SERS Platform for Integrated Enrichment, Isolation, and Identification of Multiple Respiratory Viruses in a Single Assay Using 3D Stereoscopic SERS Tags and Flocked Swabs.

Influenza (flu) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit similar clinical symptoms, complicating the diagnosis and clinical management of these critical respiratory infections. Thus, there is an urgent need for rapid on-site detection technologies that can simultaneously detect SARS-CoV-2 and influenza A viruses. Here, we have developed the first platform that combines in situ sampling with immune swabs and multichannel surface-enhanced Raman spectroscopy (SERS) for simultaneous screening of these two respiratory viruses in a single assay. A seed-mediated growth method was used to assemble a number of silver spheres on the surface of Fe3O4@SiO2 spheres, which not only creates extensive Raman hotspots but also provides numerous sites for Raman signaling molecules, enhancing the sensing sensitivity. Integrating two specific Raman signaling molecules into the nanospheres allows for the parallel detection of both viruses, improving the efficiency of SERS signal read-out. Rapid quantitative screening of both SARS-CoV-2 and H1N1 is achievable within 15 min, with detection limits of 7.76, and 8.13 pg·mL-1 for their respective target proteins. The platform demonstrated excellent performance in testing and analyzing 98 clinical samples (SARS-CoV-2:50; influenza A:48), achieving sensitivities of 88.00, and 95.83% for SARS-CoV-2 and influenza A, respectively. Pearson's correlation analysis revealed a significant correlation with the clinical CT values (P < 0.0001), underscoring the great potential of this platform for the early, rapid, and simultaneous diagnostic discrimination of multiple pathogens.

WSe2 Negative Capacitance Field-Effect Transistor for Biosensing Applications.

Field-effect transistor (FET) biosensors based on two-dimensional (2D) materials are highly sought after for their high sensitivity, label-free detection, fast response, and ease of on-chip integration. However, the subthreshold swing (SS) of FETs is constrained by the Boltzmann limit and cannot fall below 60 mV/dec, hindering sensor sensitivity enhancement. Additionally, the gate-leakage current of 2D material biosensors in liquid environments significantly increases, adversely affecting the detection accuracy and stability. Based on the principle of negative capacitance, this paper presents for the first time a two-dimensional material WSe2 negative capacitance field-effect transistor (NCFET) with a minimum subthreshold swing of 56 mV/dec in aqueous solution. The NCFET shows a significantly improved biosensor function. The pH detection sensitivity of the NCFET biosensor reaches 994 pH-1, nearly an order of magnitude higher than that of the traditional two-dimensional WSe2 FET biosensor. The Al2O3/HfZrO (HZO) bilayer dielectric in the NCFET not only contributes to negative capacitance characteristics in solution but also significantly reduces the leakage in solution. Utilizing an enzyme catalysis method, the WSe2 NCFET biosensor demonstrates a specific detection of glucose molecules, achieving a high sensitivity of 4800 A/A in a 5 mM glucose solution and a low detection limit (10-9 M). Further experiments also exhibit the ability of the biosensor to detect glucose in sweat.

Benefits of intensive lipid-lowering therapies in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS. METHODS: Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes. RESULTS: Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83-0.94; p < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71-0.96; p = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81-0.93; p < 0.001), stroke (RR, 0.83; 95% CI, 0.73-0.94; p = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33-0.99; p = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82-1.07; p = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88-1.06; p = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79-1.00; p = 0.057). CONCLUSIONS: Intensive lipid-lowering therapies may reduce the risk of three-point MACE, recurrent ACS, nonfatal MI, stroke, and hospitalization for unstable angina in patients with ACS undergoing background statin therapy. These results may assist in clinical decision-making for the secondary prevention of cardiovascular events to initiate intensive lipid-lowering therapies immediately after ACS.

Relationship between Indel Variants within the JAK2 Gene and Growth Traits in Goats.

