Dystrophin 71 deficiency causes impaired aquaporin-4 polarization contributing to glymphatic dysfunction and brain edema in cerebral ischemia.

OBJECTIVE: The glymphatic system serves as a perivascular pathway that aids in clearing liquid and solute waste from the brain, thereby enhancing neurological function. Disorders in glymphatic drainage contribute to the development of vasogenic edema following cerebral ischemia, although the molecular mechanisms involved remain poorly understood. This study aims to determine whether a deficiency in dystrophin 71 (DP71) leads to aquaporin-4 (AQP4) depolarization, contributing to glymphatic dysfunction in cerebral ischemia and resulting in brain edema. METHODS: A mice model of middle cerebral artery occlusion and reperfusion was used. A fluorescence tracer was injected into the cortex and evaluated glymphatic clearance. To investigate the role of DP71 in maintaining AQP4 polarization, an adeno-associated virus with the astrocyte promoter was used to overexpress Dp71. The expression and distribution of DP71 and AQP4 were analyzed using immunoblotting, immunofluorescence, and co-immunoprecipitation techniques. The behavior ability of mice was evaluated by open field test. Open-access transcriptome sequencing data were used to analyze the functional changes of astrocytes after cerebral ischemia. MG132 was used to inhibit the ubiquitin-proteasome system. The ubiquitination of DP71 was detected by immunoblotting and co-immunoprecipitation. RESULTS: During the vasogenic edema stage following cerebral ischemia, a decline in the efflux of interstitial fluid tracer was observed. DP71 and AQP4 were co-localized and interacted with each other in the perivascular astrocyte endfeet. After cerebral ischemia, there was a notable reduction in DP71 protein expression, accompanied by AQP4 depolarization and proliferation of reactive astrocytes. Increased DP71 expression restored glymphatic drainage and reduced brain edema. AQP4 depolarization, reactive astrocyte proliferation, and the behavior of mice were improved. After cerebral ischemia, DP71 was degraded by ubiquitination, and MG132 inhibited the decrease of DP71 protein level. CONCLUSION: AQP4 depolarization after cerebral ischemia leads to glymphatic clearance disorder and aggravates cerebral edema. DP71 plays a pivotal role in regulating AQP4 polarization and consequently influences glymphatic function. Changes in DP71 expression are associated with the ubiquitin-proteasome system. This study offers a novel perspective on the pathogenesis of brain edema following cerebral ischemia.

Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in adolescents and young adults (15-39 years): an analysis based on the global burden of disease study 2021.

BACKGROUND: Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. METHODS: Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15-39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). RESULT: In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. CONCLUSION: ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population.

Dual Infection of Different Clusters of HIV in People Living with HIV Worldwide: A Meta-Analysis Based on Next-Generation Sequencing Studies.

To understand the global dual HIV infection (DI) profiles comprehensively, the databases Cochrane Library, Embase, PubMed, and Web of Science were the data sources up to March 31, 2024 (PROSPERO: CRD42023388328). Stata and R-language software were used to analyze the extracted data. Publication bias was assessed using Egger's test. Sensitivity analysis was conducted to evaluate the stability of the combined effect values. Data from 17 eligible studies across four continents (Africa, Asia, Europe, and North America) with 1,475 subjects were used. The combined dual infection rate (DIR) was 10.47% (95% CI: 7.11%-14.38%) without a time trend (p = 0.105). The DIRs of target population groups differed significantly, with FSWs having the highest DIR (15.14%), followed by general population (12.08%), MSM (11.84%), and DUs (9.76%). The subtype profiles of 122 patients with dual infection were extracted, and the results showed that intrasubtype infections were predominant in coinfection (16/22, 72.73%) and superinfection (68/100, 68.00%) groups, with the subtype pattern B and B accounts for the largest proportion. The global dual infection rate may be underestimated, even though the data fluctuated around 10% and showed no time trend. The occurrence of DI indicated that individuals still do not acquire sufficient resistance to HIV even after primary infection, which could potentially compromise the patient's treatment effect and lead to the emergence of new subtypes, posing a significant challenge to HIV prevention, control, and treatment, suggesting that behavioral counseling and health education for all HIV-infected individuals are still crucial during the antiviral therapy.

Comprehensive insights into areca nut: active components and omics technologies for bioactivity evaluation and quality control.

Areca nut (AN), the fruit or seed of Areca catechu Linn, has many uses, including chewing and medicinal purposes. It has sparked worries about health due to the presence of alkaloids. Chewing AN may have a variety of negative consequences; however, the medicinal use of AN has no notable adverse effects. To completely understand and effectively use AN, researchers have investigated its chemical makeup or biological activity, analyzed the variations between different AN species and different periods, and improved extraction and processing procedures. Today, an increasing number of researchers are exploring the underlying reasons for AN variations, as well as the molecular mechanisms of biosynthesis of chemical components, to comprehend and change AN at the genetic level. This review presents an overview of the clinical study, pharmacology, and detection of the main bioactive components in AN, and the main factors influencing their content, delving into the omics applications in AN research. On the basis of the discussions and summaries, this review identifies current research gaps and proposes future directions for investigation.

A Farnesyl Pyrophosphate Synthase Gene Is Expressed in Fat Body Regulates Cantharidin Synthesis in Male Epicauta impressicornis Blister Beetle.

Blister beetles of Epicauta impressicornis have attracted attention because they contain a large amount of cantharidin (CTD). To date, however, the synthesis and transfer of CTD in adults of E. impressicornis are largely unknown. Here, we showed that the larvae E. impressicornis are capable of synthesizing CTD and they consume CTD during pupation. Before sexual maturity, both male and female adults synthesized a small amount of CTD, while after sexual maturity, males produced larger amounts of CTD, but females did not. The newly synthesized CTD in males first appeared in the hemolymph and then accumulated in the reproductive system. During the mating, the males transferred CTD to the reproductive system of females. In addition, a farnesyl pyrophosphate synthase (FPPS) gene was identified in male E. impressicornis. RNA-seq analysis, quantitative RT-PCR, and RNA interference analyses were conducted to investigate expression patterns and the functional roles of E. impressicornis FPPS (EiFPPS). Our results indicate that EiFPPS is highly expressed in the fat body of males. Moreover, the knock-down of EiFPPS led to a significant decrease in CTD synthesis. The current study indicates that EiFPPS is expressed in the fat body to regulate CTD synthesis in male E. impressicornis blister beetles.

Efficient and Stable Air-Processed Organic Solar Cells Enabled by an Antioxidant Additive.

Current high-efficiency organic solar cells (OSCs) are generally fabricated in an inert atmosphere that limits their real-world scalable manufacturing, while the efficiencies of air-processed OSCs lag far behind. The impacts of ambient factors on solar cell fabrication remain unclear. In this work, the effects of ambient factors on cell fabrication are systematically investigated, and it is unveiled that the oxidation and doping of organic light absorbers are the dominant reasons causing cell degradation when fabricated in air. To address this issue, a new strategy for fabricating high-performance air-processed OSCs by introducing an antioxidant additive (4-bromophenylhydrazine, BPH) into the precursor solutions, is developed. BPH can effectively inhibit oxygen infiltration from the ambient to the photoactive layer and suppress trap formation caused by oxidation. Compared with conventional air-processed OSCs, this strategy remarkably increases the cell power conversion efficiency (PCE) from 16.7% to 19.3% (independently certified as 19.2%), representing the top value of air-processed OSCs. Furthermore, BPH significantly improves the operational stability of the cells in air by two times with a T80 lifetime of over 500 h. This study highlights the potential of using antioxidant additives to fabricate high-efficiency and stable OSCs in air, significantly promoting the industrialization of OSCs.

Elucidating the role of exogenous melatonin in mitigating alkaline stress in soybeans across different growth stages: a transcriptomic and metabolomic approach.

