Cell-type specific methylation changes in the newborn child associated to obstetric pain relief.

Although it is widely known that various pharmaceuticals affect the methylome, the knowledge of the effects from anesthesia is limited, and nearly nonexistent regarding the effects of obstetric anesthesia on the newborn child. Using sequencing based-methylation data and a reference-based statistical deconvolution approach we performed methylome-wide association studies (MWAS) of neonatal whole blood, and for each cell-type specifically, to detect methylation variations that are associated with the pain relief administered to the mother during delivery. Significant findings were replicated in a different dataset and followed-up with gene ontology analysis to pinpoint biological functions of potential relevance to these neonatal methylation alterations. The MWAS analyses detected methylome-wide significant (q<0.1) alterations in the newborn for laughing gas in granulocytes (two CpGs, p<5.50x10-9, q = 0.067), and for pudendal block in monocytes (five CpGs across three loci, p<1.51 x10-8, q = 0.073). Suggestively significant findings (p<1.00x10-6) were detected for both treatments for bulk and all cell-types, and replication analyses showed consistent significant enrichment (odds ratios ranging 3.47-39.02; p<4.00×10-4) for each treatment, suggesting our results are robust. In contrast, we did not observe any overlap across treatments, suggesting that the treatments are associated with different alterations of the neonatal blood methylome. Gene ontology analyses of the replicating suggestively significant results indicated functions related to, for example, cell differentiation, intracellular membrane-bound organelles and calcium transport. In conclusion, for the first time, we investigated and detected effect of obstetric pain-relief on the blood methylome in the newborn child. The observed differences suggest that anesthetic treatment, such as laughing gas or pudendal block, may alter the neonatal methylome in a cell-type specific manner. Some of the observed alterations are part of gene ontology terms that previously have been suggested in relation to anesthetic treatment, supporting its potential role also in obstetric anesthesia.

The RhoGAP ARHGAP32 interacts with desmoplakin, and is required for desmosomal organization and assembly.

Desmosomes play a crucial role in maintaining tissue barrier integrity, particularly in mechanically stressed tissues. The assembly of desmosomes is regulated by the cytoskeleton and its regulators, and desmosomes also function as a central hub for regulating F-actin. However, the specific mechanisms underlying the crosstalk between desmosomes and F-actin remain unclear. Here, we identified that ARHGAP32, a Rho GTPase-activating protein, is located in desmosomes through its interaction with desmoplakin (DSP) via its GAB2-interacting domain (GAB2-ID). We confirmed that ARHGAP32 is required for desmosomal organization, maturation and length regulation. Notably, loss of ARHGAP32 increased formation of F-actin stress fibers and phosphorylation of the regulatory myosin light chain Myl9 at T18/S19. Inhibition of ROCK activity in ARHGAP32-knockout (KO) cells effectively restored desmosomal organization and the integrity of epithelial cell sheets. Moreover, loss of DSP impaired desmosomal ARHGAP32 location and led to decreased actomyosin contractility. ARHGAP32 with a deletion of the GAB2-ID domain showed enhanced association with RhoA in the cytosol and failed to rescue the desmosomal organization in ARHGAP32-KO cells. Collectively, our study unveils that ARHGAP32 associates with and regulates desmosomes by interacting with DSP. This interaction potentially facilitates the crosstalk between desmosomes and F-actin.

Exploring the potent enhancement effects of plyometric training on vertical jumping and sprinting ability in sports individuals.

