Mendelian randomization analysis reveals causal association of anthropometric measures on sepsis risk and mortality.

The objective of this study was to explore the potential causalities of fat mass, nonfat mass and height (henceforth, 'anthropometric measures') with sepsis risk and mortality. We conducted the Mendelian randomization (MR) investigation using genome-wide association study (GWAS) summary statistics of anthropometric measures, sepsis, and sepsis mortality. The GWAS summary data from the UK Biobank was used. Firstly, MR analysis was performed to estimate the causal effect of anthropometric measures on the risk of sepsis. The inverse-variance weighted (IVW) method was utilized as the primary analytical approach, together with weighted median-based method. Cochrane's Q test and MR-Egger intercept test were performed to assess heterogeneity and pleiotropy, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. The IVW method showed that genetically predicted weight-related measures were suggestively linked to an increased risk of sepsis. However, height displayed no causal association with sepsis risk and mortality. Furthermore, weight-related measures also displayed significant MR association with the sepsis mortality, except body nonfat mass and right leg nonfat mass. However, MVMR analysis indicated the observed effects for weight-related measures in the univariable MR analyses are more likely a bias caused by the interrelationship between anthropometric measures. According to the MR-Egger intercept assessment, our MR examination was not influenced by horizontal pleiotropy (all p>0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. In conclusion, these findings provided vital new knowledge on the role of anthropometric-related measures in the sepsis etiology.

Pharmacotherapy guideline concordance for major depressive disorder and its link to functioning via symptom change.

Introduction: Alleviation of symptom severity for major depressive disorder (MDD) is known to be associated with a lagged improvement of functioning. Pharmacotherapy guidelines support algorithms for MDD treatment. However, it is currently unclear whether concordance with guidelines influences functional recovery. A guideline concordance algorithm (GCA-8) was used to measure this pathway in a naturalistic clinical setting. Methods: Data from 1403 adults (67% female, 84% non-Hispanic/Latino White, mean age of 43 years) with nonpsychotic MDD from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System registry (visits from 02/01/2015 to 04/13/2021) were evaluated. Multivariable linear regression measured associations between GCA-8 and World Health Organization Disability Assessment Schedule 2.0 (WHODAS) scores. Mediation by MDD symptom severity using the Patient Health Questionnaire depression module (PHQ-9) was also evaluated. Results: This study found a statistically significant improvement in WHODAS scores (functioning) between baseline and final measures (-2 points, P < .001) within one year. A one standard deviation increase in the GCA-8 score was associated with a 0.48-point reduction in mean disability score (total effect; P = .02) with significant mediation by the change in MDD symptom severity (coefficient = -0.51, P < .001) and a nonsignificant natural direct effect of the GCA-8 independent of PHQ-9 change (coefficient = -0.02, P = .92). Conclusions: Higher pharmacotherapy guideline concordance is associated with better functioning for MDD patients; this association likely occurs through improvement in MDD symptom severity rather than directly.

Magnetic Exchange Mechanism and Quantized Anomalous Hall Effect in Bi2Se3 Film with a CrWI6 Monolayer.

Magnetizing the surface states of topological insulators without damaging their topological features is a crucial step for realizing the quantum anomalous Hall (QAH) effect and remains a challenging task. The TI-ferromagnetic material interface system was constructed and studied by the density functional theory (DFT). A two-dimensional magnetic semiconductor CrWI6 has been proven to effectively magnetize topological surface states (TSSs) via the magnetic proximity effect. The non-trivial phase was identified in the Bi2Se3 (BS) films with six quantum layers (QL) within the CrWI6/BS/CrWI6 heterostructure. BS thin films exhibit the generation of spin splitting near the TSSs, and a band gap of approximately 2.9 meV is observed at the Γ in the Brillouin zone; by adjusting the interface distance of the heterostructure, we increased the non-trivial band gap to 7.9 meV, indicating that applying external pressure is conducive to realizing the QAH effect. Furthermore, the topological non-triviality of CrWI6/6QL-BS/CrWI6 is confirmed by the nonzero Chern number. This study furnishes a valuable guideline for the implementation of the QAH effect at elevated temperatures within heterostructures comprising two-dimensional (2D) magnetic monolayers (MLs) and topological insulators.

