Insight into the unique role of silver single-atom in atomic-thickness ZnIn2S4/g-C3N4 Van der Waals heterojunction for photocatalytic hydrogen evolution.

The construction of ultra-close 2D atomic-thickness Van der Waals heterojunctions with high-speed charge transfer still faces challenges. Here, we synthesized single-layer ZnIn2S4 and g-C3N4, and introduced silver single atoms to regulate Van der Waals heterojunctions at the atomic level to optimize charge transfer and catalytic activity. At the atomic scale, the impact of detailed structural differences between the two characteristic surfaces of ZnIn2S4 ([Zn-S4] and [In-S4]) on catalytic performance has been first proposed. Experiments combined with the DFT study demonstrate that single atom Ag not only acts as a charge transfer bridge but also regulates the energy band and intrinsic catalytic activity. Benefiting from the enhanced electron delocalization, the synthesized catalyst ZIS/Ag@CN exhibits excellent photocatalytic performance, with a hydrogen production rate of 5.50 mmol·g-1·h-1, which is much higher than the reported Ag-based single-atom catalysts so far. This work provides a new understanding of atomic-level heterojunction interface regulation and modification.

Mining Candidate Genes for Leaf Angle in Brassica napus L. by Combining QTL Mapping and RNA Sequencing Analysis.

Leaf angle (LA) is an important trait of plant architecture, and individuals with narrow LA can better capture canopy light under high-density planting, which is beneficial for increasing the overall yield per unit area. To study the genetic basis and molecular regulation mechanism of leaf angle in rapeseed, we carried out a series of experiments. Quantitative trait loci (QTL) mapping was performed using the RIL population, and seven QTLs were identified. Transcriptome analysis showed that the cell wall formation/biogenesis processes and biosynthesis/metabolism of cell wall components were the most enrichment classes. Most differentially expressed genes (DEGs) involved in the synthesis of lignin, xylan, and cellulose showed down-regulated expression in narrow leaf material. Microscopic analysis suggested that the cell size affected by the cell wall in the junction area of the stem and petiole was the main factor in leaf petiole angle (LPA) differences. Combining QTL mapping and RNA sequencing, five promising candidate genes BnaA01G0125600ZS, BnaA01G0135700ZS, BnaA01G0154600ZS, BnaA10G0154200ZS, and BnaC03G0294200ZS were identified in rapeseed, and most of them were involved in cell wall biogenesis and the synthesis/metabolism of cell wall components. The results of QTL, transcriptome analysis, and cytological analysis were highly consistent, collectively revealing that genes related to cell wall function played a crucial role in regulating the LA trait in rapeseed. The study provides further insights into LA traits, and the discovery of new QTLs and candidate genes is highly beneficial for genetic improvement.

Interleukin-37 exacerbates liver inflammation and promotes IFN-γ production in NK cells.

Interleukin (IL)-37, a unique member of the IL-1 family, is known for its anti-inflammatory properties. However, its effects on immune-mediated liver diseases, such as primary biliary cholangitis (PBC) and acute immune-mediated hepatitis, remain unclear. Using mouse models of autoimmune cholangitis and hepatitis induced by 2-OA-OVA and concanavalin A (Con A) respectively, we introduced the human IL-37 gene via a liver-preferred adeno-associated virus vector (AAV-IL-37) to mice, as mice lack endogenous IL-37. Our findings reveal that IL-37 did not affect autoimmune cholangitis. Surprisingly, IL-37 exacerbated inflammation in Con A-induced hepatitis rather than mitigating it. Mechanistic insights suggest that this exacerbation involves the interferon (IFN)-γ pathway, supported by elevated serum IFN-γ levels in AAV-IL-37-treated Con A mice. Specifically, IL-37 heightened the number of hepatic NK and NKT cells, increased the production of the NK cell chemoattractant CCL5, and elevated the frequency of hepatic NK and NKT cells expressing IFN-γ. Moreover, IL-37 enhanced IFN-γ secretion from NK cells when combined with other proinflammatory cytokines, highlighting its synergistic effect in promoting IFN-γ production. These unexpected outcomes underscore a novel role for IL-37 in exacerbating liver inflammation during immune-mediated liver diseases, implicating its influence on NK cells and the production of IFN-γ by these cells.

