SMC5/6 complex-mediated SUMOylation stimulates DNA-protein cross-link repair in Arabidopsis.

DNA-protein cross-links (DPCs) are highly toxic DNA lesions consisting of proteins covalently attached to chromosomal DNA. Unrepaired DPCs physically block DNA replication and transcription. Three DPC repair pathways have been identified in Arabidopsis (Arabidopsis thaliana) to date: the endonucleolytic cleavage of DNA by the structure-specific endonuclease MUS81; proteolytic degradation of the crosslinked protein by the metalloprotease WSS1A; and cleavage of the cross-link phosphodiester bonds by the tyrosyl phosphodiesterases TDP1 and TDP2. Here we describe the evolutionary conserved STRUCTURAL MAINTENANCE OF CHROMOSOMEs SMC5/6 complex as a crucial component involved in DPC repair. We identified multiple alleles of the SMC5/6 complex core subunit gene SMC6B via a forward-directed genetic screen designed to identify the factors involved in the repair of DPCs induced by the cytidine analog zebularine. We monitored plant growth and cell death in response to DPC-inducing chemicals, which revealed that the SMC5/6 complex is essential for the repair of several types of DPCs. Genetic interaction and sensitivity assays showed that the SMC5/6 complex works in parallel to the endonucleolytic and proteolytic pathways. The repair of zebularine-induced DPCs was associated with SMC5/6-dependent SUMOylation of the damage sites. Thus, we present the SMC5/6 complex as an important factor in plant DPC repair.

Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial.

BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] µm versus 87.2 [95% CI, 69.9 to 104.5] µm; difference, 34.2 [95% CI, 9.7 to 58.6] µm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857.

RUVBL proteins are involved in plant gametophyte development.

The proper development of male and female gametophytes is critical for successful sexual reproduction and requires a carefully regulated series of events orchestrated by a suite of various proteins. RUVBL1 and RUVBL2, plant orthologues of human Pontin and Reptin, respectively, belong to the evolutionarily highly conserved AAA+ family linked to a wide range of cellular processes. Previously, we found that RUVBL1 and RUVBL2A mutations are homozygous lethal in Arabidopsis. Here, we report that RUVBL1 and RUVBL2A play roles in reproductive development. We show that mutant plants produce embryo sacs with an abnormal structure or with various numbers of nuclei. Although pollen grains of heterozygous mutant plants exhibit reduced viability and reduced pollen tube growth in vitro, some of the ruvbl pollen tubes are capable of targeting ovules in vivo. Similarly, some ruvbl ovules retain the ability to attract wild-type pollen tubes but fail to develop further. The activity of the RUVBL1 and RUVBL2A promoters was observed in the embryo sac, pollen grains, and tapetum cells and, for RUVBL2A, also in developing ovules. In summary, we show that the RUVBL proteins are essential for the proper development of both male and particularly female gametophytes in Arabidopsis.

Unravelling CD4+ T cell diversity and tissue adaptation of Tregs in abdominal aortic aneurysms through single-cell sequencing.

Immune cell infiltration is a significant pathological process in abdominal aortic aneurysms (AAA). T cells, particularly CD4+ T cells, are essential immune cells responsible for substantial infiltration of the aorta. Regulatory T cells (Tregs) in AAA have been identified as tissue-specific; however, the time, location, and mechanism of acquiring the tissue-specific phenotype are still unknown. Using single-cell RNA sequencing (scRNA-seq) on CD4+ T cells from the AAA aorta and spleen, we discovered heterogeneity among CD4+ T cells and identified activated, proliferating and developed aorta Tregs. These Tregs originate in the peripheral tissues and acquire the tissue-specific phenotype in the aorta. The identification of precursors for Tregs in AAA provides new insight into the pathogenesis of AAA.

Suicide attempt and death by suicide among parents of young individuals with cancer: A population-based study in Denmark and Sweden.

