The role of sulfur cycle in new particle formation: Cycloaddition reaction of SO3 to H2S.

The chemistry of sulfur cycle contributes significantly to the atmospheric nucleation process, which is the first step of new particle formation (NPF). In the present study, cycloaddition reaction mechanism of sulfur trioxide (SO3) to hydrogen sulfide (H2S) which is a typical air pollutant and toxic gas detrimental to the environment were comprehensively investigate through theoretical calculations and Atmospheric Cluster Dynamic Code simulations. Gas-phase stability and nucleation potential of the product thiosulfuric acid (H2S2O3, TSA) were further analyzed to evaluate its atmospheric impact. Without any catalysts, the H2S + SO3 reaction is infeasible with a barrier of 24.2 kcal/mol. Atmospheric nucleation precursors formic acid (FA), sulfuric acid (SA), and water (H2O) could effectively lower the reaction barriers as catalysts, even to a barrierless reaction with the efficiency of cis-SA > trans-FA > trans-SA > H2O. Subsequently, the gas-phase stability of TSA was investigated. A hydrolysis reaction barrier of up to 61.4 kcal/mol alone with an endothermic isomerization reaction barrier of 5.1 kcal/mol under the catalytic effect of SA demonstrates the sufficient stability of TSA. Furthermore, topological and kinetic analysis were conducted to determine the nucleation potential of TSA. Atmospheric clusters formed by TSA and atmospheric nucleation precursors (SA, ammonia NH3, and dimethylamine DMA) were thermodynamically stable. Moreover, the gradually decreasing evaporation coefficients for TSA-base clusters, particularly for TSA-DMA, suggests that TSA may participate in NPF where the concentration of base molecules are relatively higher. The present new reaction mechanism may contributes to a better understanding of atmospheric sulfur cycle and NPF.

A novel stoploss mutation CYB5R3 c.906A>G(p.*302Trpext*42) involved in the pathogenesis of hereditary methemoglobinemia.

Recessive congenital methemoglobinemia (RCM) is a hereditary autosomal disorder with an extremely low incidence rate. Here, we report a case of methemoglobinemia type I in a patient with congenital persistent cyanosis. The condition was attributed to a novel compound heterozygous mutation in CYB5R3, characterized by elevated methemoglobin levels (13.4 % of total hemoglobin) and undetectable NADH cytochrome b5 reductase (CYB5R3) activity. Whole-exome sequencing (WES) revealed two heterozygous mutations in CYB5R3: a previously reported pathogenic missense mutation c.611G>A(p.Cys204Tyr) inherited from the father, and a novel stop codon mutation c.906A>G(p.*302Trpext*42) from the mother, the latter mutation assessed as likely pathogenic according to ACMG guidelines. In cells overexpressing the CYB5R3 c.906A>G mutant construct, the CYB5R3 mRNA level was significantly lower than in cells overexpressing the wild-type (WT) CYB5R3 construct. However, there was no significant difference in protein expression levels between the mutant and WT constructs. Notably, an additional protein band of approximately 55 kDa was detected in the mutant cells. Immunofluorescence localization showed that, compared to wild-type CYB5R3, the subcellular localization of the CYB5R3 p.*302Trpext*42 mutant protein did not show significant changes and remained distributed in the endoplasmic reticulum and mitochondria. However, the c.906A>G(p.*302Trpext*42) mutation resulted in increased intracellular reactive oxygen species (ROS) levels and decreased NAD+/NADH ratio, suggesting impaired CYB5R3 function and implicating this novel mutation as likely pathogenic.

Conditional ablation of DIS3L2 ribonuclease in pre-meiotic germ cells causes defective spermatogenesis and infertility in male mice.

