THI exposure. VB6-deficient mice were more sensitive to THI immunotoxicity, and supplementation with VB6 had a certain protective effect on these mice. The results of the PFC and NK cell activity assays indicated that THI exposure might not affect humoral immune or innate immune function.

[Mechanism of Shexiang Tongxin Dropping Pills in treating diabetic cardiomyopathy based on network pharmacology and animal experiments].

This study aimed to explore the mechanism of Shexiang Tongxin Dropping Pills(STDP) in treating diabetic cardiomyopathy(DCM) based on network pharmacology, molecular docking, and animal experiments. BATMAN, TCMSP, and GeneCards were searched for the active ingredients and targets of STDP against DCM. STRING and Cytoscape were used to build the protein-protein interaction(PPI) network and "drug-active ingredient-target" network. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of the targets were carried out based on DAVID. The molecular docking of key receptor proteins with corresponding active ingredients was performed using AutoDock Vina. The rat model of DCM was established by a high-fat diet combined with intraperitoneal injection of streptozotocin. Rats were assigned into control, model, low-(20 mg·kg~(-1)) and high-dose(40 mg·kg~(-1)) STDP, and metformin(200 mg·kg~(-1)) groups. After 8 weeks of continuous administration, the cardiac function, myocardial pathological changes, and myocardial collagen fiber deposition of rats in each group were detected by echocardiography, hematoxylin-eosin(HE) staining, and Sirius red staining, respectively. The myocardial hypertrophy was detected by WGA staining. The expression levels of p38 mitogen-activated protein kinase(p38), phosphorylation-p38(p-p38), c-Jun N-terminal kinase(JNK), phosphorylation-JNK(p-JNK), caspase-3, and C-caspase-3 in the myocardial tissue of rats in each group were measured by Western blot. The network pharmacology predicted 199 active ingredients and 1 655 targets of STDP and 463 targets of DCM. One hundred and thirty-four potential targets of STDP for treating DCM were obtained, and the AGE-RAGE signaling pathway in diabetic complications was screened out. Molecular docking results showed that miltirone, dehydromiltirone, and tryptanthrin had strong binding affinity with RAGE. The results of animal experiments confirmed that STDP effectively protected the cardiac function of DCM rats. Compared with the DCM model group, the STDP groups showed significantly down-regulated protein levels of p-p38, p-JNK, and C-caspase-3. To sum up, STDP may protect the cardiac function of DCM rats by regulating the AGE-RAGE signaling pathway.

Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance.

Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.

Synthetic Sialosides Terminated with 8-N-Substituted Sialic Acid as Selective Substrates for Sialidases from Bacteria and Influenza Viruses.

Sialosides containing C8-modified sialic acids are challenging synthetic targets but potentially useful probes for diagnostic substrate profiling of sialidases and elucidating the binding specificity of sialic acid-interacting proteins. Here, we demonstrate efficient chemoenzymatic methods for synthesizing para-nitrophenol-tagged α2-3- and α2-6-linked sialyl galactosides containing C8-acetamido, C8-azido, or C8-amino derivatized N-acetylneuraminic acid (Neu5Ac). High-throughput substrate specificity studies showed that the C8-modification of sialic acid significantly changes its recognition by sialidases from humans, various bacteria, and different influenza A and B viruses. Sialosides carrying Neu5Ac with a C8-azido modification were generally well tolerated by all the sialidases we tested, whereas sialosides containing C8-acetamido-modified Neu5Ac were only cleaved by selective bacterial sialidases. In contrast, sialosides with C8-amino-modified Neu5Ac were cleaved by a combination of selective bacterial and influenza A virus sialidases. These results indicate that sialosides terminated with a C8-amino or C8-acetamido-modified sialic acid can be used with other sialosides for diagnostic profiling of disease-causing sialidase-producing pathogens.

Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis.

