Microstructural Characterization, Tribological and Corrosion Behavior of H111 Hot-Rolled AA5754 after Homogenization and Aging.

In this study, the microstructural properties, wear resistance, and corrosion behavior of H111 hot-rolled AA5754 alloy before heat treatment, after homogenization, and after aging were examined. The microstructure was mainly composed of the scattered forms of black and gray contrast particles on the matrix and precipitations were observed at the boundaries of the grain. The as-rolled material exhibited a dense pancake-shaped grain structure, which is typical of as-rolled material. Observation along the L-direction did not yield distinct demarcations among the grains and was not uniformly distributed, with precipitates at the grain boundary. When they aged, there was a parallel increase in fine and huge black and gray contrast particles in the zone. Therefore, it could be stated that the amount of fine grains increased due to the rise in the homogenization process. The rolled base metal with the grain orientation was found to be parallel to the rolling direction. On the other hand, the coarse grains were clearly observed in the aging heat-treatment condition. The grains had an elongated morphology consistent with the rolling process of the metal before the heat-treatment process. The aged alloy had the highest hardness with a value of 86.83 HB; the lowest hardness was seen in the alloy before heat treatment with a value of 68.67 HB. The weight loss and wear rate of this material at the end of 10,000 m were, respectively, 1.01 × 10-3 g and 5.07 × 10-9 g/Nm. It was observed that the alloy had the highest weight loss and worst wear resistance before heat treatment. Weight loss and wear rates at the end of 10,000 m were, respectively, 3.42 × 10-3 g and 17.08 × 10-9 g/Nm. According to these results, the friction coefficients during wear were parallel and the material with the lowest friction coefficient after aging was 0.045. While the alloys corroded after aging showed more weight loss, the alloys corroded before heat treatment exhibited better corrosion behavior. Among the alloys, the least weight loss after 24 h was observed in the alloy that was corroded before heat treatment and this value was 0.69 × 10-3 mg/dm2. The highest weight loss was observed in the aged alloy with a value of 1.37 × 10-3 mg/dm2. The alloy before heat treatment, which corroded after casting, showed the lowest corrosion rate with a value of 0.39 × 10-3 mg/(dm2·day) after 72 h. The alloy that was corroded before heat treatment showed the best corrosion behavior by creating a corrosion potential of 1.04 ± 1.5 V at a current density of -586 ± 0.04 µA/cm2. However, after aging, the corroded alloy showed the worst corrosion behavior with a corrosion potential of 5.16 ± 3.3 V at a current density of -880 ± 0.01 µA/cm2.

Comparison between Mechanical Properties and Joint Performance of AA 2024-T351 Aluminum Alloy Welded by Friction Stir Welding, Metal Inert Gas and Tungsten Inert Gas Processes.

The aim of this work is to study joining Al 2024-T3 alloy plates with different welding procedures. Aluminum alloy AA 2024-T351 is especially used in the aerospace industry. Aluminum plates are welded by the TIG and MIG fusion welding process, as well as by the solid-state welding process, friction stir welding (FSW), which has recently become very important in aluminum and alloy welding. For welding AA2024-T35 with MIG and TIG fusion processes, the filler material ER 4043-AlSi5 was chosen because of reduced cracking. Different methods were used to evaluate the quality of the produced joints, including macro- and microstructure evaluation, in addition to hardness and tensile tests. The ultimate tensile strength (UTS) of the FSW sample was found to be 80% higher than that of MIG and TIG samples. The average hardness value of the weld zone of metal for the MIG- and TIG-produced AA2024-T3511 butt joints showed a significant decrease compared to the hardness of the base metal AA2024-T351 by 50%, while for FSW joints, in the nugget zone, the hardness is about 10% lower relative to the base metal AA2024-T3511.

Comparison of Efficacy of Autologous Platelet Rich Plasma Therapy With 5% Topical Minoxidil Spray in Treating Alopecia Areata: A Head-to-Head Assessment of Novel Approaches.

