Efficacy and safety of telitacicept in patients with lupus nephritis.

Although telitacicept is a promising drug for treating systemic lupus erythematosus, there are limited studies on its efficacy and safety in patients with lupus nephritis in China. This lack of research data restricts its potential for broader application and acceptance on a global scale. The present study aimed to determine the efficacy and safety of telitacicept in patients with lupus nephritis (LN) in China. Using a self-controlled before-after comparison method, patients with LN were recruited at Lishui Central Hospital between February 2022 and April 2023, who received telitacicept weekly as part of the standard treatment. Data on the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), glucocorticoid dosing and the quantity of immunosuppressive medicines prescribed was collected. Additionally, serum complements, erythrocyte sedimentation rate (ESR), urinary protein levels, immunoglobulin concentrations, serum creatinine levels, plasma albumin concentrations, platelet counts and renal function parameters were documented throughout the study. A total of 13 patients were enrolled in the trial, comprising 11 women and two men. Following 12-48 weeks of treatment with telitacicept (80 or 160 mg per week), 84.6% (n=11) of all patients experienced symptom relief and their SLEDAI-2K score was reduced by more than four points. By the observation endpoint, the median glucocorticoid dosage of the 13 patients was decreased from 15 to 2.5 mg/d, and six patients discontinued their glucocorticoids. Furthermore, 46.1% of patients (n=6) reduced their dose and number of immunosuppressive medicines, while 15.4% (n=2) stopped their immunosuppressive medicines. Minimal changes were observed in serum creatinine, platelet count, C3 levels and C4 levels among patients. Immunoglobulin levels (IgG, IgA and IgM) remained stable or showed an upward trend. Plasma albumin levels remained within the normal range in three patients and increased in ten patients. It increased to the normal range in three of these ten patients. At the endpoint, ESR levels decreased in all patients. Additionally, three patients displayed varying degrees of renal function improvement, and their estimated glomerular filtration rate (ml/min/l.73 m2) increased from 127.8 to 134.2, 95.1 to 123.1 and 61.5 to 67.3, respectively. Urinary protein levels decreased in all patients. It decreased >0.5 g/l in seven patients and reached the normal levels in three patients. The adverse events of telitacicept were manageable. Among the patients infected with COVID-19, three patients had fever, 10 patients remained asymptomatic and none of them exhibited severe respiratory syndromes. In this study, telitacicept effectively stabilized LN activity and alleviated the clinical symptoms of most patients. Furthermore, it reduced the dose of glucocorticoid and immunosuppressive medicines. Therefore, telitacicept may be a promising treatment option for individuals with lupus nephritis.

Sex difference in alcohol consumption associated with colorectal cancer risk in Quzhou, China: A nested case-control study.

Objective: Colorectal cancer (CRC) incidence has been increasing worldwide over time. This study investigated whether drinking was associated with CRC risk. Methods: We designed a case-control study nested in a mass CRC screening program in Quzhou, China. Cases were newly diagnosed CRC in 2020-2022. Controls were randomly sampled using frequency match. Drinking variables included drinking status, frequency, duration, and others. Logistic regressions were used to estimate odds ratio (OR) and 95 % confidence interval (CI). Results: The crude OR (cOR) (95 % CI) of drinking between 153 cases and 650 controls was 1.46 (0.99, 2.16) in current drinkers, 3.31 (1.44, 7.60) in former drinkers, 1.82 (1.21, 2.74) in drinking 6-7 days/week, and 3.48 (1.29, 9.37) in drinking 1-19 years. Stratifying by sex, all drinking variables in women but not all in men were consistently associated with CRC risk. The adjusted OR (aOR) (95 % CI) was 1.01 (0.59, 1.74) in current drinking men, 2.27 (0.78, 6.64) in former drinking men, and 4.24 (1.61, 11.13) in current drinking women. The aOR (95 % CI) of drinking whisky was 0.19 (0.04, 0.83), 1.89 (0.86, 4.17), 2.25 (1.05, 4.83), and 1.82 (0.85, 3.92) in men drinking ≤0.5, >0.5-≤1.0, >1.0-≤1.5, and >1.5 Liter/week (P trend = 0.011), and 3.80 (1.03, 14.00) and 9.92 (2.01, 49.00) in women drinking ≤0.5 and >0.5 Liter/week (P trend = 0.001), respectively. Conclusions: There was sex difference in drinking associated with increased risk of CRC which association was stronger in women than that in men. Men's association between drinking whisky and CRC risk was J-shaped.

Acupuncture influences multiple diseases by regulating gut microbiota.

Acupuncture, an important green and side effect-free therapy in traditional Chinese medicine, is widely use both domestically and internationally. Acupuncture can interact with the gut microbiota and influence various diseases, including metabolic diseases, gastrointestinal diseases, mental disorders, nervous system diseases, and other diseases. This review presents a thorough analysis of these interactions and their impacts and examines the alterations in the gut microbiota and the potential clinical outcomes following acupuncture intervention to establish a basis for the future utilization of acupuncture in clinical treatments.

Intrauterine hyperglycaemia during late gestation caused mitochondrial dysfunction in skeletal muscle of male offspring through CREB/PGC1A signaling.

BACKGROUND: Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified. METHODS: Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon. RESULTS: Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their decreased transcription. Interestingly, we found that sarcopenia and mitochondrial dysfunction could even be inherited by the next generation. CONCLUSIONS: Short-term intrauterine hyperglycaemia significantly reduced lean mass in male offspring at 8 weeks, resulting in decreased exercise endurance and metabolic disorders. Disrupted organisation and function of the mitochondria in skeletal muscle were also observed among them. Foetal exposure to hyperglycaemia decreased the ratio of phosphorylated CREB and reduced the transcription of Ppargc1α, which inhibited the transcription of downstream genes involving in mitochondrial biogenesis and oxidative metabolism. Abnormal mitochondria, which might be transmitted through aberrant gametes, were also observed in the F2 generation.

A Novel Method for the Early Detection of Single Circulating, Metastatic and Self-Seeding Cancer Cells in Orthotopic Breast Cancer Mouse Models.

BACKGROUND: Metastasis is the main cause of cancer-related deaths, but efficient targeted therapies against metastasis are still missing. Major gaps exist in our understanding of the metastatic cascade, as existing methods cannot combine sensitivity, robustness, and practicality to dissect cancer progression. Addressing this issue requires improved strategies to distinguish early metastatic colonization from metastatic outgrowth. METHODS: Luciferase-labelled MDA-MB-231, MCF7, and 4T1 breast cancer cells were spiked into samples from tumour-naïve mice to establish the limit of detection for disseminated tumour cells. Luciferase-labelled breast cancer cells (±unlabelled cancer-associated fibroblasts; CAFs) were orthotopically implanted in immunocompromised mice. An ex vivo luciferase assay was used to quantify tumour cell dissemination. RESULTS: In vitro luciferase assay confirmed a linear and positive correlation between cancer cell numbers and the bioluminescence detected at single cell level in blood, brain, lung, liver, and mammary fat pad samples. Remarkably, single luciferase-labelled cancer cells were detectable in all of these sites, as the bioluminescence quantified in the analysed samples was substantially higher than background levels. Ex vivo, circulating tumour cells, metastasis, and tumour self-seeding were detected in all samples from animals implanted with highly metastatic luciferase-labelled MDA-MB-231 cells. In turn, detection of poorly metastatic luciferase-labelled MCF7 cells was scarce but significantly enhanced upon co-implantation with CAFs as early as 20 days after the experiment was initiated. CONCLUSIONS: These results demonstrate the feasibility of using an ultrasensitive luciferase-based method to dissect the mechanisms of early metastatic colonization to improving the development of antimetastatic therapies.

Reactivity-matched synthesis of monodisperse Ag(In,Ga)S2 QDs with efficient luminescence.

I-III-VI quantum dots (QDs) have gained widespread attention owing to their significant advantages of non-toxicity, large structural tolerance, and efficient photoluminescence potential. However, the disbalance of reactivity between the elements will result in undesired products and compromised optical properties. Reducing the activity of highly reactive group IB elements is the most common approach, but it will reduce the overall reactivity and lead to a wide dispersion of QD sizes. In this study, we propose a method to improve the overall reactivity of the reaction system using the highly active IIIA precursor InI3, which triggers rapid nucleation and promotes the formation of Ag(In,Ga)S2 (AIGS) QDs, resulting in monodisperse particle size distributions and a significantly improved photoluminescence quantum yield (PLQY) (from 12% to 72%). Furthermore, narrow band edge emission is realized by coating a gallium sulfide (GaSx) shell on the basis of obtaining high-quality AIGS QDs. The core/shell QDs exhibit a 90% PLQY with a full width at half maximum (FWHM) of only 31 nm at 530 nm. This study provides a viable design strategy to synthesize monodisperse AIGS QDs with a narrow peak width and efficient luminescence, promoting the application of AIGS QDs in the field of luminescent displays.

A high reticulocyte count is a risk factor for the onset of metabolic dysfunction-associated steatotic liver disease: Cross-sectional and prospective studies of data of 310,091 individuals from the UK Biobank.

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.

Through virtual saturation mutagenesis and rational design for superior substrate conversion in engineered d-amino acid oxidase.

The d-amino acid oxidase (DAAO) is pivotal in obtaining optically pure l-glufosinate (l-PPT) by converting d-glufosinate (d-PPT) to its deamination product. We screened and designed a Rasamsonia emersonii DAAO (ReDAAO), making it more suitable for oxidizing d-PPT. Using Caver 3.0, we delineated three substrate binding pockets and, via alanine scanning, identified nearby key residues. Pinpointing key residues influencing activity, we applied virtual saturation mutagenesis (VSM), and experimentally validated mutants which reduced substrate binding energy. Analysis of positive mutants revealed elongated side-chain prevalence in substrate binding pocket periphery. Although computer-aided approaches can rapidly identify advantageous mutants and guide further design, the mutations obtained in the first round may not be suitable for combination with other advantageous mutations. Therefore, each round of combination requires reasonable iteration. Employing VSM-assisted screening multiple times and after four rounds of combining mutations, we ultimately obtained a mutant, N53V/F57Q/V94R/V242R, resulting in a mutant with a 5097% increase in enzyme activity compared to the wild type. It provides valuable insights into the structural determinants of enzyme activity and introduces a novel rational design procedure.

[Construction of ATMT system of Fusarium oxysporum and evaluation of its promoting effect on Glycyrrhiza uralensis].

This study aims to evaluate the in vivo function of Fusarium oxysporum in Glycyrrhiza uralensis by salt tolerance,indoleacetic acid(IAA) production capacity, phosphate-dissolving capacity, and iron carrier production capacity. The stable genetic transformation system of the F. oxysporum was established by Agrobacterium tumefaciens-mediated genetic transformation( ATMT)technology, and the stability and staining efficiency of transformants were detected by the cloning of the marker gene green fluorescent protein(GFP) and the efficiency of ß-glucuronidase staining(GUS). Efficient and stable transformants were selected for restaining G. uralensis and evaluating its influence on the growth of the G. uralensis seedlings. The results show that F. oxysporum has good salt tolerance and could still grow on potato glucose agar(PDA) medium containing 7% sodium chloride, but the growth rate slows down with the increase in sodium chloride content in PDA medium. F. oxysporum has the function of producing indoleacetic acid, and the concentration of IAA in its fermentation broth is about 3. 32 mg · m L~(-1). In this study, the genetic transformation system of F. oxysporum is successfully constructed, and the ATMT system is efficient and stable. One transformant with both high staining efficiency and genetic stability is selected, and the restaining rate of the transformant in G. uralensis is 76. 92%, which could significantly improve the main root length of one-month-old G. uralensis seedlings and promote the growth and development of G. uralensis seedlings. The results of this study can lay the foundation for the development of biological bacterial fertilizer and the growth regulation of high-quality G. uralensis.

Association of early-term birth and breastfeeding practices with nutritional outcomes in singleton term infants: a multicenter cross-sectional study.

BACKGROUND: Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants. METHODS: This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5-4.0 kg). RESULTS: Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: ß = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: ß = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (ß=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (ß=-0.15, 95%CI -0.30, 0.00 and ß=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings. CONCLUSIONS: The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.

