Effect of transcranial direct current stimulation with concurrent cognitive performance targeting posterior parietal cortex vs prefrontal cortex on working memory in schizophrenia: a randomized clinical trial.

Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.

The relationship between the systemic immune inflammation index and the nonalcoholic fatty liver disease in American adolescents.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known. METHODS: We collected data from the National Health and Nutrition Examination Survey 2017-2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD. RESULTS: A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092-11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases. CONCLUSION: There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD.

Population pharmacokinetics of olanzapine in pediatric patients with psychiatric disorders.

OBJECTIVE: To develop and validate a population pharmacokinetic (PPK) model of oral olanzapine in pediatric Chinese patients in order to individualize therapy in this population. METHODS: A total of 897 serum concentrations from 269 pediatric patients taking oral olanzapine (ages 8-17 years) were collected. Demographic parameters, biological characteristics and concomitant medications were investigated as covariates. The data were analyzed using a nonlinear mixed-effects modeling approach. Bootstrapping (1000 runs), normalized prediction distribution error (NPDE), and external validation of 62 patients were employed. Simulations were performed to explore the individualized dosing regimens in various situations. RESULTS: The one-compartment model with first-order absorption and elimination had an apparent clearance (CL/F) of 10.38 L/h, a distribution volume (V/F) of 9.41 L/kg and an absorption rate constant (Ka) fixed at 0.3 h-1. The equation was CL∕F (L∕h) = 10.38 × (body weight∕60)0.25 ×1.33 (if male) × 0.71 (if co-occurrence of infection) × 0.51 (if co-therapy with fluvoxamine) × 1.27 (if co-therapy with sertraline) × 1.43 (if co-therapy with valproate). The final model had satisfactory stability, robustness, and predictive ability. The results from a simulation suggested the oral olanzapine doses required for male and female pediatric patients weighing between 40 and 60 kg without co-medication were 10-15 mg/day and 7.5-10 mg/day, respectively, and dosage adjustments should be based on sex and body weight; and co-administrated with valproate, sertraline, or fluvoxamine. CONCLUSION: This model may help individualize optimum dosing of oral olanzapine for pediatric patients.

Clickable nanozyme enhances precise colonization of probiotics for ameliorating inflammatory bowel disease.

Convincing evidence suggests that aberrant gut microbiota changes play a critical role in the progression and pathogenesis of inflammatory bowel disease (IBD). Probiotic therapeutic interventions targeting the microbiota may provide alternative avenues to treat IBD, but currently available probiotics often suffer from low intestinal colonization and limited targeting capability. Here, we developed azido (N3)-modified Prussian blue nanozyme (PB@N3) spatio-temporal guidance enhances the targeted colonization of probiotics to alleviate intestinal inflammation. First, clickable PB@N3 targets intestinal inflammation, simultaneously, it scavenges reactive oxygen species (ROS). Subsequently, utilizing "click" chemistry to spatio-temporally guide targeted colonization of dibenzocyclooctyne (DBCO)-modified Lactobacillus reuteri DSM 17938 (LR@DBCO). The "click" reaction between PB@N3 and LR@DBCO has excellent specificity and efficacy both in vivo and in vitro. Despite the complex physiological environment of IBD, "click" reaction can prolong the retention time of probiotics in the intestine. Dextran sulfate sodium (DSS)-induced colitis mice model, demonstrates that the combination of PB@N3 and LR@DBCO effectively mitigates levels of ROS, enhances the colonization of probiotics, modulates intestinal flora composition and function, regulates immune profiles, restores intestinal barrier function, and alleviates intestinal inflammation. Hence, PB@N3 spatio-temporal guidance enhances targeted colonization of LR@DBCO provides a promising medical treatment strategy for IBD.

Longitudinal changes in cognitive function in early psychosis: a meta-analysis with the MATRICS consensus cognitive battery (MCCB).

INTRODUCTION: A previous meta-analysis indicated stable progress in cognitive functions in early psychosis, assessed through various tools. To avoid assessment-related heterogeneity, this study aims to examine the longitudinal cognitive function changes in early psychosis utilizing the MATRICS Consensus Cognitive Battery (MCCB). METHODS: Embase, PubMed, and Scopus were systematically searched from their inception to September 26th 2023. The inclusion criteria were longitudinal studies that presented follow-up MCCB data for individuals experiencing first-episode psychosis (FEP) and those with ultra-high risk for psychosis (UHR). RESULTS: Twelve studies with 791 participants (566 FEP patients and 225 healthy controls) were subjected to analysis. Suitable UHR studies were absent. Over time, both FEP patients and healthy controls showed significant improvements in MCCB total scores. Furthermore, FEP patients demonstrated improvements across all MCCB domains, while healthy controls only showed augmentations in specific domains such as speed of processing, attention, working memory, and reasoning and problem-solving. Visuospatial learning improvements were significantly greater in FEP patients compared to healthy controls. Subgroup analyses suggested that neither diagnostic type nor follow-up duration influenced the magnitude of cognitive improvement in FEP patients. CONCLUSION: The magnitude of cognitive improvement for MCCB domains was not significantly different between FEP and healthy controls other than visuospatial learning. This underscores visuospatial learning as a potentially sensitive cognitive marker for early pathologic state changes in psychotic disorders.