Excessive boron fertilization-induced toxicity is related to boron transport in field-grown pomelo trees.

Boron (B) is an essential micronutrient for plant growth and development; however, the process of B toxicity in citrus production is still poorly understood. We proposed a hypothesis that B toxicity in citrus trees is related to the characteristics of B transport from soil to leaf or fruit. For this, a field experiment was conducted for two treatments, control (B free or without B) and B fertilizer treatment (100 g Na2B4O7·10H2O plant-1), to investigate the effects on plant growth, nutrient uptake, fruit yield and quality, and B transport in 10-year-old pomelo trees [Citrus grandis (L.) Osbeck cv. Guanximiyou]. Our results showed that excess B fertilization directly led to B toxicity in pomelo trees by dramatically increasing soil total B and water-soluble B contents. B toxicity induced interveinal chlorosis in leaves and decreased leaf biomass and function, resulting in a decreased 45.3% fruit yield by reducing 30.6% fruit load and 21.4% single fruit weight. Also, B toxicity induced changes in mineral elements between leaf positions and fruit parts, in which the concentrations of B, potassium, and magnesium were increased while those of nitrogen and iron were decreased. Under B toxicity conditions, fruit quality parameters of total soluble solids (TSS), TSS/titratable acidity (TA), total soluble sugar, sucrose, pH, vitamin C, and total phenol contents decreased, which were regulated by the lower carbohydrate production in new leaves and the lower transport capacity in old leaves. Moreover, B toxicity significantly increased the transfer factor and bio-concentration factor of B in pomelo plants, with higher levels in leaf organs than in fruit organs. Taken together, excess B fertilization-induced B toxicity in pomelo trees, with induced growth inhibition and nutrient disorder, results in reduced fruit yield and quality, which are related to B transport from soil to organs. The findings of this study highlight the understanding of B toxicity in citrus plants and strengthen B management in pomelo production for high yield and high quality.

Vinylene-linked Donor-π-Acceptor Metal-Covalent Organic Framework for Enhanced Photocatalytic CO2 Reduction.

Intramolecular charge separation driving force and linkage chemistry between building blocks are critical factors for enhancing the photocatalytic performance of metal-covalent organic frameworks (MCOF) based photocatalyst. However, robust achieving both simultaneously has yet to be challenging despite ongoing efforts. Here we develop a fully  π-conjugated vinylene-linked multivariate donor-π-acceptor MCOF (D-π-A, termed UJN-1)by integrating integrating benzyl cyanides linker with multiple functional building blocks of electron-rich triphenylamine and electron-deficient copper-cyclic trinuclear units (Cu-CTUs) moieties, featuring with strong intramolecular charge separation driving force, extended conjugation degree of skeleton, and abundant active sites. The incorporation of Cu-CTUs acceptor with electron-withdrawing ability and concomitantly giant charge separation driving force can efficiently accelerate the photogenerated electrons transfer from triphenylamine to Cu-CTUs, revealing by experiments and theoretical calculations. Benefiting from the synergistically effect of D-π-A configuration and vinylene linkage, the highly-efficient charge spatial separation is achieved. Consequently, UJN-1 exhibits an excellent CO formation rate of 114.8 µmol g-1 in 4 h without any co-catalysts or sacrificial reagents under visible light, outperforming those analogous MCOFs with imine-linked (UJN-2, 28.9 µmol g-1) and vinylene-linked COF without Cu-CTU active sites (UJN-3, 50.0 µmol g-1), emphasizing the role of charge separation driving force and linkage chemistry in designing novel COFs-based photocatalyst.

PCSK9 inhibitor effectively alleviated cognitive dysfunction in a type 2 diabetes mellitus rat model.

