Recognition of Semaphorin Proteins by P. sordellii Lethal Toxin Reveals Principles of Receptor Specificity in Clostridial Toxins.

Pathogenic clostridial species secrete potent toxins that induce severe host tissue damage. Paeniclostridium sordellii lethal toxin (TcsL) causes an almost invariably lethal toxic shock syndrome associated with gynecological infections. TcsL is 87% similar to C. difficile TcdB, which enters host cells via Frizzled receptors in colon epithelium. However, P. sordellii infections target vascular endothelium, suggesting that TcsL exploits another receptor. Here, using CRISPR/Cas9 screening, we establish semaphorins SEMA6A and SEMA6B as TcsL receptors. We demonstrate that recombinant SEMA6A can protect mice from TcsL-induced edema. A 3.3 Å cryo-EM structure shows that TcsL binds SEMA6A with the same region that in TcdB binds structurally unrelated Frizzled. Remarkably, 15 mutations in this evolutionarily divergent surface are sufficient to switch binding specificity of TcsL to that of TcdB. Our findings establish semaphorins as physiologically relevant receptors for TcsL and reveal the molecular basis for the difference in tissue targeting and disease pathogenesis between highly related toxins.

Riboneogenesis in yeast.

Glucose is catabolized in yeast via two fundamental routes, glycolysis and the oxidative pentose phosphate pathway, which produces NADPH and the essential nucleotide component ribose-5-phosphate. Here, we describe riboneogenesis, a thermodynamically driven pathway that converts glycolytic intermediates into ribose-5-phosphate without production of NADPH. Riboneogenesis begins with synthesis, by the combined action of transketolase and aldolase, of the seven-carbon bisphosphorylated sugar sedoheptulose-1,7-bisphosphate. In the pathway's committed step, sedoheptulose bisphosphate is hydrolyzed to sedoheptulose-7-phosphate by the enzyme sedoheptulose-1,7-bisphosphatase (SHB17), whose activity we identified based on metabolomic analysis of the corresponding knockout strain. The crystal structure of Shb17 in complex with sedoheptulose-1,7-bisphosphate reveals that the substrate binds in the closed furan form in the active site. Sedoheptulose-7-phosphate is ultimately converted by known enzymes of the nonoxidative pentose phosphate pathway to ribose-5-phosphate. Flux through SHB17 increases when ribose demand is high relative to demand for NADPH, including during ribosome biogenesis in metabolically synchronized yeast cells.

Structural insights into the transcription activation mechanism of the global regulator GlnR from actinobacteria.

In actinobacteria, an OmpR/PhoB subfamily protein called GlnR acts as an orphan response regulator and globally coordinates the expression of genes responsible for nitrogen, carbon, and phosphate metabolism in actinobacteria. Although many researchers have attempted to elucidate the mechanisms of GlnR-dependent transcription activation, progress is impeded by lacking of an overall structure of GlnR-dependent transcription activation complex (GlnR-TAC). Here, we report a co-crystal structure of the C-terminal DNA-binding domain of GlnR (GlnR_DBD) in complex with its regulatory cis-element DNA and a cryo-EM structure of GlnR-TAC which comprises Mycobacterium tuberculosis RNA polymerase, GlnR, and a promoter containing four well-characterized conserved GlnR binding sites. These structures illustrate how four GlnR protomers coordinate to engage promoter DNA in a head-to-tail manner, with four N-terminal receiver domains of GlnR (GlnR-RECs) bridging GlnR_DBDs and the RNAP core enzyme. Structural analysis also unravels that GlnR-TAC is stabilized by complex protein-protein interactions between GlnR and the conserved ß flap, σAR4, αCTD, and αNTD domains of RNAP, which are further confirmed by our biochemical assays. Taken together, these results reveal a global transcription activation mechanism for the master regulator GlnR and other OmpR/PhoB subfamily proteins and present a unique mode of bacterial transcription regulation.

Engineering pan-HIV-1 neutralization potency through multispecific antibody avidity.

Deep mining of B cell repertoires of HIV-1-infected individuals has resulted in the isolation of dozens of HIV-1 broadly neutralizing antibodies (bNAbs). Yet, it remains uncertain whether any such bNAbs alone are sufficiently broad and potent to deploy therapeutically. Here, we engineered HIV-1 bNAbs for their combination on a single multispecific and avid molecule via direct genetic fusion of their Fab fragments to the human apoferritin light chain. The resulting molecule demonstrated a remarkable median IC50 value of 0.0009 µg/mL and 100% neutralization coverage of a broad HIV-1 pseudovirus panel (118 isolates) at a 4 µg/mL cutoff-a 32-fold enhancement in viral neutralization potency compared to a mixture of the corresponding HIV-1 bNAbs. Importantly, Fc incorporation on the molecule and engineering to modulate Fc receptor binding resulted in IgG-like bioavailability in vivo. This robust plug-and-play antibody design is relevant against indications where multispecificity and avidity are leveraged simultaneously to mediate optimal biological activity.

Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.

The aim of this study was to identify serum diagnostic biomarkers associated with the severity of obstructive sleep apnea (OSA) during pregnancy. Differentially expressed proteins (DEPs) were identified in the control (C), mild (O), and moderate (MO) OSA groups (n = 3 in each group). Bioinformatics analysis was conducted to identify the underlying functions, pathways, and networks of the proteins. Receiver operating characteristic curves were used to assess the diagnostic value of the identified DEPs. The enzyme-linked immunoassay was performed to detect serum levels of the complement C1r subcomponent (C1R) and alpha-2-macroglobulin (A2M) in 79 pregnant women with OSA (mild OSA [n = 32]; moderate OSA [n = 29], and severe OSA [n = 18]) and 65 healthy pregnant women without OSA. Pearson's correlation analysis was conducted to analyze the correlation between C1R and A2M levels and OSA clinicopathological factors. In total, 141 DEPs, 29 DEPs, and 103 DEPs were identified in the three groups (i.e., the mild OSA vs control group, the moderate OSA vs mild apnea group, and the moderate OSA vs control group, respectively). C1R and A2M were identified as continuously up-regulated proteins, and the levels of C1R and A2M were associated with OSA severity. C1R and A2M were found to be correlated with body mass index, systolic blood pressure, apnea-hypopnea index, oxygen desaturation index, time with saturation below 90%, and lowest SaO2. Adverse maternal and neonatal outcomes were observed in pregnant women with OSA. C1R and A2M have been identified as diagnostic biomarkers and are associated with the severity of OSA during pregnancy.

Transcription factors NtHD9 and NtHD12 control long glandular trichome formation via jasmonate signaling.

Glandular trichomes are universal epidermal structures that produce abundant specialized metabolites. However, knowledge of the initiation of glandular heads in glandular trichomes is limited. Herein, we found an intrinsic link of morphogenesis between glandular trichomes and non-glandular trichomes. Two novel homeodomain leucine zipper II members in tobacco (Nicotiana tabacum), NtHD9 and NtHD12, played important roles in long glandular trichome formation: NtHD9 was responsible for glandular head formation, while NtHD12 simultaneously controlled the formation of stalks and glandular heads. DAP-seq analysis suggested that NtHD9 can bind to the KKGCATTWAWTR motif of the cytochromes P450 94C1 (NtCYP94C1) promoter, which is involved in jasmonoyl-isoleucine oxidation. RNA-seq analysis of non-transformed tobacco and nthd9 plants revealed that NtHD9 modulates the expression of jasmonate (JA) signaling- and six trichome development-related genes. Notably, MeJA treatment restored the morphogenesis of long glandular trichomes in nthd9 and nthd12 plants, and the size of glandular heads increased with increasing MeJA concentration. However, the phenotype of long glandular trichome absence in double mutants of NtHD9 and NtHD12 could not be restored by MeJA. Our data demonstrate that NtHD9 and NtHD12 have distinct major functions yet overlapping roles in long glandular trichome formation via JA signaling.