Lymph node dissection does not affect the survival of patients with tumor node metastasis stages I and II colorectal cancer.

BACKGROUND: The effect of the number of lymph node dissections (LNDs) during radical resection for colorectal cancer (CRC) on overall survival (OS) remains controversial. AIM: To investigate the association between the number of LNDs and OS in patients with tumor node metastasis (TNM) stage I-II CRC undergoing radical resection. METHODS: Patients who underwent radical resection for CRC at a single-center hospital between January 2011 and December 2021 were retrospectively analyzed. Cox regression analyses were performed to identify the independent predictors of OS at different T stages. RESULTS: A total of 2850 patients who underwent laparoscopic radical resection for CRC were enrolled. At stage T1, age [P < 0.01, hazard ratio (HR) = 1.075, 95% confidence interval (CI): 1.019-1.134] and tumour size (P = 0.021, HR = 3.635, 95%CI: 1.210-10.917) were independent risk factors for OS. At stage T2, age (P < 0.01, HR = 1.064, 95%CI: 1.032-1.098) and overall complications (P = 0.012, HR = 2.297, 95%CI: 1.200-4.397) were independent risk factors for OS. At stage T3, only age (P < 0.01, HR = 1.047, 95%CI: 1.027-1.066) was an independent risk factor for OS. At stage T4, age (P < 0.01, HR = 1.057, 95%CI: 1.039-1.075) and body mass index (P = 0. 034, HR = 0.941, 95%CI: 0.890-0.995) were independent risk factors for OS. However, there was no association between LNDs and OS in stages I and II. CONCLUSION: The number of LDNs did not affect the survival of patients with TNM stages I and II CRC. Therefore, insufficient LNDs should not be a cause for alarm during the surgery.

The Incorporation of Chitosan in the Antibacterial Capability and Biocompatibility of a Protein-Repellent Orthodontic Cement.

BACKGROUND: This study aimed to develop an orthodontic cement containing chitosan and 2-methacryloyloxyethyl phosphorylcholine (MPC) and to investigate its antibacterial properties and biocompatibility. METHODS:  Chitosan and MPC were incorporated into commercial cement. The enamel bonding strength and biocompatibility of the new cement were evaluated. The antibacterial properties were assessed by examining biofilm metabolic activity and colony-forming units (CFU). An evaluation of the protein repellency of the cement was also conducted. RESULTS:  The new cement containing chitosan and MPC had clinically acceptable bonding strength. In comparison to the control, the novel cement demonstrated enhanced protein-repellent properties (p < 0.05), inhibited biofilm metabolic activity (p < 0.05), and reduced CFU counts (p < 0.05) without diminishing cell viability in response to cement extracts (p > 0.05). CONCLUSIONS:  The synergistic application of chitosan and MPC endows the cement with potent antibacterial abilities, protein repellency, and favorable biocompatibility.

Association between sleep traits and risk of colorectal cancer: a bidirectional Mendelian randomization study.

Background: Sleep traits have been linked to diseases; particularly, their impact on cancer has received increasing attention. This study aimed to investigate whether sleep traits have a causal relationship with colorectal cancer (CRC) using two-sample Mendelian randomization (TSMR). Methods: Genetic instrumental variables (IVs) for seven sleep traits (sleep duration, ease of getting up in the morning, morning chronotype, daytime napping, insomnia symptoms, snoring, and daytime dozing) were selected from pooled data from published genome-wide association studies (GSWSs). Two-sample multivariate Mendelian randomization (MR) analyses were conducted to assess the causal association between sleep traits and CRC. Reverse MR analyses were performed to determine the causal relationship between CRC and sleep traits. Inverse variance weighted (IVW), MR-Egger, and weighted medians were calculated for all MR analyses. Results: The multivariable MR (MVMR) analysis found that appropriate sleep duration [odds ratio (OR) =0.989; 95% confidence interval (CI): 0.980, 0.999; P=0.04] and ease of getting up in the morning (OR =0.990; 95% CI: 0.980, 1.000; P=0.04) were protective factors for CRC. Snoring (OR =1.021; 95% CI: 1.002, 1.041; P=0.03) was associated with the risk of CRC. Ease of getting up in the morning (OR =0.990; 95% CI: 0.983, 0.997; P=0.003) was associated with reduced risk of colon cancer. Morning chronotype (OR =1.004; 95% CI: 1.000, 1.007; P=0.04) was associated with the risk of colon cancer. Insomnia symptoms (OR =0.995; 95% CI: 0.990, 0.999; P=0.03) were a protective factor for rectal cancer. There was no evidence found for a causal association between other sleep traits and CRC, colon, or rectal cancer. Conclusions: Proper sleep duration and ease of getting up in the morning may be protective factors against CRC, and snoring may increase the risk of CRC.

Gender differences in behavioral and emotional problems among school children and adolescents in China: National survey findings from a comparative network perspective.

BACKGROUND: Behavioral and emotional problems are common and often co-occur during childhood and adolescence. The aim of this study was to assess gender differences in the network structures of behavioral and emotional problems of children and adolescents in China based on a national survey. METHODS: The Parent version of Achenbach's Child Behavior Checklist (CBCL) was used to assess behavioral and emotional problems. To account for potential confounding factors between boys and girls, propensity score matching was utilized. Network model differences were assessed with a Network Comparison Test (NCT). RESULTS: Data from 60,715 children and adolescents were included for analyses. Boys exhibited more severe total behavioral and emotional problems compared to girls. While several edges showed significant differences between boys and girls, the strongest association was consistently found between "Attention problems" (CBCL6) and "Aggressive behavior"(CBCL8) in both boys and girls, regardless of age. Network centrality was higher among adolescents compared to children. The most central problems commonly found across different genders and age groups were "Aggressive behavior" (CBCL8) (centrality values were 1.142 for boys aged 6-11 years, 1.051 for boys aged 12-16 years, 1.148 for girls aged 6-11 years, and 1.028 for girls aged 12-16 years), "Anxious/depressed" (CBCL1) (centrality values of 0.892 for boys aged between 6 and 11 years, 1.031 for boys aged 12-16 years, 0.951 for girls aged 6-11 years, and 1.099 for girls aged 12-16 years) and "Social problems" (CBCL4) (centrality values of 1.080 for boys aged 6-11 years, 0.978 for boys aged 12-16 years, 1.086 for girls aged between 6 and 11 years, and 0.929 for girls aged 12-16 years). CONCLUSION: Development of interventions that address aggressive behavior, anxiety/depression, and social problems may be beneficial for reducing risk of psychopathology among children and adolescents.

Sodium aescinate alleviates neuropathic pain through suppressing OGT-mediated O-GlcNAc modification of TLR3 to inactivate MAPK signaling pathway.

Neuropathic pain results from damage to nerves or the brain, and is characterized by symptoms such as allodynia, spontaneous pain, and hyperalgesia. The causes of this type of pain are intricate, which can make it difficult to treat. Sodium aescinate (SA), a natural extract from horse chestnut tree seeds, has been shown to act as a neuroprotector by inhibiting microglia activation. This study aims to explore the therapeutic potential of SA for neuropathic pain and the molecular mechanisms regulated by SA treatment. Through in vivo animal models and experiments, we found that SA treatment significantly reduced mechanical allodynia and heat hyperalgesia in neuropathic pain models. Additionally, SA inhibited O-GlcNAc-transferase (OGT)-induced O-GlcNAcylation (O-GlcNAc) modification in neuropathic pain mice. OGT overexpression could impede the therapeutic effects of SA on neuropathic pain. Further investigation revealed that Toll-like receptor 3 (TLR3), stabilized by OGT-induced O-GlcNAc modification, could activate the Mitogen activated protein kinase (MAPK) signaling pathway. Further in vivo experiments demonstrated that TLR3-mediated p38 mitogen-activated protein kinase (p38MAPK) activation is involved in SA-mediated relief of neuropathic pain. In conclusion, this study uncovers a novel molecular pathway deactivated by SA treatment in neuropathic pain.

An efficient electrode for reversible oxygen reduction/evolution and ethylene electro-production on protonic ceramic electrochemical cells.

Protonic ceramic electrochemical cells (PCECs) have demonstrated great promise for applications in the generation of electricity, and the synthesis of chemicals (for example, ethylene). However, enhancing the electrochemical reactions kinetics and stability of PCECs electrodes is one grand challenge. Here, we present a novel electrode material via a co-doping of cesium (Cs) and niobium (Nb) on PrBaCo2O6-δ with the composition of PrBa0.9Cs0.1Co1.9Nb0.1O6-δ (PBCCN), which naturally decomposes into dual phases of a double-perovskite PBCCN (DP-PBCCN, ∼92.3 wt%) and a single-perovskite Ba0.9Cs0.1Co0.95Nb0.05O3-δ (SP-BCCN, ∼7.7 wt%) under typical powder processing conditions. PBCCN exhibits a low area-specific resistance (ASR) value of 0.107 Ω cm2, an outstanding performance of 2.04 W cm-2 in fuel cell (FC) mode, a current density of -2.84 A cm-2 at 1.3 V in electrolysis cell (EC) mode, and promising reversible operational durability of 53 cycles in ∼212 h at +/- 0.5 A cm-2 and 650 °C. Cs doping generates more oxygen vacancies and accelerates the oxygen exchange kinetics, while Nb doping effectively enhances the stability, as illustrated by the analyses of X-ray photoelectron spectroscopy, and electrical conductivity relaxations. When applied as the positrode for electrochemical non-oxidative dehydrogenation of ethane (C2H6) to ethylene (C2H4) on PCECs, it displays an encouraging C2H6 conversion of 12.75% and a C2H4 selectivity of 98.4% at 1.2 V.

Reconstruction of a robust bacterial replication module.

Chromosomal DNA replication is a fundamental process of life, involving the assembly of complex machinery and dynamic regulation. In this study, we reconstructed a bacterial replication module (pRC) by artificially clustering 23 genes involved in DNA replication and sequentially deleting these genes from their naturally scattered loci on the chromosome of Escherichia coli. The integration of pRC into the chromosome, moving from positions farther away to close to the replication origin, leads to an enhanced efficiency in DNA synthesis, varying from lower to higher. Strains containing replication modules exhibited increased DNA replication by accelerating the replication fork movement and initiating chromosomal replication earlier in the replication cycle. The minimized module pRC16, containing only replisome and elongation encoding genes, exhibited chromosomal DNA replication efficiency comparable to that of pRC. The replication module demonstrated robust and rapid DNA replication, regardless of growth conditions. Moreover, the replication module is plug-and-play, and integrating it into Mb-sized extrachromosomal plasmids improves their genetic stability. Our findings indicate that DNA replication, being a fundamental life process, can be artificially reconstructed into replication functional modules. This suggests potential applications in DNA replication and the construction of synthetic modular genomes.

Recombinant humanized type III collagen inhibits ovarian cancer and induces protective anti-tumor immunity by regulating autophagy through GSTP1.

Ovarian cancer (OC) is one of the leading causes of death from malignancy in women and lacks safe and efficient treatment. The novel biomaterial, recombinant humanized collagen type III (rhCOLIII), has been reported to have various biological functions, but its role in OC is unclear. This study aimed to reveal the function and mechanism of action of rhCOLIII in OC. We developed an injectable recombinant human collagen (rhCOL)-derived material with a molecular weight of 45 kDa, with a stable triple helix structure, high biocompatibility, water solubility and biosafety. The anti-tumor activity of rhCOLIII was comprehensively evaluated through in vitro and in vivo experiments. In vitro, our results showed that rhCOLIII inhibited the proliferation, migration, and invasion of ovarian cancer cells (OCCs), and induced apoptosis. In addition, rhCOLIII not only inhibited autophagy of OCCs but also increased the expression of MHC-1 molecule within OCCs. To further elucidate the mechanism of rhCOLIII in OC, we conducted joint analysis of RNA-Seq and proteomics, and found that rhCOLIII exerted anti-tumor function and autophagy inhibition by downregulating Glutathione S-transferase P1 (GSTP1). Furthermore, various rescue experiments were designed to demonstrate that rhCOLIII suppressed autophagy and proliferation of OCCs by mediating GSTP1. In vivo, we found that rhCOLIII could inhibit tumor growth and promote CD8+ T cell infiltration. Our results indicate that rhCOLIII has great anti-tumor potential activity in OC, and induces protective anti-tumor immunity by regulating autophagy through GSTP1. These findings illustrate the potential therapeutic prospects of rhCOLIII for OC treatment.

Effect of prehabilitation exercises on postoperative frailty in patients undergoing laparoscopic colorectal cancer surgery.

Background: To improve perioperative frailty status in patients undergoing laparoscopic colorectal cancer surgery (LCCS), we explored a new intensive prehabilitation program that combines prehabilitation exercises with standard enhanced recovery after surgery (ERAS) and explored its impact. Methods: We conducted a prospective randomized controlled trial. Between April 2021 to August 2021, patients undergoing elective LCCS were randomized into the standardized ERAS (S-ERAS) group or ERAS based on prehabilitation (group PR-ERAS). Patients in the PR-ERAS group undergoing prehabilitation exercises in the perioperative period in addition to standard enhanced recovery after surgery. We explored the effects of this prehabilitation protocol on frailty, short-term quality of recovery (QoR), psychological status, postoperative functional capacity, postoperative outcomes, and pain. Results: In total, 125 patients were evaluated, and 95 eligible patients were enrolled and randomly allocated to the S-ERAS (n = 45) and PR-ERAS (n = 50) groups. The Fried score was higher in the PR-ERAS group on postoperative day (7 (2(2,3) vs. 3(2,4), P = 0.012). The QoR-9 was higher in the PR-ERAS group than in the S-ERAS group on the 1st, 2nd, 3rd, and 7th postoperative days. The PR-ERAS group had an earlier time to first ambulation (P < 0.050) and time to first flatus (P < 0.050). Conclusion: Prehabilitation exercises can improve postoperative frailty and accelerate recovery in patients undergoing LCCS but may not improve surgical safety. Therefore, better and more targeted prehabilitation recovery protocols should be explored. Clinical trial registration: www.clinicaltrials.org , identifier NCT04964856.

Particulate matter 2.5 accelerates aging: Exploring cellular senescence and age-related diseases.

Exposure to Particulate matter 2.5 (PM2.5) accelerates aging, causing declines in tissue and organ function, and leading to diseases such as cardiovascular, neurodegenerative, and musculoskeletal disorders. PM2.5 is a major environmental pollutant and an exogenous pathogen in air pollution that is now recognized as an accelerator of human aging and a predisposing factor for several age-related diseases. In this paper, we seek to elucidate the mechanisms by which PM2.5 induces cellular senescence, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, and mitochondrial dysfunction, and age-related diseases. Our goal is to increase awareness among researchers within the field of the toxicity of environmental pollutants and to advocate for personal and public health initiatives to curb their production and enhance population protection. Through these endeavors, we aim to promote longevity and health in older adults.

An Efficient Trifunctional Spinel-Based Electrode for Oxygen Reduction/Evolution Reactions and Nonoxidative Ethane Dehydrogenation on Protonic Ceramic Electrochemical Cells.

Protonic ceramic electrochemical cells (PCECs) have received considerable attention as they can directly generate electricity and/or produce chemicals. Development of the electrodes with the trifunctionalities of oxygen reduction/evolution and nonoxidative ethane dehydrogenation is yet challenging. Here these findings are reported in the design of trifunctional electrodes for PCECs with a detailed composition of Mn0.9Cs0.1Co2O4-δ (MCCO) and Co3O4 (CO) (MCCO-CO, 8:2 mass ratio). At 600 °C, the MCCO-CO electrode exhibits a low area-specific resistance of 0.382 Ω cm2 and reasonable stability for ≈105 h with no obvious degradation. The single cell with the MCCO-CO electrode shows an encouraging peak power density of 1.73 W cm-2 in the fuel cell (FC) mode and a current density of -3.93 A cm-2 at 1.3 V in the electrolysis cell (EC) mode at 700 °C. Moreover, the MCCO-CO cell displays promising operational stability in FC mode (223 h), EC mode (209 h), and reversible cycling stability (52 cycles, 208 h) at 650 °C. The MCCO-CO single cell shows an encouraging ethane conversion to ethylene (with a conversion of 40.3% and selectivity of 94%) and excellent H2 production rates of 4.65 mL min-1 cm-2 at 1.5 V and 700 °C, respectively, with reasonable Faradaic efficiencies.

Self-Powered FTO/CdSe/Bi2Se3 Photodetector with Bipolar Photoresponse Characteristics.