Schistosoma infection is one of the major causes of liver fibrosis. Emerging roles of hepatic progenitor cells (HPCs) in the pathogenesis of liver fibrosis have been identified. Nevertheless, the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains unclear. This study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal miRNAs. The activation of HPCs was verified by immunohistochemistry (IHC) and immunofluorescence (IF) staining in fibrotic liver from patients and mice with Schistosoma japonicum infection. By coculturing HPCs with hepatic stellate cells (HSCs) and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays, we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal dysfunction. Blocking autophagy by the autophagy inhibitor chloroquine (CQ) significantly diminished liver fibrosis and granuloma formation in S. japonicum-infected mice. HPC-secreted extracellular vehicles (EVs) were further isolated and studied by miRNA sequencing. miR-1306-3p, miR-493-3p, and miR-34a-5p were identified, and their distribution into EVs was inhibited due to impaired autophagy in HPCs, which contributed to suppressing HSC activation. In conclusion, we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in schistosomiasis. Targeting the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.

Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction.

OBJECTIVE: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). METHODS: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. RESULTS: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). CONCLUSION: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

On the quality of commercial chemical vapour deposited hexagonal boron nitride.

The semiconductors industry has put its eyes on two-dimensional (2D) materials produced by chemical vapour deposition (CVD) because they can be grown at the wafer level with small thickness fluctuations, which is necessary to build electronic devices and circuits. However, CVD-grown 2D materials can contain significant amounts of lattice distortions, which degrades the performance at the device level and increases device-to-device variability. Here we statistically analyse the quality of commercially available CVD-grown hexagonal boron nitride (h-BN) from the most popular suppliers. h-BN is of strategic importance because it is one of the few insulating 2D materials, and can be used as anti-scattering substrate and gate dielectric. We find that the leakage current and electrical homogeneity of all commercially available CVD h-BN samples are significantly worse than those of mechanically exfoliated h-BN of similar thickness. Moreover, in most cases the properties of the CVD h-BN samples analysed don't match the technical specifications given by the suppliers, and the sample-to-sample variability is unsuitable for the reproducible fabrication of capacitors, transistors or memristors in different batches. In the short term, suppliers should try to provide accurate sample specifications matching the properties of the commercialized materials, and researchers should keep such inaccuracies in mind; and in the middle term suppliers should try to reduce the density of defects to enable the fabrication of high-performance devices with high reliability and reproducibility.

Identification and Quantification of a Pneumococcal Cell Wall Polysaccharide by Antibody-Enhanced Chromatography Assay.

Multivalent pneumococcal vaccines have been developed successfully to combat invasive pneumococcal diseases (IPD) and reduce the associated healthcare burden. These vaccines employ pneumococcal capsular polysaccharides (PnPs), either conjugated or unconjugated, as antigens to provide serotype-specific protection. Pneumococcal capsular polysaccharides used for vaccine often contain residual levels of cell wall polysaccharides (C-Ps), which can generate a non-serotype specific immune response and complicate the desired serotype-specific immunity. Therefore, the C-P level in a pneumococcal vaccine needs to be controlled in the vaccine process and the anti C-P responses need to be dialed out in clinical assays. Currently, two types of cell-wall polysaccharide structures have been identified: a mono-phosphocholine substituted cell-wall polysaccharide C-Ps1 and a di-phosphocholine substituted C-Ps2 structure. In our effort to develop a next-generation novel pneumococcal conjugate vaccine (PCV), we have generated a monoclonal antibody (mAb) specific to cell-wall polysaccharide C-Ps2 structure. An antibody-enhanced HPLC assay (AE-HPLC) has been established for serotype-specific quantification of pneumococcal polysaccharides in our lab. With the new anti C-Ps2 mAb, we herein extend the AE-HPLC assay to the quantification and identification of C-Ps2 species in pneumococcal polysaccharides used for vaccines.

Direct Extraction and Determination of Free Nicotine in Cigarette Smoke.