Serum IgA as a Prognostic Beacon: Anticipating Systemic Therapy Efficacy in Metastatic Clear Cell Renal Cell Carcinoma.

OBJECTIVE: Immunotherapy-tyrosine kinase inhibitor (IO-TKI) therapy has revolutionized the treatment landscape for metastatic clear cell renal cell carcinoma (mccRCC); however, the absence of effective biomarkers poses a challenge in predicting the efficacy of these regimens. This study aims to explore the predictive and prognostic value of serum immunoglobulin A (IgA) in mccRCC patients undergoing IO-TKI therapy. METHODS: Ninety-six mccRCC patients treated with IO-TKI therapy from 2019 to 2023 were enrolled and serum IgA levels were assessed at the pretreatment baseline and after 3 months of treatment. RESULTS: Notably, baseline levels of IgA showed no correlation with the objective response rate. However, patients achieving complete or partial responses exhibited a remarkable decrease in IgA levels, while those with stable or progressive disease displayed an increase in IgA levels after 3 months of treatment. Furthermore, the dynamic alteration in IgA levels after 3 months of treatment demonstrated predictive value for both progression-free survival (PFS) and overall survival (OS). The time-dependent receiver operating characteristic curves exhibited outstanding performance in predicting PFS (AUC 0.793) and OS (AUC 0.738). CONCLUSION: Taken together, this study demonstrates that dynamic alteration of serum IgA after 3 months of treatment was significantly correlated with prognosis and therapeutic efficacy in mccRCC patients.

Bioresorbable Scaffolds for Below-the-Knee Arterial Disease: A Literature Review of New Developments.

This review aimed to explore the therapeutic effect of bioabsorbable stents in the inferior genicular artery, from the emergence of absorbable bare metal stents to the latest technology in polymer and anti-proliferative eluting drugs mixed with coated bioresorbable vascular stents (BVSs). Currently, there are conflicting data regarding the safety and effectiveness of BVSs in infrapopliteal artery interventions, especially compared to the current generation of drug-eluting stents (DESs). This review will cover the existing data on BVSs in reconstructing the infrapopliteal arterial blood flow and active clinical trials for future iterations of BVSs. In terms of primary patency rate and target lesion revascularization rate, the available research on the effectiveness of BVSs in reconstructing the infrapopliteal arterial blood flow suggests that a BVS is compatible with current DESs within 3-12 months; long-term data have not yet been reported. The ABSORB BVS is the most studied BVS in cardiovascular disease (CAD). Initially, the ABSORB BVS showed promising results. Managing intricate regions in peripheral artery disorders, such as branching or lengthy lesions, continues to be a formidable undertaking. In contrast to the advanced narrowing of arteries seen in standard permanent stent procedures, bioabsorbable stents have the potential to promote the expansion and beneficial merging of blood channels in the latter stages. Furthermore, incorporating stents and re-establishing the endothelial function can diminish the probability of restenosis or thrombosis. Nevertheless, the extent to which bioabsorbable stents may simultaneously preserve arterial patency and guarantee their structural integrity remains uncertain. The powerful and intricate mechanical stresses exerted by the blood in the superficial femoral artery and popliteal artery can cause negative consequences on any implant inserted into the vessel, regardless of its composition, even metal. Furthermore, incorporating stents is advantageous for treating persistent occlusive lesions since it does not impact later treatments, including corrective bypass operations. Evidence is scarce about the use of bioabsorbable stents in treating infrapopliteal lesions. Utilizing bioabsorbable stents in minor infrapopliteal lesions can successfully maintain the patency of the blood vessel lumen, whereas balloon angioplasty cannot offer this benefit. The primary focus of testing these materials is determining whether bioabsorbable scaffolds can provide adequate radial force in highly calcified elongated lesions. Indeed, using "-limus" medication elution technology in conjunction with bioabsorbable stents has previously offered clinical benefits in treating the popliteal artery, as evidenced by limited trials.BVSs for peripheral arterial disease (PAD) show promise and have the potential to offer a less inflammatory and more vessel-friendly option compared to permanent metallic stents. However, current evidence does not yet allow for a universal recommendation for their use. Thus, ongoing, and future studies, such as those examining the newer generation of bioresorbable scaffolds (BRSs) with improved mechanical properties and resorption profiles, will be crucial in defining the role of BRSs in managing PAD.