Study on Mechanical Properties of Nanopores in CoCrFeMnNi High-Entropy Alloy Used as Drug-Eluting Stent.

The CoCrFeMnNi high-entropy alloy is commonly used for vascular stents due to its excellent mechanical support and ductility. However, as high-entropy alloy stents can cause inflammation in the blood vessels, leading to their re-narrowing, drug-eluting stents have been developed. These stents have nanopores on their surfaces that can carry drug particles to inhibit inflammation and effectively prevent re-narrowing of the blood vessels. To optimize the mechanical properties and drug-carrying capacity of high-entropy alloy stents, a high-entropy alloy system with different wide and deep square-shaped nanopore distributions is created using molecular dynamics. The mechanical characteristics and dislocation evolution mechanism of different nanopore high-entropy alloy systems under tensile stress were studied. The results showed that the CoCrFeMnNi high-entropy alloy with a rational nanopore distribution can effectively maintain the mechanical support required for a vascular stent. This research provides a new direction for the manufacturing process of nanopores on the surfaces of high-entropy alloy stents.

Vibration Analysis of Porous Cu-Si Microcantilever Beams in Fluids Based on Modified Couple Stress Theory.

The vibrations in functionally graded porous Cu-Si microcantilever beams are investigated based on physical neutral plane theory, modified coupled stress theory, and scale distribution theory (MCST&SDT). Porous microcantilever beams define four pore distributions. Considering the physical neutral plane theory, the material properties of the beams are computed through four different power-law distributions. The material properties of microcantilever beams are corrected by scale effects based on modified coupled stress theory. Considering the fluid driving force, the amplitude-frequency response spectra and resonant frequencies of the porous microcantilever beam in three different fluids are obtained based on the Euler-Bernoulli beam theory. The quality factors of porous microcantilever beams in three different fluids are derived by estimating the equation. The computational analysis shows that the presence of pores in microcantilever beams leads to a decrease in Young's modulus. Different pore distributions affect the material properties to different degrees. The gain effect of the scale effect is weakened, but the one-dimensional temperature field and amplitude-frequency response spectra show an increasing trend. The quality factor is decreased by porosity, and the degree of influence of porosity increases as the beam thickness increases. The gradient factor n has a greater effect on the resonant frequency. The effect of porosity on the resonant frequency is negatively correlated when the gradient factor is small (n<1) but positively correlated when the gradient factor is large (n>1).

Influence of reduced-port laparoscopic surgery on perioperative indicators, postoperative recovery, and serum inflammation in patients with colorectal carcinoma.

BACKGROUND: Conventional five-port laparoscopic surgery, the current standard treatment for colorectal carcinoma (CRC), has many disadvantages. AIM: To assess the influence of reduced-port laparoscopic surgery (RPLS) on perioperative indicators, postoperative recovery, and serum inflammation indexes in patients with CRC. METHODS: The study included 115 patients with CRC admitted between December 2019 and May 2023, 52 of whom underwent conventional five-port laparoscopic surgery (control group) and 63 of whom underwent RPLS (research group). Comparative analyses were performed on the following dimensions: Perioperative indicators [operation time (OT), incision length, intraoperative blood loss (IBL), and rate of conversion to laparotomy], postoperative recovery (first postoperative exhaust, bowel movement and oral food intake, and bowel sound recovery time), serum inflammation indexes [high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)], postoperative complications (anastomotic leakage, incisional infection, bleeding, ileus), and therapeutic efficacy. RESULTS: The two groups had comparable OTs and IBL volumes. However, the research group had a smaller incision length; lower rates of conversion to laparotomy and postoperative total complication; and shorter time of first postoperative exhaust, bowel movement, oral food intake, and bowel sound recovery; all of which were significant. Furthermore, hs-CRP, IL-6, and TNF-α levels in the research group were significantly lower than the baseline and those of the control group, and the total effective rate was higher. CONCLUSION: RPLS exhibited significant therapeutic efficacy in CRC, resulting in a shorter incision length and a lower conversion rate to laparotomy, while also promoting postoperative recovery, effectively inhibiting the inflammatory response, and reducing the risk of postoperative complications.

Magnetic compression anastomosis to restore biliary tract continuity after obstruction following major abdominal trauma: A case report.

BACKGROUND: The combination of magnetic compression anastomosis (MCA) and endoscopy has been used to treat biliary stricture after liver transplantation. However, its use for the treatment of complex biliary obstruction after major abdominal trauma has not been reported. This case report describes the successful use of MCA for the treatment of biliary obstruction resulting from major abdominal trauma. CASE SUMMARY: A 23-year-old man underwent major abdominal surgery (repair of liver rupture, right half colon resection, and ileostomy) following a car accident one year ago. The abdominal drainage tube, positioned at the Winslow foramen, was draining approximately 600-800 mL of bile per day. During the two endoscopic retrograde cholangiopancreatography procedures, the guide wire was unable to enter the common bile duct, which prevented placement of a biliary stent. MCA combined with endoscopy was used to successfully achieve magnetic anastomosis of the peritoneal sinus tract and duodenum, and then a choledochoduodenal stent was placed. Finally, the external biliary drainage tube was removed. The patient achieved internal biliary drainage leading to the removal of the external biliary drainage tube, which improved the quality of life. CONCLUSION: Magnetic compression technique can be used for the treatment of complex biliary obstruction with minimal operative trauma.

Novel magnetic compression technique for the treatment of postoperative anastomotic stenosis in rectal cancer: A case report.

BACKGROUND: The treatment of postoperative anastomotic stenosis after excision of rectal cancer is challenging. Endoscopic balloon dilation and radial incision are not effective in all patients. We present a new endoscopy-assisted magnetic compression technique (MCT) for the treatment of rectal anastomotic stenosis. We successfully applied this MCT to a patient who developed an anastomotic stricture after radical resection of rectal cancer. CASE SUMMARY: A 50-year-old man had undergone laparoscopic radical rectal cancer surgery at a local hospital 5 months ago. A colonoscopy performed 2 months ago indicated that the rectal anastomosis was narrow due to which ileostomy closure could not be performed. The patient came to the Magnetic Surgery Clinic of the First Affiliated Hospital of Xi'an Jiaotong University after learning that we had successfully treated patients with colorectal stenosis using MCT. We performed endoscopy-assisted magnetic compression surgery for rectal stenosis. The magnets were removed 16 d later. A follow-up colonoscopy performed after 4 months showed good anastomotic patency, following which, ileostomy closure surgery was performed. CONCLUSION: MCT is a simple, non-invasive technique for the treatment of anastomotic stricture after radical resection of rectal cancer. The technique can be widely used in clinical settings.

The Effectiveness of Auricular Acupressure on Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To assess the effectiveness of auricular acupressure (AA) in managing pain and disability in individuals with chronic musculoskeletal pain. Materials and Methods: A systematic search on six electronic databases was performed from their inception to May 7, 2023, to identified relevant randomized controlled trials (RCTs). Two independent reviewers screened the abstracts and full texts, extracted data, and assessed risk of bias using RoB 2. The primary outcomes were pain intensity and disability. The secondary outcomes were pain pressure thresholds, pain catastrophizing level, and fear avoidance beliefs. A random-effects model was used for meta-analyses. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. Sensitivity analyses were conducted after removing low-quality papers. Results: Of 633 identified records, six studies involving 496 participants were included. All included studies compared the effectiveness of AA with sham controls in treating various chronic musculoskeletal pain. Four meta-analyses were conducted to compare the effectiveness of AA with sham controls. Low-quality evidence supported that AA had a large effect size on postintervention subjective pain reduction (standardized mean difference [SMD] = -0.95; 95% confidence interval [CI]: -1.36 to -0.54; p = 0.00; I2 = 52.61%); moderate-quality evidence substantiated that AA had a large effect size on enhancing postintervention pressure pain threshold (SMD = -0.55; 95% CI: -0.88 to -0.23; p = 0.00; I2 = 0%). There was low-quality evidence that AA had a large effect on reducing postintervention disability (SMD = -0.68; 95% CI: -1.24 to -0.12; p = 0.02; I2 = 51.33%). Our sensitivity analysis reaffirmed the same conclusion regarding pain reduction immediately after the intervention. Fourteen participants reported minimal adverse events, including soreness, tenderness, irritation, and redness, which disappeared within 1-7 days. Discussion: Our systematic review revealed that AA significantly improved pain, pressure pain thresholds, and disability in individuals with various chronic musculoskeletal pain conditions immediately post-treatment compared with sham treatment. Given the paucity of studies and inconsistent protocols, future RCTs are warranted to evaluate the effectiveness of AA in people with chronic musculoskeletal pain at a longer follow-up with detailed protocols, which allows researchers and clinicians to optimize AA intervention. Conclusion: AA has immediate post-treatment benefits for chronic musculoskeletal pain, whereas its effects at the 1- or 6-month follow-up remain uncertain.

Development of crosslinked gelatin films through Maillard reaction and reinforced with poly(vinyl alcohol) for active food packaging.

In order to improve the functionality of natural gelatin films for active food packaging applications, a combined strategy of crosslinking via Maillard reaction and blending enhancement incorporated with poly(vinyl alcohol) (PVA) was explored. In this study, when the mass ratio of gelatin to glucose was 10:1, Maillard reaction of crosslinked gelatin films was the highest, UV absorption and browning index reached the maximum. Infrared analysis showed that PVA could form strong interfacial interactions with gelatin matrix. The presence of PVA could significantly improve the toughness, water absorption, transparency, and oxygen barrier properties of crosslinked gelatin films. When the amount of PVA reached 5 %, elongation at break and oxygen barrier properties of crosslinked gelatin films were improved by 76.7 % and 47.9 % compared with pure crosslinked gelatin film. Even when the amount of PVA reached 10 %, UV absorption (at 315 nm) of crosslinked gelatin films still exceeded 98.7 %. The addition of PVA could accelerate the dissolution and swelling of crosslinked gelatin films, promoting the migration and release of active substances (Maillard reaction products (MRPs)). The two antioxidant activities tests (DPPH and ABTS method) achieved the highest radical scavenging rates of 71.6 % and 91.2 %, respectively, with corresponding PVA addition of 5 % and 7.5 %. After continuing to add PVA, antioxidant activities began to significantly decrease, which was directly related to the decrease in the generation of MRPs. Therefore, crosslinked gelatin films reinforced with appropriate amount of PVA can be considerable potential as active films for renewable food packaging applications.

Insight into Interfacial Heat Transfer of ß-Ga2O3/Diamond Heterostructures via the Machine Learning Potential.

ß-Ga2O3 is an ultrawide-band gap semiconductor with excellent potential for high-power and ultraviolet optoelectronic device applications. Low thermal conductivity is one of the major obstacles to enable the full performance of ß-Ga2O3-based devices. A promising solution for this problem is to integrate ß-Ga2O3 with a diamond heat sink. However, the thermal properties of the ß-Ga2O3/diamond heterostructures after the interfacial bonding have not been studied extensively, which are influenced by the crystal orientations and interfacial atoms for the ß-Ga2O3 and diamond interfaces. In this work, molecular dynamics simulations based on machine learning potential have been adopted to investigate the crystal-orientation-dependent and interfacial-atom-dependent thermal boundary resistance (TBR) of the ß-Ga2O3/diamond heterostructure after interfacial bonding. The differences in TBR at different interfaces are explained in detail through the explorations of thermal conductivity value, thermal conductivity spectra, vibration density of states, and interfacial structures. Based on the above explorations, a further understanding of the influence of different crystal orientations and interfacial atoms on the ß-Ga2O3/diamond heterostructure was achieved. Finally, insightful optimization strategies have been proposed in the study, which could pave the way for better thermal design and management of ß-Ga2O3/diamond heterostructures according to guidance in the selection of the crystal orientations and interfacial atoms of the ß-Ga2O3 and diamond interfaces.

Association between obstructive sleep apnea severity and depression risk: a systematic review and dose-response meta-analysis.

Obstructive sleep apnea (OSA) has received considerable attention as a potential risk factor for depressive symptoms. The systematic review was conducted to confirm the dose‒response connection between OSA severity and depression risk. A systematic literature search of English and Chinese articles published in PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and SinoMed databases from their inception to 28 August 2023 was conducted. An evaluation using the Newcastle‒Ottawa Scale was performed. A meta-analysis was used to evaluate the impact of OSA severity. A random-effects dose‒response model was conducted to evaluate the linear and nonlinear dose‒response connections. We evaluated publication bias by funnel plots, and symmetry by Egger's test. We identified 18 cross-sectional researches. 3143 participants which were involved in the dose‒response meta-analysis. Contrasted with mild OSA, individuals with severe OSA had a higher adjusted risk of depression (rate ratio: 1.34, 95% confidence interval = 1.05-1.70), with substantial heterogeneity (I2 = 70.9%, Pheterogeneity<0.001). There is a significant linear connection between OSA severity and depression risk. The depression risk increased by 0.4% for every 1 event per hour increase in the apnea-hypopnea index (AHI). The protocol for this unfunded research was drafted and registered at PROSPERO (ID CRD42023474097).

Transporter function characterization via continuous-exchange cell-free synthesis and solid supported membrane-based electrophysiology.

Functional characterization of transporters is impeded by the high cost and technical challenges of current transporter assays. Thus, in this work, we developed a new characterization workflow that combines cell-free protein synthesis (CFPS) and solid supported membrane-based electrophysiology (SSME). For this, membrane protein synthesis was accomplished in a continuous exchange cell-free system (CECF) in the presence of nanodiscs. The resulting transporters expressed in nanodiscs were incorporated into proteoliposomes and assayed in the presence of different substrates using the surface electrogenic event reader. As a proof of concept, we validated this workflow to express and characterize five diverse transporters: the drug/H+-coupled antiporters EmrE and SugE, the lactose permease LacY, the Na+/H+ antiporter NhaA from Escherichia coli, and the mitochondrial carrier AAC2 from Saccharomyces cerevisiae. For all transporters kinetic parameters, such as KM, IMAX, and pH dependency, were evaluated. This robust and expedite workflow (e.g., can be executed within only five workdays) offers a convenient direct functional assessment of transporter protein activity and has the ability to facilitate applications of transporters in medical and biotechnological research.

p21/Zbtb18 repress the expression of cKit to regulate the self-renewal of hematopoietic stem cells.

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.

N-3 PUFA supplementation alleviates anxiety symptoms by manipulating erythrocyte fatty acid levels in depression.

PURPOSE: Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels. METHODS: A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression. RESULTS: Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ2 = 96.36, p = 0.000). The n-3 index (χ2 = 10.59, p = 0.001), EPA (χ2 = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ2 = 10.71, p = 0.001) were increased, while C22:4n6 (χ2 = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05). CONCLUSION: These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.

Engineering Co3O4@3DOM LaCoO3 multistage-pore nanoreactor with superior SO2 resistance for toluene catalytic combustion.

Sulfur dioxide poisoning is a significant factor in catalyst deactivation during the catalytic combustion of volatile organic compounds. In this study, we prepared the LaCoO3 and Co3O4 composite catalysts using both the Ship-in-Bottle and Building-Bottle-Around-Ship approaches. Three-dimensionally ordered macropores (3DOM LaCoO3) were utilized as nanoreactors to protect the active sites during the catalytic combustion of toluene, preventing SO2 poisoning. Additionally, we grew ZIF-67 confined in the nanoreactor to create a multistage-pore structure. The Co3O4@3DOM LaCoO3 catalysts exhibited excellent activity in the complete catalytic oxidation of toluene. Various characterization studies confirmed the presence of a significant number of Co3+ species and an abundance of surface weak acid sites in the Co3O4@3DOM LaCoO3 catalysts, which synergistically enhanced the conversion of VOCs at low temperatures. Notably, the multistage pore structure provided a favorable reaction environment, accelerating the adsorption and diffusion of toluene and intermediates, resulting in excellent sulfur resistance of the catalysts. Moreover, XPS analysis confirmed a strong interaction between Co3O4 and LaCoO3, promoting rapid electron transfer and increasing the activation of O2-. In situ DRIFTS experiments verified that toluene mainly follows the MvK mechanism over Co3O4@3DOM LaCoO3 catalysts, indicating the following reaction pathway: toluene adsorption → benzyl alcohol → benzaldehyde → benzoate → anhydride → CO2 and H2O.

Two-Phase Electrosynthesis of Dihydroxycoumestans: Discovery of a New Scaffold for Topoisomerase I Poison.

Coumestan represents a biologically relevant structural motif distributed in a number of natural products, and the rapid construction of related derivatives as well as the characterization of targets would accelerate lead compound discovery in medicinal chemistry. In this work, a general and scalable approach to 8,9-dihydroxycoumestans via two-electrode constant current electrolysis was developed. The application of a two-phase (aqueous/organic) system plays a crucial role for success, protecting the sensitive o-benzoquinone intermediates from over-oxidation. Based on the structurally diverse products, a primary SAR study on coumestan scaffold was completed, and compound 3 r exhibited potent antiproliferative activities and a robust topoisomerase I (Top1) inhibitory activity. Further mechanism studies demonstrates that compound 3 r was a novel Top1 poison, which might open an avenue for the development of Top1-targeted antitumor agent.

Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.