Screening of potentially active compounds against rheumatoid arthritis in the Juan-Bi decoction using systems pharmacology and animal experiments.

Background: The Juan-Bi decoction (JBD) is a classic traditional Chinese medicines (TCMs) prescription for the treatment of rheumatoid arthritis (RA). However, the active compounds of the JBD in RA treatment remain unclear. Aim: The aim of this study is to screen effective compounds in the JBD for RA treatment using systems pharmacology and experimental approaches. Method: Botanical drugs and compounds in the JBD were acquired from multiple public TCM databases. All compounds were initially screened using absorption, distribution, metabolism, excretion, and toxicity (ADMET) and physicochemical properties, and then a target prediction was performed. RA pathological genes were acquired from the DisGeNet database. Potential active compounds were screened by constructing a compound-target-pathogenic gene (C-T-P) network and calculating the cumulative interaction intensity of the compounds on pathogenic genes. The effectiveness of the compounds was verified using lipopolysaccharide (LPS)-induced RAW.264.7 cells and collagen-induced arthritis (CIA) mouse models. Results: We screened 15 potentially active compounds in the JBD for RA treatment. These compounds primarily act on multiple metabolic pathways, immune pathways, and signaling transduction pathways. Furthermore, in vivo and in vitro experiments showed that bornyl acetate (BAC) alleviated joint damage, and inflammatory cells infiltrated and facilitated a smooth cartilage surface via the suppression of the steroid hormone biosynthesis. Conclusion: We screened potential compounds in the JBD for the treatment of RA using systems pharmacology approaches. In particular, BAC had an anti-rheumatic effect, and future studies are required to elucidate the underlying mechanisms.

Boosting Catalytic and Anti-fluorination Performance of the Ru/Vanadia-Titania Catalyst for the Oxidative Destruction of Freon by Sulfuric Acid Modification.

Chlorofluorocarbons (CFCs) exert a strong greenhouse effect and constitute the largest contributor to ozone depletion. Catalytic removal is considered an effective pathway for eliminating low-concentration CFCs under mild conditions. The key issue is the easy deactivation of the catalysts due to their surface fluorination. We herein report a comparative investigation on catalytic dichlorodifluoromethane (CFC-12) removal in the absence or presence of water over the sulfuric-acid-modified three-dimensionally ordered macroporous vanadia-titania-supported Ru (S-Ru/3DOM VTO) catalysts. The S-Ru/3DOM VTO catalyst exhibited high activity (T90% = 278 °C at space velocity = 40 000 mL g-1 h-1) and good stability within 60 h of on-stream reaction in the presence of 1800 ppm of water due to the improvements in acid site amount and redox ability that promoted the adsorption of CFC-12 and the activation of C-F bonds. Compared with the case under dry conditions, catalytic performance for CFC-12 removal was better over the S-Ru/3DOM VTO catalyst in the presence of water. Water introduction mitigated surface fluorination by the replenishment of hydroxyl groups, inhibited the formation of halogenated byproducts via the surface fluorine species cleaning effect, and promoted the reaction pathway of COX2 (X = Cl/F) → carboxylic acid → CO2.

Lipoprotein(a), Oxidized Phospholipids, and Progression to Symptomatic Heart Failure: The CASABLANCA Study.

BACKGROUND: Higher lipoprotein(a) and oxidized phospholipid concentrations are associated with increased risk for coronary artery disease and valvular heart disease. The role of lipoprotein(a) or oxidized phospholipid as a risk factor for incident heart failure (HF) or its complications remains uncertain. METHODS AND RESULTS: A total of 1251 individuals referred for coronary angiography in the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study were stratified on the basis of universal definition of HF stage; those in stage A/B (N=714) were followed up for an average 3.7 years for incident stage C/D HF or the composite of HF/cardiovascular death. During follow-up, 105 (14.7%) study participants in stage A/B progressed to symptomatic HF and 57 (8.0%) had cardiovascular death. In models adjusted for multiple HF risk factors, including severe coronary artery disease and aortic stenosis, individuals with lipoprotein(a) ≥150 nmol/L were at higher risk for progression to symptomatic HF (hazard ratio [HR], 1.90 [95% CI, 1.15-3.13]; P=0.01) or the composite of HF/cardiovascular death (HR, 1.71 [95% CI, 1.10-2.67]; P=0.02). These results remained significant after further adjustment of the model to include prior myocardial infarction (HF: HR, 1.89, P=0.01; HF/cardiovascular death: HR, 1.68, P=0.02). Elevated oxidized phospholipid concentrations were similarly associated with risk, particularly when added to higher lipoprotein(a). In Kaplan-Meier analyses, individuals with stage A/B HF and elevated lipoprotein(a) had shorter time to progression to stage C/D HF or HF/cardiovascular death (both log-rank P<0.001). CONCLUSIONS: Among individuals with stage A or B HF, higher lipoprotein(a) and oxidized phospholipid concentrations are independent risk factors for progression to symptomatic HF or cardiovascular death. REGISTRATION: URL: https://wwwclinicaltrials.gov; Unique identifier: NCT00842868.

Strain-specific gut microbial signatures in type 2 diabetes identified in a cross-cohort analysis of 8,117 metagenomes.

The association of gut microbial features with type 2 diabetes (T2D) has been inconsistent due in part to the complexity of this disease and variation in study design. Even in cases in which individual microbial species have been associated with T2D, mechanisms have been unable to be attributed to these associations based on specific microbial strains. We conducted a comprehensive study of the T2D microbiome, analyzing 8,117 shotgun metagenomes from 10 cohorts of individuals with T2D, prediabetes, and normoglycemic status in the United States, Europe, Israel and China. Dysbiosis in 19 phylogenetically diverse species was associated with T2D (false discovery rate < 0.10), for example, enriched Clostridium bolteae and depleted Butyrivibrio crossotus. These microorganisms also contributed to community-level functional changes potentially underlying T2D pathogenesis, for example, perturbations in glucose metabolism. Our study identifies within-species phylogenetic diversity for strains of 27 species that explain inter-individual differences in T2D risk, such as Eubacterium rectale. In some cases, these were explained by strain-specific gene carriage, including loci involved in various mechanisms of horizontal gene transfer and novel biological processes underlying metabolic risk, for example, quorum sensing. In summary, our study provides robust cross-cohort microbial signatures in a strain-resolved manner and offers new mechanistic insights into T2D.

The extract of an herbal medicine Chebulae fructus inhibits hepatocellular carcinoma by suppressing the Apelin/APJ system.

Introduction: Hepatocellular carcinoma (HCC) has been a highly common and pathological disease worldwide, while current therapeutic regimens have limitations. Chebulae Fructus, a common herbal medicine in Asia, has been documented to exert potential therapeutic effects on HCC in ancient medicine clinical practice. However, the molecular mechanism underlying its inhibitory effects on HCC requires further investigation. Methods: In this study, the anti-HCC effect of the aqueous extract of Chebulae Fructus (CFE) on human HCC and its underlying mechanism were evaluated. Assays including CCK8, EdU staining, crystal violet staining, cell clone formation, flow cytometry, wound healing, and transwell were used in vitro. The cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models were used in vivo. Transcriptomics analysis, qRT-PCR, ELISA, IHC staining, and Western blotting were employed to determine the mechanism of action of CFE. Results: The results demonstrate that CFE effectively suppressed the proliferation and activity of HepG2 and PLC/PRF/5 HCC cells. CFE also induced apoptosis, and suppressed the migration and invasion abilities of these cells. Furthermore, CFE exhibited inhibitory effects on tumor growth in both H22 and PLC/PRF/5 mouse models, as well as in an HCC PDX model which is derived from patient tumor samples. Moreover, it was identified that CFE treatment specifically suppressed the Apelin/APJ system in HCC cells and tumor tissues. To investigate the role of the Apelin/APJ system in mediating the effects of CFE treatment, an APJ overexpressed cell model is established. Interestingly, it was found that the overexpression of APJ significantly diminished the inhibitory effects of CFE on HCC in vitro. Discussion: Collectively, this study provides compelling evidence that CFE exerts significant anti-HCC effects in cell and animal models. Moreover, our findings suggest that the Apelin/APJ system may play a vital role in the therapeutic effects of CFE against HCC.

Sex Differences in Coronary Artery Disease Characteristics Among Patients With Type 2 Myocardial Infarction.

Background: Type 2 myocardial infarction (MI) results from coronary supply and demand imbalance and has a poor prognosis. It is crucial to identify potential sex-based differences in the prevalence and nature of coronary artery disease (CAD) within this population. Objectives: The purpose of this study was to evaluate sex-based disease differences in type 2 MI among patients evaluated with coronary computed tomography angiography and fractional flow reserve. Methods: In a single-center, prospective study, patients with strictly adjudicated type 2 MI underwent coronary computed tomography angiography with fractional flow reserve. Results: Among 50 study participants enrolled, 50% were women. A similar mix of MI precipitants was present in both sexes. ST-segment depression was more common in women (64% vs 32%), while men were more likely to have T wave inversion (68% vs 36%). Women and men had comparable coronary artery calcium scores (median: 152 [Q1, Q3: 45, 762] vs 234 [Q1, Q3: 56, 422]). Prevalence of any CAD (84% vs 100%), obstructive CAD (24% vs 28%), and hemodynamically significant focal stenosis (20% vs 32%) were similar between sexes. Total plaque volume was similar between sexes, but women had significantly lower levels of low-attenuation plaque (median: 3 [Q1, Q3: 1, 7] vs 9 [Q1, Q3: 3, 14]). Conclusions: Among patients with type 2 MI, prevalence of any CAD and obstructive CAD did not differ according to sex. Total plaque volume was similar between sexes, but women had a lower volume of low-attenuation plaque (DEFINing the PrEvalence and Characteristics of Coronary Artery Disease Among Patients With TYPE 2 Myocardial Infarction Using CT-FFR [DEFINE TYPE2MI]; NCT04864119).

Comprehensive pan-cancer analysis of the C2ORF40 expression: Infiltration associations and prognostic implications.

In recent years, C2ORF40 has been identified as a tumor suppressor gene with multiple functions, including roles in cell proliferation, migration, and senescence. To explore the role of the C2ORF40 gene in different tumors, we used multiple databases for analysis. Compared to adjacent normal tissues, C2ORF40 is downregulated in a variety of malignant tumors, including tumors such as breast cancer, colorectal cancer, bladder cancer, hepatocellular carcinoma and prostate cancer. Notably, low expression of the gene is significantly associated with poor overall survival and relapse-free survival rates. In specific cancers including colon cancer and prostate cancer, the expression of C2ORF40 is correlated with the infiltration of CAFs. C2ORF40 is also involved in biological processes such as cell apoptosis and regulation of protein stability. In conclusion, C2ORF40 can hold promise as a prognostic marker for pan-cancer analysis.

Associations between lipoprotein(a), oxidized phospholipids, and extra-coronary vascular disease.

The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPL) in the development and progression of coronary disease is known, but their influence on extra-coronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extra-coronary vascular disease and incident major adverse limb events (MALE). 446 participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extra-coronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (OR 2.14 95% CI: 1.03, 4.44) and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extra-coronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extra-coronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries. These results lay a foundation in support of studying Lp(a) lowering medications and their effect on limb-related complications.

Deconvolution of polygenic risk score in single cells unravels cellular and molecular heterogeneity of complex human diseases.

Polygenic risk scores (PRSs) are commonly used for predicting an individual's genetic risk of complex diseases. Yet, their implication for disease pathogenesis remains largely limited. Here, we introduce scPRS, a geometric deep learning model that constructs single-cell-resolved PRS leveraging reference single-cell chromatin accessibility profiling data to enhance biological discovery as well as disease prediction. Real-world applications across multiple complex diseases, including type 2 diabetes (T2D), hypertrophic cardiomyopathy (HCM), and Alzheimer's disease (AD), showcase the superior prediction power of scPRS compared to traditional PRS methods. Importantly, scPRS not only predicts disease risk but also uncovers disease-relevant cells, such as hormone-high alpha and beta cells for T2D, cardiomyocytes and pericytes for HCM, and astrocytes, microglia and oligodendrocyte progenitor cells for AD. Facilitated by a layered multi-omic analysis, scPRS further identifies cell-type-specific genetic underpinnings, linking disease-associated genetic variants to gene regulation within corresponding cell types. We substantiate the disease relevance of scPRS-prioritized HCM genes and demonstrate that the suppression of these genes in HCM cardiomyocytes is rescued by Mavacamten treatment. Additionally, we establish a novel microglia-specific regulatory relationship between the AD risk variant rs7922621 and its target genes ANXA11 and TSPAN14. We further illustrate the detrimental effects of suppressing these two genes on microglia phagocytosis. Our work provides a multi-tasking, interpretable framework for precise disease prediction and systematic investigation of the genetic, cellular, and molecular basis of complex diseases, laying the methodological foundation for single-cell genetics.

Brain extended and closed forms glutathione levels decrease with age and extended glutathione is associated with visuospatial memory.

During aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combat OS. However, how brain GSH levels vary with age and their associations with cognitive function is unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate extended and closed forms GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (extended form, 166 females, age range 20-70 years) and 15 healthy participants (closed form, 7 females, age range 26-56 years), and examined their relationships with age and cognitive function. The results revealed decreased extended form GSH levels with age in the PCC among 276 participants. Notably, the timecourse of extended form GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between extended form GSH levels in the PCC and OC and visuospatial memory. Additionally, a decreased trend of closed form GSH levels with age was also observed in the PCC among 15 participants. Taken together, these findings enhance our understanding of the brain both closed and extended form GSH time course during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of healthy aging.

Employees' seeking preference towards influenza vaccination in organization: A discrete choice experiment in China.

To clarify the preferences of employees seeking influenza vaccination, a discrete choice experiment aims to understand the essential factors that close the gap between intention and behavior. A total of 866 employees with vaccination willingness willing to participated in a discrete choice experiment (DCE) between October 31st and December 6th, 2022 in China including the following attributes: price, vaccination setting, appointment mode, and service time. The data was analyzed using mixed logit models. Employees from smaller enterprises were more likely to get vaccinated collectively. For employees willing to get the influenza vaccine, 95.08 % of their choice was dominated by price. Employees' behavior varied according to their socioeconomic characteristics. Only female employees strongly favored work-site-based vaccination. Price was the primary factor considered by employees for getting the influenza vaccine. DCE would help to develop influenza vaccination intervention targeted at different groups in future studies.

Development and Validation of the Coronary Heart Disease Scale Among the System of Quality of Life Instruments for Chronic Diseases QLICD-CHD (V2.0) Based on Classical Test Theory and Generalizability Theory.

Objective: Coronary heart disease (CHD) is a common and frequent disease with a long and incurable course, and the quality of life of patients is severely reduced. This study was to develop and validate a quality of life scale for patients with CHD based on the Chinese context. Methods: The scale QLICD-CHD (V2.0) was developed based on the QLICD-CHD (V1.0), using a programmed decision procedures. Based on the data measuring QoL 3 times before and after treatments from 189 patients with CHD, the psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness employing correlation analysis, multi-trait scaling analysis, structural equation modeling, t-test and also G-study and D-study of generalizability theory analysis. The SF-36 scale was used as the criterion to evaluate the criterion-related validity. Paired t tests were conducted to evaluate the responsiveness on each domain/facet as well as the total of the scale, with Standardized Response Mean (SRM) being calculated. Results: The QLICD-CHD (V2.0) has been developed with 42 items in 4 domains. The Cronbach's α of the general module, the specific module and the total scale were 0.91, 0.92 and 0.91 respectively. The overall score and the test-retest reliability coefficients in all domains are higher than 0.60, except for the specific module. Correlation and factor analysis confirmed good construct validity and criterion-related validity. After treatments, the overall score and score of all domains have statistically significant changes (P<0.01). The SRM of domain-level score ranges from 0.27 to 0.50. Generalizability Theory further confirm the reliability of the scale through more accurate variance component studies. Conclusion: The QLICD-CHD (V2.0) could be used as a useful instrument in assessing QoL for patients with CHD, with good psychometric properties.

Interfacial interactions between spider silk protein and cellulose studied by molecular dynamics simulation.

CONTEXT: Due to their excellent biocompatibility and degradability, cellulose/spider silk protein composites hold a significant value in biomedical applications such as tissue engineering, drug delivery, and medical dressings. The interfacial interactions between cellulose and spider silk protein affect the properties of the composite. Therefore, it is important to understand the interfacial interactions between spider silk protein and cellulose to guide the design and optimization of composites. The study of the adsorption of protein on specific surfaces of cellulose crystal can be very complex using experimental methods. Molecular dynamics simulations allow the exploration of various physical and chemical changes at the atomic level of the material and enable an atomic description of the interactions between cellulose crystal planes and spider silk protein. In this study, molecular dynamics simulations were employed to investigate the interfacial interactions between spider silk protein (NTD) and cellulose surfaces. Findings of RMSD, RMSF, and secondary structure showed that the structure of NTD proteins remained unchanged during the adsorption process. Cellulose contact numbers and hydrogen bonding trends on different crystalline surfaces suggest that van der Waals forces and hydrogen bonding interactions drive the binding of proteins to cellulose. These findings reveal the interaction between cellulose and protein at the molecular level and provide theoretical guidance for the design and synthesis of cellulose/spider silk protein composites. METHODS: MD simulations were all performed using the GROMACS-5.1 software package and run with CHARMM36 carbohydrate force field. Molecular dynamics simulations were performed for 500 ns for the simulated system.

Item analysis on the quality of life scale for anxiety disorders QLICD-AD(V2.0) based on classical test theory and item response theory.

BACKGROUND: Anxiety disorders can cause serious physical and psychological damage, so many anxiety scales have been developed internationally to measure anxiety disorders, but due to the cultural differences and cultural dependence of quality of life between Chinese and Western cultures, it is difficult to reflect the main characteristics of Chinese patients. Therefore, we developed a scale suitable for Chinese patients with anxiety disorders: the Anxiety Disorders Scale of the Quality of Life Instruments for Chronic Diseases (QLICD-AD), hoping to achieve satisfactory QOL assessments for anxiety disorders. OBJECTIVES: Items from the Anxiety Disorders Scale of the Quality of Life in Chronic Disease Instrument QLICD-AD system were analyzed using CTT and IRT to lay the groundwork for further refinement of the scale to accurately measure anxiety disorders. METHODS: 120 patients with anxiety disorder were assessed using the QLICD-AD (V2.0). Descriptive statistics, variability method, correlation coefficient method, factor analysis and Cronbach's coefficient of CTT, and graded response model (GRM) of item response theory were used to analyze the items of the scale. RESULT: CTT analysis showed that the standard deviation of each item was between 0.928 and 1.466; Pearson correlation coefficients of item-to-domain were generally greater than 0.5 and also greater than that of item-to-other domain; the Cronbach 's of the total scale was 0.931, α of each domain was between 0.706 and 0.865. IRT analysis showed that the discrimination was between 1.14 and 1.44. The difficulty parameter of all items increased with the increase of grade. But some items (GPH6,GPH8,GPS3,GSO2-GSO4,AD2,AD5) difficulty parameters were less than 4 or greater than 4. The average of information amount was between 0.022 and 0.910. CONCLUSION: Based on CTT and IRT analysis, most items of the QLICD-AD (V2.0) scale have good performance and good differentiation, but a few items still need further revision. Suggests that the QLICD-AD (V2.0) appears to be a valid measure of anxiety disorders. It may effectively improve the diagnosticity of anxiety disorders, but due to the limitations of the current sample, further validation is needed in a broader population extrapolation trial.

Strain-Controlled Formation Energy and Migration of Nitrogen Vacancy in Al1-xScxN: A First-Principles Study.

The impact of strain on the formation energy and migration behavior of nitrogen vacancies (VNs) in Al1-xScxN has been investigated by first-principles calculations. The formation energy of VNs is obtained by total energy calculations. The migration barrier calculation utilizes the climbing nudged elastic band method. It is found that the formation energy of VNs is highly tunable with respect to the strain. The formation energy of VNs increases with the tensile strain increasing to +4% and decreases with the increasing compressive strain to -4%. A minimum formation energy of 4.11 eV is obtained when -4% strain is applied. Furthermore, the migration behavior of VNs is studied by calculating the migration barriers. Calculation results show that the migration barrier is strongly affected by strain. When the strain is -4%, the barrier is 2.46 eV while the barrier is increased to 2.71 eV under +4% strain. Therefore, a tensile strain can prevent the formation and migration of VNs. These findings suggest that strain engineering may serve as a tool for regulating VNs behavior in Al1-xScxN, potentially alleviating the ferroelectric degradations associated with VNs.

Genetic Risk, Health-Associated Lifestyle, and Risk of Early-onset Total Cancer and Breast Cancer.

Importance: Early-onset cancer (diagnosed under 50 years of age) is associated with aggressive disease characteristics and its rising incidence is a global concern. The association between healthy lifestyle and early-onset cancer and whether it varies by common genetic variants is unknown. Objective: To examine the associations between genetic risk, lifestyle, and risk of early-onset cancers. Design Setting and Participants: We analyzed a prospective cohort of 66,308 white British participants who were under age 50 and free of cancer at baseline in the UK Biobank. Exposures: Sex-specific composite total cancer polygenic risk scores (PRSs), a breast cancer-specific PRS, and sex-specific health-associated lifestyle scores (HLSs, which summarize smoking status, body mass index [males only], physical activity, alcohol consumption, and diet). Main Outcomes and Measures: Hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset total and breast cancer. Results: A total of 1,247 incident invasive early-onset cancer cases (female: 820, male: 427, breast: 386) were documented. In multivariable-adjusted analyses with 2-year latency, higher genetic risk (highest vs. lowest tertile of PRS) was associated with significantly increased risks of early-onset total cancer in females (HR, 95% CI: 1.85, 1.50-2.29) and males (1.94, 1.45-2.59) as well as early-onset breast cancer in females (3.06, 2.20-4.25). An unfavorable lifestyle (highest vs. lowest category of HLS) was associated with higher risk of total cancer and breast cancer in females across genetic risk categories; the association with total cancer was stronger in the highest genetic risk category than the lowest: HRs in females and men were 1.85 (1.02, 3.36), 3.27 (0.78, 13.72) in the highest genetic risk category and 1.15 (0.44, 2.98), 1.16 (0.39, 3.40) in the lowest. Conclusions and Relevance: Both genetic and lifestyle factors were independently associated with early-onset total and breast cancer risk. Compared to those with low genetic risk, individuals with a high genetic risk may benefit more from adopting a healthy lifestyle in preventing early-onset cancer.

Progress of research on the bonding-strength improvement of two-layer adhesive-free flexible copper-clad laminates.

The arrival of the 5G era has placed high demands on the electronic products. Developing thin, light, and portable electronic products capable of simultaneously improving the transmission rate and reducing the signal delay and transmission loss is necessary to meet such demands. The traditional three-layer, adhesive, flexible copper-clad laminate (3L-FCCL) cannot satisfy these demands because of its adhesive component. The large thickness and poor heat resistance disadvantages of 3L-FCCL can be avoided with a two-layer, adhesive-free, flexible copper-clad laminate (2L-FCCL). However, 2L-FCCL has low bonding strength. This work introduces the selection of conductor materials and insulating base films for flexible copper-clad laminates. Modification studies aimed at increasing the bonding performance of 2L-FCCL are summarized based on three aspects. These modification techniques include the surface treatment of copper foils, modification and surface treatment of polyimide films, and surface treatment of liquid-crystal polymers. Prospects are further provided.

Partial substitution of chemical fertilizer by organic fertilizer increases yield, quality and nitrogen utilization of Dioscorea polystachya.

This field experiment aimed to investigate the effects of different ratios of organic and inorganic fertilizers with maintaining equal nitrogen application rates on the yield, quality, and nitrogen uptake efficiency of Dioscorea polystachya (yam). Six treatments were set, including a control without fertilizer (CK), sole application of chemical fertilizer (CF), sole application of organic fertilizer (OM), 25% organic fertilizer + 75% chemical fertilizer (25%OM + 75%CF), 50% organic fertilizer + 50% chemical fertilizer (50%OM + 50%CF), and 75% organic fertilizer + 25% chemical fertilizer (75%OM + 25%CF). The experiment followed a randomized complete block design with three replications. Various yield parameters, morphology, quality indicators, and nitrogen utilization were analyzed to assess the differences among treatments. The results indicated that all fertilizer treatments significantly increased the yield, morphology, quality indicators, and nitrogen utilization efficiency compared to the control. Specifically, 25%OM + 75%CF achieved the highest yield of 31.96 t hm-2, which was not significantly different from CF (30.18 t hm-2). 25%OM + 75%CF exhibited the highest values at 69.23 cm in tuber length and 75.86% in commodity rate, 3.14% and 1.57% higher than CF respectively. Tuber thickness and fresh weight of 25%OM + 75%CF showed no significant differences from CF, while OM and 50%OM+50%CF exhibited varying degrees of reduction compared to CF. Applying fertilizer significantly enhanced total sugar, starch, crude protein, total amino acid, and ash contents of D. polystachya (except ash content between CK and OM). Applying organic fertilizer increased the total sugar, starch, crude protein, total amino acid, and ash contents in varying degrees when compared with CF. The treatment with 25%OM+75%CF exhibited the highest increases of 6.31%, 3.78%, 18.40%, 29.70%, and 10%, respectively. Nitrogen content in different plant parts followed the sequence of tuber > leaves > stems > aerial stem, with the highest nitrogen accumulation observed in 25%OM + 75%CF treatment. Nitrogen harvest index did not show significant differences among treatments, fluctuating between 0.69 and 0.74. The nitrogen apparent utilization efficiency was highest in 25%OM + 75%CF (9.89%), followed by CF (9.09%), both significantly higher than OM (5.32%) and 50%OM + 50%CF (6.69%). The nitrogen agronomic efficiency varied significantly among treatments, with 25%OM + 75%CF (33.93 kg kg-1) being the highest, followed by CF (29.68 kg kg-1), 50%OM + 50%CF (21.82 kg kg-1), and OM (11.85 kg kg-1). Nitrogen partial factor productivity was highest in 25%OM + 75%CF treatment (76.37 kg kg-1), followed by CF (72.11 kg kg-1), both significantly higher than 50%OM + 50%CF (64.25 kg kg-1) and OM (54.29 kg kg-1), with OM exhibiting significantly lower values compared to other treatments. In conclusion, the combined application of organic and inorganic fertilizers can effectively enhance the yield, quality, and nitrogen utilization efficiency of D. polystachya. Particularly, the treatment with 25% organic fertilizer and 75% chemical fertilizer showed the most promising results.

Imbalance in Glucose Metabolism Regulates the Transition of Microglia from Homeostasis to Disease-Associated Microglia Stage 1.

Microglia undergo two-stage activation in neurodegenerative diseases, known as disease-associated microglia (DAM). TREM2 mediates the DAM2 stage transition, but what regulates the first DAM1 stage transition is unknown. We report that glucose dyshomeostasis inhibits DAM1 activation and PKM2 plays a role. As in tumors, PKM2 was aberrantly elevated in both male and female human AD brains, but unlike in tumors, it is expressed as active tetramers, as well as among TREM2+ microglia surrounding plaques in 5XFAD male and female mice. snRNAseq analyses of microglia without Pkm2 in 5XFAD mice revealed significant increases in DAM1 markers in a distinct metabolic cluster, which is enriched in genes for glucose metabolism, DAM1, and AD risk. 5XFAD mice incidentally exhibited a significant reduction in amyloid pathology without microglial Pkm2 Surprisingly, microglia in 5XFAD without Pkm2 exhibited increases in glycolysis and spare respiratory capacity, which correlated with restoration of mitochondrial cristae alterations. In addition, in situ spatial metabolomics of plaque-bearing microglia revealed an increase in respiratory activity. These results together suggest that it is not only glycolytic but also respiratory inputs that are critical to the development of DAM signatures in 5XFAD mice.