The dorsal raphe-to-ventral hippocampal projection modulates reactive aggression through 5HT1B receptors.

Maladaptive impulsive aggression is a core symptom of neuropsychiatric disorders such as schizophrenia. While uncontrolled impulsive aggression dampens societal safety, there is a limited understanding of the neural regulation involved in impulsive aggression and its treatment. High levels of impulsivity and aggression have been linked to low serotonin (5-HT) levels. Additionally, post-weaning socially isolated (SI) mice exhibit outbursts of aggression following encountering acute stress, and hyperactivated ventral hippocampus (vHip) involves this stress-provoked escalated aggression. Here, we investigated the potential role of the raphe nucleus projecting to the vHip in modulating aggressive behavior. Chemogenetically activating the dorsal raphe nucleus (DRN) soma projecting the vHip or DRN nerve terminals in the vHip reduced impulsive aggression. The reduction of attack behavior was abolished by the pretreatment of 5HT1BR antagonist SB-224289. However, activating the median raphe nucleus (MRN)-to-vHip pathway ameliorated depression-like behavior but did not affect impulsive aggression. DRN→vHip activation suppressed the vHip downstream area, the ventromedial hypothalamus (VMH), which is a core aggression area. Intra-vHip infusion of 5HT1BR agonists (anpirtoline, CP-93129) suppressed impulsive aggression and decreased c-Fos levels in the vHip neurons projecting to the VMH, suggesting an inhibition mechanism. Our findings indicate that activating the DRN projecting to the vHip is sufficient to inhibit impulsive aggression in a 5HT1BR-dependent manner. Thus, targeting 5HT1BR could serve as a promising therapeutic approach to ameliorate symptoms of impulsive aggression.

Structural insights into the Caprin-2 HR1 domain in canonical Wnt signaling.

The canonical Wnt signaling pathway plays crucial roles in cell fate decisions as well as in pathogenesis of various diseases. Previously, we reported Caprin-2 as a new regulator of canonical Wnt signaling through a mechanism of facilitating LRP5/6 phosphorylation. Here, we resolved the crystal structure of the N-terminal homologous region 1 (HR1) domain of human Caprin-2 (hCap2_HR1). HR1 domain is so far only observed in Caprin-2 and its homologous protein Caprin-1, and the function of this domain remains largely mysterious. Here, the structure showed that hCap2_HR1 forms a homo-dimer and exhibits an overall structure roughly resembling the appearance of a pair of scissors. Moreover, we found that residues R200 and R201, which located at a basic cluster within the N-terminal "blades" region, are critical for Caprin-2's localization to the plasma membrane. In line with this, mutations targeting these two residues decrease Caprin-2's activity in the canonical Wnt signaling. Overall, we characterized a previously unknown "scissors"-like structure of the full-length HR1 domain, and revealed its function in mediating Caprin-2's localization to the plasma membrane.

Free Latissimus dorsi Flaps in Head and Neck Reconstruction at a Modern High Volume Microsurgery Center.

BACKGROUND: Over the past two decades, with the introduction of the perforator flap concept and advances in flap dissections, lower extremities have emerged as the preferred soft tissue flap donor sites. As a modern and high-volume microsurgical center, and the senior author being one of the pioneers and advocates for the use of lower extremity flap donor sites, we aim to investigate the role of latissimus dorsi free flap in head and neck reconstruction within our current practice. METHODS: All free latissimus dorsi flaps used for head and neck reconstruction performed by a single surgeon between January 2010 to June 2023 were reviewed for their indications, immediate and short-term outcomes. RESULTS: A total of 1,586 head and neck free flap reconstructions was performed, and 33 free latissimus dorsi flaps were identified. The patients' median age was 53 (IQR 48.5-63.5) years. Twenty-nine (87.9%) flaps were used to reconstruct oro-maxillo-facial and four (12.1%) flaps were used to reconstruct scalp defects. Most patients had prior radiation (n=28, 84.8%), neck dissection (n=24, 72.7%), and multiple previous head and neck flap reconstructions with a median of 3.0 (IQR 3.0-3.5) previous flaps. Six (18.2%) latissimus dorsi flaps were used to replace failed flaps from other donor sites. No major complications such as total flap failure or take-backs, and no need for vein grafts, but three (9.1%) had flap marginal necrosis. Other complications included flap one flap dehiscence (3.0%), one orocutaneous fistula (3.0%), two wound infections (6.1%), three plate exposures (9.1%), and 3 patients developed local recurrence (9.1%). The median patient follow-up time was 16 (IQR 5-27) months. CONCLUSION: This retrospective study demonstrates the role of latissimus dorsi free flap in head and neck reconstruction as a reliable and versatile backup soft tissue flap when workhorse flaps from lower extremity donor sites are either unavailable or unsuitable.

Tailored Physical Activity Interventions for Long COVID: Current Approaches and Benefits-A Narrative Review.

This narrative review explores the essential role of physical activity in managing long COVID, which is characterized by persistent symptoms such as fatigue, breathlessness, and cognitive impairments following SARS-CoV-2 infection. In this context, "physical activity" includes various exercises, such as aerobic and resistance training, as well as flexibility and balance exercises, thereby encompassing the subset known as "exercise". The methodology involved a comprehensive literature search across PubMed, EBSCO (EDS), and Google Scholar, selecting peer-reviewed articles from December 2019 to June 2024 focusing on long COVID physical activity interventions. The review highlights that tailored exercise programs, adjusted to individual health status and abilities, significantly alleviate symptoms and enhance psychological well-being. Key findings emphasize the importance of personalized exercise prescriptions due to the variability in patient responses and the need for a multidisciplinary approach in developing and monitoring interventions. Despite promising outcomes, the review identifies research gaps, including the need for long-term studies, randomized controlled trials, and deeper mechanistic insights. It suggests that standardized reporting, templates like the Consensus on Exercise Reporting Template (CERT), and integrating digital health tools are essential for optimizing interventions. Overall, the review advocates including personalized physical activity or exercise programs in standard care for long COVID to improve patient outcomes and quality of life.

Effect of different exit-site care dressings on preventing peritoneal dialysis related infection from nontropical area: a systematic review and network meta-analysis.

OBJECT: This study aims to conduct a systematic review and network meta-analysis to comprehensively evaluate the efficacy of various dressings in preventing exit-site infection (ESI) and peritonitis. METHODS: We searched PubMed, Embase, Web of Science, CINAHL Plus with Full Text (EBSCO), Sino Med, Wan Fang Data, China National Knowledge Infrastructure (CNKI) from 1 January 1999 to 10 July 2023. The language restrictions were Chinese and English. Randomized controlled trials, non-randomized controlled trials, and self-controlled trials were included in this study. We used ROB 2 tool to evaluate the quality of the included literature. Two authors independently extracted the data according to the Cochrane Handbook. A Frequentist network meta-analysis was performed using Stata17.0 according to PRISAMA with a random effects model. RESULTS: From 2092 potentially eligible studies, thirteen studies were selected for analysis, including nine randomized controlled studies, three quasi-experimental studies and one self-controlled trial. A total of 1229 patients were included to compare five types of exit site care dressings, named disinfection dressings, antibacterial dressings, non-antibacterial occlusive dressings, sterile gauze, and no-particular dressings. The outcome of prevention ESI is antibacterial dressings (SUCRA = 97.6) >non-antibacterial occlusive dressings (SUCRA = 68.3) >disinfection dressings (SUCRA = 50.6) >no-particular dressings (SUCRA = 23.9) >sterile gauze (SUCRA = 9.5). The antibacterial dressings were more effective than sterile gauze (OR = 0.13, 95%CI 0.04∼0.44), and no-particular dressing (OR = 0.18, 95%CI 0.07∼0.50) in preventing ESI; the non-antibacterial occlusive dressings were effective than sterile gauze (OR:0.30, 95%CI 0.16∼0.57). There is no statistical significance between no-particular dressings and other types of dressings in preventing the mature ESI. There is no statistical significance in the effectiveness of five types of dressings in preventing peritonitis. CONCLUSIONS: The no-particular dressings maybe more cost-effective for preventing mature ESI. None of the dressings was more effective than another in preventing peritonitis. Then, none of the different types of dressing is strongly recommended for preventing ESI or peritonitis.RegistrationCRD42022366756.

School-Based Team Sports as Catalysts for Holistic Student Wellness: A Narrative Review.

The narrative review examines how school-based team sports catalyze holistic student wellness, leveraging their inherent nature and addressing barriers to inclusivity. Utilizing the holistic wellness framework-which encompasses physical, emotional, intellectual, social, spiritual, and occupational dimensions-the review evaluates the multifaceted effects of these sports on student well-being. Supported by wellness models like Dr. Bill Hettler's Six Dimensions of Wellness and various research studies, the framework highlights the interconnectedness of these areas in achieving overall well-being. School-based team sports promote discipline, teamwork, physical fitness, and social interaction while fostering skill development, ethical behavior, and emotional resilience. These elements, collectively, may support the holistic development of students, enhancing their overall health and success. The methodological approach of this review involves a synthesis of empirical research, systematic reviews, and meta-analyses from the past two decades (2004-2024), sourced from databases such as PubMed, EBSCO (EDS), and Google Scholar. Key findings include enhanced cardiovascular fitness, emotional resilience, cognitive performance, social skills, spiritual fulfillment, and career readiness awareness. The review highlights the necessity of integrating team sports into educational curricula to promote well-rounded student development and proposes strategies to overcome socioeconomic, cultural, and structural barriers to participation. Future research should focus on longitudinal studies to examine the long-term effects of team sports and explore the potential of digital technologies and artificial intelligence (AI) in enhancing these benefits.

Adaptive Neural Control for Hysteretic Nonlinear Systems With Hysteresis Neural Direct Inverse Compensator and Its Application.

Aiming at high precision control for a class of hysteretic nonlinear systems, a new hysteresis direct inverse compensator-based adaptive output feedback control scheme is designed in this article. First, a novel long short-term memory neural network (LSTMNN)-based hysteresis inverse compensator is established to compensate the asymmetric hysteresis nonlinearity, where the LSTMNN is used as the prediction mechanism for model operator weights, rather than the overall mapping of hysteresis input and output. Second, by designing the modified high-gain K -Filter states observer and the error transformed function, the unmeasurable states are estimated with arbitrarily small estimation error and the prespecified tracking performance is achieved. Lastly, the biconical dielectric elastomer actuator (DEA) motion platform is constructed. Then, the effectiveness of the proposed LSTMNN-based hysteresis inverse compensator and control scheme are verified on the experimental platform. The experimental results illustrate the effectiveness and advantages of proposed control scheme.

DC-free Method to Evaluate Nanoscale Equivalent Oxide Thickness: Dark-Mode Scanning Capacitance Microscopy.

This study developed a DC-free technique that used dark-mode scanning capacitance microscopy (DM-SCM) with a small-area contact electrode to evaluate and image equivalent oxide thicknesses (EOTs). In contrast to the conventional capacitance-voltage (C-V) method, which requires a large-area contact electrode and DC voltage sweeping to provide reliable C-V curves from which the EOT can be determined, the proposed method enabled the evaluation of the EOT to a few nanometers for thermal and high-k oxides. The signal intensity equation defining the voltage modulation efficiency in scanning capacitance microscopy (SCM) indicates that thermal oxide films on silicon can serve as calibration references for the establishment of a linear relationship between the SCM signal ratio and the EOT ratio; the EOT is then determined from this relationship. Experimental results for thermal oxide films demonstrated that the EOT obtained using the DM-SCM approach closely matched the value obtained using the typical C-V method for frequencies ranging from 90 kHz to 1 MHz. The percentage differences in EOT values between the C-V and SCM measurements were smaller than 0.5%. For high-k oxide films, DM-SCM with a DC-free operation may mitigate the effect of DC voltages on evaluations of EOTs. In addition, image operations were performed to obtain EOT images showing the EOT variation induced by DC-stress-induced charge trapping. Compared with the typical C-V method, the proposed DM-SCM approach not only provides a DC-free approach for EOT evaluation, but also offers a valuable opportunity to visualize the EOT distribution before and after the application of DC stress.

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).

Cumulative Dose Effects of H1 Antihistamine Use on the Risk of Dementia in Patients With Allergic Rhinitis.

BACKGROUND: H1 antihistamines (AHs), categorized as first-generation antihistamines (FGAs) or second-generation antihistamines (SGAs), possess anticholinergic properties linked to heightened dementia risk. OBJECTIVES: To explore dementia risk in patients with allergic rhinitis using AHs. METHODS: Taiwanese patients with new-onset allergic rhinitis (2011-2017) constituted the study population (677,971 with FGAs or SGAs, 36,081 without AHs). AH use was measured in cumulative defined daily dose (cDDD). Patients were grouped by cDDD (nonuser, <60 cDDD, 60-120 cDDD, and >120 cDDD). A Cox proportional hazard model assessed the AH-dementia association. Sensitivity analysis explored AH effects on dementia risk across subgroups and associations between specific AHs and dementia types. RESULTS: FGAs in patients with allergic rhinitis were associated with elevated dementia risk. At less than 60 cDDD, adjusted hazard ratio (aHR) was 1.13 (95% CI, 1.09-1.17); at 60 to 120 cDDD, aHR was 1.29 (95% CI, 1.21-1.38); and at more than 120 cDDD, aHR was 1.51 (95% CI, 1.42-1.62). SGAs also raised dementia risk. At less than 60 cDDD, aHR was 1.11 (95% CI, 1.05-1.17); at 60 to 120 cDDD, aHR was 1.19 (95% CI, 1.12-1.26); and at more than 120 cDDD, aHR was 1.26 (95% CI, 1.19-1.33). CONCLUSIONS: Patients with allergic rhinitis on FGAs or SGAs face an escalating dementia risk with increasing cumulative dosage. Moreover, FGAs exhibit a higher dementia risk compared with SGAs. Nevertheless, extensive clinical trials are imperative for confirming the association between FGA use, SGA use, and dementia risk.

Dietary nutrient intake and nutritional status in maintenance hemodialysis patients: a multicenter cross-sectional survey.

PURPOSE: To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators. METHODS: This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy. RESULTS: A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients' protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = -2.880, p = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = -0.109, p = 0.001). Pearson correlation analysis revealed that dietary DPI (r = -0.109, p < 0.05), DEI (r = -0.226, p < 0.05) and phosphorus (r = -0.195, p < 0.001) intake were statistically correlated to Kt/V; dietary nDPI (r = 0.101, p < 0.05) and sodium (r = -0.144, p < 0.001) intake were statistically correlated to serum urea nitrogen; dietary DPI (r = 0.200, p < 0.001), DEI (r = 0.241, p < 0.001), potassium (r = 0.129, p < 0.05), phosphorus (r = 0.199, p < 0.001), and fiber (r = 0.157, p < 0.001) intake were statistically correlated to serum creatinine; dietary phosphorus (r = 0.117, p < 0.05) and fiber (r = 0.142, p < 0.001) intake were statistically correlated to serum phosphorus; dietary nDPI (r = 0.125, p < 0.05), DPI (r = 0.135, p < 0.05), nDEI (r = 0.116, p < 0.05), DEI (r = 0.125, p < 0.05), potassium (r = 0.148, p < 0.001), and phosphorus (r = 0.156, p < 0.001) intake were statistically correlated to subjective global assessment scores; dietary nDPI (r = 0.215, p < 0.001), DPI (r = 0.341, p < 0.001), nDEI (r = 0.142, p < 0.05), DEI (r = 0.241, p < 0.001), potassium (r = 0.166, p < 0.05), phosphorus (r = 0.258, p < 0.001), and fiber (r = 0.252, p < 0.001) intake were statistically correlated to handgrip strength in males; dietary fiber (r = 0.190, p < 0.05) intake was statistically correlated to handgrip strength in females. CONCLUSIONS: The dietary nutrient intake of MHD patients need improvement. Inadequate dietary nutrient intake among MHD patients could have a detrimental effect on their blood test indexes and overall nutritional status. It is crucial to address and optimize the dietary intake of nutrients in this patient population to enhance their health outcomes and well-being.

The Impact of Physical Exercise on Oxidative and Nitrosative Stress: Balancing the Benefits and Risks.

This review comprehensively evaluates the effects of physical exercise on oxidative and nitrosative stress, mainly focusing on the role of antioxidants. Using a narrative synthesis approach, data from empirical studies, reviews, systematic reviews, and meta-analyses published between 2004 and 2024 were collated from databases like PubMed, EBSCO (EDS), and Google Scholar, culminating in the inclusion of 41 studies. The quality of these studies was rigorously assessed to ensure the clarity of objectives, coherence in arguments, comprehensive literature coverage, and depth of critical analysis. Findings revealed that moderate exercise enhances antioxidant defenses through hormesis, while excessive exercise may exacerbate oxidative stress. The review also highlights that while natural dietary antioxidants are beneficial, high-dose supplements could impede the positive adaptations to exercise. In conclusion, the review calls for more focused research on tailored exercise and nutrition plans to further understand these complex interactions and optimize the health outcomes for athletes and the general population.

Eco-friendly electronic food labels: Development and application of Ion-SSPB double network hydrogel.

Although various conductive hydrogels have been developed for sensing, ideal materials for meeting the safety and toughness requirements of food detection are still lacking. This study introduces Ion-SSPB, a conductive hydrogel fabricated from eco-friendly, food-grade materials such as corn starch (CS), sodium alginate (SA), polyvinyl alcohol (PVA) and bentonite (BT). It leverages a green manufacturing approach designed for application in electronic food sensors. The hydrogel is achieved through a double network strategy and salt immersion method, which endows it with tunable mechanical and rheological properties. A key innovation of Ion-SSPB is the incorporation of bentonite, which enhances its performance, including low swelling, freezing resistance, and minimal residual adhesion. The hydrogel with 4% (w/v) BT concentration (Ion-SSPB4%) is an effective medium for detecting impedance changes in mangoes, correlating with their ripening stages. The Ion-SSPB hydrogel represents a significant advancement in the field of electronic food labels, combining environmental sustainability with technical efficacy.

A phase 2 trial exploring the significance of homologous recombination status in patients with platinum sensitive or platinum resistant relapsed ovarian cancer receiving combination cediranib and olaparib.

OBJECTIVE: Combination cediranib/olaparib has reported activity in relapsed ovarian cancer. This phase 2 trial investigated the activity of cediranib/olaparib in relapsed ovarian cancer and its association with homologous recombination deficiency (HRD). METHODS: Seventy patients were enrolled to cohorts of either platinum-sensitive or platinum-resistant ovarian cancer and received olaparib tablets 200 mg twice daily and cediranib tablets 30 mg once daily under a continuous dosing schedule. HRD testing was performed on pre-treatment, on-treatment and archival biopsies by sequencing key homologous recombination repair (HRR) genes and by genomic LOH analysis. The primary objective for the platinum-sensitive cohort was the association of HRD, defined as presence of HRR gene mutation, with progression-free survival (PFS). The primary objective for the platinum-resistant cohort was objective response rate (ORR), with a key secondary endpoint evaluating the association of HRD status with activity. RESULTS: In platinum-sensitive ovarian cancer (N = 35), ORR was 77.1% (95% CI 59.9-89.6%) and median PFS was 16.4 months (95% CI 13.2-18.6). Median PFS in platinum-sensitive HRR-HRD cancers (N = 22) was 16.8 months (95% CI 11.3-18.6), and 16.4 months (95% CI 9.4-NA) in HRR-HR proficient cancers (N = 13; p = 0.57). In platinum-resistant ovarian cancer (N = 35), ORR was 22.9% (95% CI 10.4-40.1%) with median PFS 6.8 months (95% CI 4.2-9.1). Median PFS in platinum-resistant HRR-HRD cancers (N = 7) was 10.5 months (95% CI 3.6-NA) and 5.6 months (95% CI 3.6-7.6) in HRR-HR proficient cancers (N = 18; p = 0.23). CONCLUSIONS: Cediranib/olaparib had clinical activity in both platinum-sensitive and -resistant ovarian cancer. Presence of HRR gene mutations was not associated with cediranib/olaparib activity in either setting.

Guizhi Fuling Wan ameliorates concanavalin A-induced autoimmune hepatitis in mice.

BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated hepatic disease associated with intense complications. AIH is more common in females and needs effective drugs to treat. Guizhi Fuling Wan (GZFLW) is a traditional Chinese herbal formula used to treat various gynecologic diseases. In this study, we aim to extend the new use of GZFLW for AIH. METHODS: The tandem MS-based analysis was used to identify secondary metabolites in GZFLW. Therapeutic effects of GZFLW were tested in a concanavalin A (Con A)-induced AIH model in mice. Ethnopharmacological mechanisms underlying the antiapoptotic, antioxidant, and immunomodulatory protective effects were determined. RESULTS: Oral administration of GZFLW attenuates AIH in a Con A-induced hepatotoxic model in vivo. The tandem MS-based analysis identified 15 secondary metabolites in GZFLW. The Con A-induced AIH syndromes, including hepatic apoptosis, inflammation, reactive oxygen species accumulation, function failure, and mortality, were significantly alleviated by GZFLW in mice. Mechanistically, GZFLW restrained the caspase-dependent apoptosis, restored the antioxidant system, and decreased pro-inflammatory cytokine production in the livers of Con A-treated mice. Besides, GZFLW repressed the Con A-induced hepatic infiltration of inflammatory cells, splenic T cell activation, and splenomegaly in mice. CONCLUSIONS: Our findings demonstrate the applicable potential of GZFLW in treating AIH. It prompts further investigation of GZFLW as a treatment option for AIH and possibly other hepatic diseases.

Nanoarchitectonics of Nanocellulose Filament Electrodes by Femtosecond Pulse Laser Deposition of ZnO and In Situ Conjugation of Conductive Polymers.

Electroactive filament electrodes were synthesized by wet-spinning of cellulose nanofibrils (CNF) followed by femtosecond pulse laser deposition of ZnO (CNF@ZnO). A layer of conducting conjugated polymers was further adsorbed by in situ polymerization of either pyrrole or aniline, yielding systems optimized for electron conduction. The resultant hybrid filaments were thoroughly characterized by imaging, spectroscopy, electrochemical impedance, and small- and wide-angle X-ray scattering. For the filaments using polyaniline, the measured conductivity was a result of the synergy between the inorganic and organic layers, while the contribution was additive in the case of the systems containing polypyrrole. This observation is rationalized by the occurrence of charge transfer between ZnO and polyaniline but not that with polypyrrole. The introduced conductive hybrid filaments displayed a performance that competes with that of metallic counterparts, offering great promise for next-generation filament electrodes based on renewable nanocellulose.

Green, tough, and heat-resistant: A GDL-induced strategy for starch-alginate hydrogels.

Hydrogels fabricated by non-covalent interaction garnered significant attention for their eco-friendly and robust mechanical attributes, and are often used in food, medicine and other fields. Although starch-alginate hydrogels exhibit high adhesion and are environmentally sustainable, their applications are limited due to their low elasticity and hardness. Addressing this challenge, we introduce a solvent-induced strategy using glucolactone (GDL) to fabricate hydrogels with enhanced strength and thermal resilience. Utilizing corn starch with varying amylose contents, sodium alginate and calcium carbonate to prepare a double network structure. This GDL-induced hydrogel outperforms most previous starch-based hydrogels in mechanical robustness and thermal stability. Typical starch-alginate hydrogel had a homogeneous network structure and exhibited a high tensile stress of 407.57 KPa, and a high enthalpy value of 1857.67 J/g. This investigation furnishes a facile yet effective method for the synthesis of hydrogels with superior mechanical and thermal properties, thereby broadening the design landscape for starch-based hydrogels.

Randomized Phase II Study of Gemcitabine With or Without ATR Inhibitor Berzosertib in Platinum-Resistant Ovarian Cancer: Final Overall Survival and Biomarker Analyses.

PURPOSE: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (hazard ratio [HR]=0.57, one-sided log-rank P = .044, which met the one-sided significance level of 0.1 used for sample size calculation). METHODS: We report here the final overall survival (OS) analysis and biomarker correlations (ATM expression by immunohistochemistry, mutational signature 3 and a genomic biomarker of replication stress) along with post-hoc exploratory analyses to adjust for crossover from gemcitabine to gemcitabine/berzosertib. RESULTS: At the data cutoff of January 27, 2023 (>30 months of additional follow-up from the primary analysis), median OS was 59.4 weeks with gemcitabine/berzosertib versus 43.0 weeks with gemcitabine alone (HR 0.79, 90% CI 0.52 to 1.2, one-sided log-rank P = .18). An OS benefit with addition of berzosertib to gemcitabine was suggested in patients stratified into the platinum-free interval ≤3 months (N = 26) subgroup (HR, 0.48, 90% CI 0.22 to 1.01, one-sided log-rank P =.04) and in patients with ATM-negative/low (N = 24) tumors (HR, 0.50, 90% CI 0.23 to 1.08, one-sided log-rank P = .06). CONCLUSION: The results of this follow-up analysis continue to support the promise of combined gemcitabine/ATRi therapy in platinum resistant ovarian cancer, an active area of investigation with several ongoing clinical trials.

Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.

3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNFα and IL-6, were induced by 3-BrFlu through phosphorylation of NF-κB p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation.