T-2 toxin induces cardiac fibrosis by causing metabolic disorders and up-regulating Sirt3/FoxO3α/MnSOD signaling pathway-mediated oxidative stress.

T-2 toxin, an omnipresent environmental contaminant, poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity. This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin. Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0, 10, and 100 nanograms per gram body weight per day (ng/(g·day)), respectively. Morphological, pathological, and ultrastructural alterations in cardiac tissue were meticulously examined. Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites. The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected. The results showed that exposure to T-2 toxin elicited myocardial tissue disorders, interstitial hemorrhage, capillary dilation, and fibrotic damage. Mitochondria were markedly impaired, including swelling, fusion, matrix degradation, and membrane damage. Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiac metabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway. T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress. In conclusion, the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway. This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.

Revealing the links between hair metal(loids) and alterations in blood pressure among children in e-waste recycling areas through urinary metabolomics.

Hypertension is prevalent in e-waste recycling areas, and elevated blood pressure in children significantly increases the risk of hypertension in adulthood. However, the associations and toxic pathways between chronic exposure to metal(loids) and elevated blood pressure are rarely investigated. In this study, we measured the levels of 29 hair metal(loids) (chronic exposure biomarkers) and blood pressure in 667 susceptible children from an e-waste recycling area to explore their relationships. Paired urine metabolomics analysis was also performed to interpret potential mechanistic pathways. Results showed that the hypertension prevalence in our recruited children (13.0 %) exceeded the average rate (9.5 %) for Chinese children aged 6-17 years. The top five abundant metal(loids), including lead, strontium, barium, and zinc, demonstrated the most profound associations with elevated systolic blood pressure. Quantile g-computation, weighted quantile sum, and Bayesian kernel machine regression analysis jointly demonstrated a significant association between chronic exposure to metal(loids) mixture and systolic blood pressure. Interestingly, selenium showed significant antagonistic interactions with these four metals, suggesting that supplementing selenium may help children resist the elevated blood pressure induced by metal(loids) exposure. Increased metal(loids) and blood pressure levels were significantly linked to changes in urine metabolomics. Structural equation model indicated that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid were the significant mediators of the associations between metal(loids) and blood pressure, with mediation effects of 77.4 % and 29.0 %, respectively, suggesting that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid may be involved in the development of metal-induced blood pressure elevating effect. Girls were more vulnerable to metal(loids)-induced hormonal imbalance, especially androsterone glucuronide, than boys. Chronic exposure to metal(loids) at e-waste recycling sites may contribute to elevated blood pressure in children through disrupting various metabolism pathways, particularly hormonal balance. Our study provides new insights into potential mechanistic pathways of metal(loids)-induced changes in children's blood pressure.

Natural α-glucosidase inhibitors from Aquilaria sinensis leaf-tea: Targeted bio-affinity screening, identification, and inhibition mechanism.

Aquilaria sinensis leaves have long been consumed as a popular replacement tea for lowering postprandial blood glucose levels, but their specific functional components remain unclear. In this study, Aquilaria sinensis leaf-tea 70 % ethanol extract (ALTE) exhibited excellent anti-α-glucosidase activity (IC50 = 6.93 ± 1.91 µg/mL) and promoted glucose consumption ability in 3 T3-L1 preadipocyte cells. Subsequently phenolic compositions of ALTE were identified for the first time. After that, five potential α-glucosidase inhibitors (α-GIs) including cynaroside-3,5-diglucose, malvidin 3-glucose, epicatechin, epigallocatechin gallate, and dihydromyricetin in ALTE were screened using a targeted bio-affinity ultrafiltration-HPLC/MS method. Moreover, these five α-GIs all showed good anti-α-glucosidase effects and glucose consumption-promoting ability. Furthermore, the binding properties and inhibition mechanisms of five α-GIs to α-glucosidase were further analyzed via enzyme inhibition kinetics, molecular docking, and molecular dynamics simulation. This study confirms that Aquilaria sinensis leaf-tea is effective in preventing post-hyperglycemia in vitro models, suggesting potential for future research in human trials.

Association between self-reported sleep apnea and biomarkers of liver injury: Evidence from National Health and Nutrition Examination Survey.