The accurate determination of the free nicotine content in cigarette smoke is crucial for assessing cigarette quality, studying harm and addiction, and reducing tar levels. Currently, the determination of free nicotine in tobacco products primarily relies on methods such as pH calculation, nuclear magnetic resonance (NMR) spectroscopy, headspace solid-phase microextraction (HS-SPME), and traditional solvent extraction. However, these methods have limitations that restrict their widespread application. In this study, the free nicotine in cigarette smoke was directly extracted by using cyclohexane according to the traditional solvent extraction method and detected via gas chromatography-mass spectrometry. Compared with the traditional two-phase solvent extraction, our experimental method is easy to execute and eliminates the influence of aqueous solutions on the original distribution of nicotine in cigarette smoke particulate matter. Furthermore, the presence of protonated nicotine in tobacco does not affect the determination. Compared with HS-SPME and NMR spectroscopy, our approach, which involves solvent extraction followed by chromatographic separation and instrumental detection, offers simplicity, improved precision, better detection limits, and reduced interference during the instrumental detection stage. The standard addition recoveries in the conducted experiment ranged from 96.2% to 102.5%. The limit of detection was 2.8 µg/cig, and the correlation coefficient (R2) for the quadratic regression of the standard curve exceeded 0.999. The relative standard deviation for parallel samples was between 1.7% and 3.4% (n = 5), fully meeting the requirements for the determination of free nicotine in cigarette smoke. Analysis of cigarette samples from 38 commercially available brands revealed that the content of free nicotine ranged from 0.376 to 0.716 mg/cig, with an average of 0.540 mg/cig, and free nicotine accounted for 39.1%-88.8% of the total nicotine content.

Identification of hub glutamine metabolism-associated genes and immune characteristics in pre-eclampsia.

OBJECTIVE: Preeclampsia (PE) is a severe complication of unclear pathogenesis associated with pregnancy. This research aimed to elucidate the properties of immune cell infiltration and potential biomarkers of PE based on bioinformatics analysis. MATERIALS AND METHODS: Two PE datasets were imported from the Gene ExpressioOmnibus (GEO) and screened to identify differentially expressed genes (DEGs). Significant module genes were identified by weighted gene co-expression network analysis (WGCNA). DEGs that interacted with key module genes (GLu-DEGs) were analyzed further by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The diagnostic value of the genes was assessed using receiver operating characteristic (ROC) curves and protein-protein interaction (PPI) networks were constructed using GeneMANIA, and GSVA analysis was performed using the MSigDB database. Immune cell infiltration was analyzed using the TISIDB database, and StarBase and Cytoscape were used to construct an RBP-mRNA network. The identified hub genes were validated in two independent datasets. For further confirmation, placental tissue from healthy pregnant women and women with PE were collected and analyzed using both RT-qPCR and immunohistochemistry. RESULTS: A total of seven GLu-DEGs were obtained and were found to be involved in pathways associated with the transport of sulfur compounds, PPAR signaling, and energy metabolism, shown by GO and KEGG analyses. GSVA indicated significant increases in adipocytokine signaling. Furthermore, single-sample Gene Set Enrichment Analysis (ssGSEA) indicated that the levels of activated B cells and T follicular helper cells were significantly increased in the PE group and were negatively correlated with GLu-DEGs, suggesting their potential importance. CONCLUSION: In summary, the results showed a correlation between glutamine metabolism and immune cells, providing new insights into the understandingPE pathogenesis and furnishing evidence for future advances in the treatment of this disease.

The effect of body mass index on stroke prognosis: A systematic review and meta-analysis of 32 cohort studies with 330,353 patients.