Janus kinase 2 (JAK2) plays a critical role in myoblast proliferation and fat deposition in animals. Our previous RNA-Seq analyses identified a close association between the JAK2 gene and muscle development. To date, research delving into the relationship between the JAK2 gene and growth traits has been sparse. In this study, we sought to investigate the relationship between novel mutations within the JAK2 gene and goat growth traits. Herein, two novel InDel (Insertion/Deletion) polymorphisms within the JAK2 gene were detected in 548 goats, and only two genotypes were designated as ID (Insertion/Deletion) and DD (Deletion/Deletion). The results indicate that the two InDels, the del19008 locus in intron 2 and del72416 InDel in intron 6, showed significant associations with growth traits (p < 0.05). Compared to Nubian and Jianzhou Daer goats, the del72416 locus displayed a more pronounced effect in the Fuqing breed group. In the Nubian breed (NB) group, both InDels showed a marked influence on body height (BH). There were strong linkages observed for these two InDels between the Fuqing (FQ) and Jianzhou (JZ) populations. The DD-ID diplotype was associated with inferior growth traits in chest width (ChW) and cannon circumference (CaC) in the FQ goats compared to the other diplotypes. In the NB population, the DD-DD diplotype exhibited a marked negative impact on BH and HuWI (hucklebone width index), in contrast to the other diplotypes. In summary, our findings suggest that the two InDel polymorphisms within the JAK2 gene could serve as valuable molecular markers for enhancing goat growth traits in breeding programs.

Protective Effect of Long Noncoding RNA OXCT1-AS1 on Doxorubicin-Induced Apoptosis of Human Myocardial Cells by the Competitive Endogenous RNA Pattern. / Efeito Protetor do RNA Não Codificante Longo OXCT1-AS1 na Apoptose de Células Miocárdicas Humanas Induzida pela Doxorrubicina pelo Padrão Competitivo de RNA Endógeno.

BACKGROUND: The anthracycline chemotherapeutic antibiotic doxorubicin (DOX) can induce cumulative cardiotoxicity and lead to cardiac dysfunction. Long non-coding RNAs (lncRNAs) can function as important regulators in DOX-induced myocardial injury. OBJECTIVE: This study aims to investigate the functional role and molecular mechanism of lncRNA OXCT1 antisense RNA 1 (OXCT1-AS1) in DOX-induced myocardial cell injury in vitro. METHODS: Human cardiomyocytes (AC16) were stimulated with DOX to induce a myocardial cell injury model. OXCT1-AS1, miR-874-3p, and BDH1 expression in AC16 cells were determined by RT-qPCR. AC16 cell viability was measured by XTT assay. Flow cytometry was employed to assess the apoptosis of AC16 cells. Western blotting was used to evaluate protein levels of apoptosis-related markers. Dual-luciferase reporter assay was conducted to verify the binding ability between miR-874-3p and OXCT1-AS1 and between miR-874-3p and BDH1. The value of p<0.05 indicated statistical significance. RESULTS: OXCT1-AS1 expression was decreased in DOX-treated AC16 cells. Overexpression of OXCT1-AS1 reversed the reduction of cell viability and promotion of cell apoptosis caused by DOX. OXCT1-AS1 is competitively bound to miR-874-3p to upregulate BDH1. BDH1 overexpression restored AC16 cell viability and suppressed cell apoptosis under DOX stimulation. Knocking down BDH1 reversed OXCT1-AS1-mediated attenuation of AC16 cell apoptosis under DOX treatment. CONCLUSION: LncRNA OXCT1-AS1 protects human myocardial cells AC16 from DOX-induced apoptosis via the miR-874-3p/BDH1 axis.

FUNDAMENTO: O antibiótico quimioterápico antraciclina doxorrubicina (DOX) pode induzir cardiotoxicidade cumulativa e levar à disfunção cardíaca. RNAs não codificantes longos (lncRNAs) podem funcionar como importantes reguladores na lesão miocárdica induzida por DOX. OBJETIVO: Este estudo tem como objetivo investigar o papel funcional e o mecanismo molecular do RNA antisense lncRNA OXCT1 1 (OXCT1-AS1) na lesão celular miocárdica induzida por DOX in vitro. MÉTODOS: Cardiomiócitos humanos (AC16) foram estimulados com DOX para induzir um modelo de lesão celular miocárdica. A expressão de OXCT1-AS1, miR-874-3p e BDH1 em células AC16 foi determinada por RT-qPCR. A viabilidade das células AC16 foi medida pelo ensaio XTT. A citometria de fluxo foi empregada para avaliar a apoptose de células AC16. Western blotting foi utilizado para avaliar os níveis proteicos de marcadores relacionados à apoptose. O ensaio repórter de luciferase dupla foi conduzido para verificar a capacidade de ligação entre miR-874-3p e OXCT1-AS1 e entre miR-874-3p e BDH1. O valor de p<0,05 indicou significância estatística. RESULTADOS: A expressão de OXCT1-AS1 foi diminuída em células AC16 tratadas com DOX. A superexpressão de OXCT1-AS1 reverteu a redução da viabilidade celular e a promoção da apoptose celular causada pela DOX. OXCT1-AS1 está ligado competitivamente ao miR-874-3p para regular positivamente o BDH1. A superexpressão de BDH1 restaurou a viabilidade das células AC16 e suprimiu a apoptose celular sob estimulação com DOX. A derrubada do BDH1 reverteu a atenuação da apoptose de células AC16 mediada por OXCT1-AS1 sob tratamento com DOX. CONCLUSÃO: LncRNA OXCT1-AS1 protege células miocárdicas humanas AC16 da apoptose induzida por DOX através do eixo miR-874-3p/BDH1.

Analysis of blood concentrations and clinical application of risdiplam in patients with spinal muscular atrophy using ultra-high performance liquid chromatography-tandem mass spectrometry.

Risdiplam, the first oral therapy approved for spinal muscular atrophy and made globally available in 2021, necessitates a highly sensitive and straightforward assay for therapeutic drug monitoring. This is crucial to manage potential toxicities linked to drug concentrations and supervise dosing regimens. A cutting-edge ultra-high performance liquid chromatography-tandem mass spectrometry bioassay for risdiplam in human serum has been developed. In this method, analytes were separated on a Phenomenex Kinetex XB C18 column using a 6.5-min gradient elution after a single-step protein precipitation. MS detection was conducted via electrospray ionization in positive mode with selected reaction monitoring. The validated range for risdiplam was determined to be 1.95-125.00 ng/mL. The precision and accuracy of intra- and inter-batch analyses were within ±15%. The novel method met all other established criteria. This assay holds promise for monitoring drug concentrations and guiding clinical decisions in patients with spinal muscular atrophy.

Pregnancy complications and birth outcomes in women with polycystic ovary syndrome undergoing frozen embryo transfer.