The community population based studies on the relationship between obstructive sleep apnea and liver injury are limited. The study aimed to clarify the association between sleep apnea (SA) and liver injury by using the data in The National Health and Nutrition Examination Survey. SA was assessed by the sleep questionnaire and liver injury was evaluated by liver function test, hepatic steatosis index, and fibrosis-4. Weighted multivariable linear regression was performed to examine the association between SA and liver injury. Subgroup analyses and sensitivity analysis were also conducted. A total of 19,362 eligible participants were included in the study. After adjusting for confounders, the presence of SA was significantly associated with increased levels of lnALT, lnAST/alanine aminotransferase, lnGGT, and lnHSI (all P values < .05), but not with lnFIB-4 (P > .05). There is a dose-response relationship between the severity of SA and increased levels of lnALT, lnGGT, and decreased levels of lnAST/alanine aminotransferase (test for trend, all P values < .05). Subgroup analyses revealed that the positive association between SA and liver function, liver steatosis showed a tendency to exist in nonobese, younger, non-Hispanic Black, and male populations. Sensitive analysis showed the relationship between SA and liver injury was stable. Self-reported SA was independently associated with elevated liver enzymes and liver steatosis among US population. The association was more pronounced among nonobese, younger, non-Hispanic Black, and male populations.

Programming Fast DNA Amplifier Circuits with Versatile Toehold Exchange Pathway.

DNA amplifier circuits establish powerful tools to dynamically control molecular assembly for computation, sensing, and biological applications. However, the slow reaction speed remains a major barrier to their practical utility. Here, diverse fast DNA amplifier circuits termed toehold exchange polymerization (TEP) and toehold exchange catalysis (TEC) using toehold exchange-mediated assembly as a fundamental mechanism are built. Both TEP and TEC with a duplex and a hairpin can respond within minutes to diverse nucleic acid inputs with high fidelity. In addition, the circuits can amplify live-cell signals for fluorescence imaging target RNA dynamics and discriminating different cell lines. Compared with existing DNA circuits that involve time scales of hours for transducing small signals, TEP and TEC exhibit much faster dynamics, simpler design, and comparable sensitivity. These features make TEP and TEC promising platforms to develop programmable nucleic acid tools and devices and to create fast sensing and processing systems, amenable to wide practical applications.

Postoperative delirium risk in patients with hyperlipidemia: A prospective cohort study.

STUDY OBJECTIVE: Hyperlipidemia and postoperative delirium (POD) significantly affect patients' quality of life; however, the question of whether hyperlipidemia constitutes a risk factor for POD remain unclear. This study aimed to investigate whether patients with hyperlipidemia face elevated risks of developing POD and to identify potential causes for this increased risk. DESIGN: A prospective cohort study. SETTING: Operating room. PATIENTS: Patients were adults scheduled for colorectal cancer surgery in 2023. EXPOSURES: The exposure factor was hyperlipidemia, and the patients were divided into hyperlipidemia group and non-hyperlipidemia group. MEASUREMENTS: POD occurrence within three days post-surgery was assessed using the 3-Minute Diagnostic Interview for Confusion Assessment Method. Over one year, these patients were monitored through telephone to evaluate their survival and cognitive function. Logistic regression analysis was performed to evaluate the risk factors for POD development in patients with hyperlipidemia and to construct a clinical prediction model. MAIN RESULTS: This study included 555 patients. POD incidence was 21.6% in the hyperlipidemia group and 12.7% in the non-hyperlipidemia group. One year following surgery, patients with hyperlipidemia and POD exhibited significantly higher rates of mortality and cognitive decline than did those without POD (p < 0.001). A multifactorial logistic clinical prediction model was constructed from seven independent risk factors for POD development in patients with hyperlipidemia, including education, preoperative total cholesterol (TC), preoperative triglyceride (TG), diet, history of hypertension, Sedation-Agitation Scale, and postoperative trimethylamine N-oxide expression level, and it had the highest predictive value for POD development in patients with hyperlipidemia. CONCLUSIONS: Compared with those without hyperlipidemia, patients with hyperlipidemia had higher POD incidence. Elevated serum TC and TG levels are independent risk factors for POD in patients with hyperlipidemia. The study's findings could help develop strategies for improving POD and hyperlipidemia treatment.

Multi-active photocatalysts of biochar-doped g-C3N4 incorporated with polyoxometalates for the high-efficient degradation of sulfamethoxazole.

Sulfamethoxazole (SMX) is one of major antibiotic contaminants in current aqueous environment. In this paper, waste loofah and melamine were co-carbonized to prepare biochar-doped g-C3N4 (CCN) by a one-pot method and then combined with Co2PMo11VO40 (CoPMoV) using a binder to obtain the novel polyoxometalates (POMs) photocatalytic composites (CCN/CoPMoV). The incorporation of CoPMoV dramatically reduced the photogenerated carrier recombination and led to a small band gap. Under visible light, the synergetic activation from biochar, g-C3N4 and POMs can remove 98.5% of SMX (k = 0.215 min-1) in the peroxymonosulfate (PMS) system within 20 min and keep its high stability with the degradation of 88.9% after five cycles. Multi-active sites from CCN/CoPMoV are contributed to develop the most active species of SO4-∙, ·OH, 1O2, and h+. The validity in the degradation of SMX makes CCN/CoPMoV a promising and potential material for the removal of aqueous pollutants in the future.

Characterization of PANoptosis-related genes with immunoregulatory features in osteoarthritis.

This study aimed to characterize PANoptosis-related genes with immunoregulatory features in osteoarthritis (OA) and investigate their potential diagnostic and therapeutic implications. Gene expression data from OA patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis and functional enrichment analysis were conducted to identify PANoptosis-related genes (PRGs) associated with OA pathogenesis. A diagnostic model was developed using LASSO regression, and the diagnostic value of key PRGs was evaluated using Receiver Operating Characteristic Curve (ROC) analysis. The infiltration of immune cells and potential small molecule agents were also examined. A total of 39 differentially expressed PANoptosis-related genes (DE-PRGs) were identified, with functional enrichment analysis revealing their involvement in inflammatory response regulation and immune modulation pathways. Seven key PRGs, including CDKN1A, EZH2, MEG3, NR4A1, PIK3R2, S100A8, and SYVN1, were selected for diagnostic model construction, demonstrating high predictive performance in both training and validation datasets. The correlation between key PRGs and immune cell infiltration was explored. Additionally, molecular docking analysis identified APHA-compound-8 as a potential therapeutic agent targeting key PRGs. This study identified and analyzed PRGs in OA, uncovering their roles in immune regulation. Seven key PRGs were used to construct a diagnostic model with high predictive performance. The identified PRGs' correlation with immune cell infiltration was elucidated, and APHA-compound-8 was highlighted as a potential therapeutic agent. These findings offer novel diagnostic markers and therapeutic targets for OA, warranting further in vivo validation and exploration of clinical applications.

Non-covalent interaction between lactoferrin and theaflavin: Focused on the structural changes, binding mechanism, and functional properties.

In this study, non-covalent binding mechanism of lactoferrin (LaF)-theaflavin (TF) complex and its functional properties were investigated. Multi-spectroscopic analyses showed that the secondary structure of LaF was altered with increasing TF concentration. The non-covalent binding of TF to LaF resulted in a reduction in the content of the α-helix and ß-sheet, as well as a decrease in the fluorescence intensity of LaF. DSC result showed that non-covalent binding of TF improved thermal stability of LaF. Molecular dynamics simulations confirmed that the stable binding of LaF-TF was driven by hydrogen bonding and hydrophobic interactions. Additionally, non-covalent binding of TF increased the antioxidant capacity and emulsifying properties of LaF. Dynamic interfacial tension indicated that the strong interaction between LaF and TF reduced the interfacial tension, but improved the rheological properties of LaF. The functional characteristics of the non-covalent complex was effectively enhanced, paving the way for its potential use in the food industry.

A Comprehensive Model Outperformed the Single Radiomics Model in Noninvasively Predicting the HER2 Status in Patients with Breast Cancer.