Objective: This meta-analysis examines the impact of different combinations of plyometric training (complexity, training volume, and rest intervals) on immediate vertical jump and sprint performance in athletes. Methods: A systematic search was conducted in four databases, and Cochrane guidelines were used to evaluate the quality of included studies. Review Manager 5.4 software was employed to analyze outcome measures. Nineteen randomized controlled trials involving 293 participants were included. Results: Single plyometric training-induced post-activation potentiation (PAP) had a slight positive effect on vertical jump performance [SMD = -0.24, 95% CI (-0.38, -0.1), P = 0.0009]. Optimal results were observed with rest intervals of 0.3-4 min (SMD = 0.30, P = 0.0008). Sprint performance showed slight improvement [SMD = 0.27, 95% CI (0.03, 0.52), P = 0.03]. Complex plyometric training had a moderate effect on vertical jump performance [SMD = 0.58, 95% CI (-0.86, -0.23), P = 0.002], with the best outcomes seen with rest intervals exceeding 8 min (SMD = 0.77). Sprint performance also improved significantly [SMD = 0.8, 95% CI (0.01, 1.59), P = 0.05]. Single-session plyometric training did not significantly enhance vertical jump performance [SMD = -0.19, 95% CI (-0.41, -0.02), P = 0.07], but had a notable effect on sprint performance [SMD = 0.8, 95% CI (0.01, 1.59), P = 0.05], particularly with rest intervals exceeding 8 min (SMD = 0.77). Multiple-session plyometric training improved vertical jump (SMD = 0.43, 95% CI [0.01, 1.59), P = 0.00001 < 0.05], with optimal effects observed at rest intervals of 5-7 min (SMD = 0.64). Sprint performance also improved [SMD = 0.46, 95% CI (0.01, 0.81), P = 0.01 < 0.05]. Conclusion: Plyometric training as an activation method has significant enhancing effects, depending on training complexity, volume, and rest intervals.

Improving Perovskite Solar Cell Performance and Stability via Thermal Imprinting-Assisted Ion Exchange Passivation.

The latest development in perovskite solar cell (PSC) technology has been significantly influenced by advanced techniques aimed at passivating surface defects. This work presents a new approach called thermal imprinting-assisted ion exchange passivation (TIAIEP), which delivers a different approach to conventional solution-based methods. TIAIEP focuses on addressing surface imperfections in solid-state films by using a passivator that promotes ion exchange specifically at the defect sites within the perovskite layer. By adjusting the time and temperature of the TIAIEP process, we achieve substantial enhancement in the creation of a compositional gradient within the films. This optimization slows the cooling rate of hot carriers, leading to minimizing charge recombination and improving the device performance. Remarkably, devices treated with TIAIEP achieve a 22.29% power conversion efficiency and show outstanding stability, with unencapsulated PSCs maintaining 91% of their original efficiency after over 2000 h of storage and 90% efficiency after 1200 h of constant illumination. These results highlight TIAIEP's effectiveness in mitigating surface defects, improving both the photoelectric and stability performance of PSCs, and indicating significant potential for large-scale application in perovskite film passivation, promoting the widespread adoption of this technology.

Evaluation of peripheral blood inflammation indexes as prognostic markers for colorectal cancer metastasis.

The aim of this study was to evaluate the prognostic value of peripheral blood inflammation indexes in patients with metastatic Colorectal Cancer (CRC) and to establish a predictive scoring system. A total of 324 CRC patients diagnosed through pathological examination from January 2017 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were included. The prognosis of patients with metastatic CRC was examined, and the correlation between IL-10 expression in pathological tissues and IL-10 expression in serum was analyzed. The results showed that the prognosis of CRC was poorer when metastasis occurred (P < 0.001). Additionally, IL-10 was highly expressed in the metastatic CRC group (P = 0.018), and the expression of IL-10 in pathological tissues of patients with metastatic CRC was positively correlated with the expression of IL-10 in serum (P = 0.037). The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-white blood cell ratio (LWR), aggregate index of systemic inflammation (AISI), monocyte-to-lymphocyte ratio (MLR), systemic inflammatory response index (SIRI), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and interleukin-10 (IL-10) were calculated and determined by ROC curve. The critical values were 2.135, 3.735, 353.745, 0.265, 1.025, 52.975, 353.635, and 11.25, respectively. Inflammatory indexes with an AUC of more than 0.6 were selected, and each colorectal cancer patient with any of these risk factors was assigned a score of one. The 324 patients were then divided into two groups: 0-4 for the low-risk group and 4-8 for the high-risk group. The occurrence of distant metastases in the two groups was statistically analyzed. The results showed that the OS and PFS of the low-risk group were significantly superior to those of the high-risk group (P < 0.05). These findings indicate that NLR, LWR, AISI, MLR, SIRI, PNI, ALI, and IL-10 are risk factors for distant metastasis in CRC patients. Therefore, the prediction scores of these indexes can be used to effectively evaluate the prognosis of patients with metastatic CRC.