Rationale: Spermatogenesis is a highly organized cell differentiation process in mammals, involving mitosis, meiosis, and spermiogenesis. DIS3L2, which is primarily expressed in the cytoplasm, is an RNA exosome-independent ribonuclease. In female mice, Dis3l2-deficient oocytes fail to resume meiosis, resulting in arrest at the germinal vesicle stage and complete infertility. However, the role of DIS3L2 in germ cell development in males has remained largely unexplored. Methods: We established a pre-meiotic germ cell conditional knockout mouse model and investigated the biological function of DIS3L2 in spermatogenesis and male fertility through bulk RNA-seq and scRNA-seq analyses. Results: This study unveils that conditional ablation of Dis3l2 in pre-meiotic germ cells with Stra8-Cre mice impairs spermatogonial differentiation and hinders spermatocyte meiotic progression coupled with cell apoptosis. Such conditional ablation leads to defective spermatogenesis and sterility in adults. Bulk RNA-seq analysis revealed that Dis3l2 deficiency significantly disrupted the transcriptional expression pattern of genes related to the cell cycle, spermatogonial differentiation, and meiosis in Dis3l2 conditional knockout testes. Additionally, scRNA-seq analysis indicated that absence of DIS3L2 in pre-meiotic germ cells causes disrupted RNA metabolism, downregulated expression of cell cycle genes, and aberrant expression of spermatogonial differentiation genes, impeding spermatogonial differentiation. In meiotic spermatocytes, loss of DIS3L2 results in disturbed RNA metabolism, abnormal translation, and disrupted meiotic genes that perturb meiotic progression and induce cell apoptosis, leading to subsequent failure of spermatogenesis and male infertility. Conclusions: Collectively, these findings highlight the critical role of DIS3L2 ribonuclease-mediated RNA degradation in safeguarding the correct transcriptome during spermatogonial differentiation and spermatocyte meiotic progression, thus ensuring normal spermatogenesis and male fertility.

ProNGF elicits retrograde axonal degeneration of basal forebrain neurons through p75NTR and induction of amyloid precursor protein.

Basal forebrain cholinergic neurons (BFCNs) extend long projections to multiple regions in the brain to regulate cognitive functions. Degeneration of BFCNs is seen with aging, after brain injury, and in neurodegenerative disorders. An increase in the amount of the immature proform of nerve growth factor (proNGF) in the cerebral cortex results in retrograde degeneration of BFCNs through activation of proNGF receptor p75NTR. Here, we investigated the signaling cascades initiated at the axon terminal that mediate proNGF-induced retrograde degeneration. We found that local axonal protein synthesis and retrograde transport mediated proNGF-induced degeneration initiated from the axon terminal. Analysis of the nascent axonal proteome revealed that proNGF stimulation of axonal terminals triggered the synthesis of numerous proteins within the axon, and pathway analysis showed that amyloid precursor protein (APP) was a key upstream regulator in cultured BFCNs and in mice. Our findings reveal a functional role for APP in mediating BFCN axonal degeneration and cell death induced by proNGF.

Effect of Alloying on Microstructure and Mechanical Properties of AlCoCrFeNi2.1 Eutectic High-Entropy Alloy.

In order to explore the effect of alloying on the microstructures and mechanical properties of AlCoCrFeNi2.1 eutectic high-entropy alloys (EHEAs), 0.1, 0.2, and 0.3 at.% V, Mo, and B were added to the AlCoCrFeNi2.1 alloy in this work. The effects of the elements and contents on the phase composition, microstructures, mechanical properties, and fracture mechanism were investigated. The results showed that the crystal structures of the AlCoCrFeNi2.1 EHEAs remained unchanged, and the alloys were still composed of FCC and BCC structures, whose content varied with the addition of alloying elements. After alloying, the aggregation of Co, Cr, Al, and Ni elements remained unchanged, and the V and Mo were distributed in both dendritic and interdendritic phases. The tensile strengths of the alloys all exceeded 1000 MPa when the V and Mo elements were added, and the Mo0.2 alloy had the highest tensile strength, of 1346.3 MPa, and fracture elongation, of 24.6%. The alloys with the addition of V and Mo elements showed a mixed ductile and brittle fracture, while the B-containing alloy presented a cleavage fracture. The fracture mechanism of Mo0.2 alloy is mainly crack propagation in the BCC lamellae, and the FCC dendritic lamellae exhibit the characteristics of plastic deformation.

CIB2 mediates acquired gefitinib resistance by inducing ZEB1 expression and epithelial-mesenchymal transition.