RATIONALE AND OBJECTIVES: This study aimed to develop predictive models based on conventional magnetic resonance imaging (cMRI) and radiomics features for predicting human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC) and compare their performance. MATERIALS AND METHODS: A total of 287 patients with invasive BC in our hospital were retrospectively analyzed. All patients underwent preoperative breast MRI consisting of fat-suppressed T2-weighted imaging, axial dynamic contrast-enhanced MRI, and diffusion-weighted imaging sequences. From these sequences, radiomics features were derived. Three distinct models were established utilizing cMRI features, radiomics features, and a comprehensive model that amalgamated both. The predictive capabilities of these models were assessed using the receiver operating characteristic curve analysis. The comparative performance was then determined through the DeLong test and net reclassification improvement (NRI). RESULTS: In a randomized split, the 287 patients with BC were allotted to either training (234; 46 HER2-zero, 107 HER2-low, 81 HER2-positive) or test (53; 8 HER2-zero, 27 HER2-low, 18 HER2-positive) at an 8:2 ratio. The mean area under the curve (AUCs) for cMRI, radiomics, and comprehensive models predicting HER2 status were 0.705, 0.819, and 0.859 in training set and 0.639, 0.797, and 0.842 in test set, respectively. DeLong's test indicated that the combined model's AUC surpassed the radiomics model significantly (p < 0.05). NRI analysis verified superiority of the combined model over the radiomics for BC HER2 prediction (NRI 25.0) in the test set. CONCLUSION: The comprehensive model based on the combination of cMRI and radiomics features outperformed the single radiomics model in noninvasively predicting the three-tiered HER2 status in patients with BC.

Healthcare professionals' perspectives towards the role of ward-based advanced practice nurses: A cross-sectional study.

AIMS: 1. To explore the perceptions of physicians, registered nurses (RN) and allied health professionals (AHP) towards the role of ward-based advanced practice nurse (APN). 2. To examine healthcare professionals' perception of APN role expansion in inpatient care. DESIGN: Cross-sectional study. METHODS: A 43-item survey comprising of five domains was conducted on healthcare professionals' perceptions towards ward-based APNs in five medical wards of a tertiary hospital from November 2022 to February 2023. The participants were recruited using convenience sampling via email and cross-platform messaging service. RESULTS: A total of 181 completed respondents including 26 physicians, 102 nurses and 45 AHPs. Statistical analysis was performed with IBM SPSS Version 28.0. APNs were perceived to be spending a great extent of time across all five domains, namely, 'direct comprehensive care', 'support of systems', 'research', 'education' and 'publication and professional leadership'. Significant differences were noted in perceptions based on prior experience with APNs and between different healthcare professions. The majority recognized APNs' positive impact on patient safety, efficiency and patient-centeredness. CONCLUSION: This study offers valuable insights into ward-based APNs' practice patterns, roles and impact, revealing a positive shift in their acceptance and expanding roles within inpatient general wards. It also highlights the valuable roles and impact of ward-based APNs in direct patient care, system support, research, education and leadership, despite ongoing challenges in role clarity, particularly in treatment planning and ward rounds. IMPLICATIONS FOR THE PROFESSION: APNs are highly regarded as competent and a consistent personnel in the wards. However, there are divided views on clinical activities that APNs undertake. IMPACT (ADDRESSING): What problem did the study address? ○ Role ambiguity for ward-based APNs. ○ Healthcare professionals' readiness and acceptance of APNs. What were the main findings? ○ APNs are perceived to have a strong involvement in direct patient care, support of system, research, education and leadership. ○ APNs are recognized for their significant impact on patient safety, efficiency and patient-centredness, but there were varied perceptions on the extent of time they spend in different practice domains. ○ The critical roles of APNs participating in daily ward rounds and initiating discharge plans were highlighted, emphasizing their importance in timeliness and continuity of care. Where and on whom will the research have an impact? ○ It will affect healthcare professionals including physicians, nurses, allied health professionals and healthcare administrators by providing insights into the roles and contributions of ward-based APNs. ○ The findings will guide policymakers and nurse leaders in making informed decisions about the implementation and development of APN roles, ultimately improving patient care and outcomes. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis.

Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RT­PCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting inter­EC adhesion proteins (zona occludens­1, connexin 43 and Vascular endothelial­Cadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4,  solute carrier family 7 member 11 and acyl­CoA synthase long­chain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting inter­EC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. In vivo, inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.

LncRNA SNHG1 knockdown attenuates lipopolysaccharide-induced acute lung injury via regulating miR199a-3p/ROCK2 axis.

Acute lung injury (ALI) is a significant health condition with notable rates of morbidity and mortality globally. Long non-coding ribose nucleic acids (lncRNAs) play vital roles in mitigating various inflammation-related diseases, including ALI. The study aimed to investigate the functional role and molecular mechanisms of lncRNA SNHG1 on ALI in lipopolysaccharide (LPS)-treated A549 cells and in LPS-induced ALI mice. The expression of SNHG1 was initially examined in LPS-treated A549 cells. We further demonstrated the critical function of SNHG1 through various cellular assessments following SNHG1 knockdown, including cell counting kit (CCK)-8 assay, flow cytometry analysis, as well as enzyme-linked immunosorbent assay (ELISA). Reducing SNHG1 levels hindered the negative effects of LPS on cell viability, apoptosis, and inflammation. Moreover, SNHG1 acted as a negative regulator for miR-199a-3p, which targeted downstream ROCK2. Depletion of miR-199a-3p or enhanced expression of ROCK2 abolished the protective effects of SNHG1 knockdown on LPS-induced apoptosis and inflammation. Consistently, silencing SNHG1 alleviated LPS-induced lung injury in mice, demonstrating its potential therapeutic benefits in managing ALI. Overall, this study sheds light on the role of SNHG1 in modulating inflammation and apoptosis in ALI through the miR-199a-3p/ROCK2 pathway, offering new insights for the treatment of this condition.

Can Bisphosphonate Therapy Reduce Overall Mortality in Patients With Osteoporosis? A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: For patients with osteoporosis, bisphosphonate therapy can reduce the risk of fractures, but its effect on reducing mortality remains unclear. Previous studies on this topic have produced conflicting results and generally have been too small to definitively answer the question of whether bisphosphonate therapy reduces mortality. Therefore, a meta-analysis may help us arrive at a more conclusive answer. QUESTIONS/PURPOSES: In a large meta-analysis of placebo-controlled randomized controlled trials (RCTs), we asked: (1) Does bisphosphonate use reduce mortality? (2) Is there a subgroup effect based on whether different bisphosphonate drugs were used (zoledronate, alendronate, risedronate, and ibandronate), different geographic regions where the study took place (Europe, the Americas, and Asia), whether the study was limited to postmenopausal female patients, or whether the trials lasted 3 years or longer? METHODS: We conducted a systematic review using multiple databases, including Embase, Web of Science, Medline (via PubMed), Cochrane Library, and ClinicalTrials.gov, with each database searched up to November 20, 2023 (which also was the date of our last search), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included randomized, placebo-controlled clinical trials with participants diagnosed with osteoporosis and receiving bisphosphonate treatment. We excluded papers posted to preprint servers, other unpublished work, conference abstracts, and papers that were registered on ClinicalTrials.gov but were not yet published. We collected 2263 records. After excluding records due to study type, study content not meeting the inclusion criteria, and duplicates, our meta-analysis included 47 placebo-controlled RCTs involving 59,437 participants. Data extraction, quality assessment, and statistical analyses were performed. The evaluation of randomized trials for potential bias was conducted using the revised Cochrane Risk of Bias tool. This assessment encompassed factors such as sequence generation, allocation concealment, subject blinding, outcome assessor blinding, incomplete outcome data, and reporting bias. Some studies did not provide explicit details regarding random sequence generation, leading to a high risk of selection bias. A few studies, due to their open-label nature, were unable to achieve double-blind conditions for both the subjects and the researchers, resulting in intermediate performance bias. Nevertheless, the overall study quality was high. Due to the low heterogeneity among the studies, as evidenced by the low statistical heterogeneity (that is, a low I2 statistic), we opted for a fixed-effects model, indicating that the effect size is consistent across the studies. In such cases, the fixed-effects model can provide more precise estimates. According to the results of the funnel plot, we did not find evidence of publication bias. RESULTS: The use of bisphosphonates did not reduce the overall risk of mortality in patients with osteoporosis (risk ratio 0.95 [95% CI 0.88 to 1.03]). Subgroup analyses involving different bisphosphonate drugs (zoledronate, alendronate, risedronate, and ibandronate), regions (Europe, the Americas, and Asia), diverse populations (postmenopausal female patients and other patients), and trials lasting 3 years or longer revealed no associations with reduced overall mortality. CONCLUSION: Based on our comprehensive meta-analysis, there is high-quality evidence suggesting that bisphosphonate therapy for patients with osteoporosis does not reduce the overall risk of mortality despite its effectiveness in reducing the risk of fractures. The primary consideration for prescribing bisphosphonates to individuals with osteoporosis should continue to be centered on reducing fracture risk, aligning with clinical guidelines. Long-term studies are needed to investigate potential effects on mortality during extended treatment periods. LEVEL OF EVIDENCE: Level I, therapeutic study.

Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disease characterized by subchondral osteosclerosis, mainly due to osteoblast activity. This research investigates the function of Sik1, a member of the AMP-activated protein kinase family, in OA. Proteomic analysis was conducted on clinical samples from 30 OA patients, revealing a negative correlation between Sik1 expression and OA. In vitro experiments utilized BMSCs to examine the effect of Sik1 on osteogenic differentiation. BMSCs were cultured and induced toward osteogenesis with specific media. Sik1 overexpression was achieved through lentiviral transfection, followed by analysis of osteogenesis-associated proteins using Western blotting, RT-qPCR, and alkaline phosphate staining. In vivo experiments involved destabilizing the medial meniscus in mice to establish an OA model, assessing the therapeutic potential of Sik1. The CT scans and histological staining were used to analyze subchondral bone alterations and cartilage damage. The findings show that Sik1 downregulation correlates with advanced OA and heightened osteogenic differentiation in BMSCs. Sik1 overexpression inhibits osteogenesis-related markers in vitro and reduces cartilage damage and subchondral osteosclerosis in vivo. Mechanistically, Sik1 modulates osteogenesis and subchondral bone changes through Runx2 activity regulation. The research emphasizes Sik1 as a promising target for treating OA, suggesting its involvement in controlling bone formation and changes in the subchondral osteosclerosis.

[Developmental and epileptic encephalopathy 33 caused by EEF1A2 gene mutation: a case report]. / EEF1A2åŸºå› å˜å¼‚è‡´å‘è‚²æ€§ç™«ç—«æ€§è„‘ç— 33型1例.

A boy, aged 7 months, presented with severe global developmental delay (GDD), refractory epilepsy, hypotonia, nystagmus, ocular hypertelorism, a broad nasal bridge, everted upper lip, a high palatal arch, and cryptorchidism. Genetic testing revealed a de novo heterozygous missense mutation of c.364G>A(p.E122K) in the EEF1A2 gene, and finally the boy was diagnosed with autosomal dominant developmental and epileptic encephalopathy 33 caused by the EEF1A2 gene mutation. This case report suggests that for children with unexplained infancy-onset severe to profound GDD/intellectual disability and refractory epilepsy, genetic testing for EEF1A2 gene mutations should be considered. This is particularly important for those exhibiting hypotonia, nonverbal communication, and craniofacial deformities, to facilitate a confirmed diagnosis.

[NFIX gene mutation causes Marshall-Smith syndrome in a pair of identical twins and literature review]. / NFIXåŸºå› å˜å¼‚å¯¼è‡´ä¸€å¯¹åŒåµåŒèƒžèƒŽMarshall-Smithç»¼åˆå¾å¹¶æ–‡çŒ®å¤ä¹ .

This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome (MRSHSS) due to a mutation in the NFIX gene, along with a review of related literature. Both patients presented with global developmental delays, a prominent forehead, shallow eye sockets, and pectus excavatum. Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children, with parents showing wild-type at this locus. According to the guidelines of the American College of Medical Genetics and Genomics, this mutation is considered likely pathogenic and has not been previously reported in the literature. A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations. Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS. Genetic testing results are crucial for the diagnosis of this condition.

Comparative effects of various dietary selenium sources on growth performance, meat quality, essential trace elements content, and antioxidant capacity in broilers.

This study aimed to compare the effects of various dietary selenium (Se) sources (0.5 mg/kg) on performance, meat quality, and antioxidant capacity in broilers as well as essential trace elements concentrations in their blood and tissues. A total of 360 one-day-old male yellow-feathered chickens (37.00 ± 0.17 g) were randomly allocated to 5 diet treatments: the basal diet (CON) and 4 diets supplemented with sodium selenite (SS), selenomethionine (SM), selenium-enriched yeast (SY), and nano-selenium (NS) for 56 d, respectively, with 6 replicates per treatment and 12 chickens per replicate. Dietary Se supplementation did not affect growth performance and carcass characteristics in broilers (P > 0.05). Supplemental SM enhanced the redness in the pectoral muscle compared to CON and NS (P < 0.05). Supplementation of SY and NS improved the concentrations of Se, copper, manganese, and zinc in the serum (P < 0.05). Supplemental SS also elevated the zinc content in the serum (P < 0.05). Broilers fed the SY diet showed increased Se content in the liver and pectoral muscle compared to those fed CON, SM, and NS diets (P < 0.05). Also, SY improved the pectoral muscle Se concentration compared to SS (P < 0.05). Besides, dietary Se supplementation increased the Se content in the thigh muscle (P < 0.05), with SY showing highest Se deposition. Dietary supplementation with SS, SM, and NS improved the activities of total superoxide dismutase and total antioxidant capacity (T-AOC) in the serum (P < 0.05). Supplemental SY also elevated the T-AOC in the serum (P < 0.05). Additionally, SS and SM enhanced the T-AOC in the liver (P < 0.05). In conclusion, supplemental SM affected meat color. Supplementing diets with various Se sources increased antioxidant capacity and Se content in the thigh muscle of broilers, with SY showing a more pronounced deposition efficiency. Besides, diets supplemented with different Se sources had variable effects on the concentrations of essential trace elements in the serum and tissues of broilers.

NGS and FISH for MET amplification detection in EGFR TKI resistant non-small cell lung cancer (NSCLC) patients: A prospective, multicenter study in China.

OBJECTIVES: Comprehensive data using Next-Generation Sequence (NGS) and fluorescence in situ hybridization (FISH) for detecting MET amplification is limited in Chinese patients, we evaluating NGS performance both in tissue and plasma samples using FISH as reference. We also sought to find optimal thresholds value for NGS in detecting MET amplification via bioinformatics methods. METHOD: Patients progressed after 1st-, 2nd-, or 3rd-generation (G) EGFR-TKIs were enrolled. Tissue biopsy samples were performed for MET amplification detection via both NGS and FISH. Paired plasma samples were collected for MET amplification detection by NGS. The sensitivity, specificity and agreement were analyzed between NGS and FISH. RESULTS: 116 eligible patients were analyzed. 44 patients were male. 82 patients were after 3rd generation EGFR-TKI. MET amplification was detected in 43 (37.1 %) patients by FISH, including 19 (16.4 %) polysomy and 24 (20.7 %) focal amplification. The positive rate of MET amplification in post 3rd generation EGFR-TKI and post 1st/2ndgeneration EGFR-TKI resistant patients was 42.7 % (35/82), and 23.5 % (8/34). The sensitivity, specificity and agreement of detecting MET amplification by NGS in tissue were 39.5 % (17/43), 98.6 % (72/73) and 76.7 % (89/116), respectively, 66.7 % (16/24), 98.6 % (72/73) and 90.7 % (88/97) for focal MET amplification in tissue and 29.2 % (7/24), 94.5 % (69/73), 78.4 % (76/97) for focal amplification in plasma. Results were shown in the table below. CONCLUSION: NGS is an alternative method for MET focal amplification detection in tissue. While the sensitivity of NGS testing in plasma needs further improvement to maximize identification of patients with potential benefit from dual-targeted therapy.