BACKGROUND: The psychological toll on parents of a child receiving a cancer diagnosis is known to be high, but there is a knowledge gap regarding suicidal behavior among these parents. The aim of this study was to investigate the risk of suicide attempt and death by suicide in relation to having a child with cancer. METHODS AND FINDINGS: We performed a binational population-based and sibling-controlled cohort study, including all parents with a child diagnosed with cancer in Denmark (1978 to 2016) or Sweden (1973 to 2014), 10 matched unexposed parents per exposed parent (population comparison), and unaffected full siblings of the exposed parents (sibling comparison). Suicide attempt was identified through the Patient Register and the Psychiatric Central Register in Denmark and the Patient Register in Sweden, whereas death by suicide was identified through the Danish Causes of Death Register and the Swedish Causes of Death Register. In population comparison, we used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of suicide attempt and death by suicide associated with cancer diagnosis of a child, adjusting for sex, age, country of residence, calendar year, marital status, highest attained educational level, household income, history of cancer, history of psychiatric disorder, and family history of psychiatric disorder. The sibling comparison was performed to assess the role of familial confounding in the studied associations. The population comparison consisted of 106,005 exposed parents and 1,060,050 matched unexposed parents, with a median age of 56 at cohort entry and 46.9% male. During the median follow-up of 7.3 and 7.2 years, we observed 613 (incidence rate [IR], 58.8 per 100,000 person-years) and 5,888 (IR, 57.1 per 100,000 person-years) cases of first-onset suicide attempt among the exposed and unexposed parents, respectively. There was an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis (HR, 1.15; 95% CI, [1.03, 1.28]; p = 0.01), particularly when the child was 18 or younger at diagnosis (HR, 1.25; 95% CI, [1.08, 1.46]; p = 0.004), when the child was diagnosed with a highly aggressive cancer (HR, 1.60; 95% CI, [1.05, 2.43]; p = 0.03), or when the child died due to cancer (HR, 1.63; 95% CI, [1.29, 2.06]; p < 0.001). The increased risk did not, however, maintain thereafter (HR, 0.86; 95% CI: [0.75, 0.98]; p = 0.03), and there was no altered risk of parental death by suicide any time after the child's cancer diagnosis. Sibling comparison corroborated these findings. The main limitation of the study is the potential residual confounding by factors not shared between full siblings. CONCLUSIONS: In this study, we observed an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis, especially when the child was diagnosed during childhood, or with an aggressive or fatal form of cancer. There was, however, no altered risk of parental death by suicide at any time after a child's cancer diagnosis. Our findings suggest extended clinical awareness of suicide attempt among parents of children with cancer, especially during the first few years after cancer diagnosis.

POSTN promotes the progression of NSCLC via regulating TNFAIP6 expression.

Aberrant upregulation of Periostin (POSTN) expression has been implicated in various disease-related pathological cascades, notably inflammatory responses, fibrotic processes and tumor progression, including non-small cell lung cancer (NSCLC). The present study aimed to elucidate the functional role and underlying mechanisms of POSTN in NSCLC. Immunohistochemical and Western blot analysis consistently revealed elevated POSTN levels in NSCLC tissues and cell lines. POSTN expression negatively correlated with patient prognosis. Functional experiments utilizing POSTN-targeting siRNAs demonstrated a significant suppression of NSCLC cell proliferation, epithelial-to-mesenchymal transition (EMT), migration and invasion, whereas POSTN overexpression via plasmid transfection enhanced these oncogenic properties. Mechanistically, RNA sequencing analysis and subsequent validation studies revealed that POSTN positively modulates the transcriptional expression of tumor necrosis factor alpha-induced protein 6 (TNFAIP6) in NSCLC. Notably, a positive correlation was observed between POSTN and TNFAIP6 expression levels, and their overexpression positively correlated with NSCLC progression. Furthermore, TNFAIP6 overexpression rescued the inhibitory effects of POSTN knockdown on NSCLC malignant phenotypes. Collectively, our findings indicate that POSTN promotes NSCLC malignancy through TNFAIP6 upregulation, positioning POSTN as a promising biomarker and potential therapeutic target for NSCLC prognosis and treatment strategies in clinical settings.

Defects in meiotic chromosome segregation lead to unreduced male gametes in Arabidopsis SMC5/6 complex mutants.

Structural maintenance of chromosome 5/6 (SMC5/6) complex is a crucial factor for preserving genome stability. Here, we show that mutants for several Arabidopsis (Arabidopsis thaliana) SMC5/6 complex subunits produce triploid offspring. This phenotype is caused by a meiotic defect leading to the production of unreduced male gametes. The SMC5/6 complex mutants show an absence of chromosome segregation during the first and/or the second meiotic division, as well as a partially disorganized microtubule network. Importantly, although the SMC5/6 complex is partly required for the repair of SPO11-induced DNA double-strand breaks, the nonreduction described here is SPO11-independent. The measured high rate of ovule abortion suggests that, if produced, such defects are maternally lethal. Upon fertilization with an unreduced pollen, the unbalanced maternal and paternal genome dosage in the endosperm most likely causes seed abortion observed in several SMC5/6 complex mutants. In conclusion, we describe the function of the SMC5/6 complex in the maintenance of gametophytic ploidy in Arabidopsis.

High expression of small nucleolar host gene RNA may predict poor prognosis of Hepatocellular carcinoma, based on systematic reviews and meta-analyses.

BACKGROUND: The prognosis of patients with hepatocellular cancer is substantially correlated with the abnormal expression of growing long non-coding RNA small nucleolar host gene RNA (SNHG) families in liver cancer tissues. This study aimed to examine the relationship between SNHG expression and liver cancer prognosis. METHODS: After searching six internet databases, pertinent manuscripts were found based on inclusion and exclusion criteria. To determine whether SNHG expression levels affect liver cancer prognosis, raw data were collected and hazard ratios (HRs) and odds ratios (ORs) were calculated. The results were examined for potential publication bias using the sensitivity analysis and Beeg's test. RESULTS: Most SNHG family members were up-regulated in liver cancer tissues. High SNHG expression predicts poor liver cancer outcomes of, including overall survival (OS) (HR: 1.697, 95% confidence interval [CI]: 1.373-2.021), especially SNHG5 (the HR of OS is 4.74, 95%CI range from 1.35 to 6.64), progression-free survival (HR: 1.85, 95% CI: 1.25-2.73), tumor, node, metastasis (TNM) stage (OR: 1.696, 95% CI: 1.436-2.005), lymph node metastasis (OR: 2.383, 95% CI: 1.098-5.173), and tumor size (OR: 1363, 95% CI: 1.165-1.595). The OS results were found to be reliable and robust, as indicated by the sensitivity analysis. Additionally, Beeg's test demonstrated the absence of any potential publication bias for each result. CONCLUSION: In liver cancer tissues, most SNHGs are highly expressed, which may signal poor prognosis. SNHG has the potential to be an intriguing predictive marker and a prospective therapeutic target for liver cancer.

Genomic epidemiology of CVA10 in Guangdong, China, 2013-2021.

Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness primarily affecting children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-Enterovirus A71 (EV-A71) and non-Coxsackievirus A16 (CVA16) enteroviruses (EVs). Our study conducts a retrospective examination of 36,461 EV-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, Coxsackievirus A6 (CVA6) and Coxsackievirus A10 (CVA10) have emerged as the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, cases of CVA10 infection were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, possibly indicating accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2 A protein, contributing to a predominant subcluster within genogroup C of CVA10 circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of EV genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of EV genotypes. Moreover, given the shifting dominance of EV genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily target EV-A71.

Macrophage targeted graphene oxide nanosystem synergize antibiotic killing and host immune defense for Tuberculosis Therapy.

Tuberculosis (TB), a deadly disease caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the top killers among infectious diseases worldwide. How to increase targeting effects of current anti-TB chemotherapeutics and enhance anti-TB immunological responses remains a big challenge in TB and drug-resistant TB treatment. Here, mannose functionalized and polyetherimide protected graphene oxide system (GO-PEI-MAN) was designed for macrophage-targeted antibiotic (rifampicin) and autophagy inducer (carbamazepine) delivery to achieve more effective Mtb killings by combining targeted drug killing and host immunological clearance. GO-PEI-MAN system demonstrated selective uptake by in vitro macrophages and ex vivo macrophages from macaques. The endocytosed GO-PEI-MAN system would be transported into lysosomes, where the drug loaded Rif@Car@GO-PEI-MAN system would undergo accelerated drug release in acidic lysosomal conditions. Rif@Car@GO-PEI-MAN could significantly promote autophagy and apoptosis in Mtb infected macrophages, as well as induce anti-bacterial M1 polarization of Mtb infected macrophages to increase anti-bacterial IFN-γ and nitric oxide production. Collectively, Rif@Car@GO-PEI-MAN demonstrated effectively enhanced intracellular Mtb killing effects than rifampicin, carbamazepine or GO-PEI-MAN alone in Mtb infected macrophages, and could significantly reduce mycobacterial burdens in the lung of infected mice with alleviated pathology and inflammation without systemic toxicity. This macrophage targeted nanosystem synergizing increased drug killing efficiency and enhanced host immunological defense may be served as more effective therapeutics against TB and drug-resistant TB.

Different Anti-inflammatory Drugs on High-Sensitivity C-Reactive Protein in Patients After Percutaneous Coronary Intervention: A Pilot Randomized Clinical Trial.

ABSTRACT: Colchicine reduces atherothrombotic cardiovascular events in coronary artery disease because of its anti-inflammatory effect. However, the effects of the other anti-inflammatory drugs in coronary artery disease remain unclear. This study included 132 patients aged 18-80 years who completed the planned percutaneous coronary interventions and were treated with aggressive secondary prevention strategies for 4 weeks. The subjects were randomly assigned to 1 of the following treatment groups for 4 weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in high-sensitivity C-reactive protein (hsCRP) levels at the end of 4 weeks. In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male, and 28 (25.69%) were female. The percentage changes in hsCRP after 4 weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups, respectively. Compared with the control group, only the colchicine group showed significantly greater reduction in hsCRP levels ( P = 0.022). In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin, myeloperoxidase, and myeloblastin), platelet aggregation (glycoprotein VI), and endothelial damage (galectin-3) were reduced with colchicine therapy. These results show that of 3 anti-inflammatory drugs only colchicine could reduce hsCRP in patients after percutaneous coronary interventions.

Enhanced therapeutic potential of Flotillins-modified MenSCs by improve the survival, proliferation and migration.

Menstrual blood-derived endometrial stem cells (MenSCs) have attracted increasing interest due to their excellent safety, and lack of ethical dilemma as well as their ability to be periodically obtained in a noninvasive manner. However, although preclinical research as shown the therapeutic potential of MenSCs in several diseases, their poor cell survival and low engraftment at disease sites reduce their clinical efficacy. Flotillins (including Flot1 and Flot2) are implicated in various cellular processes, such as vesicular trafficking, signal transduction, cell proliferation, migration and apoptosis. In this study, we aimed to determine the effects of Flotillins on MenSCs survival, proliferation and migration. Our experimental results show that MenSCs were modified to overexpress Flot1 and/or Flot2 without altering their intrinsic characteristics. Flot1 and Flot2 co-overexpression promoted MenSC viability and proliferation capacity. Moreover, Flot1 or Flot2 overexpression significantly promoted the migration and inhibited the apoptosis of MenSCs compared with the negative control group, and these effects were stronger in the Flot1 and Flot2 gene co-overexpression group. However, these effects were significantly reversed after Flot1 and/or Flot2 knockdown. In conclusion, our results indicate that Flot1 and Flot2 overexpression in MenSCs improved their proliferation and migration and inhibited their apoptosis, and this might be an effective approach to improve the efficiency of cell-based therapies.

LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer.

Lysine-specific demethylase 1 (LSD1) exerts pathway-specific activity in animal development and has been linked to several high-risk cancers. Here, we report that LSD1 is an integral component of the Mi-2/nucleosome remodeling and deacetylase (NuRD) complex. Transcriptional target analysis revealed that the LSD1/NuRD complexes regulate several cellular signaling pathways including TGFbeta1 signaling pathway that are critically involved in cell proliferation, survival, and epithelial-to-mesenchymal transition. We demonstrated that LSD1 inhibits the invasion of breast cancer cells in vitro and suppresses breast cancer metastatic potential in vivo. We found that LSD1 is downregulated in breast carcinomas and that its level of expression is negatively correlated with that of TGFbeta1. Our data provide a molecular basis for the interplay of histone demethylation and deacetylation in chromatin remodeling. By enlisting LSD1, the NuRD complex expands its chromatin remodeling capacity to include ATPase, histone deacetylase, and histone demethylase.

Plasma amplifiers: multiscale light-enhanced uniform SERS composite substrates for breaking through resonance limitations.

A phenomenon known as plasmon resonance constitutes a unique optical effect that can induce an enhancement in localized electromagnetic fields, resulting in a substantial increase in the electromagnetic field intensity surrounding metallic nanostructures. In this work, the coupling effect of excitation of surface plasmon polaritons and local surface plasmons in nanoparticles is deeply studied under the background of nanoparticles/one-dimension grating composite structures through grating matching. By employing finite-difference time-domain simulations as our methodological approach, we discern gratings with a periodicity of 1.5 µm support surface plasmon bound states between the gratings. Furthermore, the modulation of SPs along the vertical sidewalls of the grating due to standing wave effects exhibits oscillatory behavior with varying grating heights. Experimental results obtained from the nanoparticle/grating composite SERS substrate validate theoretical predictions, demonstrating higher enhanced Raman signals at 633 nm compared to 532 nm. Remarkably, this structure exhibits good performance, with R6G detection sensitivity down to concentrations as low as 10-10 M and mapping achieving a relative standard deviation of 7.79%, underscoring its uniformity and capability of electromagnetic field enhancement.

Nanomaterial-mediated host directed therapy of tuberculosis by manipulating macrophage autophagy.

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a major public health issue worldwide. Mtb has developed complicated strategies to inhibit the immunological clearance of host cells, which significantly promote TB epidemic and weaken the anti-TB treatments. Host-directed therapy (HDT) is a novel approach in the field of anti-infection for overcoming antimicrobial resistance by enhancing the antimicrobial activities of phagocytes through phagosomal maturation, autophagy and antimicrobial peptides. Autophagy, a highly conserved cellular event within eukaryotic cells that is effective against a variety of bacterial infections, has been shown to play a protective role in host defense against Mtb. In recent decades, the introduction of nanomaterials into medical fields open up a new scene for novel therapeutics with enhanced efficiency and safety against different diseases. The active modification of nanomaterials not only allows their attractive targeting effects against the host cells, but also introduce the potential to regulate the host anti-TB immunological mechanisms, such as apoptosis, autophagy or macrophage polarization. In this review, we introduced the mechanisms of host cell autophagy for intracellular Mtb clearance, and how functional nanomaterials regulate autophagy for disease treatment. Moreover, we summarized the recent advances of nanomaterials for autophagy regulations as novel HDT strategies for anti-TB treatment, which may benefit the development of more effective anti-TB treatments.

Chitinases as a potential diagnostic and prognostic biomarker for amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons, and there is currently a lack of reliable diagnostic biomarkers. This meta-analysis aimed to evaluate CHIT1, CHI3L1, and CHI3L2 levels in the cerebrospinal fluid (CSF) or blood and their diagnostic potential in ALS patients. A systematic, comprehensive search was performed of peer-reviewed English-language articles published before April 1, 2023, in PubMed, Scopus, Embase, Cochrane Library, and Web of Science. After a thorough screening, 13 primary articles were included, and their chitinases-related data were extracted for systematic review and meta-analysis. In ALS patients, the CSF CHIT1 levels were significantly elevated compared to controls with healthy control (HC) (SMD, 1.92; 95% CI, 0.78 - 3.06; P < 0.001). CHIT1 levels were elevated in the CSF of ALS patients compared to other neurodegenerative diseases (ONDS) control (SMD, 0.74; 95% CI, 0.22 - 1.27; P < 0.001) and exhibited an even more substantial increase when compared to ALS-mimicking diseases (AMDS) (SMD, 1.15; 95% CI, 0.35 - 1.94, P < 0.001). Similarly, the CSF CHI3L1 levels were significantly higher in ALS patients compared to HC (SMD, 3.16; 95% CI, 1.26 - 5.06, P < 0.001). CHI3L1 levels were elevated in the CSF of ALS patients compared to ONDS (SMD, 0.75; 95% CI, 0.32 - 1.19; P = 0.017) and exhibited a more pronounced increase when compared to AMDS (SMD, 1.92; 95% CI, 0.41 - 3.42; P < 0.001). The levels of CSF chitinases in the ALS patients showed a significant increase, supporting the role of CSF chitinases as diagnostic biomarkers for ALS.

The mediating role of children's intergenerational support in association between grandparenting and cognitive function among middle-aged and older Chinese: findings from the CHARLS cohort study.

OBJECTIVES: With the world's population increasing in age, there has been a significant rise in the prevalence of cognitive impairment and dementia among individuals. This study aims to investigate the association between grandparenting and cognitive function among middle-aged and older Chinese using data from 2011 to 2018 China Health and Retirement Longitudinal Study (CHARLS). Additionally, the study seeks to explore the potential mediating effect of intergenerational support from children on this relationship, using data from the CHARLS 2011 database. METHODS: 5254 participants were recruited at the baseline survey in CHARLS 2011. Subsequently, a follow-up survey was conducted over 8 years, from CHARLS 2011 to 2018, with 1472 individuals completing the follow-up survey. The CHARLS included surveys on grandparenting and cognitive assessments. Grandparenting was categorized as yes and no. The assessment of cognitive function involved the evaluation of episodic memory and mental intactness. The present study used cross-sectional and longitudinal analyses to examine the relationship between grandparenting and cognitive function. The bootstrap method assessed the mediating effect of children's intergenerational support. RESULTS: The results of both cross-sectional and longitudinal studies indicated a positive association between grandparenting and cognitive function in middle-aged and older Chinese (B = 0.138, p < 0.05; B = 0.218, p < 0.05). Children's emotional and economic support played intermediary roles between grandparenting and cognitive function. CONCLUSION: The results emphasized the significance of policymakers considering the consequences of intergenerational care and family support when formulating and executing social service policies targeted at the middle-aged and older population in China.

Prenatal per- and polyfluoroalkyl substances exposure and gut microbiota of infants: A prospective cohort study.

Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) has been reported to be linked to a series of adverse health outcomes in mothers and their children. As the gut microbiota is a sensitive biomarker for assessing the toxicity of environmental contaminants, this study attempted to investigate whether prenatal PFASs exposure was associated with the gut microbiota of infants. Based on the Shanghai-Minhang Birth Cohort Study, this prospective cohort study included 69 mother-infant pairs. Fasting blood samples were collected from pregnant women for the PFASs assay. We collected fecal samples of infants at 1 year of age and analyzed the V3-V4 hypervariable region of the bacterial 16 S rRNA gene by high-throughput sequencing. Among the detected 11 PFASs, the concentration of perfluorooctanoic acid (22.19 ng/mL) was the highest, followed by perfluorooctane sulfonic acid (12.08 ng/mL). Compared with infants whose mothers' total PFASs concentrations during pregnancy were at the 40th percentile or lower (reference group), the species richness and diversity of microbiota were lower in infants prenatally exposed to a high level of PFASs (the sum of PFASs concentrations above the 60th percentile). Prenatal exposure to PFASs was associated with a higher proportion of Acidaminococcaceae, Acidaminococcus, Megamonas, Megasphaera micronuciformis and Megamonas funiformis in infants. The changes of the species have been suggested to be associated with immune and metabolic dysfunction in humans. Functional alterations of gut microbiota due to PFASs exposure were dominated by an enrichment of butanoate metabolism. Our preliminary findings may shed light on the potential role of the microbiota underlying the well-known impact of prenatal PFASs exposure on health outcomes of humans in later life.

Clinical efficacy of ilaprazole combined with somatostatin on severe acute pancreatitis and the effects on oxidative stress and inflammatory response.

This study investigates the clinical efficacy of ilaprazole combined with somatostatin on severe acute pancreatitis (SAP) and the effects on oxidative stress and inflammatory response. Seventy SAP patients were randomized to the control and observation groups, which received the somatostatin treatment and ilaprazole combined with somatostatin treatment for seven days, respectively. Results found that, the time of abdominal pain relief, time of serum amylase recovery, time of urinary amylase recovery and time of defecation recovery in the observation group were shorter than those in the control group (P<0.05). After the treatment, comparing to the control group, in the observation group the heart rate decreased (P<0.05), the mean arterial pressure and the central venous pressure increased (P<0.05), the serum levels of super oxide dismutase and glutathione peroxidase increased (P<0.05) and the serum levels of malondialdehyde, tumor necrosis factor α, interleukin-6, C-reactive protein decreased (P<0.05). In treatment of SAP, ilaprazole combined with somatostatin can enhance the curative efficacy and decrease the oxidative stress and the inflammatory response in patients. In addition, it cannot increase the adverse reactions, with good safety.

Proteome and phosphoproteome profiling of non-small cell lung cancer cell line A549 treated with TRAIL.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is recognized for its promising therapeutic effects against cancer. However, mechanisms underlying the effect of TRAIL on protein expression, signal transduction, and apoptosis induction remain unclear. We surmised that a systematic analysis of the proteome and phosphoproteome associated with TRAIL signaling may help elucidate the mechanisms involved and facilitate the development of therapeutics. Therefore, we investigated the proteome and phosphoproteome of non-small cell lung cancer cell line A549 treated with TRAIL. Our results indicated that 126 proteins and 1684 phosphosites were markedly differentially expressed between the phosphate-buffered saline- and TRAIL-treated groups. The expression at protein and phosphosite levels were not completely consistent. Gene ontology functional analysis revealed that metal ion (zinc) binding was highly affected by TRAIL treatment. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that almost all pathways that involved differentially expressed phosphosites were associated with apoptosis. We also identified an important kinase, AKT1, and its series of substrates in TRAIL signaling. The results of this study may provide guidance for future research on tumor therapy using TRAIL.