Topical Transdermal Administration of Supramolecular Self-Assembled Carnosine for Anti-Melanin and Anti-Aging.

The structure of natural proteins has inspired the hypothesis that L-carnosine (LC), acetyl carnosine (AC), and decarboxy carnosine (DC) self-assemble into highly bioactive carnosine with supramolecular structures. These structures are proposed to combat skin pigmentation and aging through the coordination of weak interactions between molecules. Simulations are conducted to ascertain the precise free energies of the potential supramolecular structures and to identify the equilibrium structure. The mechanism of transdermal action of supramolecular carnosine is investigated through experiments and molecular dynamics simulations. The results demonstrate that supramolecular carnosine exhibits a more pronounced reactivity with the skin than LC, primarily due to the interaction of AC and DC with the lipid matrix, which reduces interfacial resistance. The anti-photoaging and anti-glycation cell models demonstrate that supramolecular carnosine upregulates the expression of the Nrf2 protein, activates the antioxidant defense system of melanocytes, inhibits the expression of the receptor for advanced glycosylation end products (AGEs), and reduces the level of AGEs in vivo. Moreover, supramolecular carnosine has demonstrated satisfactory whitening efficacy in cells and clinical efficacy tests, thereby underscoring its considerable potential for biomedical and aesthetic applications.

Exploring the molecular mechanism of ginseng against anthracycline-induced cardiotoxicity based on network pharmacology, molecular docking and molecular dynamics simulation.

BACKGROUND: Previous clinical and basic studies have revealed that ginseng might have cardioprotective properties against anthracycline-induced cardiotoxicity (AIC). However, the underlying mechanism of ginseng action against AIC remains insufficiently understood. The aim of this study was to explore the related targets and pathways of ginseng against AIC using network pharmacology, molecular docking, cellular thermal shift assay (CETSA) and molecular dynamics (MD) simulations. RESULTS: Fourteen drug-disease common targets were identified. Enrichment analysis showed that the AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathway were potentially involved in the action of ginseng against AIC. Molecular docking demonstrated that the core components including Kaempferol, beta-Sitosterol, and Fumarine had notable binding activity with the three core targets CCNA2, STAT1, and ICAM1. Furthermore, the stable complex of STAT1 and Kaempferol with favorable affinity was further confirmed by CETSA and MD simulation. CONCLUSIONS: This study suggested that ginseng might exert their protective effects against AIC through the derived effector compounds beta-Sitosterol, Kaempferol and Fumarine by targeting CCNA2, STAT1, and ICAM1, and modulating AGE-RAGE in diabetic complications, fluid shear stress and atherosclerosis, and TNF signaling pathways.

Maternal Gestational Diabetes Mellitus and High-Fat Diet Influenced Hepatic Polyunsaturated Fatty Acids Profile in the Offspring of C57BL/6J Mice.

SCOPE: This research examines the effects of maternal high-fat (HF) diet and gestational diabetes mellitus (GDM) on offspring lipid metabolism and polyunsaturated fatty acids (PUFA) profile. METHODS AND RESULTS: GDM is induced using the insulin receptor antagonist S961. Weaning offspring are categorized into HF-GDM, HF-CON, NC-GDM, and NC-CON groups based on maternal diet or GDM. Adult offspring are then grouped into NC-CON-NC, NC-CON-HF, NC-GDM-NC, NC-GDM-HF, HF-CON-NC, HF-CON-HF, HF-GDM-NC, and HF-GDM-HF according to dietary patterns. Gas chromatography determines PUFA composition. Western blot assesses PI3K/Akt signaling pathway-related protein expression. Feeding a normal chow diet until adulthood improves the distribution of hepatic PUFA during weaning across the four groups. PI3K expression is upregulated during weaning in HF-CON and HF-GDM, particularly in HF-CON-NC and HF-GDM-NC, compared to NC-CON-NC during adulthood. Akt expression increases in NC-GDM-NC after weaning with a normal diet. The hepatic PUFA profile in HF-CON-HF significantly distinguishes among the maternal generation health groups. Maternal HF diet exacerbates the combined impact of maternal GDM and offspring HF diet on hepatic PUFA and PI3K/Akt signaling pathway-related proteins during adulthood. CONCLUSIONS: Early exposure to HF diets and GDM affects hepatic PUFA profiles and PI3K/Akt signaling pathway protein expression in male offspring during weaning and adulthood.