BACKGROUND: Alopecia areata (AA) remains one of the most challenging afflictions encountered in dermatology clinics. It is characterized by an autoimmune-mediated inflammatory process of and around hair follicles, causing reversible, non-scarring hair loss. With the ongoing search for optimal treatment strategies, the potentially positive role of autologous platelet-rich plasma (PRP) therapy as well as minoxidil has been reported in various studies; however, the comparison of the two treatment modalities is largely underexplored. This research aims to compare and assess the effectiveness of intralesional PRP with topical minoxidil therapy in AA to identify efficacious management options amongst the newly described treatment modalities. METHODOLOGY: The research work was conducted over four months and included 40 (31 males and 9 females) patients suffering from alopecia areata. They were divided into Group A, which was administered monthly autologous PRP injections, while Group B was given daily topical 5% minoxidil therapy. In group A, four treatments of PRP were given, each one month apart. While in group B, daily topical minoxidil spray was administered for the same duration. The alopecia areata severity grade was recorded by employing the "Severity of Alopecia Tool" (SALT) scoring system. The pre- and post-treatment SALT scores were noted and compared at each monthly visit. RESULTS: The study comprised nine (22.5%) female and 31 (77.5%) male patients. At the beginning of the study and after one month of treatment, the difference in the SALT score was not statistically significant between the two groups, suggesting that both interventions had similar effects during the early stages of the treatment. At two months, a statistically significant difference emerged (p-value 0.037), indicating that a more significant fall in the SALT score was observed with autologous PRP treatment compared to topical minoxidil. After four months, a highly significant difference was noted between the two groups (p-value <0.0001), implying that intralesional PRP therapy led to a far more significant decrease in the SALT score compared to topical minoxidil therapy. CONCLUSION: Monthly intralesional autologous PRP therapy for four months manifests better outcomes in alopecia areata than daily 5% topical minoxidil therapy.

Characterizing disparities in receipt of palliative care for Asian Americans, Native Hawaiians, and Pacific Islanders with metastatic cancer in the United States.

PURPOSE: Palliative care plays essential roles in cancer care. However, differences in receipt among individuals identifying as Asian American, Native Hawaiian, and Other Pacific Islanders (AA&NHPI) with cancer are not well-characterized, especially when these diverse groups are disaggregated. We characterized disparities in receipt of palliative care among AA&NHPI patients with AJCC Stage IV prostate, breast, or lung cancer. METHODS: We performed multivariable logistic regressions were performed in this retrospective cohort analysis, using deidentified data from the National Cancer Database (NCDB) of patients diagnosed with AJCC analytic group stage IV breast, lung, or prostate cancer (2004-2018) who were White or of Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. We conducted multivariable logistic regression analyses in a retrospective cohort study using deidentified data from the National Cancer Database (NCDB). The study included patients diagnosed with AJCC analytic group Stage IV breast, lung, or prostate cancer between 2004 and 2018, who were White or identified as Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. Adjusted odds ratios and 95% confidence intervals of receiving palliative care were measured when comparing White vs. AA&NHPI patients as one cohort and White vs. disaggregated AA&NHPI patients, adjusting for clinical, socioeconomic, and demographic covariates. RESULTS: Among 775,289 individuals diagnosed with cancer (median age: 68 years), no significant differences in palliative care receipt were observed between White patients and aggregated AA&NHPI patients among patients with prostate, breast, or lung cancer. However, disaggregated analyses revealed reduced palliative care receipt for breast cancer patients of Asian Indian/Pakistani descent (AOR 0.75, 95% CI, 0.60-0.94, P = 0.011) and for lung cancer patients of Chinese, Vietnamese, Thai, and Asian Indian/Pakistani descent compared to White patients (Chinese AOR 0.88, [0.81-0.94], P = 0.001; Vietnamese AOR 0.89, [0.80 to 0.99], P = 0.032; Thai AOR 0.64, [0.44-0.92], P = 0.016; Asian Indian/Pakistani AOR 0.83, [0.74-0.93], P = 0.001). Palliative care was greater for patients of Japanese and Hawaiian descent with prostate cancer (Japanese AOR 1.92, [1.32-2.75], P = 0.001; Hawaiian AOR 2.09, [1.20-3.66], P = 0.009), breast cancer (Japanese AOR 1.72, [1.21-2.43], P = 0.001; Hawaiian AOR 1.70, [1.08-2.67], P = 0.021), and lung cancer (Japanese AOR 1.92, [1.70-2.17], P < 0.001; Hawaiian AOR 2.95, [2.5-3.5], P < 0.001), as well as patients of Other Pacific Islander descent with lung cancer (AOR 1.62, [1.34-1.96], P < 0.001). CONCLUSIONS AND RELEVANCE: Our findings demonstrate disparities in receipt of palliative care upon disaggregation of diverse AA&NHPI groups, the need for disaggregated research and targeted interventions that address the unique cultural, socioeconomic, and healthcare system barriers to palliative care receipt.

[Clinical effects of transesophageal echocardiography in different surgical methods for nephrectomy combined with Mayo â ¢-â £ vena tumor thrombectomy].

OBJECTIVE: To analyze the clinical effects of intraoperative transesophageal echocardiography (TEE) in different surgical methods for nephrectomy combined with Mayo Ⅲ-Ⅳ inferior vena cave (IVC) tumor thrombectomy. METHODS: In the study, 28 patients who did surgery of nephrectomy and Mayo Ⅲ-Ⅳ IVC thrombectomys in Peking University Third Hospital from 2022 January to 2024 February were included. Of the 28 patients, 16 patients did robotic surgery, 2 patients did laparoscopic surgery, and 10 patients did open surgery. All patients' clinical data were collected. RESULTS: Intra-operative TEE was used in 9 robotic surgeries, of which 7 cases showed image changes compared with preoperative image results. Intraoperative TEE indicated that tumor thrombus entered the right atrium in 2 cases, showed that tumor thrombus grade rose from Mayo Ⅲ to Mayo Ⅳ in 2 cases, and indicated that tumor thrombus adhered to IVC wall in 3 cases. All of these surgical plans were timely adjusted. Intra-operative TEE was used in 6 cases of open surgery, and 4 cases of them showed Mayo grade changes compared with preoperative image results. Intraoperative TEE indicated that tumor thrombus adhered to the IVC wall in 3 cases, and tumor thrombus adhered to the IVC wall with thrombus in one case. The surgical plans were adjusted, and the tumor thrombus was left or segmentally removed. Laparoscopic surgery did not use intraoperative TEE. The effects of intraoperative TEE included: the combination of exploration and TEE monitoring was used in open surgery, and tumor thrombus removal process was fully monitored by intraoperative TEE in the robotic surgery. Intraoperative TEE real-time monitored circulatory status and cardiac function changes. CONCLUSION: In different surgical methods for nephrectomy combined with Mayo Ⅲ-Ⅳ tumor thrombectomy, intraoperative TEE can re-determine the tumor thrombus grade and degree of tumor thrombus adhered to IVC, track the tumor thrombus removal process in real-time, and monitor circulatory status and cardiac function changes. Intraoperative TEE plays an important role in different surgical methods, but its clinical application is still insufficient. Intraoperative TEE is recommended to such type of surgeries.

The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

Loneliness and global cognitive functioning in racially and ethnically diverse US midlife and older adults.

