Catalytic Glycosylation for Minimally Protected Donors and Acceptors.

Oligosaccharides have myriad functions throughout biology.1,2 To investigate these functions requires multi-step chemical synthesis of these structurally complex molecules. With a dense concentration of stereocentres and hydroxyl groups, oligosaccharide assembly through O-glycosylation requires simultaneous control of site-, stereo-, and chemoselectivities3,4. Chemists have traditionally relied on protecting group manipulations for this purpose,5-8 adding a lot of synthetic work. Here, we report a glycosylation platform that enables selective coupling between unprotected or minimally protected donor and acceptor sugars, producing 1,2-cis-O-glycosides in a catalyst-controlled, site-selective manner. Radical-based activation9 of allyl glycosyl sulfones forms glycosyl bromides. A designed aminoboronic acid catalysts bring this reactive intermediate close to an acceptor through a network of noncovalent hydrogen bonding and reversible covalent B-O bonding interactions, allowing precise glycosyl transfer. The site of glycosylation can be switched with different aminoboronic acid catalysts by affecting their interaction modes with substrates. The method accommodates a wide range of sugar types, amenable to preparing naturally occurring sugar chains and pentasaccharides containing 11 free hydroxyls. Experimental and computational studies provide insights into the origin of selectivity outcomes.

Melatonin Delays Arthritis Inflammation and Reduces Cartilage Matrix Degradation through the SIRT1-Mediated NF-κB/Nrf2/TGF-ß/BMPs Pathway.

Cartilage, a flexible and smooth connective tissue that envelops the surfaces of synovial joints, relies on chondrocytes for extracellular matrix (ECM) production and the maintenance of its structural and functional integrity. Melatonin (MT), renowned for its anti-inflammatory and antioxidant properties, holds the potential to modulate cartilage regeneration and degradation. Therefore, the present study was devoted to elucidating the mechanism of MT on chondrocytes. The in vivo experiment consisted of three groups: Sham (only the skin tissue was incised), Model (using the anterior cruciate ligament transection (ACLT) method), and MT (30 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage, synovium, and subchondral bone were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via Enzyme-linked immunosorbent assay (ELISA) assays. In in vitro experiments, primary chondrocytes were divided into Control, Model, MT, negative control, and inhibitor groups. Western blotting (WB) and Quantitative RT-PCR (q-PCR) were used to detect Silent information regulator transcript-1 (SIRT1)/Nuclear factor kappa-B (NF-κB)/Nuclear factor erythroid-2-related factor 2 (Nrf2)/Transforming growth factor-beta (TGF-ß)/Bone morphogenetic proteins (BMPs)-related indicators. Immunofluorescence (IF) analysis was employed to examine the status of type II collagen (COL2A1), SIRT1, phosphorylated NF-κB p65 (p-p65), and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2). In vivo results revealed that the MT group exhibited a relatively smooth cartilage surface, modest chondrocyte loss, mild synovial hyperplasia, and increased subchondral bone thickness. ICH results showed that MT downregulated the expression of components related to matrix degradation. ELISA results showed that MT reduced serum inflammatory cytokine levels. In vitro experiments confirmed that MT upregulated the expression of SIRT1/Nrf2/TGF-ß/BMPs while inhibiting the NF-κB pathway and matrix degradation-related components. The introduction of the SIRT1 inhibitor Selisistat (EX527) reversed the effects of MT. Together, these findings suggest that MT has the potential to ameliorate inflammation, inhibit the release of matrix-degrading enzymes, and improve the cartilage condition. This study provides a new theoretical basis for understanding the role of MT in decelerating cartilage degradation and promoting chondrocyte repair in in vivo and in vitro cultured chondrocytes.

Unraveling the role of sulfiredoxin-1 in early-onset preeclampsia: A key player in trophoblast ferroptosis.

Preeclampsia (PE) significantly contributes to obstetric complications and maternal mortality, yet its pathogenesis and mechanisms are not well understood. Sulfiredoxin-1 (SRXN1) is known for its antioxidant activity and its role in defending against oxidative stress; it is also linked to various cancers. However, the role of SRXN1 in PE remains unclear. Our study found a significant decrease in SRXN1 levels in the serum and placental tissues of patients with early-onset preeclampsia (EOPE). Similarly, a PE-like mouse model showed reduced SRXN1 expression. Our in vitro experiments showed that reducing SRXN1 impaired trophoblast viability, decreased invasion and migration, and led to cell death, primarily through ferroptosis. These results are consistent with analyses of placental tissues from EOPE patients. In summary, lower SRXN1 levels during pregnancy contribute to trophoblast ferroptosis, potentially affecting the development and progression of EOPE.