Background: The incidence of diabetes-associated cognitive dysfunction (DACD) is increasing; however, few clinical intervention measures are available for the prevention and treatment of this disease. Research has shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, particularly SBC-115076, have a protective effect against various neurodegenerative diseases. However, their role in DACD remains unknown. In this study, we aimed to explore the impact of PCSK9 inhibitors on DACD. Methods: Male Sprague-Dawley (SD) rats were used to establish an animal model of type 2 diabetes mellitus (T2DM). The rats were randomly divided into three groups: the Control group (Control, healthy rats, n = 8), the Model group (Model, rats with T2DM, n = 8), and the PCSK9 inhibitor-treated group (Treat, T2DM rats treated with PCSK9 inhibitors, n = 8). To assess the spatial learning and memory of the rats in each group, the Morris water maze (MWM) test was conducted. Hematoxylin-eosin staining and Nissl staining procedures were performed to assess the structural characteristics and functional status of the neurons of rats from each group. Transmission electron microscopy was used to examine the morphology and structure of the hippocampal neurons. Determine serum PCSK9 and lipid metabolism indicators in each group of rats. Use qRT-PCR to detect the expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) in the hippocampal tissues of each group of rats. Western blot was used to detect the expression of PCSK9 and low-density lipoprotein receptor (LDLR) in the hippocampal tissues of rats. In addition, a 4D label-free quantitative proteomics approach was used to analyse protein expression in rat hippocampal tissues. The expression of selected proteins in hippocampal tissues was verified by parallel reaction monitoring (PRM) and immunohistochemistry (IHC). Results: The results showed that the PCSK9 inhibitor alleviated cognitive dysfunction in T2DM rats. PCSK9 inhibitors can reduce PCSK9, total cholesterol (TC), and low-density lipoprotein (LDL) levels in the serum of T2DM rats. Meanwhile, it was found that PCSK9 inhibitors can reduce the expression of PCSK9, IL-1ß, IL-6, and TNF-α in the hippocampal tissues of T2DM rats, while increasing the expression of LDLR. Thirteen potential target proteins for the action of PCSK9 inhibitors on DACD rats were identified. PRM and IHC revealed that PCSK9 inhibitors effectively counteracted the downregulation of transthyretin in DACD rats. Conclusion: This study uncovered the target proteins and specific mechanisms of PCSK9 inhibitors in DACD, providing an experimental basis for the clinical application of PCSK9 inhibitors for the potential treatment of DACD.

Preparation of Double-Layer Composite Coffee Filtration Nonwovens.

The coffee industry is developing rapidly in the world, and the use of coffee filtration nonwovens (CFNs) is becoming more and more extensive; however, there is a lack of standards and research for its production and trade, and the quality of related products on the market is uneven at present. Here, eight double-layer composite coffee filtration nonwovens (D-LCCFNs) were prepared by using 5 g/m2 and 10 g/m2 polypropylene (PP) melt-blown nonwovens (MNs), 20 g/m2 PP spunbonded nonwovens and 20 g/m2 viscose/ES fiber chemically bonded nonwovens, and the physical properties, morphology and the filtration effect of coffee and purified water for the prepared samples were tested. It was found that the surface density of the microfiber layer (MNs) in the D-LCCFNs was negatively correlated with the coffee filtration rate; when the microfiber layer in the D-LCCFNs was in direct contact with the coffee, the liquid started to drip later, and the filtration rate of the coffee was slower; the filtration rate of the samples with the viscose/ES chemically bonded nonwovens was very fast. However, the samples without viscose/ES fibers basically did not filter pure water much, but they could filter out the coffee liquid normally, and the samples' hydrophilicity increased significantly after filtering coffee.

Enantioconvergent Hydroboration of E/Z-Mixed Trisubstituted Alkenes.

The lack of mode for chirality recognition makes it particularly challenging to carry out asymmetric transformations on E/Z-mixed minimally functionalized trisubstituted alkenes. Here, we report a catalytic enantioconvergent hydroboration of minimally functionalized trisubstituted E/Z-mixed alkenes to construct chiral organoboronic esters with excellent enantioselectivity using chiral radical cobalt catalyst. This C(sp3)-H borylation protocol showed good functional group tolerance and products could be converted to valuable compounds via C-B derivatizations. The mechanistic studies, which included control experiments, nonlinear effect experiments, deuterated labeling experiments, and X-ray diffraction, demonstrated that the favorable compatibility between the thermodynamically unfavorable isomerization and hydroboration was the key factor in achieving convergent transformation.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

Repetitive Administration of Low-Dose Lipopolysaccharide Improves Repeated Social Defeat Stress-Induced Behavioral Abnormalities and Aberrant Immune Response.

Repetitive exposure of innate immune cells to a subthreshold dosage of endotoxin components may modulate inflammatory responses. However, the regulatory mechanisms in the interactions between the central nervous system (CNS) and the immune system remain unclear. This study aimed to investigate the effects of lipopolysaccharide (LPS) preconditioning in repeated social defeat stress (RSDS)-induced abnormal immune responses and behavioral impairments. This study aimed to elucidate the mechanisms that underlie the protective effects of repeated administration of a subthreshold dose LPS on behavioral impairments using the RSDS paradigm. LPS preconditioning improved abnormal behaviors in RSDS-defeated mice, accompanied by decreased monoamine oxidases and increased glucocorticoid receptor expression in the hippocampus. In addition, pre-treated with LPS significantly decreased the recruited peripheral myeloid cells (CD11b+CD45hi), mainly circulating inflammatory monocytes (CD11b+CD45hiLy6ChiCCR2+) into the brain in response to RSDS challenge. Importantly, we found that LPS preconditioning exerts its protective properties by regulating lipocalin-2 (LCN2) expression in microglia, which subsequently induces expressions of chemokine CCL2 and pro-inflammatory cytokine. Subsequently, LPS-preconditioning lessened the resident microglia population (CD11b+CD45intCCL2+) in the brains of the RSDS-defeated mice. Moreover, RSDS-associated expressions of leukocytes (CD11b+CD45+CCR2+) and neutrophils (CD11b+CD45+Ly6G+) in the bone marrow, spleen, and blood were also attenuated by LPS-preconditioning. In particular, LPS preconditioning also promoted the expression of endogenous antioxidants and anti-inflammatory proteins in the hippocampus. Our results demonstrate that LPS preconditioning ameliorates lipocalin 2-associated microglial activation and aberrant immune response and promotes the expression of endogenous antioxidants and anti-inflammatory protein, thereby maintaining the homeostasis of pro-inflammation/anti-inflammation in both the brain and immune system, ultimately protecting the mice from RSDS-induced aberrant immune response and behavioral changes.

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Clarifying current situation of farmers' fertilization and yield in citrus producing areas and the effects of different fertilization measures can provide a scientific basis for improving the yield and quality of citrus in China. We retrieved 92 literatures on citrus fertilization from the CNKI and Web of Science to examine the impacts of nitrogen (N), phosphorus (P or P2O5), and potassium (K or K2O) fertilizer dosage and partial productivity under farmers' conventional fertilization and experts' optimized fertilization, as well as the effects of optimized fertilization measures on citrus yield and quality by using meta-analysis approach. The average conventional application rates of N, P2O5, and K2O were 507.3, 262.2, and 369.3 kg·hm-2 in citrus production in China. Compared with conventional fertilization, optimized fertilization resulted in a reduction of N and P2O5 by 14.7% and 8.3%, an increase in K2O application by 6.6%, which promoted partial productivity of N, P2O5, and K2O fertilizers by 7.8%, 18.4%, and 14.7%, correspondingly. The optimized fertilization resulted in 11.9% and 2.8% increase in fruit yield and single fruit weight, while improved vitamin C content (Vc, 3.1%), total soluble solids (TSS, 5.9%) and total sugar content (TSC, 8.6%). Additionally, it also led to a reduction in titratable acid (TA, -3.4%) and total acid content (TAC, -3.6%), and consequently elevated the TSS/TA (14.0%) and TSC/TAC (9.5%). Among different optimized fertilization methods, the effect of optimized NPK + medium and/or micro element fertilizer on citrus yield and fruit quality was the best, especially NPK decrement ≤25% between optimized NPK measures. The effect of conventional NPK + organic fertilizer was higher than conventional NPK + medium and/or micro element fertilizer. However, different citrus varieties, including mandarins, pomelos, and oranges, showed different responses to optimized fertilization. Optimized fertilization management could synergistically improve citrus yield, fertilizer use efficiency, and fruit quality. Therefore, the strategy of integrated nutrient management1 with reducing NPK fertilizer, balancing medium and/or micro nutrient fertilizer and improving soil fertility by organic fertilizer should be adopted according to local conditions in citrus producing areas of China.

Role of Gpr124 in the Migration and Proliferation of Retinal Microvascular Endothelial Cells and Microangiopathies in Diabetic Retinopathy.

Retinal microangiopathies, such as neovascularization and preretinal and vitreous hemorrhages, are the primary pathological features of diabetic retinopathy (DR). These conditions can worsen visual impairment and may result in blindness. Furthermore, multiple metabolic pathways are associated with microangiopathy in DR. However, the specific underlying pathological mechanisms remain unclear. Several studies have demonstrated the important role of G protein-coupled receptor 124 (Gpr124) in cerebral vascular endothelial cells, but its effect on the retinal endothelium has not been elucidated. In this study, we found that Gpr124 is expressed in both pathological retinal fibrous vascular membranes of DR patients and retinal blood vessels of mice, with elevated protein expression specifically observed in the retinas of DR model mice. Furthermore, Gpr124 expression was elevated after high-glucose treatment of human retinal microvascular endothelial cells (HRMECs). Inhibition of Gpr124 expression affected the high glucose-induced proliferation, migration, and tube-forming ability of HRMECs. We concluded that Gpr124 expression was upregulated in DR and promoted HRMECs angiogenesis in a high-glucose environment. This finding may help to elucidate the pathogenesis of DR and provide a critical research basis for identifying effective treatments.

Photochemistry of Imidazole-2-carbaldehyde in Droplets as a Potential Source of H2O2 and Its Oxidation of SO2.

Hydrogen peroxide (H2O2) plays a crucial role as an oxidizing agent within the tropospheric environment, making a substantial contribution to sulfate formation in hydrated aerosols and cloud and fog droplets. Field observations show that high levels of H2O2 are often observed in heavy haze events and polluted air. However, the source of H2O2 remains unclear. Here, using the droplets formed in situ by the deliquescence of hygroscopic compounds under a high relative humidity (RH), the formation of H2O2 by the photochemistry of imidazole-2-carbaldehyde (2-IC) under ultraviolet irradiation was explored. The results indicate that 2-IC produces IM-C•-OH and IM-C•═O radicals via H transfer itself to its excited triplet state and generates H2O2 and organic peroxides in the presence of O2, which has an evident oxidizing effect on SO2, suggesting the potential involvement of this pathway in the formation of atmospheric sulfate. H2O2 formation is limited in acidic droplets or droplets containing ammonium ions, and no H2O2 is detected in droplets containing nitrate, whereas droplets containing citric acid have an obvious promotion effect on H2O2 formation. These findings provide valuable insights into the behaviors of atmospheric photosensitizers, the source of H2O2, and the formation of sulfate in atmospheric droplets.

Ramelteon protects against social defeat stress-associated abnormal behaviors.

Psychological stress affects the neuroendocrine regulation, which modulates mental status and behaviors. Melatonin, a hormone synthesized primarily by the pineal gland, regulates many brain functions, including circadian rhythms, pain, sleep, and mood. Selective pharmacological melatonin agonist ramelteon has been clinically used to treat mood and sleep disorders. Posttraumatic stress disorder (PTSD) is a psychiatric condition associated with severe trauma; it is generally triggered by traumatic events, which lead to severe anxiety and uncontrollable trauma recall. We recently reported that repeated social defeat stress (RSDS) may induce robust anxiety-like behaviors and social avoidance in mice. In the present study, we investigated whether melatonin receptor activation by melatonin and ramelteon regulates RSDS-induced behavioral changes. Melatonin treatment improved social avoidance and anxiety-like behaviors in RSDS mice. Moreover, treatment of the non-selective MT1/MT2 receptor agonist, ramelteon, markedly ameliorated RSDS-induced social avoidance and anxiety-like behaviors. Moreover, activating melatonin receptors also balanced the expression of monoamine oxidases, glucocorticoid receptors, and endogenous antioxidants in the hippocampus. Taken together, our findings indicate that the activation of both melatonin and ramelteon regulates RSDS-induced anxiety-like behaviors and PTSD symptoms. The current study also showed that the regulatory effects of neuroendocrine mechanisms and cognitive behaviors on melatonin receptor activation in repeated social defeat stress.

Global daily mask use estimation in the pandemic and its post environmental health risks: Analysis based on a validated dynamic mathematical model.

The outbreak of the COVID-19 pandemic led to a sharp increase in disposable surgical mask usage. Discarded masks can release microplastic and cause environmental pollution. Since masks have become a daily necessity for protection against virus infections, it is necessary to review the usage and disposal of masks during the pandemic for future management. In this study, we constructed a dynamic model by introducing related parameters to estimate daily mask usage in 214 countries from January 22, 2020 to July 31, 2022. And we validated the accuracy of our model by establishing a dataset based on published survey data. Our results show that the cumulative mask usage has reached 800 billion worldwide, and the microplastics released from discarded masks due to mismanagement account for 3.27% of global marine microplastic emissions in this period. Furthermore, we illustrated the response relationship between mask usage and the infection rates. We found a marginally significant negative correlation existing between the mean daily per capita mask usage and the rate of cumulative confirmed cases within the range of 25% to 50%. This indicates that if the rate reaches the specified threshold, the preventive effect of masks may become evident.

Genome­wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan.

Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome­wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)­R software and chi­square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome­wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5x10­8, located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between HLA­A*02:07 and HLA­C*06:02 in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta­analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.

GCTNet: a graph convolutional transformer network for major depressive disorder detection based on EEG signals.

Objective.Identifying major depressive disorder (MDD) using objective physiological signals has become a pressing challenge.Approach.Hence, this paper proposes a graph convolutional transformer network (GCTNet) for accurate and reliable MDD detection using electroencephalogram (EEG) signals. The developed framework integrates a residual graph convolutional network block to capture spatial information and a Transformer block to extract global temporal dynamics. Additionally, we introduce the contrastive cross-entropy (CCE) loss that combines contrastive learning to enhance the stability and discriminability of the extracted features, thereby improving classification performance.Main results. The effectiveness of the GCTNet model and CCE loss was assessed using EEG data from 41 MDD patients and 44 normal controls, in addition to a publicly available dataset. Utilizing a subject-independent data partitioning method and 10-fold cross-validation, the proposed method demonstrated significant performance, achieving an average Area Under the Curve of 0.7693 and 0.9755 across both datasets, respectively. Comparative analyses demonstrated the superiority of the GCTNet framework with CCE loss over state-of-the-art algorithms in MDD detection tasks.Significance. The proposed method offers an objective and effective approach to MDD detection, providing valuable support for clinical-assisted diagnosis.

Early Therapeutic Drug Monitoring Optimizes Teicoplanin Use in Febrile Neutropenic Patients with Hematological Malignancies.

INTRODUCTION: A target trough concentration (Cmin) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-Cmin relationship and clinical outcome and estimate the optimal early target Cmin for FN in patients with hematological malignancies. METHODS: This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48 h) post-loading doses, day 5 (96 h), and day 8 (when applicable) and determined by ultrahigh-pressure liquid chromatography-triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed α value of 0.05 was considered statistically significant. RESULTS: The mean Cmin values at 48 h, 96 h, and on day 8 were 23.4, 21.4, and 27.8 mg/L, respectively. The patients achieving Cmin ≥ 20 mg/L at 48 h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of Cmin at 48 h was 18.85 mg/L (95% confidence interval 0.55-0.87; P = 0.018). CONCLUSIONS: The Cmin of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85 mg/L.

Unraveling resistance mechanisms in anti-CD19 chimeric antigen receptor-T therapy for B-ALL: a novel in vitro model and insights into target antigen dynamics.

BACKGROUND: Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application. METHODS: We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro. RESULTS: In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them. CONCLUSIONS: We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.