BACKGROUND: Many studies have explored the impact of body mass index (BMI) on stroke prognosis, yet findings remain inconsistent. AIMS: The aims of this study were to conduct a systematic review and meta-analyses to summarize the existing evidence on BMI and stroke outcomes. METHODS: PubMed, Web of Science, Embase, The Cochrane Library, CNKI, CBM, Wanfang Database, and VIP Database were systematically searched from inception to 1 January 2023. Cohort studies were included if they reported on a population of patients with stroke, evaluated BMI on stroke outcomes (mortality/recurrence/score of modified Rankin scale (mRs)), and reported original data. Data extraction and quality assessment were independently undertaken by two reviewers. Stata 16.0 software was used for meta-analysis. RESULTS: Thirty-two studies involving 330,353 patients (5 Chinese language articles) were included in the analysis. The proportion of underweight, overweight, and obese patients was 1.85%, 18.2%, and 15.6%, respectively. Compared with normal weight, being underweight was associated with an increased risk of mortality (relative risk (RR) = 1.78, 95% confidence interval (CI) = 1.60-1.96), poor functional outcomes defined as modified Rankin scale ⩾ 3 (RR = 1.33, 95% CI = 1.22-1.45), and stroke recurrence (RR = 1.19, 95% CI = 1.04-1.37). Being overweight but not obese was associated with reduced mortality (RR = 0.81, 95% CI = 0.74-0.89) and better functional outcomes (RR = 0.92, 95% CI = 0.89-0.96), but did not alter the risk of stroke recurrence (RR = 1.03, 95% CI = 0.90-1.17). Obesity was associated with lower risk of mortality (RR = 0.76, 95% CI = 0.72-0.81) and better functional outcomes (RR = 0.89, 95% CI = 0.84-0.94). CONCLUSIONS: Our findings indicate that in patients with stroke, being underweight is associated with an increased risk of mortality, poor functional outcomes, and stroke recurrence. In contrast, being overweight but not obese, or being obese, was associated with a decreased risk of mortality and better functional outcomes. This is consistent with the obesity paradox in stroke, whereby obesity increases stroke risk in the general population but is associated with improved outcome in patients suffering stroke.

Histone variant H2A.Z is required for plant salt response by regulating gene transcription.

As a well-conserved histone variant, H2A.Z epigenetically regulates plant growth and development as well as the interaction with environmental factors. However, the role of H2A.Z in response to salt stress remains unclear, and whether nucleosomal H2A.Z occupancy work on the gene responsiveness upon salinity is obscure. Here, we elucidate the involvement of H2A.Z in salt response by analysing H2A.Z disorder plants with impaired or overloaded H2A.Z deposition. The salt tolerance is dramatically accompanied by H2A.Z deficiency and reacquired in H2A.Z OE lines. H2A.Z disorder changes the expression profiles of large-scale of salt responsive genes, announcing that H2A.Z is required for plant salt response. Genome-wide H2A.Z mapping shows that H2A.Z level is induced by salt condition across promoter, transcriptional start site (TSS) and transcription ending sites (-1 kb to +1 kb), the peaks preferentially enrich at promoter regions near TSS. We further show that H2A.Z deposition within TSS provides a direct role on transcriptional control, which has both repressive and activating effects, while it is found generally H2A.Z enrichment negatively correlate with gene expression level response to salt stress. This study shed light on the H2A.Z function in salt tolerance, highlighting the complex regulatory mechanisms of H2A.Z on transcriptional activity for yielding appropriate responses to particularly environmental stress.

Microbial synthesis of antimony sulfide to prepare catechol and hydroquinone electrochemical sensor by pyrolysis and carbonization.

The application of antimony sulfide sensors, characterized by their exceptional stability and selectivity, is of emerging interest in detection research, and the integration of graphitized carbon materials is expected to further enhance their electrochemical performance. This study represents a pioneering effort in the synthesis of carbon-doped antimony sulfide materials through the pyrolysis of the mixture of microorganisms and their synthetic antimony sulfide. The prepared materials are subsequently applied to electrochemical sensors for monitoring the highly toxic compounds catechol (CC) and hydroquinone (HQ) in the environment. Via cyclic voltammetry (CV) and impedance testing, we concluded that the pyrolytic product at 700 °C (Sb-700) demonstrated the best electrochemical properties. Differential pulse voltammetry (DPV) revealed impressive separation when utilizing Sb-700/GCE for simultaneous detection of CC and HQ, exhibiting good linearity within the concentration range of 0.1-140 µM. The achieved sensitivities of 24.62 µA µM-1 cm-2 and 22.10 µA µM-1 cm-2 surpassed those of most CC and HQ electrochemical sensors. Meanwhile, the detection limits for CC and HQ were as low as 0.18 µM and 0.16 µM (S/N = 3), respectively. Additional tests confirmed the good selectivity, reproducibility, and long-term stability of Sb-700/GCE, which was effective in detecting CC and HQ in tap water and river water, with recovery rates of 100.7%-104.5% and 96.5%-101.4%, respectively. It provides a method that combines green microbial synthesis and simple pyrolysis for the preparation of electrode materials in CC and HQ electrochemical sensors, and also offers a new perspective for the application of microbial synthesized materials.