EGFR-TKIs have been used as frontline treatment in patients with advanced non-small cell lung cancer (NSCLC) suffering from the EGFR mutation. Gefitinib, the first-generation EGFR-TKI, has greatly improved survival rates in lung cancer patients, whereas acquired gefitinib resistance is still a critical issue that needs to be overcome. In our research, high expression levels of CIB2 were found in gefitinib-resistant lung cancer cells. CIB2 knockout rendered gefitinib-resistant cells more sensitive to gefitinib, and overexpression of CIB2 in parental cells was sufficient to induce more resistance to gefitinib. Inhibition of CIB2 in gefitinib-resistant lung cancer cells significantly induced cell apoptosis. To clarify the major molecular mechanism by which CIB2 increases gefitinib resistance, we demonstrated that raised CIB2 in lung cancer cells promoted epithelial-to-mesenchymal transition (EMT) through upregulation of ZEB1. Moreover, FOSL1 transcriptionally regulated CIB2 expression. Finally, CIB2 rendered tumors resistant to gefitinib treatment in vivo. Our results explored a new mechanism: upregulated CIB2 promoted EMT through ZEB1 to regulate gefitinib resistance, which could be a candidate therapeutic target for overcoming acquired resistance to EGFR-TKIs in NSCLC patients.

IGFBP7 promotes the proliferation and differentiation of primary myoblasts and intramuscular preadipocytes in chicken.

Though it is well known that insulin-like growth factor (IGF) binding protein 7 (IGFBP7) plays an important role in myogenesis and adipogenesis in mammals, its impact on the proliferation, differentiation, and lipid deposition in chicken primary myoblasts (CPM) and intramuscular preadipocytes remains unexplored. In the present study, we firstly examined the correlation between SNPs within the genomic sequence of the IGFBP7 gene and carcass and blood chemical traits in a F2 resource population by genetic association analysis, and found that a significant correlation between the SNP (4_49499525) located in the intron region of IGFBP7 and serum high-density lipoproteins (HDL). We then examined the expression patterns of IGFBP7 across different stages of proliferation and differentiation in CPMs and intramuscular preadipocytes via qPCR, and explored the biological functions of IGFBP7 through gain- and loss-of-function experiments and a range of techniques including qPCR, CCK-8, EdU, flow cytometry, Western blot, immunofluorescence, and Oil Red O staining to detect the proliferation, differentiation, and lipid deposition in CPMs and intramuscular preadipocytes. We ascertained that the expression levels of the IGFBP7 gene increased as cell differentiation progresses in CPMs and intramuscular preadipocytes, and that IGFBP7 promotes the proliferation and differentiation of these cells, as well as facilitates intracellular lipid deposition. Furthermore, we investigated the regulatory mechanism of IGFBP7 expression by using co-transfection strategy and dual-luciferase reporter assay, and discovered that the myogenic transcription factors (MRF), myoblast determination factor (MyoD) and myogenin (MyoG), along with the adipocyte-specific transcription factor (TF) CCAAT/enhancer-binding protein α (C/EBPα), can bind to the core transcription activation region of the IGFBP7 promoter located 500 bp upstream from the transcription start site, thereby promoting IGFBP7 transcription and expression. Taken together, our study underscores the role of IGFBP7 as a positive regulator for myogenesis and adipogenesis, while also elucidating the functional and transcriptional regulatory mechanisms of IGFBP7 in chicken skeletal muscle development and intramuscular adipogenesis.

Structural and Functional Differences in Small Intestinal and Fecal Microbiota: 16S rRNA Gene Investigation in Rats.

To compare the differences in floral composition and functions between the two types of microbiota, ileal contents and feces were collected from Sprague Dawley (SD) rats fed in a conventional or specific-pathogen free (SPF) environment and rats fed a high-fat diet (HFD), and the V3-V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene in these rats was then amplified and sequenced. Compared with feces, about 60% of the bacterial genera in the ileum were exclusive, with low abundance (operational taxonomic units (OTUs) < 1000). Of bacteria shared between the ileum and feces, a few genera were highly abundant (dominant), whereas most had low abundance (less dominant). The dominant bacteria differed between the ileum and feces. Ileal bacteria showed greater ß-diversity, and the distance between in-group samples was nearer than that between paired ileum-feces samples. Moreover, the ileum shared various biomarkers and functions with feces (p < 0.05). The HFD and SPF conditions had a profound influence on α-diversity and abundance but not on the exclusive/shared features or ß-diversity of samples. The present findings suggested that, under conventional circumstances, fecal bacteria can represent approximately 40% of the low abundant ileal bacterial genera and that dominant fecal bacteria failed to represent the ileal dominant flora. Moreover, fecal flora diversity does not reflect ß-diversity in the ileum.

Sex differences in brain functional specialization and interhemispheric cooperation among children with autism spectrum disorders.

The prevalence of autism spectrum disorders (ASDs) differs substantially between males and females, suggesting that sex-related neurodevelopmental factors are central to ASD pathogenesis. Numerous studies have suggested that abnormal brain specialization patterns and poor regional cooperation contribute to ASD pathogenesis, but relatively little is known about the related sex differences. Therefore, this study examined sex differences in brain functional specialization and cooperation among children with ASD. The autonomy index (AI) and connectivity between functionally homotopic voxels (CFH) derived from resting-state functional magnetic resonance imaging (rs-fMRI) were compared between 58 male and 13 female children with ASD. In addition, correlations were examined between regional CFH values showing significant sex differences and symptom scores on the autism behavior checklist (ABC) and childhood autism rating scale (CARS). Male children with ASD demonstrated significantly greater CFH in the left fusiform gyrus (FG) and right opercular part of the inferior frontal gyrus (IFGoperc) than female children with ASD. In addition, the CFH value of the left FG in male children with ASD was negatively correlated with total ABC score and subscale scores for sensory and social abilities. In contrast, no sex differences were detected in brain specialization. These regional abnormalities in interhemispheric cooperation among male children with ASD may provide clues to the neural mechanisms underlying sex differences in ASD symptomatology and prevalence. Autism spectrum disorders, sex, resting-state functional magnetic resonance imaging, cerebral specialization, interhemispheric cooperation.

Combination treatment with interferon-γ may be a potential strategy to improve the efficacy of cytotherapy for rheumatoid arthritis: A network meta-analysis.

Background: Mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for rheumatoid arthritis (RA), but the current clinical results are varied. This study is to analyze the therapeutic effect of cell-based strategies on RA. Materials and Methods: The searches were performed with public databases from inception to June 17, 2021. Randomized controlled trials researching cell-based therapies in RA patients were included. Results: Eight studies, including 480 patients, were included in the analysis. The results showed that compared to the control, MSC treatment significantly reduced the disease activity score (DAS) at the second standardized mean difference (SMD): -0.70; 95% confidence interval (CI): -1.25, -0.15; P = 0.01) and 3rd month (SMD: -1.47; 95% CI: -2.77, -0.18; P < 0.01) and significantly reduced the rheumatoid factor (RF) level at the first (SMD: -0.38; 95% CI: -0.72, -0.05; P = 0.03) and 6th months (SMD: -0.81; 95% CI: -1.32, -0.31; P < 0.01). In the network meta-analysis, MSCs combined with interferon-γ (MSC_IFN) had a significant effect on increasing the American college of rheumatology criteria (ACR) 20, ACR50, and DAS <3.2 populations, had a significant effect on reducing the DAS, and decreased the RF level for a long period. Conclusion: MSCs could relieve the DAS of RA patients in the short term and reduce the level of RF. MSC_IFN showed a more obvious effect, which could significantly improve the results of ACR20, ACR50, and DAS <3.2 and reduce the DAS and RF levels.

PRMT1 promotes radiotherapy resistance in glioma stem cells by inhibiting ferroptosis.

PURPOSE: The existence of glioma stem cells (GSCs) in cancer is related to glioma radiotherapy resistance. In this research, the effect of protein arginine methyltransferase 1 (PRMT1) on the radiosensitivity of glioma stem cell (GSC)-like cells, as well as its underlying mechanism, was investigated. METHODS: GSCs-like cells were analyzed and identified by flow cytometry. The self-renewal capability was evaluated by sphere-forming assay. The PRMT1 expression level in glioblastoma were analyzed using the Gene Expression Profiling Interactive Analysis database. The mRNA and protein were scrutinized by RT-qPCR and western blot, respectively. The radiosensitivity was evaluated by clonogenic survival assay. Ferroptosis was evaluated by detecting the levels of reactive oxygen species, malondialdehyde, Fe2+, glutathione, and 4-hydroxynonenal. RESULTS: U87 and SHG44 cells with GSC-like phenotype (GSC-U87 and GSC-SHG44) displayed strong expression of CD133 and nestin versus the glioma cells. GSC-U87 and GSC-SHG44 possess the self-renewal capability. The level of PRMT1 was higher in glioblastoma tumor tissues than in the normal paracancer tissues. Knockdown of PRMT1 enhanced the radiotherapy sensitivity of GSCs-like cells, which was evidenced by reduced survival fraction in GSC-U87 and GSC-SHG44 underwent sh-PRMT1 transfection. But, this effect was attenuated by Fer-1 (a ferroptosis inhibitor) treatment, accompanied by the abatement of ferroptosis. CONCLUSION: PRMT1 promoted radiotherapy resistance in GSCs-like cells by inhibiting ferroptosis.

Chinese Herbal Compound Xiaoliu Pingyi Recipe Inhibits the Growth of Lung Adenocarcinoma by Regulating the Tumor Vascular Microenvironment.

BACKGROUND: The traditional Chinese medicine (TCM) Xiaoliu Pingyi recipe (XLPYR) has been clinically used for several decades, demonstrating favorable therapeutic effects. However, the underlying regulatory mechanisms remain unclear. The aim of this study was to explore the anti-tumor effects of XLPYR and its regulatory role in the vascular microenvironment through in vivo and in vitro experiment. MATERIALS AND METHODS: In the in vivo study, a C57BL/6J mouse model of lung adenocarcinoma (LUAD) allografts was established, and various interventions were administered for 14 days (Model group: administered normal saline via oral gavage; Pemetrexed (PEM) group: intraperitoneally injected with a solution of pemetrexed, once every 3d; XLPYR group: administered XLPYR via oral gavage; Combination (COMBI) group: received XLPYR via oral gavage simultaneously with intraperitoneal injection of pemetrexed solution). Tumor volume and weight were then compared among the groups. The impact of XLPYR on the tumor vascular microenvironment was assessed using immunohistochemistry staining. In the in vitro study, XLPYR-containing serum was prepared by oral administration to SD rats. The CCK-8 assay evaluated the effect of the serum on the proliferation of normal lung epithelial BEAS-2B cells and LUAD A549 cells, determining the optimal intervention concentrations. The cell migration and invasion abilities were evaluated using the wound-healing assay and Transwell assay, respectively. Finally, ELISA assay measured VEGF secretion levels in the LUAD cell supernatant, and RT-qPCR and Western Blot were employed to detect differences in HIF-1α, VEGFA, Ang-2, and PI3K/Akt mRNA and protein expression levels in both in vivo and in vitro experiments. RESULTS: In the in vivo study, XLPYR significantly inhibited the growth of mice LUAD allografts, with enhanced anti-tumor effects observed with prolonged drug intervention. Immunohistochemistry staining revealed reduced MVD and increased pericyte coverage in all intervention groups. Regarding vascular function, FITC-Dextran extravasation in the tumor tissues of the Model group was significantly higher than in the intervention groups, particularly with lower extravasation in the COMBI group compared to the PEM group. In the in vitro study, XLPYR demonstrated a time- and concentration-dependent inhibitory effect on LUAD cells, and with greater sensitivity in inhibiting LUAD cells compared to BEAS-2B cells. The wound-healing assay and Transwell assay confirmed that XLPYR significantly suppressed the migration and invasion abilities of LUAD cells. ELISA experiments further revealed a significant decrease in VEGF expression in the supernatant of each intervention group. RT-qPCR and Western Blot results showed consistent findings between the in vivo and in vitro experiments. HIF-1α, VEGFA, and Ang-2 mRNA and protein expression levels were significantly downregulated in the PEM group, XLPYR group, and COMBI group. There were no significant differences in the expression of PI3K and Akt mRNA and total protein, but the expression levels of phosphorylated p-PI3K and p-Akt were notably downregulated. CONCLUSION: XLPYR significantly inhibited C57BL/6J mouse LUAD allograft growth and improved the vascular microenvironment, thereby intervening in tumor angiogenesis and inducing vascular normalization. It suppressed LUAD cell proliferation, migration, and invasion, while reducing VEGF concentration in the cell supernatant. The regulatory mechanism may involve inhibiting PI3K/Akt protein phosphorylation and downregulating angiogenesis-related factors, such as HIF-1α, VEGF, and Ang-2.

Single-Molecule Studies of Cognate and Near-Cognate Elongation in an in vitro Eukaryotic Translation System.