Self-powered photodetectors with bipolar photoresponse characteristics are expected to play a critical role in the field of secure optical communication, artificial neuromorphic systems, and intelligent color sensors. In this work, asymmetric heterojunction devices exhibiting wavelength-dependent bipolar photoresponse with a structure of Glass/FTO/CdSe/Bi2Se3/Au were fabricated. Under a short wavelength light irradiation, the top CdSe absorber generates a high carrier concentration; the excited carriers are quickly separated by the built-in electric field induced by the FTO/CdSe diode, resulting in a negative photocurrent. For light with wavelengths beyond the CdSe absorption edge, it is absorbed by the bottom Bi2Se3 absorber, and a positive photocurrent can be observed. Therefore, based on the bandgap difference between the top CdSe absorber and the bottom Bi2Se3 absorber, combined with the photogenerated carriers separated by asymmetric back-to-back diode, a wavelength-dependent bipolar response is realized. In this work, by employing this structure, the responsivities of -33.3 and 0.3 mA/W were achieved under the illumination of 405 and 830 nm, respectively. This work provides important indications in the preparation and performance optimization for wavelength-dependent bipolar photodetectors.

Sandwich Layer-Modified Ω-Shaped Fiber-Optic LSPR Enables the Development of an Aptasensor for a Cytosensing-Photothermal Therapy Circuit.

The metastasis of cancer cells is a principal cause of morbidity and mortality in cancer. The combination of a cytosensor and photothermal therapy (PTT) cannot completely eliminate cancer cells at one time. Hence, this study aimed to design a localized surface plasmonic resonance (LSPR)-based aptasensor for a circuit of cytosensing-PTT (COCP). This was achieved by coating a novel sandwich layer of polydopamine/gold nanoparticles/polydopamine (PDA/AuNPs/PDA) around the Ω-shaped fiber-optic (Ω-FO). The short-wavelength peak of the sandwich layer with strong resonance exhibited a high refractive index sensitivity (RIS). The modification with the T-shaped aptamer endowed FO-LSPR with unique characteristics of time-dependent sensitivity enhancement behavior for a sensitive cytosensor with the lowest limit of detection (LOD) of 13 cells/mL. The long-wavelength resonance peak in the sandwich layer appears in the near-infrared region. Hence, the rate of increased localized temperature of FO-LSPR was 160 and 30-fold higher than that of the bare and PDA-coated FO, indicating strong photothermal conversion efficiency. After considering the localized temperature distribution around the FO under the flow environment, the FO-LSPR-enabled aptasensor killed 77.6% of cancer cells in simulated blood circulation after five cycles of COCP. The FO-LSPR-enabled aptasensor improved the efficiency of the cytosensor and PTT to effectively kill cancer cells, showing significant potential for application in inhibiting cancer metastasis.

Quercetin protects against sepsis-associated encephalopathy by inhibiting microglia-neuron crosstalk via the CXCL2/CXCR2 signaling pathway.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a common brain lesion associated with severe sepsis, for which ferroptosis is a key driving factor. Thus, suppressing ferroptosis may be an effective strategy for treating SAE. Quercetin (QUE) is a natural flavonoid with antioxidant and anti-inflammatory properties. However, its role on ferroptosis in SAE remains unclear. PURPOSE: This study aimed to investigate the mechanism underlying the therapeutic effect of QUE on cecal ligation perforation (CLP)-induced SAE. METHODS: In vivo and in vitro SAE models were established using CLP and lipopolysaccharide (LPS), respectively. Both models underwent pre-treatment with QUE. RESULTS: QUE attenuated CLP-induced symptoms, including temperature changes, neurological severity scores, learning and memory dysfunction, inflammatory cytokine release, and microglia activation in SAE mice, and inhibited LPS-induced microglia recruitment and chemotaxis. Bioinformatics analysis revealed that the C-X-C motif chemokine ligand 2 (CXCL2)/C-X-C motif chemokine receptor 2 (CXCR2) axis may play a key role in QUE-mediated protection against SAE. Moreover, QUE significantly inhibited LPS-induced CXCL2 up-regulation and protein secretion from microglia. Recombinant mouse-derived CXCL2 (rmCXCL2) promoted inflammatory cytokine secretion, NF-κB/NLRP3 signaling activation, and microglia recruitment and chemotaxis. Furthermore, rmCXCL2 induced ferroptosis in mouse hippocampal neurons, as evidenced by elevated malondialdehyde levels, decreased glutathione levels, excessive iron uptake, and altered ferroptosis-related protein expression. The CXCR2 antagonist SB225002 effectively reversed the effects of rmCXCL2. Importantly, in vivo experiments further demonstrated that the therapeutic effect of QUE on SAE was inhibited by rmCXCL2. CONCLUSION: This study demonstrates that CXCL2 secreted by activated microglia mediates microglia self-activation and induces hippocampal neuronal ferroptosis via CXCR2 and that QUE exerts neuroprotective effects on SAE by blocking interactions between microglia and neurons via CXCL2/CXCR2 pathway inhibition.

Decentralized Kernel Ridge Regression Based on Data-Dependent Random Feature.

Random feature (RF) has been widely used for node consistency in decentralized kernel ridge regression (KRR). Currently, the consistency is guaranteed by imposing constraints on coefficients of features, necessitating that the RFs on different nodes are identical. However, in many applications, data on different nodes vary significantly on the number or distribution, which calls for adaptive and data-dependent methods that generate different RFs. To tackle the essential difficulty, we propose a new decentralized KRR algorithm that pursues consensus on decision functions, which allows great flexibility and well adapts data on nodes. The convergence is rigorously given, and the effectiveness is numerically verified: by capturing the characteristics of the data on each node, while maintaining the same communication costs as other methods, we achieved an average regression accuracy improvement of 25.5% across six real-world datasets.

Two novel carbon skeleton compounds from Portulaca oleracea L. and their effects on nitric oxide.

Two new carbon skeleton compounds, identified as 2-(1-(3-hydroxy-2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran-3-yl)-2-methylpropoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol named Olerapyran A (1), and (E)-3-(6-acetyl-2-methyl-5-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)cyclooctylidene)butan-2-one named Oleraoctyl (2), were first isolated from Portulaca oleracea L., then their structures were determined using spectroscopic methods, including UHPLC-ESI-QTOF/MS, 1D and 2D NMR. In addition, the activities of Olerapyran A and Oleraoctyl inhibiting nitric oxide (NO) were studied.

Randomized, double-blind, placebo-controlled trial of aripiprazole oral solution in children and adolescents with Tourette's disorder.

BACKGROUND: Aripiprazole is the most frequently recommended antipsychotic for the treatment of tics in children and adolescents with Tourette's disorder (TD). However, to date, a randomized controlled trial for aripiprazole oral solution has not been conducted despite being widely preferred by children. Therefore, we examined whether aripiprazole oral solution is effective for treating tics. METHODS: All patients received a flexible dose of aripiprazole oral solution (1 mg/mL, range: 2-20 mg) with a starting dose of 2 mg. The target dose for patients weighing < 50 kg was 2, 5, and 10 mg/day, and that for patients weighing ≥ 50 kg was 5, 10, 15, and 20 mg/day. The primary efficacy endpoint was the mean change in the Yale Global Tic Severity Scale-total tic score (YGTSS-TTS) from baseline to week 8. RESULTS: Of the 121 patients enrolled, 59 patients (96.7%) in the aripiprazole group and 53 patients (88.3%) in the placebo group completed the study. The aripiprazole group showed significantly greater improvement in the YGTSS-TTS from baseline to week 8 than the placebo group (least squares mean difference [95% confidence interval (CI)] -5.5 [95% CI - 8.4 to - 2.6]). At week 8, the response rate (i.e., percentage of patients with a Tourette's Syndrome Clinical Global Impression-Improvement score of 1 or 2) of the aripiprazole group (86.4%) was significantly higher than that of the placebo group (56.6%; odds ratio: 3.6, p < 0.001). The incidence of treatment-emergent adverse events (TEAEs) reported in at least one patient was 86.9% in the aripiprazole group and 65.5% in the placebo group. All TEAEs were mild or moderate in severity. No serious adverse events or deaths occurred during the study. CONCLUSIONS: Our findings suggest that aripiprazole oral solution is an effective, well-tolerated, and safe treatment for children and adolescents with TD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03487783. Registered 4 April 2018.