BACKGROUND: Soybean (Glycine max), a vital grain and oilseed crop, serves as a primary source of plant protein and oil. Soil salinization poses a significant threat to soybean planting, highlighting the urgency to improve soybean resilience and adaptability to saline stress. Melatonin, recently identified as a key plant growth regulator, plays crucial roles in plant growth, development, and responses to environmental stress. However, the potential of melatonin to mitigate alkali stress in soybeans and the underlying mechanisms remain unclear. RESULTS: This study investigated the effects of exogenous melatonin on the soybean cultivar Zhonghuang 13 under alkaline stress. We employed physiological, biochemical, transcriptomic, and metabolomic analyses throughout both vegetative and pod-filling growth stages. Our findings demonstrate that melatonin significantly counteracts the detrimental effects of alkaline stress on soybean plants, promoting plant growth, photosynthesis, and antioxidant capacity. Transcriptomic analysis during both growth stages under alkaline stress, with and without melatonin treatment, identified 2,834 and 549 differentially expressed genes, respectively. These genes may play a vital role in regulating plant adaptation to abiotic stress. Notably, analysis of phytohormone biosynthesis pathways revealed altered expression of key genes, particularly in the ARF (auxin response factor), AUX/IAA (auxin/indole-3-acetic acid), and GH3 (Gretchen Hagen 3) families, during the early stress response. Metabolomic analysis during the pod-filling stage identified highly expressed metabolites responding to melatonin application, such as uteolin-7-O-(2''-O-rhamnosyl)rutinoside and Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside, which helped alleviate the damage caused by alkali stress. Furthermore, we identified 183 differentially expressed transcription factors, potentially playing a critical role in regulating plant adaptation to abiotic stress. Among these, the gene SoyZH13_04G073701 is particularly noteworthy as it regulates the key differentially expressed metabolite, the terpene metabolite Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. WGCNA analysis identified this gene (SoyZH13_04G073701) as a hub gene, positively regulating the crucial differentially expressed metabolite of terpenoids, Hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)glucoside. Our findings provide novel insights into how exogenous melatonin alleviates alkali stress in soybeans at different reproductive stages. CONCLUSIONS: Integrating transcriptomic and metabolomic approaches, our study elucidates the mechanisms by which exogenous melatonin ameliorates the inhibitory effects of alkaline stress on soybean growth and development. This occurs through modulation of biosynthesis pathways for key compounds, including terpenes, flavonoids, and phenolics. Our findings provide initial mechanistic insights into how melatonin mitigates alkaline stress in soybeans, offering a foundation for molecular breeding strategies to enhance salt-alkali tolerance in this crop.

Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.

BACKGROUND: The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well-tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin-induced heart failure. METHODS AND RESULTS: Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

Exploring Dynamic Changes in HIV-1 Molecular Transmission Networks and Key Influencing Factors: Cross-Sectional Study.

BACKGROUND: The HIV-1 molecular network is an innovative tool, using gene sequences to understand transmission attributes and complementing social and sexual network studies. While previous research focused on static network characteristics, recent studies' emphasis on dynamic features enhances our understanding of real-time changes, offering insights for targeted interventions and efficient allocation of public health resources. OBJECTIVE: This study aims to identify the dynamic changes occurring in HIV-1 molecular transmission networks and analyze the primary influencing factors driving the dynamics of HIV-1 molecular networks. METHODS: We analyzed and compared the dynamic changes in the molecular network over a specific time period between the baseline and observed end point. The primary factors influencing the dynamic changes in the HIV-1 molecular network were identified through univariate analysis and multivariate analysis. RESULTS: A total of 955 HIV-1 polymerase fragments were successfully amplified from 1013 specimens; CRF01_AE and CRF07_BC were the predominant subtypes, accounting for 40.8% (n=390) and 33.6% (n=321) of the specimens, respectively. Through the analysis and comparison of the basic and terminal molecular networks, it was discovered that 144 sequences constituted static molecular networks, and 487 sequences contributed to the formation of dynamic molecular networks. The findings of the multivariate analysis indicated that the factors occupation as a student, floating population, Han ethnicity, engagement in occasional or multiple sexual partnerships, participation in anal sex, and being single were independent risk factors for the dynamic changes observed in the HIV-1 molecular network, and the odds ratio (OR; 95% CIs) values were 2.63 (1.54-4.47), 1.83 (1.17-2.84), 2.91 (1.09-7.79), 1.75 (1.06-2.90), 4.12 (2.48-6.87), 5.58 (2.43-12.80), and 2.10 (1.25-3.54), respectively. Heterosexuality and homosexuality seem to exhibit protective effects when compared to bisexuality, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. Additionally, the National Eight-Item score and sex education experience were also identified as protective factors against dynamic changes in the HIV-1 molecular network, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. CONCLUSIONS: The HIV-1 molecular network analysis showed 144 sequences in static networks and 487 in dynamic networks. Multivariate analysis revealed that occupation as a student, floating population, Han ethnicity, and risky sexual behavior were independent risk factors for dynamic changes, while heterosexuality and homosexuality were protective compared to bisexuality. A higher National Eight-Item score and sex education experience were also protective factors. The identification of HIV dynamic molecular networks has provided valuable insights into the characteristics of individuals undergoing dynamic alterations. These findings contribute to a better understanding of HIV-1 transmission dynamics and could inform targeted prevention strategies.

Nanoplastics Detected in Commercial Sea Salt.

People of all ages consume salt every day, but is it really just salt? Plastic nanoparticles [nanoplastics (NPs)] pose an increasing environmental threat and have begun to contaminate everyday salt in consumer goods. Herein, we developed a combined surface enhanced Raman scattering (SERS) and stimulated Raman scattering (SRS) approach that can realize the filtration, enrichment, and detection of NPs in commercial salt. The Au-loaded (50 nm) anodic alumina oxide substrate was used as the SERS substrate to explore the potential types of NP contaminants in salts. SRS was used to conduct imaging and quantify the presence of the NPs. SRS detection was successfully established through standard plastics, and NPs were identified through the match of the hydrocarbon group of the nanoparticles. Simultaneously, the NPs were quantified based on the high spatial resolution and rapid imaging of the SRS imaging platform. NPs in sea salts produced in Asia, Australasia, Europe, and the Atlantic were studied. We estimate that, depending on the location, an average person could be ingesting as many as 6 million NPs per year through the consumption of sea salt alone. The potential health hazards associated with NP ingestion should not be underestimated.

Pangenome analyses of Clostridium butyricum provide insights into its genetic characteristics and industrial application.

Clostridium butyricum is a Gram-positive anaerobic bacterium known for its ability to produce butyate. In this study, we conducted whole-genome sequencing and assembly of 14C. butyricum industrial strains collected from various parts of China. We performed a pan-genome comparative analysis of the 14 assembled strains and 139 strains downloaded from NCBI. We found that the genes related to critical industrial production pathways were primarily present in the core and soft-core gene categories. The phylogenetic analysis revealed that strains from the same clade of the phylogenetic tree possessed similar antibiotic resistance and virulence factors, with most of these genes present in the shell and cloud gene categories. Finally, we predicted the genes producing bacteriocins and botulinum toxins as well as CRISPR systems responsible for host defense. In conclusion, our research provides a desirable pan-genome database for the industrial production, food application, and genetic research of C. butyricum.

Electrospray Nano-Micro Composite Sodium Alginate Microspheres with Shape-Adaptive, Antibacterial, and Angiogenic Abilities for Infected Wound Healing.

Nonhealing infectious wounds, characterized by bacterial colonization, wound microenvironment destruction, and shape complexity, present an intractable problem in clinical practice. Inspired by LEGOs, building-block toys that can be assembled into desired shapes, we proposed the use of electrospray nano-micro composite sodium alginate (SA) microspheres with antibacterial and angiogenic properties to fill irregularly shaped wounds instantly. Specifically, porous poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) encapsulating basic fibroblast growth factor (bFGF) were produced by a water-in-oil-in-water double-emulsion method. Then, bFGF@MSs were blended with the SA solution containing ZIF-8 nanoparticles. The resultant solution was electrosprayed to obtain nano-micro composite microspheres (bFGF@MS/ZIF-8@SAMSs). The composite MSs' size could be regulated by PLGA MS mass proportion and electrospray voltage. Moreover, bFGF, a potent angiogenic agent, and ZIF-8, bactericidal nanoparticles, were found to release from bFGF@MS/ZIF-8@SAMSs in a controlled and sustainable manner, which promoted cell proliferation, migration, and tube formation and killed bacteria. Through experimentation on rat models, bFGF@MS/ZIF-8@SAMSs were revealed to adapt to wound shapes and accelerate infected wound healing because of the synergistic effects of antibacterial and angiogenic abilities. In summation, this study developed a feasible approach to prepare bioactive nano-micro MSs as building blocks that can fill irregularly shaped infected wounds and improve healing.

Air-Processed Perovskite Solar Cells with >25% Efficiency and High Stability Enabled by Crystallization Modulation and Holistic Passivation.

Organic semiconductors (e.g., PCBM and IDIC) frequently serve as interface passivants for perovskite solar cells (PSCs) due to their beneficial passivation effects on perovskite interfaces. However, their passivation to the interiors of perovskite films is greatly limited by their poor solubility in polar solvents and compatibility issues. Here the facile synthesis of organic semiconductor nanoparticle (NP) passivants that readily disperse in perovskite inks is reported. Adding these NPs into perovskite inks not only modulates perovskite crystallization, improves film quality and conductivity, but also achieves holistic bulk film passivation. Consequently, blade-coated p-i-n PSCs with ICBA NPs achieve an impressive efficiency of 25.1% (independently certified as 25.0%), the highest reported value for air-processed PSCs irrespective of fabrication methods or device structures. This work develops a novel approach for effective and holistic perovskite passivation by converting conventional passivants to perovskite-compatible NPs, paving the way for more efficient and stable perovskite solar devices.

Physiological and transcriptomic responses of silkworms to graphene oxide exposure.

The growing use of nanomaterials has sparked significant interest in assessing the insect toxicities of nanoparticles. The silkworm, as an economically important insect, serves as a promising model for studying how insects respond to harmful substances. Here, we conducted a comprehensive investigation on the impact of graphene oxide (GO) on silkworms using a combination of physiological and transcriptome analyses. GO can enter the midguts and posterior silk glands of silkworms. High GO concentrations (> 25 mg/L) significantly (P < 0.01) inhibited larval growth. Additionally, GO (> 5 mg/L) significantly reduced the cocooning rate, and GO (> 15 mg/L) hindered oviduct development and egg laying in silkworms. GO increased the reactive oxygen species content and regulated catalase activity, suggesting that it may affect insect growth by regulating reactive oxygen detoxification. The transcriptome data analysis showed that 35 metabolism-related genes and 20 ribosome biogenesis-related genes were differentially expressed in response to GO, and their expression levels were highly correlated. Finally, we propose that a Ribosome biogenesis-Metabolic signaling network is involved in responses to GO. The research provides a new perspective on the molecular responses of insects to GO.

Exploring the mechanism of agarwood moxa smoke in treating sleep disorders based on GC-MS and network pharmacology.

Background: Agarwood moxibustion is a folk therapy developed by individuals of the Li nationality in China. There is evidence that agarwood moxa smoke (AMS) generated during agarwood moxibustion therapy can treat sleep disorders via traditional Chinese medicines' multiple target and pathway characteristics. However, the specific components and mechanisms involved have yet to be explored. Objective: GC-MS (Gas Chromatography-Mass Spectrometry) and network pharmacology were used to investigate AMS's molecular basis and mechanism in treating sleep deprivation. Method: GC-MS was used to determine the chemical composition of AMS; component target information was collected from TCMSP (Traditional Chinese Medicine Systems Pharmacology), PubChem (Public Chemical Database), GeneCards (Human Gene Database), and DisGeNet (Database of Genes and Diseases) were used to identify disease targets, and JVenn (Joint Venn) was used to identify the common targets of AMS and sleep disorders. STRING was used to construct a protein interaction network, Cytoscape 3.9.1 was used to build a multilevel network diagram of the "core components-efficacy targets-action pathways," the targets were imported into Metascape and DAVID for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses and Autodock was used for molecular docking. This research used a network pharmacology methodology to investigate the therapeutic potential of Agarwood Moxa Smoke (AMS) in treating sleep problems. Examining the target genes and chemical constituents of AMS offers insights into the molecular processes and targets of the disease. Result: Nine active ingredients comprising anti-inflammatory substances and antioxidants, such as caryophyllene and p-cymene, found seven sleep-regulating signaling pathways and eight targets linked to sleep disorders. GC-MS was used to identify the 94 active ingredients in AMS, and the active ingredients had strong binding with the key targets. Key findings included active components with known medicinal properties, such as p-cymene, eucalyptol, and caryophyllene. An investigation of network pharmacology revealed seven signaling pathways for sleep regulation and eight targets linked to sleep disorders, shedding light on AMS's effectiveness in enhancing sleep quality. Conclusion: AMS may alleviate sleep disorders by modulating cellular and synaptic signaling, controlling hormone and neurotransmitter pathways, etc. Understanding AMS's material basis and mechanism of action provides a foundation for future research on treating sleep disorders with AMS. According to the study, Agarwood Moxa Smoke (AMS) may improve sleep quality by modifying cellular and synaptic signaling pathways for those who suffer from sleep problems. This might lead to the development of innovative therapies with fewer side effects.

Utilizing metabolomics and network analysis to explore the effects of artificial production methods on the chemical composition and activity of agarwood.

Introduction: Agarwood is a traditional aromatic southern medicine. It has a long history of being used in traditional Chinese aromatherapy to treat insomnia, anxiety and depression. Due to the scarcity of wild resources, people have planted trees successfully and begun to explore various agarwood-inducing techniques. This study comparative analysis of volatile metabolites in agarwood produced by various inducing techniques and its potential sleep-promoting, anti-anxiety and anti-depressant network pharmacological activities. Methods: A total of 23 batches of two types of agarwood were collected, one of which was produced by artificial techniques, including 6 batches of TongTi (TT) agarwood produced by "Agar-Wit" and 6 batches of HuoLao (HL) agarwood produced by "burning, chisel and drilling", while the other was collected from the wild, including 6 batches of BanTou (BT) agarwood with trunks broken due to natural or man-made factors and 5 batches of ChongLou (CL) agarwood with trunks damaged by moth worms. The study employed metabolomics combined with network analysis to compare the differences in volatile metabolites of agarwood produced by four commonly used inducing techniques, and explored their potential roles and possible action targets in promoting sleep, reducing anxiety, and alleviating depression. Results: A total of 147 volatile metabolites were detected in agarwood samples, mainly including small aromatic hydrocarbons, sesquiterpenes and 2-(2-phenylethyl) chromone and their pyrolysis products. The results showed composition of metabolites was minimally influenced by the agarwood induction method. However, their concentrations exhibited significant variations, with 17 metabolites showing major differences. The two most distinct metabolites were 6-methoxy-2-(2-phenylethyl) chromone and 6,7-dimethoxy-2-(2-phenylethyl) chromone. Among the volatile metabolites, 142 showed promising potential in treating insomnia, anxiety, and depression, implicating various biological and signaling pathways, predominantly ALB and TNF targets. The top three active metabolites identified were 2-(2-phenylethyl) chromone, 1,5-diphenylpent-1-en-3-one, and 6-methoxy-2-[2-(4'-methoxyphenyl) ethyl] chromone, with their relative content in the four types of agarwood being TT>HL>CL>BT. Conclusion: The differences in the content of 2-(2-phenylethyl) chromones suggest that they may be responsible for the varying therapeutic activities observed in different types of agarwood aromatherapy. This study offers theoretical support for the selection of agarwood in aromatherapy practices.

Acupuncture alleviates inflammatory pain by activating CXCL1/CXCR2 signaling in the primary somatosensory cortex in adjuvant induced arthritis rats. / S1脑区CXCL1/CXCR2å‚ä¸Žé’ˆåˆºæ”¹å–„ä½å‰‚æ€§å ³èŠ‚ç‚Žå¤§é¼ ç‚Žæ€§ç—›çš„ä½œç”¨æœºåˆ¶.

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups (n=2 in each group). AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study. In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions. After thermal pain screening, the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta, then were randomized into model and manual acupuncture groups (n=12 in each group). Other 12 rats that received planta injection of saline were used as the control group. Manual acupuncture (uniform reinforcing and reducing manipulations) was applied to bilateral "Zusanli" (ST36) for 4×2 min, with an interval of 5 min between every 2 min, once daily for 7 days. The thermal pain threshold was assessed by detecting the paw withdrawal latency (PWL) using a thermal pain detector. The contents of CXCL1 in the primary somatosensory cortex (S1), medial prefrontal cortex, nucleus accumbens, amygdala, periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA, and the expression levels of CXCL1, CXCR2 and mu-opioid receptor (MOR) mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction. The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain. The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein (GFAP) or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them. RESULTS: In AIA mice, results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+CXCL1 in any organ of the body, while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain. In rats, compared with the control group, the PWL from day 0 to day 7 was significantly decreased (P<0.01) and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group (P<0.05), while in comparison with the model group, the PWL from day 2 to day 7, CXCL1 content, CXCR2 mRNA expression and CXCR2 content, and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group (P<0.05, P<0.01). Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region, indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes. CONCLUSIONS: Acupuncture can increase the content of CXCL1 in S1 region, up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats, which may contribute to its effect in alleviating inflammatory pain.

Coupled conversion of polyethylene and carbon dioxide catalyzed by a zeolite-metal oxide system.

Zeolite-catalyzed polyethylene (PE) aromatization achieves reduction of the aromatic yield via hydrogenation and hydrogenolysis reactions. The hydrogen required for CO2 hydrogenation can be provided by H radicals formed during aromatization. In this study, we efficiently convert PE and CO2 into aromatics and CO using a zeolite-metal oxide catalyst (HZSM-5 + CuZnZrOx) at 380°C and under hydrogen- and solvent-free reaction conditions. Hydrogen, derived from the aromatization of PE over HZSM-5, diffuses through the Brønsted acidic sites of the zeolite to the adjacent CuZnZrOx, where it is captured in situ by CO2 to produce bicarbonate and further hydrogenated to CO. This favors aromatization while inhibiting hydrogenation and secondary hydrogenolysis reactions. An aromatic yield of 62.5 wt % is achieved, of which 60% consisted of benzene, toluene, and xylene (BTX). The conversion of CO2 reaches values as high as 0.55 mmol gPE-1. This aromatization-hydrogen capture pathway provides a feasible scheme for the comprehensive utilization of waste plastics and CO2.

Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer.

Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period.

Ginsenoside Rb1 attenuates doxorubicin induced cardiotoxicity by suppressing autophagy and ferroptosis.

Ginsenoside Rb1 (Rb1), an active component isolated from traditional Chinese medicine Ginseng, is beneficial to many cardiovascular diseases. However, whether it can protect against doxorubicin induced cardiotoxicity (DIC) is not clear yet. In this study, we aimed to investigate the role of Rb1 in DIC. Mice were injected with a single dose of doxorubicin (20 mg/kg) to induce acute cardiotoxicity. Rb1 was given daily gavage to mice for 7 days. Changes in cardiac function, myocardium histopathology, oxidative stress, cardiomyocyte mitochondrion morphology were studied to evaluate Rb1's function on DIC. Meanwhile, RNA-seq analysis was performed to explore the potential underline molecular mechanism involved in Rb1's function on DIC. We found that Rb1 treatment can improve survival rate and body weight in Dox treated mice group. Rb1 can attenuate Dox induced cardiac dysfunction and myocardium hypertrophy and interstitial fibrosis. The oxidative stress increase and cardiomyocyte mitochondrion injury were improved by Rb1 treatment. Mechanism study found that Rb1's beneficial role in DIC is through suppressing of autophagy and ferroptosis. This study shown that Ginsenoside Rb1 can protect against DIC by regulating autophagy and ferroptosis.