The efficacy of postoperative radiotherapy in resected pâ ¢A-N2 EGFR mutant and wild-type lung adenocarcinoma.

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Positive feedback loop of c-myc/XTP6/NDH2/NF-κB to promote malignant progression in glioblastoma.

BACKGROUND: Recent studies have highlighted the significant role of the NF-κB signaling pathway in the initiation and progression of cancer. Furthermore, long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in sustaining the NF-κB signaling pathway's functionality. Despite these findings, the underlying molecular mechanisms through which lncRNAs influence the NF-κB pathway remain largely unexplored. METHODS: Bioinformatic analyses were utilized to investigate the differential expression and prognostic significance of XTP6. The functional roles of XTP6 were further elucidated through both in vitro and in vivo experimental approaches. To estimate the interaction between XTP6 and NDH2, RNA pulldown and RNA Immunoprecipitation (RIP) assays were conducted. The connection between XTP6 and the IκBα promoter was examined using Chromatin Isolation by RNA Purification (ChIRP) assays. Additionally, Chromatin Immunoprecipitation (ChIP) assays were implemented to analyze the binding affinity of c-myc to the XTP6 promoter, providing insights into the regulatory mechanisms at play. RESULTS: XTP6 was remarkedly upregulated in glioblastoma multiforme (GBM) tissues and was connected with adverse prognosis in GBM patients. Our investigations revealed that XTP6 can facilitate the malignant progression of GBM both in vitro and in vivo. Additionally, XTP6 downregulated IκBα expression by recruiting NDH2 to the IκBα promoter, which resulted in elevated levels of H3K27me3, thereby reducing the transcriptional activity of IκBα. Moreover, the progression of GBM was further driven by the c-myc-mediated upregulation of XTP6, establishing a positive feedback loop with IκBα that perpetuated the activation of the NF-κB signaling pathway. Notably, the application of an inhibitor targeting the NF-κB signaling pathway effectively inhibited the continuous activation induced by XTP6, leading to a significant reduction in tumor formation in vivo. CONCLUSION: The results reveal that XTP6 unveils an innovative epigenetic mechanism instrumental in the sustained activation of the NF-κB signaling pathway, suggesting a promising therapeutic target for the treatment of GBM.

The clinical application value of 3.0T magnetic resonance T2 mapping imaging in evaluating the degree of acetabular cartilage degeneration in joint replacement surgery running title: MRI and acetabular cartilage degeneration.

BACKGROUND: To explore and compare the values of 3.0T magnetic resonance imaging (MRI) T2 mapping in evaluating the degree of acetabular cartilage degeneration in hip replacement surgery. METHODS: A total of 26 elderly patients with femoral neck fractures who were scanned in 3.0T MRI T2 mapping quantification technique were included. Basing on MRI images, the degree of acetabular cartilage degeneration was classified into Grade 0, 1, 2, 3 and 4, according to the International Cartilage Repair Society (ICRS) scores. In addition, 8 healthy volunteers were included for control group. RESULTS: By comparison with health population, T2 relaxation values in the anterior, superior, and posterior regions of acetabular cartilage in patients with femoral neck fracture were obviously increased (P < 0.001). Among the patients with femoral neck fractures, there were 16 hip joint with Grade 1-2 (mild degeneration subgroup) and 10 hip joints with Grade 3-4 (severe degeneration subgroup), accounting for 61.54% and 38.46%, respectively. Additionally, T2 relaxation values in the anterior and superior bands of articular cartilage were positively related to the MRI-based grading (P < 0.05); while there was no significant difference of T2 relaxation values in the posterior areas of articular cartilage between severe degeneration subgroup and mild degeneration subgroup (P > 0.05). Importantly, acetabular cartilage degeneration can be detected through signal changes of T2 mapping pseudo-color images. CONCLUSION: 3.0T MRI T2 mapping technology can be used to determine the degree of acetabular cartilage degeneration, which can effectively monitor the disease course.

Critical Role of Tripartite Fusion and LBD Truncation in Certain RARA- and all RARG-Related Atypical APL.

Atypical acute promyelocytic leukemia (aAPL) presents a complex landscape of retinoic acid receptor (RAR) fusion genes beyond the well-known PML::RARA fusion. Among these, 31 individually rare RARA and RARG fusion genes have been documented, often reported in the canonical X::RAR bipartite fusion form. Intriguingly, some artificially mimicked bipartite X::RAR fusions respond well to all-trans retinoic acid (ATRA) in vitro, contrasting with the ATRA resistance observed in patients. To unravel the underlying mechanisms, we conducted a comprehensive molecular investigation into the fusion transcripts in 27 RARA fusion gene-positive aAPL (RARA-aAPL) and 21 RARG-aAPL cases. Our analysis revealed an unexpected novel form of X::RAR::X or X::RAR::Y-type tripartite fusions in certain RARA- and all RARG-aAPL cases, with shared features and notable differences between these two disease subgroups. In RARA-aAPL cases, the occurrence of RARA 3' splices was associated with their 5' fusion partner genes, mapping across the coding region of helix 11_12 (H11_12) within the ligand-binding domain (LBD), resulting in LBD-H12 or H11_12 truncation. In RARG-aAPL cases, RARG 3' splices were consistently localized to the terminus of exon 9, leading to LBD-H11_12 truncation. Significant differences were also observed between RARA and RARG 5' splice patterns. Our analysis also revealed extensive involvement of transposable elements in constructing RARA and RARG 3' fusions, suggesting transposition mechanisms for fusion gene ontogeny. Both protein structural analysis and experimental results highlighted the pivotal role of LBD-H11_12/H12 truncation in driving ATRA unresponsiveness and leukemogenesis in tripartite fusion-positive aAPL, through a protein allosteric dysfunction mechanism.

HOO• as the Chain Carrier for the Autocatalytic Photooxidation of Benzylic Alcohols.

The oxidation of benzylic alcohols is an important transformation in modern organic synthesis. A plethora of photoredox protocols have been developed to achieve the aerobic oxidation of alcohols into carbonyls. Recently, several groups described that ultraviolet (UV) or purple light can initiate the aerobic oxidation of benzylic alcohols in the absence of an external catalyst, and depicted different mechanisms involving the photoinduction of •O2- as a critical reactive oxygen species (ROS). However, based on comprehensive mechanistic investigations, including control experiments, radical quenching experiments, EPR studies, UV-vis spectroscopy, kinetics studies, and density functional theory calculations (DFT), we elucidate here that HOO•, which is released via the H2O2 elimination of α-hydroxyl peroxyl radicals [ArCR(OH)OO•], serves as the real chain carrier for the autocatalytic photooxidation of benzylic alcohols. The mechanistic ambiguities depicted in the precedent literature are clarified, in terms of the crucial ROS and its evolution, the rate-limiting step, and the primary radical cascade. This work highlights the necessity of stricter mechanistic analyses on UV-driven oxidative reactions that involve aldehydes' (or ketones) generation.

A Study on the Application Performance of High-Aspect-Ratio Nano-Ettringite in Photocurable Resin Composites.

In this study, the impact of the addition of high-aspect-ratio nano-ettringite to photocurable epoxy acrylate resin was explored. The nano-ettringite samples were modified using γ-Aminopropyltriethoxysilane (KH-550) and γ-methacryloxypropyl trimethoxy silane (KH-570). Then, 3 wt% or 6 wt% KH-550-modified, KH-570-modified, and unmodified nano-ettringite samples were dispersed into resin via ultrasonic treatment in conjunction with mechanical stirring. The grafting effects of nano-ettringite onto KH-550 or KH-570 were analyzed through scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and thermogravimetric (TG) analysis. The results demonstrate that KH-550 and KH-570 have been successfully grafted onto the surface of nano-ettringite. In addition, this study also focuses on the variations of composite materials in the viscosity, shrinkage, tensile strength, and elongation at break. The results indicate that increased dosages of unmodified, KH-550-modified, and KH-570-modified nano-ettringite led to increased viscosity of the composite while reducing shrinkage. At the same dosage, the photocurable resin containing KH-570-modified nano-ettringite demonstrated a lower shrinkage and a higher tensile strength. From the analysis of tensile fracture surfaces, it was observed that compared to the KH-550 modified and unmodified variants, the KH-570 modified nano-ettringite exhibits superior dispersibility in photocurable epoxy acrylate resin. Notably, when the amount of KH-570-modified nano-ettringite was 3 wt%, the highest tensile strength of the composite was 64.61 MPa, representing a 72.57% increase compared to the blank sample. Furthermore, the incorporation of KH-570-modified nano-ettringite as a filler provides a new perspective for improving the performance of photocurable epoxy acrylate resin composites.

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Comparative simulations of methanol steam reforming on PdZn alloy using kinetic Monte Carlo and mean-field microkinetic model.

Methanol steam reforming (MSR) is an attractive route for producing clean energy hydrogen. PdZn alloys are extensively studied as potential MSR catalysts for their stability and high CO2 selectivity. Here, we investigated the reaction mechanism using density functional calculations, mean-field microkinetic modeling (MF-MKM), and kinetic Monte Carlo (kMC) simulations. To overcome the over-underestimation of CO2 selectivity by log-kMC, an ads-kMC algorithm is proposed in which the adsorption/desorption rate constants were reduced under certain requirements and the diffusion process was treated by redistributing surface species each time an event occured. The simulations show that the dominant pathway to CO2 at low temperatures is CH3OH → CH3O → CH2O → H2COOH → H2COO → HCOO → CO2. The ads-kMC predicted OH coverage is 2-3 times that of MF-MKM, while they produce similar coverage for other species. Analyses indicate that surface OH promotes the dehydrogenation of CH3OH, CH3O, and H2COOH significantly and plays a key role in the MSR process. The dissociation of water/methanol is the most important rate-limiting/rate-inhibiting step. The CO2 selectivity obtained by the two methods is close to each other and consistent with the experimental trend with temperature. Generally, the ads-kMC results agree with the MF-MKM ones, supporting the previous finding that kMC and MF-MKM predict similar results if the diffusion is very fast and adsorbate interactions are neglected. The present study sheds light on the MSR process on PdZn alloys, and the proposed scheme to overcome the stiff problems in kMC simulations is worthy of being extended to other systems.

Long-term blood pressure variability and risk of cardiovascular diseases in populations with different blood pressure status: an ambispective cohort study.

OBJECTIVE: We aimed to investigate the correlation between long-term blood pressure variability (BPV) and the risk of cardiovascular diseases (CVDs) among population with different blood pressure statuses (normotension, well-controlled hypertension, and uncontrolled hypertension). METHODS: In this ambispective cohort study, CVD-free residents aged over 50 years were consecutively enrolled from two community health service centers (CHCs) in Tianjin, China from April 2017 to May 2017. Information on blood pressure was retrospectively extracted from electronic medical records of CHCs between January 2010 and May 2017, and the occurrence of new-onset CVDs was prospectively observed during follow-up until September 2019. Long-term variation of SBP and DBP was assessed using four indicators: SD, coefficient of variation (CV), average successive variability (ASV), and average real variability (ARV). Cox proportional hazards regression model was developed to identify the potential impact of BPV on the incidence of CVDs. The receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of BPV indicators for the occurrence of CVDs. RESULTS: Of 1275 participants included, 412 (32.3%) experienced new CVD events during the median 7.7 years of follow-up, with an incidence density of 499/10 000 person-year in the whole cohort. Cox regression analysis revealed that almost all SBP and DBP variability indicators (except for SBP-SD) were significantly related to the risk of CVDs, especially among individuals with well-controlled hypertension. A trend toward an increased risk of CVDs across BPV quartiles was also observed. Moderate predictive abilities of BPV were observed, with the area under ROC curves ranging between 0.649 and 0.736. For SBP variability, SD had the lowest predictive ability, whereas for DBP variability, ARV had the lowest predictive ability. No significant association of CVDs with SBP-SD was found in all analyses, no matter as a continuous or categorical variable. CONCLUSION: Elevated long-term BPV is associated with an increased risk of CVDs, especially among individuals with well-controlled hypertension. CV and ASV had higher predictive values than SD and ARV.