Acute Neck Pain from Crowned Dens Syndrome: A Case Report and Clinical Insights.

BACKGROUND Crowned dens syndrome (CDS) is a rare condition characterized by deposition of calcium pyrophosphate crystals on the odontoid process of the second cervical vertebra, forming a calcified 'crown', with neck pain being a common symptom. The disorder exhibits unique clinical and radiological features, resembling manifestations of meningitis, such as acute headaches and cervical stiffness. There are few case reports and case series related to CDS. Patients generally respond well to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), although there is a certain rate of recurrence. Since there are few reports of CDS, we sought to publish this case report, aiming of increasing clinicians' awareness and reducing misdiagnosis rates. CASE REPORT A 62-year-old man presented to the Emergency Department with "cutting-like" headaches and neck pain for 2 days, and was subsequently diagnosed with CDS by cervical computed tomography (CT) scan, and hematological tests revealed inflammatory manifestations. He was advised to take oral nonsteroidal anti-inflammatory drugs and to rest; his symptoms improved after 3 days and his neck pain had almost resolved after 2 months. CONCLUSIONS In older patients experiencing new headaches and neck pain, along with increased inflammatory markers, particularly those with a history of pseudogout, the possibility of CDS should be considered. Case reports suggest that oral NSAIDs and short courses of corticosteroids can generally alleviate symptoms. Further research is needed on CDS diagnosis and treatment.

Uromodulin and progression of IgA nephropathy.

Background: This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression. Methods: We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results: The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14-3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression. Conclusion: The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.

Effect of Various Fruit Extracts on Angiotensin I-Converting Enzyme (ACE) and Kallikrein (KLK) Activities.

Hypertension is one of the main risk factors for cardiovascular disease and causes widespread morbidity and mortality worldwide. The aim of this work was to screen the fruit with high angiotensin I-converting enzyme (ACE) inhibitory activity and kallikrein (KLK) promotion activity by three different extraction methods from 22 kinds of fruits. Results showed that the aqueous extracts of fresh kiwifruit significantly inhibited ACE activity (47.71%), whereas the KLK activity was also inhibited (4.56%). This indicated that the substances inhibiting ACE activity existed in kiwifruit might be small molecular substances such as polyphenols. The nonpolar substance existed in the ethanol extracts of grape inhibited ACE activity significantly. The enzymatic hydrolysates of red grape significantly promoted KLK activity, whereas its ethanol extracts significantly inhibited KLK activity. This results suggested that the components that lower blood pressure and raise blood pressure are generally presented in the same fruit, the former are mostly water-soluble substances, while the latter are generally alcohol-soluble substances. If certain or individual components can be isolated from edible fruits, they may significantly affect blood pressure in humans.

mir-744-5p inhibits cell growth and angiogenesis in osteosarcoma by targeting NFIX.

BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor that commonly occurs in children and adolescents under the age of 20. Dysregulation of microRNAs (miRNAs) is an important factor in the occurrence and progression of OS. MicroRNA miR-744-5p is aberrantly expressed in various tumors. However, its roles and molecular targets in OS remain unclear. METHODS: Differentially expressed miRNAs in OS were analyzed using the Gene Expression Omnibus dataset GSE65071, and the potential hub miRNA was identified through weighted gene co-expression network analysis. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-744-5p in OS cell lines. In vitro experiments, including CCK-8 assays, colony formation assays, flow cytometry apoptosis assays, and tube formation assays, were performed to explore the effects of miR-744-5p on OS cell biological behaviors. The downstream target genes of miR-744-5p were predicted through bioinformatics, and the binding sites were validated by a dual-luciferase reporter assay. RESULTS: The lowly expressed miRNA, miR-744-5p, was identified as a hub miRNA involved in OS progression through bioinformatic analysis. Nuclear factor I X (NFIX) was confirmed as a direct target for miR-744-5p in OS. In vitro studies revealed that overexpression of miR-744-5p could restrain the growth of OS cells, whereas miR-744-5p inhibition showed the opposite effect. It was also observed that treatment with the conditioned medium from miR-744-5p-overexpressed OS cells led to poorer proliferation and angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, NFIX overexpression restored the suppression effects of miR-744-5p overexpression on OS cell growth and HUVECs angiogenesis. CONCLUSION: Our results indicated that miR-744-5p is a potential tumor-suppressive miRNA in OS progression by targeting NFIX to restrain the growth of OS cells and angiogenesis in HUVECs.

Unlocking the potential: strategic synthesis of a previously predicted pyrazolate-based stable MOF with unique clusters and high catalytic activity.

The metal-organic framework (MOF) constructed from [Co4Pz8] clusters (Pz = pyrazolate) and 1,3,5-tris(pyrazolate-4-yl) benzene (BTP3-) ligands was structurally predicted many years ago, and expected to be a promising candidate for various applications owing to its unique clusters and highly open 3D framework structure. However, this MOF has not been experimentally prepared yet, despite extensive efforts were made. In this work, we present the successful construction of this MOF, hereinafter referred to as BUT-124(Co), by adopting a two-step synthesis strategy, involving the initial construction of a template framework (BUT-124(Cd)) followed by a post-synthetic metal metathesis process. The effects of various cobalt sources and solvents were systematically investigated, and an innovative stepwise metathesis strategy was employed to optimize the exchange rates and the porosity of the material. BUT-124(Co) demonstrates high catalytic activity in the oxygen evolution reaction (OER), achieving a competitive performance with an overpotential of 393 mV at a current density of 10 mA cm-2, and also affords remarkable long-term stability during potentiostatic electrolysis in 1 M KOH solution, surpassing the durability of many benchmark catalysts. This work not only introduces a novel MOF material with promising properties but also exemplifies a strategic synthesis approach for pyrazolate-based MOFs, paving the way for advancements in diverse application fields.

Novel long noncoding lncARF mediated hyperhomocysteinemia-induced atherosclerosis via autophagy inhibition in foam cells.

INTRODUCTION: Homocysteine (Hcy) is well recognized to be an independent risk factor for atherosclerosis. Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis, while the underlying mechanisms of its involvement in Hcy induced-atherosclerosis remain largely unknown. OBJECTIVES: The primary aim of this study is to assess the role of lncARF (autophagy-related factor induced by Hcy) in Hcy induced-atherosclerosis and related mechanism. METHODS: RNA sequencing of foam cells treated with Hcy revealed a novel specific long noncoding RNA called lncARF. Locked nucleic acid gapmeRs-mediated lncARF knockdown was used to explore the role of lncARF both in vivo and in vitro. Mass spectrometry, RNA pull-down and RNA immunoprecipitation (RIP) assays were employed to uncover a mechanistic role of lncARF. Mass array assay and chromatin immunoprecipitation (ChIP) were used to detect the transcriptional activation of lncARF mediated by transcription factor. Clinically, receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of lncARF in atherosclerotic patients with hyperhomocysteinemia (HHcy). RESULTS: We observed that the expression of lncARF was substantially upregulated in atherosclerotic plaques, and knockdown of lncARF decreased the formation of atherosclerotic lesions by promoting autophagy in foam cells. Mechanistically, lncARF physically binds to RRAGD and inhibits its ubiquitination, further activating the PI3K/Akt and MAPK signaling pathways. Moreover, in vitro experiments showed that transcription factor FosB inhibited the binding of DNMT1 at the lncARF promoter, leading to transcriptional activation through DNA hypomethylation. Clinically, lncARF expression was positively correlated with serum Hcy levels, and it could distinguish atherosclerotic patients with HHcy with a high area under the ROC curve, sensitivity and specificity. CONCLUSIONS: Our study highlights the mechanisms of lncARF in protecting against the development of atherosclerosis involving the epigenetic modifications and RRAGD/PI3K/Akt and RRAGD/MAPK signaling pathways, which may provide novel diagnostic biomarkers to improve atherosclerosis treatment.

Adherence and persistence among people with type 2 diabetes newly initiating oral semaglutide versus DPP-4is in a US real-world setting.

AIMS: To investigate real-world treatment adherence and persistence in people with type 2 diabetes newly initiating oral semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), or a dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: This retrospective cohort study used the Merative™ MarketScan® Commercial and Medicare databases. Index date was the first fill for the cohort medication. Adherence was defined as proportion of days covered (PDC) over the 12-month post-index period ('adherent' = ≥0.8). Persistence was number of days until discontinuation, based on a 45-day gap. Results were compared between cohorts using inverse probability treatment weighting. RESULTS: Oral semaglutide (n=5485) and DPP-4i (n=4980) cohorts had similar percentages of people who were adherent (PDC ≥0.8; 41.6 % vs. 42.9 %; P = 0.182) and persistent for ≥9 months (45.0 % vs. 46.3 %; P = 0.185). The DPP-4i cohort used significantly more anti-diabetic medication (ADM) classes over the post-index period (mean±SD: 2.6±1.0 vs. 2.9±1.1, P < 0.001), with 23.2 % filling a GLP-1 RA in the post-period. CONCLUSIONS: Adherence and persistence were similar between cohorts. However, there are potential benefits to prescribing oral semaglutide over DPP-4is, including reduced need for additional ADM.

Maturation-specific enhancements in lower extremity explosive strength following plyometric training in adolescent soccer players: A systematic review and meta-analysis.

Background: For adolescent soccer players, good sprinting and jumping abilities are crucial for their athletic performance. The application of plyometric training on boosting explosive strength in adolescent soccer players is contingent upon the maturation phase, which can mediate the training-induced adaptations. Purpose: This systematic review and meta-analysis aim to explore the maturation effect of plyometric training on the lower limb explosive power of adolescent soccer players, with vertical countermovement jump (CMJ) and 20-m sprint as the main outcome indicators. Methods: An extensive search of the literature was carried out on various databases including PubMed, Web of Science, Scopus, ProQuest, and the China National Knowledge Infrastructure (CNKI), covering the time period from the establishment of each database to February 6, 2023. The search was conducted using English keywords such as 'Plyometric,' 'Adolescent,' 'football,' and 'Explosive strength.' This study utilized the Cochrane risk of bias assessment tool to conduct a standardized quality evaluation of all the included literature. Additionally, the Review Manager 5.4 software was employed to perform data analysis on all the extracted data. Results: A total of 17 studies involving 681 adolescent soccer players aged 10 to 19 were included. Plyometric training significantly improved CMJ performance across different maturation stages, especially in the post-peak height velocity stage (POST-PHV) [MD = 4.35, 95 % CI (2.11, 6.59), P < 0.01, I2 = 60 %]. The pre-peak height velocity stage (PRE-PHV) showed the next best improvement [MD = 3.00, 95 % CI (1.63, 4.37)], while the middle-peak height velocity stage (MID-PHV) showed the least improvement [MD = 2.79, 95 % CI (1.16, 4.41), P < 0.01, I2 = 49 %]. However, improvements in 20 m sprint ability were only observed in the PRE-PHV [MD = -0.06, 95 % CI (-0.12, 0), P < 0.01, I2 = 0 %] and MID-PHV [MD = -0.18, 95 % CI (-0.27, -0.08), P < 0.01, I2 = 0 %] stages. Conclusion: Plyometric training serves as a potent strategy for boosting the lower limb explosive strength of adolescent soccer players, and the training effect is closely related to the players' biological maturity. Considering biological maturity is a key aspect that this study deems essential for the formulation of effective training programs for these adolescent players.

Minimally invasive posterior cervical foraminotomy versus anterior cervical fusion and arthroplasty: Systematic review and updated meta-analysis.