Efficacy and safety of esketamine for perioperative depression in patients undergoing elective surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a prevalent mood disorder during the perioperative period, with both preoperative concurrent depression and new-onset postoperative depression impacting postoperative recovery. Recent studies have indicated that the dissociative anesthetic esketamine may alleviate perioperative depressive symptoms. OBJECTIVE: This meta-analysis aimed to assess the efficacy and safety of esketamine in treating perioperative depression. METHODS: We selected randomized controlled trials comparing esketamine to placebo in terms of postoperative depressive symptoms. The primary outcome was postoperative depression scores, with secondary outcomes including the prevalence of postoperative depression, pain scores using the Visual Analogue Scale or Numeric Rating Scale, and incidences of adverse reactions such as nausea/vomiting, dizziness, dreams/nightmares, hallucinations. RESULTS: We enrolled a total of 17 studies involving 2462 patients. The esketamine group demonstrated a significant reduction in postoperative depression scores within one week after surgery (SMD -0.47, 95% CI (-0.66, -0.27), P < 0.001) and over the long term (SMD -0.44, 95% CI (-0.79, -0.09), P = 0.01). Furthermore, esketamine significantly decreased the prevalence of postoperative depression both within one week (RR 0.46, 95% CI (0.33, 0.63), P < 0.001) and over the long term (RR 0.50, 95% CI (0.36, 0.70), P < 0.001). Additionally, esketamine effectively relieved pain on the first postoperative day compared to control. However, it also increased the risks of dizziness and hallucinations for a short time. CONCLUSION: This meta-analysis suggests that the intraoperative or postoperative application of esketamine could be a potentially effective treatment for perioperative depression, although the increased risk of adverse reactions should be considered.

Experimental study of energy­absorbing and support characteristics of glass microsphere-filled steel tube columns under uniaxial compression.

An innovative energy-absorbing and bearing structure was proposed, which incorporated the coupling of glass microspheres with a metal tube. Glass microsphere-filled steel tube (GMFST) column, consisting of external steel tube and inner glass microspheres, was expected to give full play to the energy-absorbing and load-bearing capacities of the particle while restricting particle flow from collapsing, thereby enhancing the overall structural strength. Four groups of steel tubes and the GMFST specimens were designed and subjected to axial compression tests at four different loading rates to investigate the performance of the structure. These tests aimed to analyze the deformation mode, mechanical response, and energy absorption capacity of the GMFST columns under quasi-static to low-speed compression conditions. The results indicated that the deformation process and failure mode of GMFST columns were similar to those of hollow steel tubes, albeit with a different post-buckling mode. Filling the steel tubes with glass microspheres reduced the load fluctuation range, moderated load-displacement curves, and exhibited a strain rate strengthening effect. The GMFST columns demonstrated superior energy absorption capacity, with significant increases in crush force efficiency, the averaged crush force, and the total absorbed energy, particularly in terms of subsequent support capacity. The load-increasing reinforcement properties enabled GMFST columns to overcome the limitations associated with the unstable post-buckling path of energy­absorbing damping structure, exhibiting outstanding load-bearing performance and stability in the later stages. The results provided valuable guidelines for designing and engineering high-performance GMFST columns, serving as a new type of energy-absorbing and supporting structure.

Association between serum uric acid/high-density lipoprotein cholesterol ratio and hypertension among reproductive-aged women.

BACKGROUND: Uric acid/high-density lipoprotein cholesterol ratio (UHR) is a novel index of inflammation and metabolism that has been investigated in various diseases. However, association between UHR and hypertension among reproductive-aged women is unclear. METHODS: In this cross-sectional study, we investigated the association between serum UHR and hypertension among 5485 women aged 20-44 years based on the National Health and Nutrition Examination Survey (NHANES) database using various methods, including univariate and multivariate logistic regression analysis, stratified analysis, and spline regression. P < 0.05 was considered statistically significant. RESULTS: There was significant difference in UHR between the women with and without hypertension (P < 0.001). After adjusting for several covariates, UHR was positively correlated with hypertension (OR > 1, P < 0.001). In the subgroup analysis, the positive correlations still remained between UHR and hypertension in women with various age and those with BMI ≥ 30 kg/m2 (P < 0.05) excepted for adjusting for all covariates. We further found an inflection point of the threshold effect for UHR, and the prevalence of hypertension showed different increased trends below and above the threshold. CONCLUSION: This study indicated a positive association between serum UHR and hypertension among reproductive-aged women, indicating that UHR is a potential clinical marker of hypertension in women.