OBJECTIVE: To determine whether polycystic ovary syndrome (PCOS) increases adverse pregnancy and birth outcomes in women undergoing frozen embryo transfer (FET). DESIGN: Retrospective cohort study. The PCOS group was matched 1:2 with the control group population using propensity score matching (PSM). PATIENTS: During an 8-year period, 2,955 patients aged 20 to 40 years who underwent FET and delivered between January 2015 and December 2022 at the Reproductive Medical Center of Ruijin Hospital were evaluated for adverse pregnancy outcomes. INTERVENTION(S): None. MAIN OUTCOME MEASURES: All patients were assessed for specific pregnancy complications and birth outcomes, with a sub-group analysis conducted to compare PCOS patients with and without hyperandrogenism. RESULTS: Women with PCOS demonstrated higher rates of gestational diabetes mellitus (24.9% vs. 16.4%; relative risk (RR) 1.51 [95% confidence interval (CI): 1.26-1.82]; P <0.001), gestational hypertension (12.2% vs. 8.9%; RR 1.37 [95% CI: 1.05-1.80]; P = 0.022), preterm prelabour rupture of membranes (7.0% vs. 3.6%; RR 1.92 [95% CI: 1.29-2.86]; P = 0.001), cervical length shortening (1.8% vs. 0.4%; RR 8.39 [95% CI: 1.56-12.49]; P = 0.002), large-for-gestational age (17.4% vs. 13.7%; RR 1.27 [95% CI: 1.02-1.57]; P = 0.032), and low birth weight (19.9% vs. 16.0%; RR 1.25 [95% CI: 1.02-1.52]; P = 0.030) in overall PSM analysis. Newborns of patients with PCOS had a higher risk of preterm birth < 37 weeks (10.5% vs. 6.6%; RR 1.59 [95% CI: 1.12-2.26]; P = 0.009) in singleton pregnancies. PCOS patients with hyperandrogenism showed a higher incidence of cervical length shortening (5.5% vs. 0.5%; adjusted odds ratio (AOR) 15.62 [95% CI: 2.25-108.48]; P = 0.005) compared to those without, after adjusting for relevant confounders. CONCLUSION: PCOS increases the incidence of adverse pregnancy outcomes after FET cycles. Our study suggests women with PCOS may warrant further monitoring and additional counseling before and during pregnancy.

Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

Double Balloon Combined with Oxytocin in Labor Induction: Analysis of Multivariate Factors Affecting the Efficacy of Cervical Ripening.

Objective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction. Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups. Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257-2.112), fetal distress (OR = 1.371, 95% CI: 1.331-2.633), and the placement of cervical ripening balloon catheter for >12h (OR = 1.563, 95% CI: 1.231-3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455-0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for >12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714-0.811). Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.

Preparation and characterization of metal-polyphenol networks encapsulated in sodium alginate microbead hydrogels for catechin and vitamin C delivery.

A novel encapsulation system was designed, utilizing sodium alginate (SA) polysaccharide as the matrix and easily absorbed Fe2+ as the metal-organic framework, to construct microbead scaffolds with both high catechins (CA) and vitamin C (Vc) loading and antioxidant properties. The structure of microbead hydrocolloids was investigated using SEM, XPS, FTIR, XRD and thermogravimetry, and the antioxidant activity, in vitro digestion and the release of CA and Vc were evaluated. These results revealed that the microbead hydrocolloids SA-CA-Fe and SA-CA-Vc-Fe exhibited denser and stronger cross-linking structures, and the formation of inter- and intramolecular hydrogen and coordination bonds improved thermal stability. Moreover, SA-CA-Fe (44.9 % DPPH and 47.8 % ABTS) and SA-CA-Vc-Fe (89.9 % DPPH and 89.3 % ABTS) displayed strong antioxidant activity. Importantly, they were non-toxic in Caco2 cells. The SA-CA-Fe and SA-CA-Vc-Fe achieved significantly higher CA (56.9 and 62.7 %, respectively) and Vc (42.2 %) encapsulation efficiency while maintaining higher CA and Vc release in small intestinal environment. These results suggested that SA polysaccharide-based encapsulation system using Fe2+ framework as scaffold had greater potential for delivery and controlled release of CA and Vc than conventional hydrocolloids, which could provide new insights into the construction of high loading, safe, targeted polyphenol delivery system.

Efficacy and Safety of Anti-Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Antibodies Plus Chemotherapy as First-Line Treatment for NSCLC in the People's Republic of China: a Systematic Review and Meta-Analysis.

Introduction: The available approved anticancer drugs for Chinese patients are relatively limited because of China's low participation rate in international clinical trials. Therefore, a focus on approved anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) drugs in China is needed. This study aims to assess the heterogeneity of anti-PD-1/PD-L1 antibodies manufactured in China (domestic PD-1/PD-L1) and overseas (imported PD-1/PD-L1) when combined with chemotherapy as the first-line treatment of NSCLC. Methods: A systematic search was performed using PubMed, EMBASE, and Cochrane Library of publications up to July 13, 2023. Meta-analysis was applied to compare the efficacy and safety profile between anti-PD-1/PD-L1 antibodies plus chemotherapy (PD-1/PD-L1+Chemo) and chemotherapy alone using STATA software. Pooled hazard ratios for progression-free survival and overall survival, odds ratios for objective response rate, and incidence rate of grade greater than or equal to three treatment-related adverse events with 95% confidence intervals were calculated in the domestic group and imported group by a random-effects model, and the heterogeneity between the two estimates was assessed. Results: There were 14 eligible clinical studies with a total of 3951 patients involved in this analysis, including eight studies of domestic PD-1/PD-L1+Chemo and six studies of imported PD-1/PD-L1+Chemo. The study revealed that there was no significant difference between domestic and imported PD-1/PD-L1+Chemo in overall survival (p = 0.80), progression-free survival (p = 0.53), and incidence rate of grade greater than or equal to three treatment-related adverse events (p = 0.10). Nevertheless, the objective response rate of imported PD-1/PD-L1+Chemo was significantly higher than that of domestic PD-1/PD-L1+Chemo (p = 0.03). Conclusions: Domestic anti-PD-1/PD-L1 antibodies plus chemotherapy were found to have comparable efficacy and safety to those combined with imported anti-PD-1/PD-L1 antibodies based on current evidence.

Hippocampal GPR35 Participates in the Pathogenesis of Cognitive Deficits and Emotional Alterations Induced by Aß1-42 in Mice.

The amyloid-beta (Aß) aggregation in Alzheimer's disease (AD) triggers neuroinflammation, and neurodegeneration, which lead to cognitive deficits along with other neuropsychiatric symptoms, including depression and anxiety. G protein-coupled receptor 35 (GPR35) is expressed in the brain and is involved in metabolic stresses. However, the role of GPR35 in AD pathogenesis remains unknown. Herein, pharmacological blockade, shRNA-mediated knockdown or knockout of GPR35 was performed to investigate the role and mechanisms of GPR35 in Aß1-42-induced cognitive impairment and emotional alterations in mice. A series of behavioral, histopathological, and biochemical tests were performed in mice. Our results showed that hippocampal GPR35 expression was significantly increased in Aß1-42-induced and APP/PS1 AD mouse models. Pharmacological blockade or knockdown of GPR35 ameliorated cognitive impairment and emotional alterations induced by Aß1-42 in mice. We also found that blockade or knockdown of GPR35 decreased the accumulation of Aß, and improved neuroinflammation, cholinergic system deficiency, and neuronal apoptosis via the RhoA/ROCK2 pathway in Aß1-42-treaed mice. However, activation of GPR35 aggravates Aß1-42-induced cognitive deficits and emotional alterations in mice. In addition, genetic deletion of GPR35 protects against the Aß1-42-induced cognitive deficits and emotional alterations in mice. Moreover, GPR35 could bind to TLR4. These results indicate that GPR35 participates in the pathogenesis of cognitive deficits and emotional alterations induced by Aß1-42 in mice, suggesting that GPR35 could be a potential therapeutic target for AD.

Combined associations of visceral adipose tissue and adherence to a Mediterranean lifestyle with T2D and diabetic microvascular complications among individuals with prediabetes.

BACKGROUND: It's unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes. METHODS: 11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as "Mediterranean food consumption," "Mediterranean dietary habits," and "Physical activity, rest, social habits, and conviviality." Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors. RESULTS: Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71-0.98) and 31% for incident DMC (0.69, 0.56-0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72-7.49) and incident any DMC (1.79, 1.36-2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08-0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC. CONCLUSION: High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT's risk partly. The Mediterranean lifestyle's adaptability to diverse populations suggests promise for preventing T2D.

Micro-Milling of Additively Manufactured Al-Si-Mg Aluminum Alloys.

Additively manufactured aluminum alloy parts attract extensive applications in various felids. To study the machinability of additively manufactured aluminum alloys, micro-milling experiments were conducted on the additively manufactured AlSi7Mg and AlSi10Mg. By comparing the machinability of Al-Si-Mg aluminum alloys with different Si content, the results show that due to the higher hardness of the AlSi10Mg, the cutting forces are higher than the AlSi7Mg by about 11.8% on average. Due to the increased Si content in additively manufactured Al-Si-Mg aluminum alloys, the surface roughness of AlSi10Mg is 26.9% higher than AlSi7Mg on average. The burr morphology of additively manufactured aluminum alloys in micro-milling can be divided into fence shape and branch shape, which are, respectively, formed by the plastic lateral flow and unseparated chips. The up-milling edge exhibits a greater burr width than the down-milling edge. Due to the better plasticity of AlSi7Mg, the burr width of the down-milling edge is 28.1% larger, and the burr width of the up-milling edge is 10.1% larger than the AlSi10Mg. This research can provide a guideline for the post-machining of additively manufactured aluminum alloys.

Promotion and Mechanism of Acupotomy on Chondrocyte Autophagy in Knee Osteoarthritis Rabbits.

OBJECTIVE: To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis (KOA), and to determine the possible mechanisms of acupotomy to alleviate cartilage degeneration. METHODS: The modified Videman method was used to construct a KOA rabbit model. After modeling, 40 rabbits were randomly divided into 4 groups by a random number table: control; KOA (model); KOA + acupotomy (acupotomy), and KOA + sham acupotomy (sham), 10 in each group. After a 3-week treatment course, the knee joint activity was determined by the modified Lequesne MG index. Hematoxylin-eosin staining staining was used to examine the morphological changes of chondrocytes. Autophagy of chondrocytes was observed by transmission electron microscopy. The surface morphology of cartilage tissue was observed by scanning electron microscope. The mRNA and protein levels of AMP kinase/mammalian target of rapamycin/Unc-51 (AMPK/mTOR/ULK1) signal pathway key proteins, autophagy-related factor Beclin-1 and microtubule-associated protein 1A/1B light chain 3 (LC3) in rabbit knee cartilage were assessed by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. RESULTS: The modified Lequesne MG score of acupotomy group was significantly lower than that of model group (P<0.05). Pathological results showed that chondrocyte autophagy decreased and cartilage surface was rough in the model group, which recovered after acupotomy treatment. The mRNA expressions of AMPK, ULK1, Beclin-1 and the protein levels of p-AMPK, p-ULK1, Beclin-1, and LC3 II/LC3 I were decreased in the model group, while the mRNA and protein expressions of mTOR were increased (P<0.01). However, acupotomy treatment reversed these abnormal changes (P<0.05). CONCLUSIONS: Acupotomy could effectively up-regulate the expressions of AMPK, ULK1 and Beclin1, reduce the expression of mTOR, promote autophagy, and alleviate joint degeneration. Acupotomy is a promising complementary and alternative therapy for KOA.

Insights into spinal muscular atrophy from molecular biomarkers.

ABSTRACT: Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness. It is one of the most common genetic causes of mortality among infants aged less than 2 years. Biomarker research is currently receiving more attention, and new candidate biomarkers are constantly being discovered. This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons. We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy, which are classified as either specific or non-specific biomarkers. This review provides new insights into the pathogenesis of spinal muscular atrophy, the mechanism of biomarkers in response to drug-modified therapies, the selection of biomarker candidates, and would promote the development of future research. Furthermore, the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

Raman spectroscopic quantification of graphene oxide in soil: Transport, surficial enrichment and environmental effects.