Perspective view of allogeneic IgG tumor immunotherapy.

Allogeneic tumors are eradicated by host immunity; however, it is unknown how it is initiated until the report in Nature by Yaron Carmi et al. in 2015. Currently, we know that allogeneic tumors are eradicated by allogeneic IgG via dendritic cells. AlloIgG combined with the dendritic cell stimuli tumor necrosis factor alpha and CD40L induced tumor eradication via the reported and our proposed potential signaling pathways. AlloIgG triggers systematic immune responses targeting multiple antigens, which is proposed to overcome current immunotherapy limitations. The promising perspectives of alloIgG immunotherapy would have advanced from mouse models to clinical trials; however, there are only 6 published articles thus far. Therefore, we hope this perspective view will provide an initiative to promote future discussion.

The Efficacy of Drug-Coated Balloons and Drug-Eluting Stents in Infrapopliteal Revascularization: A Meta-analysis.

OBJECTIVE: The study aimed to compare the effectiveness of drug-coated balloon (DCB) and drug-eluting stents (DESs) to standard endovascular techniques like percutaneous transluminal angioplasty (PTA) and bare metal stent (BMS) for treating infrapopliteal artery disease. METHODS: Including 8 DCB trials and 4 DES trials, this meta-analysis of 12 recent randomized controlled trials (RCTs) is comprehensive. We searched MEDLINE, EMBASE, Science of Web, Cochrane, and PubMed for this meta-analysis. We searched these databases for papers from their inception to February 2023. We also analyzed the references given in the listed studies and any future study that cited them. No language or publication date restrictions were applied to the 12 RCTs. The experimental group includes 8 DCB studies and 4 DES investigations, the DCB group is primarily concerned with the paclitaxel devices, whereas the DES group is preoccupied with the "-limus" devices. Key clinical outcomes in this study were primary patency and binary restenosis rates. This study's secondary outcomes are late lumen loss (LLL), clinically-driven target lesion revascularization (CD-TLR), limb amputation, and all-cause mortality. The evidence quality was assessed using Cochrane risk-of-bias. The PROSPERO registration number for this study is CRD42023462038. FINDINGS: Only 108 of 1152 publications found satisfied qualifying criteria and contained data. All 13 RCTs have low to moderate bias. Drug-coated balloons and DESs were compared in the excluded study. The analysis comprised 2055 participants from 12 RCTs that met the inclusion criteria, including 1417 DCB patients and 638 DES patients. Drug-coated balloons outperform traditional methods in short-term monitoring of primary patency, binary restenosis, and CD-TLR. The benefits fade over time, and the 2 techniques had similar major amputation rates, mortality rates, and LLL. Drug-eluting stents outperform conventional procedures in primary patency, binary restenosis, and CD-TLR during medium-term to short-term follow-up. Comparing the 2 methods, major and minor amputations, death rate, and LLL were similar. CONCLUSION: Comparison of DES and DCB with PTA or BMS shows that DES had better follow-up results. DCB has positive short-term results, but long-term effects differ, however, more research is needed to determine when DES and DCB should be used in medical procedures. CLINICAL IMPACT: The provision of additional evidence to substantiate the advancement of drug-coated balloon (DCB) therapy in the treatment of lower limb arteriosclerosis obliterans, particularly in the below-the-knee area characterized by high calcium load and significant occlusion, is comparable in efficacy to conventional procedures. This finding is advantageous for the progress of interventional revascularization. The advancement and efficacy of DCB have resulted in improved treatment outcomes for medical practitioners in clinical settings. Our research incorporates the most recent randomized experiments.

The Effects of Different Dosages on Micronized Purified Flavonoid Fraction's Treatment of Lower Limb Chronic Venous Disease: A Meta-Analysis.

BACKGROUND: Micronized purified flavonoid fraction (MPFF) is a widely prescribed and extensively investigated venoactive drug (VAD). The standard dosage for MPFF is 500 mg administered twice daily. However, a new daily dose of 1000 mg has just been introduced. OBJECTIVE: This study investigated whether a daily dose of 1000 mg MPFF could be implemented and embraced by the public and still has the same therapeutic effects as conventional pharmaceuticals. METHODS: For this meta-analysis, we searched MEDLINE, Embase, Science of Web, Cochrane, and PubMed databases and forward and backward citations for studies published between database inception and March 2023. Three randomized controlled trials (RCTs) of comparison of different dosages of MPFF to evaluate whether there is a significant difference between them were included, without language or date restrictions. Due to the small sample size of the study included, we conducted a simple sensitivity test using a one-by-one exclusion method, and the results showed that the study did not affect the final consolidation conclusion. The quality of the evidence was assessed using the Cochrane risk-of-bias tool. RESULTS: Out of 232 studies, 99 were eligible and 39 RCTs had data, all with low to moderate bias. Overall, 1924 patients (experimental group: 967, control group: 957) in 3 RCTs met the criteria. There is no significant difference in patient compliance, efficacy, clinical adverse events, and quality of life scores between MPFF 1000 mg once daily and MPFF 500 mg twice daily (standardized mean difference [SMD]: 0.049 [0.048, 0.145], p=0.321, risk ratio [RR]: 0.981 [0.855, 1.125], p=0.904, and SMD: 0.063 [0.034, 0.160], p=0.203). INTERPRETATION: In symptomatic chronic venous disease patients, MPFF 1000 mg once daily and MPFF 500 mg twice daily improve patient compliance, lower limb discomfort, clinical adverse events, and quality of life scores similarly. Regular medical care should recommend MPFF 1000 mg daily more often. CLINICAL IMPACT: Micronized purified flavonoid fraction (MPFF) is a popular venoactive medication (VAD) in modern medicine.MPFF is effective in treating lower extremity venous problems.Currently, besides conventional 500 mg tablets, there exist alternative dosage forms such as solutions, chewable tablets, and other novel formulations for MPFF.The excessive frequency and amount of medication may have a negative impact on patient adherence.

Morphology, genetic characterization and phylogeny of Moniliformis tupaia n. sp. (Acanthocephala: Moniliformidae) from the northern tree shrew Tupaia belangeri chinensis Anderson (Mammalia: Scandentia).

A new species of Moniliformis, M. tupaia n. sp. is described using integrated morphological methods (light and scanning electron microscopy) and molecular techniques (sequencing and analysing the nuclear 18S, ITS, 28S regions and mitochondrial cox1 and cox2 genes), based on specimens collected from the intestine of the northern tree shrew Tupaia belangeri chinensis Anderson (Scandentia: Tupaiidae) in China. Phylogenetic analyses show that M. tupaia n. sp. is a sister to M. moniliformis in the genus Moniliformis, and also challenge the systematic status of Nephridiacanthus major. Moniliformis tupaia n. sp. represents the third Moniliformis species reported from China.

Emergency cervical cerclage in delayed-interval delivery of twin pregnancies: a scoping review.

BACKGROUND: The protocol for delayed-interval delivery of the second twin in twin pregnancies has not been standardized. Cervical cerclage is often performed, but its use is debated. To conduct a scoping review on cervical cerclage for prolonging the intertwin delivery interval and improving second twin survival and maternal outcomes after preterm delivery or spontaneous abortion of the first twin in twin pregnancies. METHODS: Seven Chinese and English language databases were searched from inception to March 1, 2023, including PubMed, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP Chinese Science Journal Database, and Sinomed. Relevant observational studies that assessed the effectiveness of the use of cervical cerclage in delayed-interval delivery of twins were screened and selected, and raw data were extracted, and descriptive statistics and chi-square analysis were performed. RESULTS: A total of 102 articles were retrieved. After screening and exclusion of duplicate and irrelevant articles, 22 articles meeting the inclusion criteria were obtained. Studies in which cerclage was performed reported longer intertwin delivery intervals than those that did not perform cerclage, and the difference was statistically significant. The cerclage group also tended to have lower rates of chorioamnionitis and maternal complications, but the difference between the two groups was not statistically significant. CONCLUSION: After excluding patients with contraindications, emergency cervical cerclage can be considered in cases of spontaneous abortion of the first twin in twin pregnancies to prolong the gestation and improve the prognosis of the remaining fetus until it becomes viable and increases its birth weight.

The vaginal microbial signatures of preterm birth woman.

To explore the differences of vaginal microbes in women with preterm birth (PTB), and to construct prediction model. We searched for articles related to vaginal microbiology in preterm women and obtained four 16S rRNA-sequence datasets. We analyzed that for species diversity and differences, and constructed a random forest model with 20 differential genera. We introduce an independent whole genome-sequencing (WGS) data for validation. In addition, we collected vaginal and cervical swabs from 33 pregnant women who delivered spontaneously full-term and preterm infants, performed WGS in our lab to further validate the model. Compared to term birth (TB) samples, PTB women vagina were characterized by a decrease in Firmicutes, Lactobacillus, and an increase in diversity accompanied by the colonization of pathogenic bacteria such as Gardnerella, Atopobium and Prevotella. Twenty genus markers, including Lactobacillus, Prevotella, Streptococcus, and Gardnerella performed well in predicting PTB, with study-to-study transfer validation and LODO validation, different gestation validation showing good results, and in two independent cohorts (external WGS cohorts and woman samples WGS cohorts) in which the accuracy was maintained. PTB women have unique vaginal microbiota characteristics. A predictive model of PTB was constructed and its value validated from multiple perspectives.

Dose-response associations of maternal prenatal noise exposure duration with antepartum depression status.

BACKGROUND: Antepartum depression has been reported to be associated with the intensity of maternal prenatal noise exposure; however, the association between noise exposure duration and the development of antepartum depression has not been established. This study aimed to determine the total and trimester-specific association of prenatal noise exposure duration with the development of antepartum depression. METHODS: From May 2018 to June 2021, we recruited 2,166 pregnant women from Shengjing Hospital, northeast China. We used a standardized questionnaire to assess women's prenatal noise exposure and used the Edinburgh Postnatal Depression Scale to assess pregnant women's antepartum depression during the 1st -, 2nd -, and 3rd - trimesters. We calculated a cumulative noise exposure score ranging from 0 to 3, with a higher score reflecting higher frequency and longer duration of noise exposure during pregnancy. RESULTS: Women who were exposed to noise for ≥ 15 min per day had an increased risk of antepartum depression compared with women who were not exposed to noise during pregnancy [odds ratio (OR) = 1.83, 95%CI:1.18, 2.83]. Noise exposure in a specific trimester was associated with higher risk of depression in the same trimester and subsequent trimesters. We observed increases in antepartum depression risk with increasing cumulative noise exposure scores (P for trend < 0.05 for all). Pregnant women with the highest scores had the highest risk of antepartum depression during the first (OR = 1.30, 95%CI:1.02, 1.65), second (OR = 1.75, 95%CI:1.23, 2.50) trimesters. Women with a cumulative noise exposure score of 2 had the highest risk of antepartum depression during the third trimester (OR = 1.79, 95%CI:1.14, 2.80), as well as during the whole pregnancy (OR = 1.94, 95%CI:1.14, 3.30). CONCLUSIONS: Maternal prenatal noise exposure duration was positively associated with antepartum depression risk in a dose-response manner. It is necessary to develop strategies by which pregnant women can avoid excessive exposure to noise to prevent antepartum depression.

Transcriptomic Hallmarks of Hypoxic-Ischemic Brain Injury: Insights from an in Vitro Model.

BACKGROUND: Hypoxic-ischemic injury of neurons is a pathological process observed in several neurological conditions, including ischemic stroke and neonatal hypoxic-ischemic brain injury (HIBI). An optimal treatment strategy for these conditions remains elusive. The present study delved deeper into the molecular alterations occurring during the injury process in order to identify potential therapeutic targets. METHODS: Oxygen-glucose deprivation/reperfusion (OGD/R) serves as an established in vitro model for the simulation of HIBI. This study utilized RNA sequencing to analyze rat primary hippocampal neurons that were subjected to either 0.5 or 2 h of OGD, followed by 0, 9, or 18 h of reperfusion. Differential expression analysis was conducted to identify genes dysregulated during OGD/R. Time-series analysis was used to identify genes exhibiting similar expression patterns over time. Additionally, functional enrichment analysis was conducted to explore their biological functions, and protein-protein interaction (PPI) network analyses were performed to identify hub genes. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for validation of hub-gene expression. RESULTS: The study included a total of 24 samples. Analysis revealed distinct transcriptomic alterations after OGD/R processes, with significant dysregulation of genes such as Txnip, Btg2, Egr1 and Egr2. In the OGD process, 76 genes, in two identified clusters, showed a consistent increase in expression; functional analysis showed involvement of inflammatory responses and signaling pathways like tumor necrosis factor (TNF), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and interleukin 17 (IL-17). PPI network analysis suggested that Ccl2, Jun, Cxcl1, Ptprc, and Atf3 were potential hub genes. In the reperfusion process, 274 genes, in three clusters, showed initial upregulation followed by downregulation; functional analysis suggested association with apoptotic processes and neuronal death regulation. PPI network analysis identified Esr1, Igf-1, Edn1, Hmox1, Serpine1, and Spp1 as key hub genes. qRT-PCR validated these trends. CONCLUSIONS: The present study provides a comprehensive transcriptomic profile of an in vitro OGD/R process. Key hub genes and pathways were identified, offering potential targets for neuroprotection after hypoxic ischemia.

Mode of delivery and neonatal outcomes in preterm twins less than 32 weeks of gestation or birthweight under 1500 g: a systematic review and meta-analyses.

BACKGROUND: The mode of delivery for twins born before 32 weeks of gestation remains controversial. Our purpose is to conduct a meta-analysis of twin pregnancies less than 32 weeks or twin weight less than 1500 g, so as to find a suitable delivery mode. METHODS: We searched PubMed database, Cochrane Library database, and EMBASE database through December 2022. This protocol was registered with PROSPERO (CRD42023386946) prior to initiation. Studies that compared vaginal delivery to cesarean section for newborns less than 32 weeks of gestation or birthweight under 1500 g were included. The primary result was neonatal mortality rate. Secondary result was neonatal morbidity. The quality of literatures included in the research was evaluated in accordance with Newcastle-Ottawa Scale (NOS) literature quality evaluation scale. We use odds ratio (OR) as the effect index for binary variables. Point estimates and 95% confidence intervals (95% CI) were calculated. P < 0. 05 indicated statistically significant difference. RESULTS: Our search generated 5310 articles, and a total of 8 articles comprising a total of 14,703 newborns were included in the analysis. The odds ratios of neonatal mortality rate were for twins delivered by vaginal delivery compared to cesarean section were 0.84 (95% CI 0.57-1.24, P = 0.38). The 5-min Apgar score < 7 (95% CI 0.44-1.75, P = 0.72), necrotizing enterocolitis (95% CI 0.81-1.19, P = 0.82), intraventricular hemorrhage (95% CI 0.41-1.86, P = 0.71), periventricular leukomalacia (95% CI 0.16-4.52, P = 0.84), bronchopulmonary dysplasia (95% CI 0.88-1.36, P = 0.42), and respiratory distress syndrome (95% CI 0.23-2.01, P = 0.48) were not statistically significant between the two groups. CONCLUSION: We have observed that vaginal delivery does not confer an increased risk of neonatal morbidity and mortality in twins born before 32 weeks of gestation. However, the current results are affected by substantial heterogeneity and confounding factors. We still need high-quality randomized-controlled studies require to address this important question.

MiRNA-26a-5p inhibits preterm labor initiation by targeting and regulating TRPC3 ion channel protein expression.

The incidence of preterm birth (PTB) is increasing annually worldwide, leading to various health problems or even fetal deaths. Our previous work demonstrated the activation of transient receptor potential cation channel subfamily C 3 (TRPC3) in mice with PTB, and its activation could promote inward flow of calcium ions and uterine smooth muscle (USM) contraction via regulation of Cav3.2, Cav3.1, and Cav1.2. However, the upstream regulators of TRPC3 and its mechanisms remain unknown. In the present study, the binding of miR-26a-5p to the 3' untranslated region of TRPC3 was predicted by bioinformatics databases (TargetScanHuman and starBase v3.0) and confirmed by a dual-luciferase assay. MiR-26a-5p was downregulated, while TRPC3 was upregulated in the USM tissues of patients with PTB compared to people without PTB. The results showed that miR-26a-5p mimic transfection markedly reduced TRPC3 expression in LPS-stimulated USM cells. Additionally, miR-26a-5p regulated intracellular Ca2+ levels in USM cells by targeting TRPC3. Furthermore, miR-26a-5p inhibited the CPI17/PKC/PLCγ signaling pathway and reduced the expression of Cav3.2, Cav3.1, and Cav1.2. In conclusion, miR-26a-5p regulated the initiation of PTB by targeting TRPC3 and regulating intracellular Ca2+ levels. This study provides a promising diagnostic biomarker and therapeutic target for PTB.

Constituents of Chimaphila japonica and Their Diuretic Activity.

Three new phenols (1-3), one new cyclohexanol (4), two known phenols (5-6), and six known flavonoids (7-12) were isolated from the n-butanol of the 75% ethanol extract of all plants of Chimaphila japonica Miq. Among them, compound 5 was named and described in its entirety for the first time, and compounds 9 and 10 were reported in C. japonica for the first time. The structures of all compounds were confirmed using a comprehensive analysis of 1D and 2D NMR and HRESIMS data. Biological results show that compounds 4, 7, and 11 exhibited potent diuretic activity. The modes of interaction between the selected compounds and the target diuretic-related WNK1 kinase were investigated in a preliminary molecular docking study. These results provided insight into the chemodiversity and potential diuretic activities of metabolites in C. japonica.

Comparison of the Efficacy of Indwelling Gastric Tubes in Preoperative and Postoperative Patients With Oral and Maxillofacial Malignancies.

PURPOSE: To explore the optimal plan for the timing of indwelling gastric tube placement in oral and maxillofacial malignant tumor patients. DESIGN: A prospective randomized controlled trial. METHODS: 80 patients with oral and maxillofacial tumor were selected, and 40 patients were Pre-operative group. The remaining 40 patients were the control group, called Postoperative group. The body weight and hospital stay of the two groups were observed before and after surgery. Blood samples were taken before surgery and 1, 3 and 7 days after surgery to detect hemoglobin and plasma albumin. FINDINGS: The number of postoperative hospitalization days in the pre-operative group was significantly lower than that in the post-operative group; postoperative hemoglobin and plasma albumins were lower in both groups compared with the preoperative level. CONCLUSIONS: Preoperative nasogastric tube ensured early postoperative administration of gastrointestinal nutrition, promoted postoperative plasma albumin recovery, and shortened the days of hospitalization.