Introduction: This study is a systematic review and meta-analysis that investigates the efficacy of different surgical methods for treating cervical disc herniation or cervical foraminal stenosis. Research question: The research aimed to compare the efficacy of Minimally Invasive Posterior Cervical Foraminotomy (MI-PCF) with anterior approaches, namely Anterior Cervical Discectomy and Fusion (ACDF) and Cervical Disc Arthroplasty (CDA). Material and methods: The study included a comprehensive review of eight articles that compared ACDF and MI-PCF, and four articles that compared CDA to MI-PCF. Results: The results indicated no significant difference in surgical duration, hospital stay, complication rates, and reoperation rates between MI-PCF and ACDF. However, when comparing CDA with MI-PCF, it was found that CDA had a higher complication rate, while MI-PCF had a higher reoperation rate. Discussion and conclusion: Despite these findings, the study recommends MI-PCF as the preferred surgical method for cervical radiculopathy, owing to the advancements in minimally invasive techniques. However, these findings are preliminary, and further research with longer follow-up periods and larger sample sizes is necessary to confirm these findings and to further explore the potential advantages and disadvantages of these surgical methods.

Suppression of MyD88 disturbs gut microbiota and activates the NLR pathway and hence fails to ameliorate DSS-induced colitis.

Background: Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism. Methods: MyD88 knockout (MyD88-/-) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism. Results: In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88-/- mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal Proteobacteria and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed. Conclusion: Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.

Inhibition of autophagy via 3-methyladenine alleviates the progression of preeclampsia.

Autophagy is a cellular mechanism for self-renewal that involves the breakdown of cytoplasmic proteins or organelles within lysosomes. Although preeclampsia (PE) exhibits several characteristics that could imply disrupted autophagy, there is limited evidence supporting the notion that impaired placental autophagy directly causes PE, as indicated by differential expression profiling of whole placental tissue. In this study, we aim to explore the significance of autophagy in maintaining pregnancy and its association with PE. First, the RNA-seq results show that 218 genes are differentially expressed in placentas from preeclamptic pregnancies. Notably, KEGG pathway analysis reveals significant enrichment of genes related to autophagy-related signaling pathways, including the PI3K-Akt signaling pathway, the AMPK signaling pathway, and the mTOR signaling pathway. Additionally, our findings indicate an increase in autophagy in placentas from pregnancies complicated by preeclampsia as well as in trophoblasts subjected to hypoxic conditions. Next, we examine the impact of 3-methyladenine (3-MA), a targeted inhibitor of autophagy, on the progression of PE. The administration of 3-MA profoundly alleviates the severity of PE-like symptoms in rats subjected to reduced uterine perfusion pressure (RUPP). The findings from our study suggest that inhibiting autophagy may serve as a promising approach for adjuvant chemotherapy for PE.

Development of a machine learning-based model to predict major adverse events after surgery for type A aortic dissection complicated by malnutrition.

Objective: This study aims to develop a predictive model for the risk of major adverse events (MAEs) in type A aortic dissection (AAAD) patients with malnutrition after surgery, utilizing machine learning (ML) algorithms. Methods: We retrospectively collected clinical data from AAAD patients with malnutrition who underwent surgical treatment at our center. Through least absolute shrinkage and selection operator (LASSO) regression analysis, we screened for preoperative and intraoperative characteristic variables. Based on the random forest (RF) algorithm, we constructed a ML predictive model, and further evaluated and interpreted this model. Results: Through LASSO regression analysis and univariate analysis, we ultimately selected seven feature variables for modeling. After comparing six different ML models, we confirmed that the RF model demonstrated the best predictive performance in this dataset. Subsequently, we constructed a model using the RF algorithm to predict the risk of postoperative MAEs in AAAD patients with malnutrition. The test set results indicated that this model has excellent predictive efficacy and clinical applicability. Finally, we employed the Shapley additive explanations (SHAP) method to further interpret the predictions of this model. Conclusion: We have successfully constructed a risk prediction model for postoperative MAEs in AAAD patients with malnutrition using the RF algorithm, and we have interpreted the model through the SHAP method. This model aids clinicians in early identification of high-risk patients for MAEs, thereby potentially mitigating adverse clinical outcomes associated with malnutrition.