The role of the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve in chronic inflammatory pain and comorbid spatial working memory impairment in complete Freund's adjuvant mice.

Chronic inflammatory pain (CIP) is a common public medical problem, often accompanied by memory impairment. However, the mechanisms underlying CIP and comorbid memory impairment remain elusive. This study aimed to examine the role of the gut-microbiota-brain axis in CIP and comorbid memory impairment in mice treated with complete Freund's adjuvant (CFA). 16S rRNA analysis showed the altered diversity of gut microbiota from day 1 to day 14 after CFA injection. Interestingly, fecal microbiota transplantation (FMT) from healthy naive mice ameliorated comorbidities, such as mechanical allodynia, thermal hyperalgesia, spatial working memory impairment, neuroinflammation, and abnormal composition of gut microbiota in the CFA mice. Additionally, subdiaphragmatic vagotomy (SDV) blocked the onset of these comorbidities. Interestingly, the relative abundance of the bacterial genus or species was also correlated with these comorbidities after FMT or SDV. Therefore, our results suggest that the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve is crucial for the development of CIP and comorbid spatial working memory impairment in CFA mice.

High glucose inhibits neural differentiation by excessive autophagy via peroxisome proliferator-activated receptor gamma.

The high prevalence of prediabetes and diabetes globally has led to the widespread occurrence of severe complications, such as diabetic neuropathy, which is a result of chronic hyperglycemia. Studies have demonstrated that maternal diabetes can lead to neural tube defects by suppressing neurogenesis during neuroepithelium development. While aberrant autophagy has been associated with abnormal neuronal differentiation, the mechanism by which high glucose suppresses neural differentiation in stem cells remains unclear. Therefore, we developed a neuronal cell differentiation model of retinoic acid induced P19 cells to investigate the impact of high glucose on neuronal differentiation in vitro. Our findings indicate that high glucose (HG) hinders neuronal differentiation and triggers excessive. Furthermore, HG treatment significantly reduces the expression of markers for neurons (Tuj1) and glia (GFAP), while enhancing autophagic activity mediated by peroxisome proliferator-activated receptor gamma (PPARγ). By manipulating PPARγ activity through pharmacological approaches and genetically knocking it down using shRNA, we discovered that altering PPARγ activity affects the differentiation of neural stem cells exposed to HG. Our study reveals that PPARγ acts as a downstream mediator in high glucose-suppressed neural stem cell differentiation and that refining autophagic activity via PPARγ at an appropriate level could improve neuronal differentiation efficiency. Our data provide novel insights and potential therapeutic targets for the clinical management of gestational diabetes mellitus.

Risk of esketamine anesthesia on the emergence delirium in preschool children after minor surgery: a prospective observational clinical study.

Emergence delirium (ED) is a common mental complication during recovery from anesthesia. However, studies on the effects of esketamine, an intravenous anesthetic for pediatrics, on ED are still lacking. This study aimed to investigate the effects of a single-dose of esketamine during anesthesia induction on ED after minor surgery in preschool children. A total of 230 children (aged 2-7 years) completed the study. The exposed group (0.46 mg kg-1: average dose of esketamine) was associated with an increased incidence of ED and a higher maximum Pediatric Anesthesia Emergence Delirium score than the non-exposed group. The length of post-anesthesia care unit stay was longer in the exposed group than the non-exposed group. In contrast, extubation time, face, legs, activity, cry, and consolability (FLACC) scores, and the proportions of rescue analgesics were comparable between the two groups. Furthermore, five factors, including preoperative anxiety scores, sevoflurane and propofol compared with sevoflurane alone for anesthesia maintenance, dezocine for postoperative analgesia, FLACC scores, and esketamine exposure, were associated with ED. In conclusion, a near-anesthetic single-dose of esketamine for anesthesia induction may increase the incidence of ED in preschool children after minor surgery. The use of esketamine in preschool children for minor surgery should be noticed during clinical practice.

Direct Stannylation and Silylation of Arylmethanols by Palladium Catalysis.

A direct transformation of non-preactivated benzyl alcohols to benzyl stannanes and benzyl silanes was realized through Pd-catalyzed C(sp3)-O activation process. By using versatile tin and silicon sources, these reactions exhibit a broad substrate scope and a high efficiency under mild conditions, affording functionalized benzyl and allylic stannanes and benzylsilanes with high yields. The successful implementation of gram-scale stannylation/silylation as well as the one-pot Stille coupling reaction demonstrates the potential application of this method in organic synthesis. Both experimental and theoretical investigations reveal the mechanistic details of this reaction.

A Critical Review of Machine Learning Techniques on Thermoelectric Materials.

Thermoelectric (TE) materials can directly convert heat to electricity and vice versa and have broad application potential for solid-state power generation and refrigeration. Over the past few decades, efforts have been made to develop new TE materials with high performance. However, traditional experiments and simulations are expensive and time-consuming, limiting the development of new materials. Machine learning (ML) has been increasingly applied to study TE materials in recent years. This paper reviews the recent progress in ML-based TE material research. The application of ML in predicting and optimizing the properties of TE materials, including electrical and thermal transport properties and optimization of functional materials with targeted TE properties, is reviewed. Finally, future research directions are discussed.

Effect of Remimazolam on Postoperative Delirium in Older Adult Patients Undergoing Orthopedic Surgery: A Prospective Randomized Controlled Clinical Trial.

Background: Postoperative delirium is common in older adult patients and associated with a poor prognosis. The use of benzodiazepine was identified as an independent risk factor for delirium, but there is no randomized controlled trial regarding the relationship between remimazolam, a new ultra-short acting benzodiazepine, and postoperative delirium. We designed a randomized controlled trial to evaluate if remimazolam increases the incidence of postoperative delirium compared with propofol in older adult patients undergoing orthopedic surgery with general anesthesia. Patients and Methods: We enrolled 320 patients aged more than 60 with American Society of Anesthesiologists physical status I-III who underwent orthopedic surgery. Patients were randomized to two groups to receive intraoperative remimazolam or propofol, respectively. Our primary outcome was the incidence of delirium within 3 days after surgery. Secondary outcome was emergence quality including the incidence of emergence agitation, extubation time, and length of post-anesthesia care unit (PACU) stay. Adverse events were also recorded. Results: The incidence of postoperative delirium was 15.6% in the remimazolam group and 12.4% in the propofol group (Risk ratio, 1.26; 95% CI, 0.72 to 2.21; Risk difference, 3.2%; 95% CI, -4.7% to 11.2%; P = 0.42). No significant differences were observed for time of delirium onset, duration of delirium, and delirium subtype between the two groups. Patients in remimazolam group had a lower incidence of hypotension after induction and consumed less vasoactive drugs intraoperatively, but had a longer postoperative extubation time and PACU stay. Conclusion: General anesthesia with remimazolam was not associated with an increased incidence of postoperative delirium compared with propofol in older adult patients undergoing orthopedic surgery.

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies.

Ketamine, a commonly used general anesthetic, can produce rapid and sustained antidepressant effect. However, the efficacy and safety of the perioperative application of ketamine on postoperative depression remains uncertain. We performed a meta-analysis to determine the effect of perioperative intravenous administration of ketamine on postoperative depression. Randomized controlled trials comparing ketamine with placebo in patients were included. Primary outcome was postoperative depression scores. Secondary outcomes included postoperative visual analog scale (VAS) scores for pain and adverse effects associated with ketamine. Fifteen studies with 1697 patients receiving ketamine and 1462 controls were enrolled. Compared with the controls, the ketamine group showed a reduction in postoperative depression scores, by a standardized mean difference (SMD) of -0.97, 95% confidence interval [CI, -1.27, -0.66], P < 0.001, I2 = 72% on postoperative day (POD) 1; SMD-0.65, 95% CI [-1.12, -0.17], P < 0.001, I2 = 94% on POD 3; SMD-0.30, 95% CI [-0.45, -0.14], P < 0.001, I2 = 0% on POD 7; and SMD-0.25, 95% CI [-0.38, -0.11], P < 0.001, I2 = 59% over the long term. Ketamine reduced VAS pain scores on POD 1 (SMD-0.93, 95% CI [-1.58, -0.29], P = 0.005, I2 = 97%), but no significant difference was found between the two groups on PODs 3 and 7 or over the long term. However, ketamine administration distinctly increased the risk of adverse effects, including nausea and vomiting (risk ratio [RR] 1.40, 95% CI [1.12, 1.75], P = 0.003, I2 = 30%), headache (RR 2.47, 95% CI [1.41, 4.32], P = 0.002, I2 = 19%), hallucination (RR 15.35, 95% CI [6.24, 37.34], P < 0.001, I2 = 89%), and dizziness (RR 3.48, 95% CI [2.68, 4.50], P < 0.001, I2 = 89%) compared with the controls. In conclusion, perioperative application of ketamine reduces postoperative depression and pain scores with increased risk of adverse effects.

Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy: A Randomized Clinical Trial.

Importance: Postoperative sleep disturbance (PSD) is common in patients after surgery. Objective: To examine the effect of intraoperative esketamine infusion on the incidence of PSD in patients who underwent gynecological laparoscopic surgery. Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted from August 2021 to April 2022 in the First Affiliated Hospital of Zhengzhou University in China. Participants included patients aged 18 to 65 years with an American Society of Anesthesiologist Physical Status classification of I to III (with I indicating a healthy patient, II a patient with mild systemic disease, and III a patient with severe systemic disease) who underwent gynecological laparoscopic surgery. Patients were randomly assigned to either the esketamine group or control group. Data were analyzed using the per protocol principle. Interventions: Patients in the esketamine group received a continuous infusion of esketamine, 0.3 mg/kg/h, intraoperatively. Patients in the control group received an equivalent volume of saline. Main Outcomes and Measures: The primary outcome was the incidence of PSD on postoperative days (PODs) 1 and 3. Postoperative sleep disturbance was defined as a numeric rating scale score of 6 or higher or an Athens Insomnia Scale score of 6 points or higher. The secondary outcomes included postoperative anxiety and depression scores using the Hospital Anxiety and Depression Scale, postoperative pain using the visual analog scale, postoperative hydromorphone consumption, and risk factors associated with PSD. Results: A total of 183 female patients were randomized to the control group (n = 91; median [IQR] age, 45 [35-49] years) and the esketamine group (n = 92; median [IQR] age, 43 [32-49] years). The incidence of PSD in the esketamine group was significantly lower than in the control group on POD 1 (22.8% vs 44.0%; odds ratio [OR], 0.38 [95% CI, 0.20-0.72]; P = .002) and POD 3 (7.6% vs 19.8%; OR, 0.33 [95% CI, 0.13-0.84]; P = .02). There were no differences in postoperative depression and anxiety scores between the 2 groups. Postoperative hydromorphone consumption in the first 24 hours (3.0 [range, 2.8-3.3] mg vs 3.2 [range, 2.9-3.4] mg; P = .04) and pain scores on movement (3 [3-4] vs 4 [3-5] points; P < .001) were significantly lower in the esketamine group than in the control group. On multivariable logistic regression, preoperative depression (OR, 1.31; 95% CI, 1.01-1.70) and anxiety (OR, 1.67; 95% CI, 1.04-1.80) scores, duration of anesthesia (OR, 1.04; 95% CI, 1.00-1.08), and postoperative pain score (OR, 1.92; 95% CI, 1.24-2.96) were identified as risk factors associated with PSD. Conclusions and Relevance: Results of this trial showed the prophylactic effect of intraoperative esketamine infusion on the incidence of PSD in patients who underwent gynecological laparoscopic surgery. Further studies are needed to confirm these results. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100048587.

A Library of Rare Earth Oxide Ultrathin Nanowires with Polymer-Like Behaviors.

Ultrathin nanowires (NWs) have always attracted the attention of researchers due to their unique properties, but their facile synthesis is still a great challenge. Herein we developed a general method for the synthesis of rare earth (RE) oxide ultrathin NWs at atmospheric pressure and low temperature (50 °C). The formation mechanism of ultrathin NWs lies in two aspects: thermodynamic advantage of one dimensional (1D) growth at low temperature, and supplement of effective monomers. As an extension, fifteen kinds of RE oxide ultrathin NWs were synthesized through this strategy, and they all exhibited polymer-like behaviors. Meanwhile, the high viscosity, organic gel, wet- and electro-spinning of Ce-Mo-O NWs were studied in detail, demonstrating the similarity of ultrathin inorganic NWs to polymers. In addition, the Ce-Mo-O ultrathin NWs were used as photocatalysts for toluene oxidation and showed excellent performance with toluene conversion ratio of 83.8 %, suggesting their potential application in organic photocatalysis.

Inhibition of the NLRP3/caspase-1 signaling cascades ameliorates ketamine-induced renal injury and pyroptosis in neonatal rats.

Ketamine is a widely-used anesthetic in the field of pediatrics and obstetrics. Multiple studies have revealed that ketamine causes neurotoxicity in developing animals. However, further studies are needed to determine whether clinical doses of ketamine (20 mg/kg) are able to cause kidney damage in developing animals. Herein, we investigated the effects of continuous ketamine exposure on kidney injury and pyroptosis in seven-day-old rats. Serum renal function indicators, renal histopathological analysis, pyroptosis, as well as oxidative stress indicators, were tested. Additionally, the NLRP3 inhibitor MCC950 and the Caspase-1 inhibitor VX765 were used to evaluate the role of the NLRP3/Caspase-1 axis in ketamine-induced kidney injury among developing rats. Our findings indicate that ketamine exposure causes renal histopathological injury, increased the levels of blood urea nitrogen (BUN) and creatinine (Cre), and led to upregulation in the levels of pyroptosis. Furthermore, we found that ketamine induced an increase in levels of reactive oxygen species (ROS) and malonaldehyde (MDA), as well as a decrease in the content of glutathione (GSH) and catalase (CAT) in the kidneys of neonatal rats. Moreover, targeting NLRP3 and caspase-1 with MCC950 or VX765 improved pyroptosis and reduced renal damage after continuous ketamine exposure. In conclusion, this study suggested that continued exposure to ketamine caused kidney damage among neonatal rats and that the NLRP3/Caspase-1 axis-related pyroptosis may be involved in this process.

Associations Between Adult Triceps Skinfold Thickness and All-Cause, Cardiovascular and Cerebrovascular Mortality in NHANES 1999-2010: A Retrospective National Study.

Background: The association between triceps skinfold (TSF) thickness and mortality in previous studies was controversial. This study aimed to explore how TSF thickness affects all-cause, cardiovascular, and cerebrovascular mortality among the United States (U.S.) general population. Methods: Our research included 25,954 adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Participants were categorized by the baseline TSF quartiles [quartile 1 (Q1): < 11.8, (Q2): 11.8-17.4, (Q3): 17.4-25, and (Q4): ≥25; unit: millimeter (mm)]. Cox regression models were used to assess the association of TSF with all-cause, cardiovascular, and cerebrovascular mortality. The association between mid-arm muscle circumference (MAMC) and mortality was also explored. Subgroup analyses were conducted to assess heterogeneity in different subgroups. Results: The highest TSF group (Q4) had the lowest risk to experience all-cause (HR, 0.46; 95% CI, 0.38-0.59; P < 0.001) and cardiovascular mortality (HR, 0.35; 95% CI, 0.23-0.54; P < 0.001) than the lowest TSF group (Q1) after multivariate adjustment. However, there was no relationship between TSF quartiles and cerebrovascular mortality (HR, 0.98; 95%CI, 0.42-2.30; P = 0.97). The protective effects of TSF thickness on mortality still existed after adjusting for BMI and MAMC. For every 1 mm increase in TSF thickness, the risk of all-cause and cardiovascular death decreased by 4% (HR, 0.96; 95% CI, 0.95-0.97; P < 0.001) and 6% (HR, 0.94; 95% CI, 0.93-0.96; P < 0.001), respectively. In the stratified analysis, the relationships between TSF and mortality risk were generally similar across all subgroups. Conclusions: Higher TSF thickness was associated with lower all-cause and cardiovascular mortality, independent of BMI and MAMC. Our study revealed that the TSF thickness may be a convenient and credible indicator to predict mortality, especially in those with severe cardiovascular diseases.

Analysis of DWI in the classification of glioma pathology and its therapeutic application in clinical surgery: a case-control study.

Background: Glioma is a common primary craniocerebral malignant tumor, due to the lack of specificity of imaging examination and clinical manifestations, its diagnostic accuracy is relatively low, which may result in misdiagnosis and missed diagnosis. The apparent diffusion coefficient (ADC) in magnetic resonance diffusion weighted imaging (DWI) can reflect the histological characteristics of gliomas, which can be widely applied to classify gliomas and evaluate the extent of metastasis of glioma. The present study aimed to assess the clinical value of magnetic resonance DWI in the pathological grading of glioma and its therapeutic application in clinical surgery. Methods: This article retrospectively analyzed the clinical data of 41 patients with glioma confirmed by surgical pathology results from January 1, 2019 to March 31, 2020 in the People's Hospital of Gaozhou. Among them, 16 patients had low-grade gliomas [World Health Organization (WHO) grade I-II] and 25 patients had high-grade gliomas (WHO grade III-IV). They were subjected to conventional T1WI and T2WI plain scans, along with DWI and enhanced scans before surgery. The ADC values of the glioma parenchyma, the peritumoral edema area, the surrounding white matter, and the contralateral normal white matter were measured. We selected some tumor tissues for pathological analysis as well, and conducted pathological grading according to WHO grading standards. Results: We compared and evaluated the ADC values of the observed areas for low-grade gliomas and high-grade gliomas. The ADC values of low-grade gliomas in the tumor parenchyma, peritumoral edema, and white matter around the edema area were significantly lower than those of high-grade gliomas, and the differences were statistically significant (P<0.05). The difference in ADC values of normal white matter between the two groups of patients was not statistically significant (P=0.125). Conclusions: DWI has prognostic predictive value in the preoperative differential diagnosis and pathological classification of gliomas. This advanced technology can verify the extent of glioma infiltration in the surrounding brain tissue. It can help clinicians formulate a safer and more effective therapeutic strategy by providing accurate information on prognostic evaluation before the successful surgical intervention of gliomas.

Downregulation of the NLRP3/Caspse-1 Pathway Ameliorates Ketamine-Induced Liver Injury and Inflammation in Developing Rats.

Ketamine is an anesthetic drug that is widely used in human and veterinary medicine. In the developmental stage, long-term exposure to ketamine may cause serious side effects. MCC950 and VX765 play protective roles in many disease models by regulating the NLRP3/Caspase-1 pathway. This study aims to explore the potential protective effect of MCC950 and VX765 on ketamine-induced liver injury in neonatal rats and clarify its underlying mechanism. After administration of MCC950 and VX765 in a ketamine-induced liver injury rat model, liver function and inflammatory factors were determined, and immunohistochemistry and western blotting were performed. We found that ketamine caused liver injury in 7-day-old SD rats, decreased liver function indexes, and increased inflammation. MCC950 and VX765 effectively alleviated liver damage and inflammation, and downregulated the expression of proteins such as NLRP3, Caspase-1, and GSDMD-N. In summary, these results indicated that MCC950 and VX765 could have potential protective effects on ketamine-induced liver injury through inhibiting the NLRP3/Caspase-1 pathway.

Liraglutide Is Protective against Brain Injury in Mice with Febrile Seizures by Inhibiting Inflammatory Factors.

The febrile seizure (FS) is a common disease in emergency pediatrics, and about 30% of patients are children aged between 6 months and 5 years. Therefore, we aim to observe the protective impact of liraglutide (LIR) on brain injury in mice with FS and to explore its relevant mechanisms. Male SD mice were selected, and the FS model was established by heat bath method. The behavioral score was performed on mice with Racine grading, and nerve cells in apoptosis in the hippocampus were determined by TUNEL. The content of glutamate was determined by ELISA. mRNA levels and protein expression of GLP-1, GLP-1R, IL-1ß, IL-6, TNF-α, and cleaved-caspase 3 were examined in mice by q-PCR and WB. Protein expression of γ-aminobutyric acid was influenced by WB as well. LIR prolonged the seizure latency and seizure duration in mice with FS. The GLP-1 and GLP-1R in the mouse hippocampus with FS expressed highly and also inhibited the number of nerve cells in apoptosis, decreased glutamate content, and increased γ-aminobutyric acid expression in the mouse hippocampus with FS. In addition, The IL-1ß, IL-6, and TNF-α, in the mouse hippocampus with FS expressed to reduce with LIR. LIR is protective against brain injury in mice with FS and protects brain injury by inhibiting inflammatory factors in mice with FS. Our finding provides a reference for mitigating and delaying the development of FS as well as the prevention and treatment of brain injury caused by FS.