Introduction: Few studies have examined the association of loneliness and cognitive functioning in the US. We used two common measures of loneliness and examined their association in a large sample of US Black, Latino, and White adults (ages ≥ 50). Methods: We analyzed Wave 3 of the National Social Life, Health, and Aging Project (N = 2,757). We examined loneliness using one item from the CES-D and the Felt Loneliness Measure (NFLM); cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA) tool, where higher scores indicated better functioning. We used weighted ordinary least squares regressions to examine the effects of loneliness (CES-D loneliness and NFLM in separate models) on MoCA scores. In exploratory analyses, we examined if these relationships varied by race and ethnicity. We adjusted all models for sociodemographic and other salient factors (e.g., chronic disease, depressive symptoms, living alone). Results: Mean age was 63.49 years, 52% were female, and 9% were Black and 6% Latino persons. Approximately 54% endorsed feeling lonely on at least one measure; 31% (CES-D) and 46% (NFLM). The relationship between loneliness measures was positive and significant, X 2 (1, N = 2,757) = 435.493 p < 0.001. However, only 40% of lonely individuals were identified as lonely on both assessments. CES-D loneliness was inversely (߈ = -0.274, p = 0.032) associated with MoCA scores and this association did not vary by race and ethnicity. Greater NFLM loneliness was positively associated (߈ = 0.445, p < 0.001) with higher MoCA scores for Latino participants only. Discussion: Loneliness appears to be an important predictor of cognitive functioning. However, the association of loneliness and cognitive functioning varied when using the CES-D loneliness item or the NFLM. Future work is needed to understand how loneliness and its clinically relevant dimensions (social, emotional, existential, chronicity) relate to global and individual cognitive domains. Research is needed with racially and ethnically diverse midlife and older adults, particularly to understand our counterintuitive finding for Latino participants. Finally, findings also support the need for research on interventions to prevent cognitive decline targeting loneliness.

Could tocilizumab be used in familial Mediterranean Fever? A systematic review.

INTRODUCTION: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1ß (IL-1ß), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1ß inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented. OBJECTIVE: To evaluate the efficacy and safety of tocilizumab in the treatment of FMF. METHODS: Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF. RESULTS: After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF. CONCLUSION: This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1ß inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.

Gut microbiota, skin microbiota, and alopecia areata: A Mendelian randomization study.

BACKGROUND: Observational studies have shown an association between skin microbiota and alopecia areata (AA), but the causal connection remains ambiguous. METHODS: We obtained data on skin microbiota and AA from summary statistics of Genome-Wide Association Studies and applied statistical methods from Mendelian randomization (MR) to assess causal relationships. Additionally, we investigated whether the skin microbiota acts as a mediator in the pathway from gut microbiota to AA. RESULTS: In the MR analysis of KORA FF4 and AA, the inverse-variance weighting method indicated that Corynebacterium (odds ratio [OR] = 0.82, 95% confidence interval [CI]: 0.70-0.96, p = 0.02) and asv037 (OR = 0.87, 95% CI: 0.76-0.99, p = 0.05) exerted protective effects, while Betaproteobacteria (OR = 1.21, 95% CI: 1.01-1.44, p = 0.03), asv015 (OR = 1.27, 95% CI: 1.05-1.54, p = 0.02), and Burkholderiales (OR = 1.20, 95% CI: 1.04-1.38, p = 0.01) were identified as risk factors in AA. In the MR analysis of PopGen and AA, asv001 (OR = 1.12, 95% CI: 1.01-1.24, p = 0.04), asv054 (OR = 1.13, 95% CI: 1.01-1.25, p = 0.03), and asv059 (OR = 1.14, 95% CI: 1.02-1.27, p = 0.02) were found to potentially increase the risk in AA. Furthermore, in the influence of gut microbiota on AA, the skin microbiota did not act as a mediator. CONCLUSION: Our analysis suggests potential causal relationships between certain skin microbiota and AA, revealing insights into its pathogenesis and potential intervention strategies.

Genome-wide DNA methylation profile and its function in regulating Vip3Aa tolerance in fall armyworm (Spodoptera frugiperda).

BACKGROUND: Vegetative insecticidal proteins (Vips) are widely used in pest management, but Vip tolerance poses a significant threat. DNA methylation plays important roles in regulating the response of biological organisms to environmental stress, and it may also regulate fall armyworm (FAW, Spodoptera frugiperda) Vip3Aa tolerance. RESULTS: In this study, a DNA methylation map was developed for FAW, and its function in regulating FAW Vip3Aa tolerance was explored. The FAW genome-wide DNA methylation map showed that exons were preferred regions for DNA methylation and housekeeping genes were highly methylated. FAW was screened using Vip3Aa for ten generations, and bioassays indicated that Vip3Aa tolerance increased trans-generationally. A comparison of DNA methylation maps between Vip3Aa-tolerant and -susceptible strains showed that gene body methylation was positively correlated with gene expression level. FAW exhibits significant variation in DNA methylation among individuals, and Vip3Aa screening induces epigenetic variation based on DNA methylation. Moreover, the study demonstrated that a reduction in methylation density within the gene body of a 3'5'-cyclic nucleotide phosphodiesterase gene resulted in decreased expression and increased tolerance of FAW to Vip3Aa, which was validated through RNA interference experiments. CONCLUSION: The DNA methylation map and mechanism of Vip3Aa tolerance improve our understanding of DNA methylation and its function in Lepidoptera and provide a new perspective for developing pest management strategies. © 2024 Society of Chemical Industry.

Assessing the conservation value of cemeteries to urban biota worldwide.

Cemeteries are key urban green spaces with multifaceted societal and ecological importance. Their biodiversity is shaped by unique environmental and cultural factors. They can potentially protect rare and endangered species, yet their conservation value compared with other urban green spaces remains largely unexplored. We sought to fill this gap by systematically reviewing literature to investigate the conservation value of cemeteries relative to other urban green spaces (botanical gardens, institutional premises, natural remnants, and parks) by comparing species richness and proportions of native and unique species. We analyzed data from 70 papers covering 50 cities in 27 countries with linear and binomial mixed-effects models at both site and city level. Cemetery conservation value was similar to urban parks, except for the proportion of unique species, for which parks had significantly higher proportions (21.9% vs. 14.2%, p < 0.001). Cemeteries hosted slightly higher proportions of native species at the city level than botanical gardens (99.7% vs. 99.6%, p < 0.001) and institutional green spaces (96.3% vs. 94.1%, p = 0.034) and proportions comparable to parks and natural remnants (p > 0.05). They also had similar or higher values than institutional premises in species richness and unique species proportions (p > 0.05) and a higher site-level proportion of native species (p < 0.001). In contrast, species richness (slopes = -0.11 and -0.25, respectively) and unique species proportions (4.4% and 6.9%, respectively, p < 0.001 for both) were lower in cemeteries than in remnants of natural areas and in botanical gardens. The conservation value of cemeteries and parks was similar for animals, but parks had a higher value for plants. Overall, cemeteries were generally at least as valuable as some other green spaces for urban biodiversity and mostly native biota. Their religious and cultural significance suggests they will remain intact in the long term; thus, it is essential to prioritize and further promote their biodiversity in conservation and sustainable urban design plans.

Análisis del valor de conservación que tienen los cementerios para la biota urbana a nivel mundial Resumen Los cementerios son espacios urbanos verdes con una importancia social y ecológica multifacética. Su biodiversidad está moldeada por factores ambientales y culturales únicos. Los cementerios tienen el potencial para proteger especies raras y en peligro, pero su valor de conservación sigue sin ser explorado cuando se compara con otros espacios urbanos verdes. Buscamos llenar este vacío con una revisión sistemática de la bibliografía para investigar el valor de conservación de los cementerios en relación a otros espacios urbanos verdes (jardines botánicos, sedes institucionales, remanentes naturales y parques) al comparar la riqueza de especies y la proporción de especies nativas y únicas. Analizamos con modelos lineales y binomiales de efectos mixtos a nivel de sitio y de ciudad los datos de 70 artículos enfocados en 50 ciudades de 27 países. El valor de conservación de los cementerios fue similar al de los parques urbanos, excepto para la proporción de especies únicas, para la cual los parques tuvieron una proporción significativamente más alta (21.9% vs. 14.2%, p<0.001). A nivel de ciudad, los cementerios albergaron una proporción ligeramente mayor de especies nativas en comparación con los jardines botánicos (99.7% vs. 99.6%, p<0.001) y las sedes institucionales (96.3% vs. 94.1%, p = 0.034) y tuvieron una proporción comparable a los parques y los remanentes naturales (p>0.05). Los cementerios también tuvieron un valor similar o mayor a los espacios verdes institucionales en cuanto a riqueza de especies y proporción de especies únicas (p>0.05) y una proporción mayor a nivel de sitio de especies nativas (p<0.001). Al contrario, la riqueza de especies (pendientes = ­0.11 y ­0.25, respectivamente) y la proporción de especies únicas (4.4% y 6.9%, respectivamente, p<0.001 para ambas) fueron menores en los cementerios que en los remanentes de las áreas naturales y en los jardines botánicos. El valor de conservación de los cementerios y los parques fue similar para los animales, pero los parques tuvieron un valor mayor para las plantas. En general, los cementerios fueron al menos tan valiosos como otros espacios verdes para la biodiversidad urbana y casi toda la biota nativa. El significado religioso y cultural que tienen los cementerios sugiere que seguirán intactos a largo plazo; por ello, es esencial priorizar y promover aún más su biodiversidad en la conservación y en los planes de diseño urbano sustentable.

Unleashing the Neurotherapeutic Potential: The Crucial Role of miR-206-3p in Facilitating Hsp90aa1-Mediated Central Nervous System Injuries During Heat Stroke.

This study aims to explore the molecular mechanisms of miR-206-3p in regulating Hsp90aa1 and its involvement in the central nervous system (CNS) injury in heat stroke. Weighted gene co-expression network analysis (WGCNA) was performed on the GSE64778 dataset of heat stroke to identify module genes most closely associated with disease characteristics. Through the selection of key genes and predicting upstream miRNAs using RNAInter and miRWalk databases, the regulatory relationship between miR-206-3p and Hsp90aa1 was determined. Through in vitro experiments, various methods, including bioinformatics analysis, dual-luciferase reporter gene assay, RIP experiment, and RNA pull-down experiment, were utilized to validate this regulatory relationship. Furthermore, functional experiments, including CCK-8 assay to test neuron cell viability and flow cytometry to assess neuron apoptosis levels, confirmed the role of miR-206-3p. Transmission electron microscopy, real-time quantitative PCR, DCFH-DA staining, and ATP assay were employed to verify neuronal mitochondrial damage. Heat stroke rat models were constructed, and mNSS scoring and cresyl violet staining were utilized to assess neural functional impairment. Biochemical experiments were conducted to evaluate inflammation, brain water content, and histopathological changes in brain tissue using H&E staining. TUNEL staining was applied to detect neuronal apoptosis in brain tissue. RT-qPCR and Western blot were performed to measure gene and protein expression levels, further validating the regulatory relationship in vivo. Bioinformatics analysis indicated that miR-206-3p regulation of Hsp90aa1 may be involved in CNS injury in heat stroke. In vivo, animal experiments demonstrated that miR-206-3p and Hsp90aa1 co-localized in neurons of the rat hippocampal CA3 region, and with prolonged heat stress, the expression of miR-206-3p gradually increased while the expression of Hsp90aa1 gradually decreased. Further in vitro cellular mechanism validation and functional experiments confirmed that miR-206-3p could inhibit neuronal cell viability and promote apoptosis and mitochondrial damage by targeting Hsp90aa1. In vivo, experiments confirmed that miR-206-3p promotes CNS injury in heat stroke. This study revealed the regulatory relationship between miR-206-3p and Hsp90aa1, suggesting that miR-206-3p could regulate the expression of Hsp90aa1, inhibit neuronal cell viability, and promote apoptosis, thereby contributing to CNS injury in heat stroke.

Layer-by-layer fabrication of alginate/polyethyleneimine multilayer on magnetic interface with enhanced efficiency in immuno-capturing circulating tumor cells.

BACKGROUND: The technology of capturing circulating tumor cells (CTCs) plays a crucial role in the diagnosis, evaluation of therapeutic efficacy, and prediction of prognosis in lung cancer. However, the presence of complex blood environment often results in severe nonspecific protein adsorption and interferences from blood cells, which negatively impacts the specificity of CTCs capture. There is a great need for development of novel nanomaterials for CTCs capture with prominent anti-nonspecific adsorptions from proteins or blood cells. RESULTS: We present a novel immune magnetic probe Fe3O4@(PEI/AA)4@Apt. The surface of Fe3O4 particles was modified with four layers of PEI/AA composite by layer-by-layer assembly. Furthermore, aptamers targeting epithelial marker EpCAM (SYL3C) and mesenchymal marker CSV (ZY5C) were simultaneously connected on Fe3O4@(PEI/AA)4 to improve the detection of different phenotypic CTCs and reduce false negatives. The results demonstrated that the (PEI/AA)4 coatings not only minimized non-specific protein adsorptions, but also significantly reduced the adsorption rate of red blood cells to a mere 1 %, as a result of which, the Fe3O4@(PEI/AA)4@Apt probe achieved a remarkably high capture efficiency toward CTCs (95.9 %). In the subsequent validation of clinical samples, the probe was also effective in capturing rare CTCs from lung cancer patients. SIGNIFICANCE AND NOVELTY: A (PEI/AA) polymerized composite with controllable layers was fabricated by layer-by-layer self-assembly technique, which displayed remarkable anti-nonspecific adsorption capabilities toward proteins and cells. Importantly, Fe3O4@(PEI/AA)4@Apt probe significantly improved CTCs capture purity in lung cancer patients to 89.36 %. For the first time, this study combined controllable (PEI/AA) layers with magnetic separation to innovatively build a resistant interface that significantly improves the specific capture performances of CTCs, broadening the application of this polymerized composite.

Binding Analysis of Sf-SR-C MAM Domain and Sf-FGFR Ectodomain to Vip3Aa.

Bacillus thuringiensis Vip3Aa has been widely used in transgenic crops to resist the erosion of insects. The Scavenger Receptor-C (SR-C) and Fibroblast Growth Factor Receptor (FGFR) of Spodoptera frugiperda (Sf-SR-C and Sf-FGFR) have formerly been identified as the cell receptors of Vip3Aa. However, the interaction mechanism of Vip3Aa binding to Sf-SR-C or Sf-FGFR is still unknown. Here, we purified the MAM domain of Sf-SR-C (Sf-MAM) and the Sf-FGFR ectodomain expressed extracellularly by Sf9 cells. We then solved the crystal structure of the Sf-MAM domain. Structure docking analysis of the Sf-MAM and Vip3Aa C-terminal domain (CTD) excluded the possibility of the two proteins binding. A further surface plasmon resonance (SPR) assay also revealed that the Sf-MAM and Sf-FGFR ectodomain could not bind to the Vip3Aa protein. Our results have raised the urgency of determining the authentic cell receptor for Vip3Aa.

Mesenchymal stem cell-derived exosomes ameliorate hypoxic pulmonary hypertension by inhibiting the Hsp90aa1/ERK/pERK pathway.

Hypoxic pulmonary hypertension (HPH) is a serious and life-threatening chronic cardiopulmonary disease characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular remodeling. Mesenchymal stem cell- derived exosomes (MSC-Exos) can relieve HPH by reversing pulmonary vascular remodeling. The HPH model was established in healthy male Sprague-Dawley (SD) rats aged 6 to 8 weeks. The rats were placed in a room with oxygen concentration of (10 ± 1) % for 8 hours a day over 28 days, were then injected intravenously with MSC-Exos (100 ug protein/kg) or equal-volume phosphate buffer saline (PBS) once a day over 1 week. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI) and pulmonary vascular remodeling were observed after anesthesia. In addition, platelet-derived growth factor BB (PDGF-BB) was used to stimulate rat pulmonary artery smooth muscle cells (PASMCs) to construct HPH pathological cell models. The results showed that MSC-Exos could not only reduce the elevation of RVSP, right ventricular hypertrophy and the degree of pulmonary vascular remodeling in HPH rats, but also reduce the proliferation, migration and apoptosis resistance of PASMCs. Finally, GSE53408 and GSE113439 datasets were analyzed and showed that the expression of Hsp90aa1 and pERK/ERK were significantly increased in HPH, also could be inhibited by MSC-Exos. Meanwhile, inhibition of Hsp90aa1 also reduced PASMCs migration and pERK/ERK protein level. In conclusion, MSC-Exos alleviated HPH by suppressing PASMCs proliferation, migration and apoptosis resistance through inhibiting the Hsp90aa1/ERK/pERK pathway.

Effects of immune cells on ischemic stroke and the mediating roles of metabolites.

Objective: Previous studies have not shown an association between IgD-CD24-B-cell absolute count (IgD-CD24-AC) and ischemic stroke (IS). Our study aimed to assess the causal effect of IgD-CD24-AC on IS and to explore the role of ascorbic acid 2-sulfate (AA2S) as a potential mediator. Methods: Our study was based on the largest available genome-wide association study (GWAS). Inverse variance weighting (IVW), MR-Egger, weighted median (WMN), simple mode, and weighted mode methods were used to assess causal effects, with IVW as the primary outcome. Subsequently, we further performed a two-step MR analysis to evaluate whether AA2S mediated this causal effect. In addition, several sensitivity analyses were conducted to evaluate heterogeneity, including Cochran's Q test, the MR-Egger intercept test, the MR-PRESSO global test, and the leave-one-out analysis. Results: Using the IVW approach, the risk ratio of IgD-CD24-AC to IS was estimated to be 1.216 (95% CI = 1.079-1.371, p = 0.001). This result was supported by the WMN method (OR = 1.204, 95% CI = 1.020-1.421, p = 0.028) and the MR-Egger method (OR = 1.177, 95% CI = 0.962-1.442, p = 0.133). We also observed the same trend with the simple model and weighted model. Furthermore, the proportion of genetically predicted IgD-CD24-AC mediated through AA2S levels was 3.73%. Conclusion: Our study revealed a causal relationship between IgD-CD24-AC and IS, a small part of which was mediated by AA2S. These findings offer critical insights for developing immune-targeted therapies in the future and lay a strong foundation for advancements in precision medicine.

New insights into the effects of small permanent charge on ionic flows: A higher order analysis.

This study investigated how permanent charges influence the dynamics of ionic channels. Using a quasi-one-dimensional classical Poisson-Nernst-Planck (PNP) model, we investigated the behavior of two distinct ion species-one positively charged and the other negatively charged. The spatial distribution of permanent charges was characterized by zero values at the channel ends and a constant charge $ Q_0 $ within the central region. By treating the classical PNP model as a boundary value problem (BVP) for a singularly perturbed system, the singular orbit of the BVP depended on $ Q_0 $ in a regular way. We therefore explored the solution space in the presence of a small permanent charge, uncovering a systematic dependence on this parameter. Our analysis employed a rigorous perturbation approach to reveal higher-order effects originating from the permanent charges. Through this investigation, we shed light on the intricate interplay among boundary conditions and permanent charges, providing insights into their impact on the behavior of ionic current, fluxes, and flux ratios. We derived the quadratic solutions in terms of permanent charge, which were notably more intricate compared to the linear solutions. Through computational tools, we investigated the impact of these quadratic solutions on fluxes, current-voltage relations, and flux ratios, conducting a thorough analysis of the results. These novel findings contributed to a deeper comprehension of ionic flow dynamics and hold potential implications for enhancing the design and optimization of ion channel-based technologies.