The ribosome plays a central role in translation of the genetic code into amino acid sequences during synthesis of polypeptides. During each cycle of peptide elongation, the ribosome must discriminate between correct and incorrect aminoacyl-tRNAs according to the codon present in its A-site. Ribosomes rely on a complex sequence of proofreading mechanisms to minimize erroneous selection of incorrect aminoacyl-tRNAs that would lead to mistakes in translation. These mechanisms have been studied extensively in prokaryotic organisms, but eukaryotic elongation is less well understood. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) with an in vitro eukaryotic translation system to investigate tRNA selection and subsequent steps during peptide elongation. We compared accommodation of a tryptophan-aminoacyl-tRNA into the ribosomal A-site containing either a cognate or near-cognate codon and unexpectedly found that, following an initial slow sampling event, subsequent near-cognate sampling events proceeded more rapidly than the initial event. Further, we found a strong negative correlation between the concentration of near-cognate aminoacyl-tRNA and the efficiency of tRNA accommodation. These novel characteristics of near-cognate interaction with the eukaryotic ribosome suggest that rejection of a near-cognate tRNAs leads to formation of an altered ribosomal conformation that assists in rejecting subsequent incorrect tRNA interactions.

The Release of Lipolytic Hormones during Various High-Intensity Interval and Moderate-Intensity Continuous Training Regimens and Their Effects on Fat Loss.

To investigate the release of lipolytic hormones during various high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), and their effects on fat loss. 39 young women categorized as obese (with a body fat percentage (BFP) ≥30%) were randomly allocated to one of the following groups: all-out sprint interval training (SIT, n =10); supramaximal HIIT (HIIT120, 120%V̇O2peak, n = 10); HIIT (HIIT90, 90%V̇O2peak, n = 10), or MICT, (60%V̇O2peak, n = 9) for a twelve-week observation period consisting of 3 to 4 exercise sessions per week. Serum epinephrine (EPI) and growth hormone (GH) were measured during the 1st, 20th, and 44th training sessions. Body weight (BW), body mass index (BMI), whole-body fat mass (FM) and BFP were assessed pre- and post-intervention. Following the 1st and 20th sessions, significant increases in EPI (p < 0.05) were observed post-exercise in HIIT120 and HIIT90, but not in SIT and MICT. In the 44th session, the increased EPI was found in SIT, HIIT120, and HIIT90, but not in MICT (p < 0.05). For the GH, a significant increase was observed post-exercise in all groups in the three sessions. The increased EPI and GH returned to baselines 3 hours post-exercise. After the 12-week intervention, significant reductions in FM and BFP were found in all groups, while reductions in BW and BMI were only found in the SIT and HIIT groups. Greater reductions in FM and BFP, in comparison to MICT, were observed in the SIT and HIIT groups (p < 0.05). 12-week SIT, HIIT120, and HIIT90, in comparison to MICT, were more efficacious in fat reduction in obese women, partly benefiting from the greater release of lipolytic hormones during training sessions.

Changes in the medial prefrontal cortex metabolites after 6 months of medication therapy for patients with bipolar disorder: A 1H-MRS study.

AIMS: The study aimed to assess brain metabolite differences in the medial prefrontal cortex (mPFC) between acute and euthymic episodes of bipolar disorder (BD) with both mania and depression over a 6-month medication treatment period. METHODS: We utilized 1H-MRS technology to assess the metabolite levels in 53 individuals with BD (32 in depressive phase, 21 in manic phase) and 34 healthy controls (HCs) at baseline. After 6 months of medication treatment, 40 subjects underwent a follow-up scan in euthymic state. Metabolite levels, including N-acetyl aspartate (NAA), glutamate (Glu), and Glutamine (Gln), were measured in the mPFC. RESULTS: Patients experiencing depressive and manic episodes exhibited a notable reduction in NAA/Cr + PCr ratios at baseline compared to healthy controls (p = 0.004; p = 0.006) in baseline, compared with HCs. Over the 6-month follow-up period, the manic group displayed a significant decrease in Gln/Cr + PCr compared to the initial acute phase (p = 0.03). No significant alterations were found in depressed group between baseline and follow-up. CONCLUSION: This study suggests that NAA/Cr + PCr ratios and Gln/Cr + PCr ratios in the mPFC may be associated with manic and depressive episodes, implicating that Gln and NAA might be useful biomarkers for distinguishing mood phases in BD and elucidating its mechanisms.

Effect of single blastocyst-stage versus single cleavage-stage embryo transfer on cumulative live births in women with good prognosis undergoing in vitro fertilization: Multicenter Randomized Controlled Trial.

In this multicenter, non-inferiority, randomized trial, we randomly assigned 992 women undergoing in-vitro fertilization (IVF) with a good prognosis (aged 20-40, ≥3 transferrable cleavage-stage embryos) to strategies of blastocyst-stage (n = 497) or cleavage-stage (n = 495) single embryo transfer. Primary outcome was cumulative live-birth rate after up to three transfers. Secondary outcomes were cumulative live-births after all embryo transfers within 1 year of randomization, pregnancy outcomes, obstetric-perinatal complications, and livebirths outcomes. Live-birth rates were 74.8% in blastocyst-stage group versus 66.3% in cleavage-stage group (relative risk 1.13, 95%CI:1.04-1.22; Pnon-inferiority < 0.001, Psuperiority = 0.003) (1-year cumulative live birth rates of 75.7% versus 68.9%). Blastocyst transfer increased the risk of spontaneous preterm birth (4.6% vs 2.0%; P = 0.02) and neonatal hospitalization >3 days. Among good prognosis women, a strategy of single blastocyst transfer increases cumulative live-birth rates over single cleavage-stage transfer. Blastocyst transfer resulted in higher preterm birth rates. This information should be used to counsel patients on their choice between cleavage-stage and blastocyst-stage transfer (NCT03152643, https://clinicaltrials.gov/study/NCT03152643 ).

Effects of a nurse-led staged integral art-based cognitive intervention for older adults on the Alzheimer's disease spectrum: A randomized controlled trial.

BACKGROUND: Combined art activities can improve the neural network function within various brain regions involved in emotions, cognition, and behavior, thereby preventing or reversing cognitive decline. However, few studies have systematically examined its effects. Furthermore, the impact of nurse-led art-based cognitive intervention on cognitive and psychological health is unclear. OBJECTIVE: To evaluate the effects of a nurse-led staged integral art-based cognitive intervention in older adults on the Alzheimer's disease spectrum. DESIGN: This was a randomized wait-list controlled trial with allocation concealment and blinding of outcome assessors and data analysts. All data were collected between April 2021 and January 2023 and analyzed from January to March 2023. SETTING: One memory clinic and four medical partnership communities. PARTICIPANTS: A total of 144 participants with subjective or objective memory decline (aged ≥60 years). METHODS: Participants were randomized into an intervention group (n = 72) and a wait-list control group (n = 72), in a 1:1 ratio. The intervention group underwent a 16-week, 24-session nurse-led staged integral art-based cognitive intervention program, which was based on neurocognitive function training patterns. The control group underwent the program after the follow-up assessment. General and specific domains of cognitive function and other health-related outcomes were measured at baseline (T0), immediately after the intervention (T1), and at the 6-month follow-up (T2). RESULTS: Of the 144 participants (mean [SD] age, 71.6 [5.8] years; 50 [34.7 %] males and 94 [65.3 %] females), 130 and 115 completed the questionnaires at T1 and T2, respectively. The average attendance rate in the intervention group was 86.0 %. At T1, the intervention group showed greater improvement than the control group did in general cognitive functions (MoCA, between-group mean difference, 1.4 [95 % CIs, 0.4 to 2.5], p = 0.009). Additionally, the intervention group demonstrated statistically significant improvement compared to the control group in language, memory, quality of life, sleep quality and physical activity level at T1. Statistically significant group differences remained in sleep quality (PSQI, between-group mean difference, -1.3 [95 % CIs, -2.5 to -0.1], p = 0.035) at the 6-month follow-up. CONCLUSIONS: In this randomized controlled trial of a nurse-led staged integral art-based cognitive intervention program, older adults on the Alzheimer's disease spectrum who participated in the program experienced improved cognition and psychological health. REGISTRATION: This study was registered with ChiCTR.org (ChiCTR2100044959) on April 3, 2021. TWEETABLE ABSTRACT: A nurse-led staged integral art-based intervention for older adults on the Alzheimer's disease spectrum experienced improved cognition and psychological health.

Isolate distribution and antifungal susceptibility of Saccharomyces cerevisiae in the national regional medical center of Southwest China for women and children during 2018-2023.

BACKGROUND: Saccharomyces cerevisiae has been considered a harmless yeast, but in recent years, increasing evidence has shown that it can cause disease in humans, especially invasive infections in infants/children and vulvovaginal infections in women. This study aimed to investigate the clinical information and antifungal susceptibility of clinical cases with S. cerevisiae and establish a foundation for the prevention and treatment of fungal infections. METHODS: This study was conducted from May 2018 to May 2023 at a national regional medical center in Southwest China for women and children. The demographic and clinical characteristics of patients isolated with S. cerevisiae were collected and analyzed. All the isolates were cultured on Sabouraud medium plates and identified by MALDI-TOF MS. The antifungal susceptibility of S. cerevisiae to 10 agents (amphotericin B, fluconazole, itraconazole, voriconazole, micafungin, caspofungin, terbinafine and 5-flucytosine) was determined via the microdilution broth method to determine the minimum inhibitory concentrations (MICs). RESULTS: A total of 75 cases of S. cerevisiae isolated from patients with vulvovaginal candidiasis (VVC, 44 cases), pneumonia (13 cases), or diarrhea (18 cases) were included after data review. The MICs of voriconazole and flucytosine for S. cerevisiae isolated from different body sites differed, with higher resistance in intestinal isolates. In this study, S. cerevisiae caused VVC, but there was no clear evidence that it was involved in pneumonia or diarrhea. Compared with those of Candida albicans, the primary pathogen of VVC, the MICs of fluconazole (11.96 ± 5.78 µg/mL vs. 67.64 ± 16.62 µg/mL, p = 0.002), itraconazole (0.77 ± 0.19 µg/mL vs. 2.31 ± 0.53 µg/mL, p = 0.008), voriconazole (0.22 ± 0.09 µg/mL vs. 5.02 ± 1.09 µg/mL, p < 0.001), and terbinafine (10.41 ± 0.84 µg/mL vs. 14.93 ± 4.77 µg/mL, p < 0.001) for S. cerevisiae (isolated from the genital tract) were significantly lower, while those of micafungin (0.14 ± 0.01 µg/mL vs. 0.06 ± 0.01 µg/mL, p < 0.001) and caspofungin (0.27 ± 0.04 µg/mL vs. 0.06 ± 0.01 µg/mL, p < 0.001) were significantly greater. CONCLUSION: Azoles remain the recommended regimen for S. cerevisiae-related VVC, and the use of amphotericin B vaginal effervescent tablets could be considered for the treatment of azole-resistant isolates. The antifungal susceptibility of S. cerevisiae varies according to the isolated source, and the pathogenicity trend of S. cerevisiae should be studied.

The causal association between epilepsy and amyotrophic lateral sclerosis: A two-sample Mendelian randomization study.

OBJECTIVES: Epilepsy and amyotrophic lateral sclerosis (ALS) are common neurological disorders. The association between the two disorders has been raised in observational studies. However, it is uncertain to what extent they have mutual causal effects. In this study, we aimed to investigate their causal association using a two-sample Mendelian randomization (MR) method. METHODS: We performed a two-sample bidirectional MR analysis to evaluate the causal association of epilepsy with the risk of ALS. Publicly published genome-wide association study statistics for epilepsy and ALS were used in the study. The primary analysis included genetic variants with a p value of less than 1 × 10-5 as instrumental variables. We applied several alternative methods, including inverse variance weighting, weighted median, simple mode, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier, and statistical graphs to assess the associations of epilepsy and its subtype with the risk of ALS. Reverse MR analyses were also performed to examine the association of ALS with the risk of epilepsy. RESULTS: The primary MR analysis found no causal effect of epilepsy on risk of ALS (odds ration [OR]: 1.133, 95% confidence interval [CI]: 0.964-1.332, p = .130). Among subtypes of epilepsy, it also failed to observe any causal association between general epilepsy and ALS (OR: 1.036, 95% CI: 0.969-1.108, P = .300). However, focal epilepsy contributed to an increase in the risk of ALS (OR: 1.177, 95% CI: 1.027-1.348, p = .019). Moreover, the investigation of reverse causalities did not reveal significant results. CONCLUSIONS: The current study supports a causal influence of focal epilepsy on ALS risk. Future studies are needed to explore its potential role in ALS.