The transport and retention data in environmental media are indispensable for the hazard evaluations of graphene materials. Due to the complexity of soil, the transport of graphene is hard to quantify without isotope labeling. Herein, we developed 2D Raman mapping as a label-free technique to quantify graphene oxide (GO) in soil. After pre-treatment by hydrazine hydrate to quench its fluorescence, the quantification of GO in soil was achieved in the range of 0.1-1000 mg/L by measuring the average G-band intensity. In column transport experiment, the transport and retention of GO in soil depended on the solution chemistry. Lower pH and higher ionic strength hindered the transport of GO. In particular, Ca2+ showed the most obvious retardation on the transport of GO. GO enriched in the surficial soil layer by several folds of the initial concentrations, and higher GO concentration led to more surficial enrichment. The sowing manner of seeds affected the soil enrichment of GO, too. The surficial enrichment of GO reduced its direct contact with seedling roots, resulting in the alleviation of GO toxicity. Our results provided a facile method to study the environmental behaviors of graphene and highlighted the crucial impacts of environmental media on the graphene toxicity.

Effect of Polymer and Cell Membrane Coatings on Theranostic Applications of Nanoparticles: A Review.

The recent decade has witnessed a remarkable surge in the field of nanoparticles, from their synthesis, characterization, and functionalization to diverse applications. At the nanoscale, these particles exhibit distinct physicochemical properties compared to their bulk counterparts, enabling a multitude of applications spanning energy, catalysis, environmental remediation, biomedicine, and beyond. This review focuses on specific nanoparticle categories, including magnetic, gold, silver, and quantum dots (QDs), as well as hybrid variants, specifically tailored for biomedical applications. A comprehensive review and comparison of prevalent chemical, physical, and biological synthesis methods are presented. To enhance biocompatibility and colloidal stability, and facilitate surface modification and cargo/agent loading, nanoparticle surfaces are coated with different synthetic polymers and very recently, cell membrane coatings. The utilization of polymer- or cell membrane-coated nanoparticles opens a wide variety of biomedical applications such as magnetic resonance imaging (MRI), hyperthermia, photothermia, sample enrichment, bioassays, drug delivery, etc. With this review, the goal is to provide a comprehensive toolbox of insights into polymer or cell membrane-coated nanoparticles and their biomedical applications, while also addressing the challenges involved in translating such nanoparticles from laboratory benchtops to in vitro and in vivo applications. Furthermore, perspectives on future trends and developments in this rapidly evolving domain are provided.

Revealing the vertical structure of in-situ fabricated perovskite nanocrystals films toward efficient pure red light-emitting diodes.

The development of efficient perovskite light-emitting diodes (PeLEDs) relies strongly on the fabrication of perovskite films with rationally designed structures (grain size, composition, surface, etc.). Therefore, an understanding of structure-performance relationships is of vital importance for developing high-performance perovskite devices, particularly for devices with in-situ fabricated perovskite nanocrystal films. In this study, we reveal the vertical structure of an in-situ fabricated quasi-two-dimensional perovskite film. By combining time-of-flight secondary ion mass spectrometry, energy dispersive spectroscopy, grazing incidence wide-angle X-ray scattering (GIWAXS), and low-temperature photoluminescence spectra, we illustrate that the resulting in-situ fabricated DPPA2Csn-1Pbn(Br0.3I0.7)3n+1 (DPPA+: 3,3-diphenylpropylammonium) film has a gradient structure with a very thin layer of ligands on the surface, predominantly small-n domains at the top, and predominantly large-n domains at the bottom owing to the solubility difference of the precursors. In addition, GIWAXS measurements show that the domain of n = 2 on the top layer has an ordered in-plane alignment. Based on the understanding of the film structure, we developed an in-situ fabrication process with ligand exchange to achieve efficient pure red PeLEDs at 638 nm with an average external quantum efficiency (EQE) of 7.4%. The optimized device had a maximum luminance of 623 cd/m2 with a peak EQE of 9.7%.

The role of age and AMH on cumulative live birth rates over multiple frozen-thawed embryo transfer cycles: a study based on low prognosis patients of POSEIDON 3 and 4 groups.

BACKGROUND: Among the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported. METHODS: This retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves. RESULTS: Under optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles. CONCLUSIONS: The patients of POSEIDON group 3 may not be considered as traditional "low prognosis" in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial.