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Ethnopharmacological Relevance: Paeonol (PAE) and glycyrrhizic acid (GLY) are predominate components of 14 blood-entering ones of Piantongtang No. 1, which is a traditional Chinese medicine prescription for chronic migraine with minimal side effects. Both paeonol and glycyrrhizic acid exhibit analgesic, neuroprotective and anti-inflammatory properties individually. Our previous research has highlighted their combined effect (PAE + GLY) in ameliorating migraine symptoms. However, there are not yet any studies exploring the mechanism of action of PAE + GLY in the treatment of migraine., Aim of the Study: This research aimed to determine the mechanism of PAE + GLY in ameliorating the recurrent nitroglycerin-induced migraine-like phenotype in rats., Materials and Methods: Using a nitroglycerin-induced migraine model via subcutaneous injection in the neck, we evaluated the effect of PAE + GLY on migraine-like symptoms. Behavioural tests and biomarkers analysis were employed, alongside transcriptome sequencing (RNA-seq). Mechanistic insights were further verified utilising reverse transcription quantitative PCR (RT-qPCR), Western blot (WB), ELISA and immunofluorescence (IF) techniques., Results: Following treatment with PAE + GLY, hyperalgesia threshold and 5-hydroxytryptamine (5-HT) levels increased, and migraine-like head scratching, histamine and calcitonin gene-related peptide (CGRP) levels were reduced. RNA-Seq experiments revealed that PAE + GLY upregulated the expression of Glutamate decarboxylase 2 (GAD2) and γ-aminobutyric acid type B receptor subunit 2 (GABBR2) genes. This upregulation activated the GABAergic synapse pathway, effectively inhibiting migraine attacks. Further validation demonstrated an increase in γ-aminobutyric acid (GABA) content in cerebrospinal fluid post PAE + GLY treatment, coupled with increased expression of dural GAD2, GABBR2 and transient receptor potential channel M8 (TRPM8). Consequently, this inhibited the expression of dural cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and transient receptor potential channel type 1 (TRPV1), subsequently downregulating p-ERK1/2, p-AKT1, IL-1β and TNF-α., Conclusions: Our findings underscore that PAE + GLY ameliorates inflammatory hyperalgesia migraine by upregulating inhibitory neurotransmitters and modulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare, and all the authors have approved this manuscript for publication., (Copyright © 2024. Published by Elsevier B.V.)

The effectuation of the Zn-air battery (ZAB) is appealing for active and durable catalysts to kinetically drive the sluggish cathodic oxygen reduction reaction (ORR). Atomic metal-N x -C sites are widely witnessed with Pt-like activity, but their demetalations still severely restrict the durability in ORR. Here we have profiled an ordered hierarchical porous carbon supported Fe-N 4 single-atom (FeNC) catalyst by a template derivation method for efficient ORR and flexible ZAB studies. The FeNC structure is observed with a sub-polarized graphitic Fe-N 4 coordination with a shortened Fe-N bond for potentially consolidating the ORR, together with the hierarchical porous matrix for kinetical mass transfer. Resultantly, the optimized FeNC catalyst showcases Pt-beyond alkaline ORR activity ( E 1/2 = 0.95 V) with long-term durability for 100 h, delivering the flexible ZAB device with high power density (251 mW cm -2 ) and durable cycle life (80 h). This research underscores the criterion in rationalizing active and robust ORR catalysts through metal-nitrogen bond modulation.

Atomically dispersed catalysts anchored on nitrogen-rich substrates present promising application potential for the persulfate-based advanced oxidation process. Nevertheless, efficient activation efficiency and a clear activated mechanism of persulfate remain challenging in carbon nitride-based single-atom catalysts (SACs). To these, combined with the regulation strategy of metal-ligand section and carrier's architecture, an atomically dispersed Co single-atom catalyst anchored on regular hollow tubular carbon nitride (Co/TCN SAC) herein was devised and utilized to activate permonosulfate. As a result, Co/TCN SACs show excellent catalytic performance for the degradation of common antibiotics. Combined with X-ray absorption fine structure and theory calculation, it is confirmed that superficially anchored CoO 3 sites of the Co 2 N 2 O 2 -CoO 3 unit are the catalytic active center for peroxymonosulfate (PMS) activation. The electrochemical test and in situ electron paramagnetic resonance results demonstrate radical (SO 4 •- and • OH) and nonradical (electron transfer process and 1 O 2 ) paths contributing to the superior catalytic performance. In addition, the catalyst exhibits high reaction efficiency and structural stability considering water quality parameters. Finally, a continuous and efficient device was operated on a laboratory scale, which exhibited satisfactory efficiency in continuously removing electron-rich antibiotics such as tetracycline. This work reveals the atomic-level modulation of cobalt atomic sites on hollow tubular carbon nitride and their structure-activity relationship with persulfate activation.

The constrained enzymatic activity and aggregation challenges encountered of nanozymes pose an obstacle to their practical utility, necessitating a strategy to alleviate this problem and improve the enzymatic catalytic efficiency. Herein, MOF-confined ultrafine ZnIrO x clusters (ZnIrO x /ZnIrMOFs) nanozyme have been synthesized by controlling the in-situ growth of ZnIrO x via a one-pot method. Notably, due to the domain-limiting effect of MOF, the ZnIrO x clusters with small size grew uniformly in the structure of ZnIrMOFs nanosheets, while the presence of Zn atoms improved the crystallinity of the MOF phase and the dispersion of ZnIrO x clusters. Moreover, the obtained ZnIrO x /ZnIrMOFs exhibited excellent oxidase- and peroxidase-like activities and better substrate affinity, which can directly and effectively catalyze chromogenic reaction to produce corresponding color and signal changes. Adopting this strategy, we established a visual, sensitive, and selective colorimetric method for glucose detection with a linear range and detection limit of 2.66-319 μM and 1.9 μM, respectively. The successful detection of glucose in real serum and food samples implies the promising MOF-confined ultrafine nanozymes in biomedical diagnostics and in food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To construct a prediction model for renal involvement in patients with hyperuricemia (HUA) based on logistic regression analysis, to achieve early risk stratification., Method: In this cross-sectional study, we collected data from the National Health and Nutrition Examination Survey (NHANES), and constructed a predicted model for renal involvement in HUA patients. The discriminative ability of the model was assessed using the receiver operating characteristic (ROC) curve. Model accuracy was evaluated using the Hosmer-Lemeshow test and calibration curve, while clinical utility was assessed using decision curve analysis (DCA). Furthermore, internal and external validation cohorts were also applied to validate the model., Results: A total of 1669 patients from NHANES between 2007 and 2010 were included in the final analysis for modeling and validation. Six predictive factors including age, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Cr, Uric Acid (UA), and sex were identified by binary logistic regression analysis for renal involvement in HUA patients and used to construct a nomogram with good consistency and accuracy. The AUC values for the predictive model, internal validation, and external validation were 0.881 (95% CI: 0.836-0.926), 0.908 (95% CI: 0.871-0.944), and 0.927 (95% CI: 0.897-0.957), respectively. The calibration curves demonstrated consistency between the nomogram and observed values. The DCA curves of the model and validation cohort indicated good clinical utility., Conclusion: This study developed a predictive model for renal involvement in hyperuricemia patients with strong predictive performance and validated by internal and external cohorts, aiding in the early detection of high-risk populations for renal involvement., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Platelet-rich plasma (PRP) has been recognized as an effective therapy in regenerative medicine and surgery, which can reduce the risk of antibiotic abuse and promote the healing of infected wounds. Recent advances in PRP-based treatments have focused on the controlled release of growth factors in PRP with biocompatible hydrogels and antimicrobial promotion by introducing hydrogel components or antibiotics, while the inherent antimicrobial activity of PRP is mostly neglected or sacrificed. Here, we demonstrate the combination of an antimicrobial polysaccharide, carboxymethyl chitosan, and PRP to construct an antimicrobial hydrogel via dynamic bonding with oxidized chondroitin sulfate. Significant inhibitory effects against Staphylococcus aureus and Escherichia coli (95 % of inhibition rate) are achieved through the synergistic contributions of the polysaccharide and PRP. Additionally, the resulting hydrogel promotes the migration of NIH-3T3 fibroblasts and collagen deposition by approximately 1.7 and 1.8 times, respectively, thereby accelerating the healing process of infected wounds. This work may bring new perspectives for potent applications of PRP-based hydrogel dressings for antibiotic-free management of infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Distant metastases and drug resistance account for poor survival of patients with gastrointestinal (GI) malignancies such as gastric cancer, pancreatic cancer, and colorectal cancer. GI cancers most commonly metastasize to the liver, which provides a unique immunosuppressive tumour microenvironment to support the development of a premetastatic niche for tumor cell colonization and metastatic outgrowth. Metastatic tumors often exhibit greater resistance to drugs than primary tumors, posing extra challenges in treatment. The liver metastases and drug resistance of GI cancers are regulated by complex, intertwined, and tumor-dependent cellular and molecular mechanisms that influence tumor cell behavior (e.g. epithelial-to-mesenchymal transition, or EMT), tumor microenvironment (TME) (e.g. the extracellular matrix, cancer-associated fibroblasts, and tumor-infiltrating immune cells), tumor cell-TME interactions (e.g. through cytokines and exosomes), liver microenvironment (e.g. hepatic stellate cells and macrophages), and the route and mechanism of tumor cell dissemination (e.g. circulating tumor cells). This review provides an overview of recent advances in the research on cellular and molecular mechanisms that regulate liver metastases and drug resistance of GI cancers. We also discuss recent advances in the development of mechanism-based therapy for these GI cancers. Targeting these cellular and molecular mechanisms, either alone or in combination, may potentially provide novel approaches to treat metastatic GI malignancies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Small-sized microplastics (MPs) pose greater ecological toxicity due to their larger surface area, which makes them more likely to act as carriers for other pollutants and to be ingested by aquatic organisms. However, traditional visual analysis often neglects small-sized MPs and their associated ecological risk. This study utilized Laser Direct Infrared (LDIR) spectroscopy and traditional visual analysis to examine MPs in 31 sediment samples from Jinzhou Bay, a typical semi-enclosed bay located at the economic center of Dalian, China. The results showed significant heterogeneity in MP distribution, with averages of 1192 and 2361 items/kg dry weight reported by visual analysis and LDIR spectroscopy, respectively. LDIR spectroscopy identified MPs as small as 10 μm, with the majority of MPs (89.21 %) within the 10-250 μm range, and a significant proportion (46.45 %) between 10 and 50 μm among them. However, visual analysis was limited to detecting MPs >50 μm, and significant portions were identified between 50 and 100 μm (49.36 %) and 100-250 μm (31.01 %), missing a substantial fraction of smaller MPs. The predominant polymers identified were polyamide (PA), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). LDIR spectroscopy demonstrated a strong positive correlation between MP abundance and clay content, a relationship not observed with traditional visual analysis. The Potential Ecological Risk Index (PERI) indicated that over 87 % of sites posed an extremely high risk according to LDIR spectroscopy, compared to 51 % by traditional visual analysis. These discrepancy underscores the underestimation of ecological risks by traditional methods, particularly for small-sized MPs. High-risk polymers such as polyvinyl chloride (PVC), ABS, and polyurethane (PUR) significantly influenced PERI values. These findings highlight the critical need for precise identification and thorough risk assessment of small-sized MPs in environmental studies and offer insights for understanding of MP vertical migration in aquatic environments, particularly in the context of co-settlement with sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Awareness of federal dietary guidelines has been associated with better perceived and objective diet quality. Little is known about the awareness of federal dietary recommendations among persons with chronic kidney disease (CKD) and the associations between recognition of guidelines, perception of diet quality, and objective quality of the diet in this population., Design and Methods: We compared awareness of, and engagement with, MyPlate (a representation of 5 food groups from the US Department of Agriculture) along with perceived and objective diet quality, the latter assessed via Dietary Approaches to Stop Hypertension index scores, among US adults with and without CKD during 2017-2020., Results: Among noninstitutionalized adults in the United States, 8.3% had albuminuria with normal or near-normal kidney function, 4.0% had estimated glomerular filtration rate 45-59 mL/minute/1.73 m 2 (CKD stage G3a) and 1.6% had estimated glomerular filtration rate <45 mL/minute/1.73 m 2 (CKD stages G3b/G4/G5). MyPlate awareness was lower among persons with CKD compared with those without CKD (19.6% vs. 26.4%, P < .001) and was lower among persons with more advanced CKD stages: 20.8%, 18.2%, and 16.3% in persons with CKD stages G1/G2, G3a, and G3b/G4/G5, respectively (trend P < .001). Among persons aware of MyPlate, a numerically higher proportion with CKD attempted to follow MyPlate recommendations (43.9% vs. 32.3%, P = .10); the proportion was highest among persons with moderate-to-advanced CKD (41.9%, 42.9%, and 56.9% among persons with CKD stages G1/G2, G3a, and G3b/G4/G5, respectively (trend P < .001)). Perceived and objective dietary quality (the latter based on concordance with the Dietary Approaches to Stop Hypertension diet) were slightly higher among persons with CKD relative to those without CKD., Conclusions: Adults with CKD have lower MyPlate awareness than adults without CKD. Enhancing diet education to persons with CKD could improve diet quality and potentially ameliorate CKD-associated complications., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

In this study, lincomycin was successfully purified by macroporous adsorption resin column chromatography using the HZ3 resin. The optimal separation parameters were set as follows: the column bed height was 33 cm, sample loading capacity was 48 mg/mL and flow rate of loading was 1 mL/min. A mixture of 0.02 mol/L of Na 2 HPO 4 ∙12H 2 O (pH = 8.5, adjusted using H 3 PO 4 ) and acetone (80:20, v/v) was used as the eluent. The elution flow rate was maintained at 3 mL/min. Under these parameters, the purity of lincomycin calculated using the standard curve was 99.00 %, with the yield being 97.84 %. This enrichment and separation method of lincomycin is highly regarded owing to its remarkable efficiency and straightforward operation. Thus, the proposed method for the separation and purification of lincomycin holds considerable promise for pharmaceutical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The early diagnosis of liver injury and in situ real-time monitoring of tumor therapy efficacy are important for the enhancement of personalized precision therapy but remain challenging due to the lack of reliable in vivo visualization tools with integrated diagnostic, therapeutic, and efficacy monitoring functions. Herein, a smart second near-infrared window (NIR-II) molecule (BITX-OH) is rationally designed for diagnosis and therapy by vinyl-bridging hydroxyl diphenyl xanthine unit and benzo[cd]indolium skeleton. BITX-OH exhibits high selectivity and sensitivity toward viscosity, exhibiting a significant enhancement (1167-fold) in NIR-II fluorescence at 962 nm. With the assistance of BITX-OH and NIR-II fluorescence imaging, early diagnosis and therapeutic evaluation of non-alcoholic fatty liver (NAFL), as well as in-site real-time monitoring of hepatic fibrosis (HF) in live mice have been successfully achieved, which is at least several hours earlier than the typical clinical test. Notably, BITX-OH displays excellent photothermal conversion efficiency when exposed to an 808 nm laser, which can induce tumor ablation and increase viscosity, thereby enhancing NIR-II fluorescence for the real-time evaluation of photothermal therapy (PTT). This viscosity-based "self-monitoring" strategy provides a convenient and reliable platform for timely obtaining therapeutic feedback to avoid over- or under-treatment, thus enabling personalized precision therapy., (© 2024 Wiley‐VCH GmbH.)

As the landscape of information storage and security continues to evolve, the deployment of sophisticated anticounterfeiting strategies with robust security features and multimodal luminescent capabilities becomes imperative. In this work, Eu 3+ and Er 3+ ions are codoped into CaF 2 phosphors to achieve multimodel optical output. The self-reduction of Eu 3+ within the CaF 2 matrix gives rise to the coexistence of Eu 3+ and Eu 2+ ions, which manifests as a color transition from orange to blue as the excitation wavelength is varied from 300 to 335 nm. Moreover, the distinct temperature-dependent behaviors of Eu 3+ and Eu 2+ ions underscore the material's visible temperature-sensitive luminescence properties, characterized by remarkable thermal sensitivity ( S a = 0.0156 K -1 , S r = 0.83%K -1 ). Additionally, the strategic introduction of Er 3+ ions adds an extra dimension, enabling the realization of color-tunable upconversion luminescence through the fine-tuning of Er 3+ concentration. This synergistic integration culminates in the establishment of an efficient three-path authentication model within the CaF 2 host matrix, facilitating a dynamic multicolor response to changes in the excitation wavelength and temperature. By harnessing these diverse luminescent modalities, the study delivers a versatile and potent anticounterfeiting solution, advancing the frontiers of information security.

Background: Heart failure (HF) is a condition caused by a malfunction of the heart's pumping function. The single-point insulin sensitivity estimator (SPISE) index is a novel indicator for assessing insulin resistance in humans. However, the connection between the SPISE index and the risk of HF in the elderly is unknown. Therefore, our study aims to evaluate the connection between the SPISE index and HF in older adults., Methods: The study was based on data collected from the 1999-2020 National Health and Nutrition Examination Survey database and included 6165 participants aged ≥60 years. The multivariable linear regression model and the smooth fitting curve model were applied to investigate the connection between the SPISE index and HF in the elderly. Furthermore, the subgroup analysis was performed to investigate the interactive factors., Results: In this study, the mean age of the population was 69.38 years. After adjusting for all covariates, we observed that the SPISE index was inversely related to the prevalence of HF (OR = 0.87, 95 % CI = 0.80-0.94, P < 0.001) in older adults. The interaction analysis showed that the association might be affected by diabetes mellitus and smoking status. Additionally, an inflection point between the SPISE index and HF was found among older women., Conclusions: An inverse correlation was detected between the SPISE index and HF in the elderly. This could provide new insight into the prevention and management of HF in the elderly population., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chiral inorganic nanomaterials (CINMs) have garnered significant interest due to their exceptional optical, electronic, and catalytic properties, offering promising advancements in energy conversion, data storage, catalysis, and biomedicine. While traditional optical spectrophotometers reveal the chiroptical performance of CINMs on an ensemble level, the direct structural visualization for the qualitative and quantitative discernment of their chiral features has become increasingly distinct with the advancements of transmission electron microscopy (TEM) techniques. The need for reasonable and high-standard discrimination requirements of CINMs has driven the progress of chirality-based TEM technologies. Therefore, this review in the good season takes the initiative to summarize the current advancements in TEM technologies for CINMs characterization, emphasizing a qualitative analysis of chiral atomic-level features, 0D, 1D, and 2D nanocrystals, and assembled nanomaterials. Then, the quantitative methods for determining chirality is also highlighted, such as 3D electron tomography, and further address the evolution of chiral structures monitored by the Ex-situ and In-situ TEM technologies. By providing a roadmap for the current challenges and proposing future advancements in TEM technologies for the qualitative, quantitative, and real-time analysis of CINMs, it can drive innovations in the field of chiral nanomaterials as well as the development of TEM technologies., (© 2024 Wiley‐VCH GmbH.)

Riboswitches regulate downstream gene expression by binding to specific small molecules or ions with multiple mechanisms to transfer the binding information. In the case of the fluoride riboswitch, the transcription termination signal is conveyed through a transient excited state (ES). In this work, we performed conventional molecular dynamics (MD) simulations, totaling 180 μs, to obtain the ES structure and investigate the mechanism underlying information transmission in Mg 2+ /F - binding within the fluoride riboswitch aptamer. The Mg 2+ /F - binding pocket exhibits various conformations in its apo form. A series of ES structures were extracted from the MD trajectories of the apo form. The dynamics of the Mg 2+ /F - binding pocket influenced key pair A40-U48 in ES structures. The pathway connecting the binding pocket to the pair involves interactions between the phosphate groups of U7 and G8 and the nucleobases of G8-C47-U48. Our work presents a structural ensemble of the ES and elucidates a pathway for transferring Mg 2+ /F - binding information, thereby facilitating the understanding of how the holo-like apo state achieves transcriptional repression.

Elaborating and understanding disparities in the burden of cardiovascular disease attributable to high fasting plasma glucose is important to improve diabetes prevention and promote cardiovascular health. In this study, we pool data on 791,373 people aged 25 years and older from three population-based surveys, and estimate the burden of cardiovascular disease attributable to high fasting plasma glucose between 2010 and 2018 in China by age, sex, region and socio-demographic index. In 2018, an estimated total of 498.61 thousand (95% uncertainty interval 463.93 to 534.12) cardiovascular disease-related deaths are attributable to high fasting plasma glucose in China. High fasting plasma glucose accounts for 1076.09 years of life lost per 100,000 people (95% uncertainty interval 1026.88-1129.04) due to cardiovascular disease in 2018, with substantial variation across provinces. In 2018, the higher age-standardised cardiovascular disease mortality rate attributable to high fasting plasma glucose is observed in the high-middle socio-demographic index region and the middle socio-demographic index region. Nationally, compared to 2010, exposure to high fasting plasma glucose and population aging in 2018 are the primary drivers of increased fasting plasma glucose-related deaths due to cardiovascular disease. Findings of this study emphasize the importance of developing population-specific tailored measures in China and other regions with similar condition., (© 2024. The Author(s).)

High-purity dichlorosilane (DCS) is an important raw material for thin film deposition in the semiconductor industry, such as epitaxial silicon, which is mainly produced by trichlorosilane (TCS) catalytic decomposition in a fixed-bed reactor. The productivity of DCS is strongly dependent on the controlling of the TCS decomposition reaction process, associated with the cost in practical application. In this study, we have performed computational fluid dynamics (CFD) simulation on the TCS decomposition reaction kinetics in a cylindrical fixed-bed reactor, in which the effects of catalyst bed height, feed temperature, and feed flow rate are stressed to predict the conversion rate of TCS and the generation rate of DCS. This indicates that the increase of bed height helps the reaction to proceed adequately, but too large a bed height does not improve the DCS generation rate. Meanwhile, the feed temperature and reactor temperature have important effects on the DCS generation rate. However, it is found that changing the feed flow rate and L/D ratio cannot effectively improve the DCS generation rate while the bed volume remains constant. Furthermore, we have designed a fixed-bed reactor to verify the simulation results, which are in good agreement with each other. These results are of significance for the practical industrial production of high-purity DCS in a fixed-bed reactor., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Alzheimer's disease (AD) is the most common cause of dementia, but the disease lacks convenient and cost-effective alternative biomarkers currently. We utilized targeted lipid metabolomics based on nuclear magnetic resonance (NMR) spectroscopy to identify plasma biomarkers in AD patients. Our study was a cross-sectional study that enrolled 58 AD patients and 40 matched health controls (HCs). Firstly, we identified plasma lipid metabolites that were significantly different between the two groups based on P < 0.05 and variable importance in the projection (VIP) > 1. Then we examined the correlation between the lipid metabolites and cognitive function using partial correlation analysis and assessed the diagnostic ability of the lipid metabolites using receiver operating characteristic (ROC) curves. Seventeen lipoproteins showed significant differences between AD patients and HCs among 114 lipid metabolites. All 17 lipoproteins were subtypes of low-density lipoprotein (LDL). Among them, LDL-3 particle number, LDL-3 apolipoprotein-B, LDL-3 phospholipids, LDL free cholesterol and LDL phospholipids were significantly correlated with cognitive function. The ROC curves showed that LDL-2 triglycerides (TG) and LDL-3 TG could significantly distinguish AD patients from HCs, with the area under the curve (AUC) above 0.7. In addition, we explored a strategy of combined diagnosis that significantly improved the diagnostic efficacy for AD (AUC = 0.879). Our study provides insight into the lipoprotein alterations associated with AD and potential biomarkers for its diagnosis and cognitive function assessment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The heterogeneous nuclear ribonucleoprotein (hnRNP A2B1) is a key component of the hnRNP complex involving RNA modulation in eukaryotic cells and it has also been reported to be involved in the replication of the hepatitis E virus, influenza A virus, and hepatitis B virus. However, it is not clear whether the role of the hnRNP A2B1 in viral replication is conserved among RNA viruses and what is the mechanism of hnRNP A2B1 in RNA virus replication. In this study, we first used severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne RNA virus that causes a severe viral hemorrhagic fever as well as other RNA viruses including VSV-GFP, SeV, EV71, and ZIKV to demonstrate that knockout hnRNPA2B1 gene inhibited viral RNA replication and overexpression of hnRNP A2B1 could restore the RNA levels of all tested RNA viruses. These results suggest that hnRNPA2B1 upregulation of viral replication is conserved among RNA viruses. Next, we demonstrated that hnRNP A2B1 was translocated from the nucleus to the cytoplasm under RNA virus infection including SFTSV, VSV-GFP, SeV, EV71, and ZIKV, suggesting translocation of hnRNP A2B1 from the nucleus to the cytoplasm is crucial for RNA virus replication. We then used SFTSV as a model to demonstrate the mechanism of hnRNP A2B1 in the promotion of RNA virus replication. We found that overexpression of SFTSV nucleoprotein can also cause hnRNP A2B1 translocation from the nucleus to the cytoplasm and that the SFTSV NP interacted with the RNA recognition motif 1 domain of hnRNP A2B1. We further demonstrated that the hnRNP A2B1 interacted with the 5' UTR of SFTSV RNA. In conclusion, we revealed that the hnRNP A2B1 upregulation of viral RNA replication is conserved among RNA viruses; the mechanism of hnRNP A2B1 in promotion of SFTSV viral RNA replication is that SFTSV NP interacted with the hnRNPA2B1 to retain it in the cytoplasm where the hnRNP A2B1 interacted with the 5' UTR of SFTSV RNA to promote the viral RNA replication.IMPORTANCESevere fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus with a high mortality rate of up to 30%. In this study, we first used SFTSV as a model to demonstrate that the role of hnRNPA2B1 in viral replication is conserved in SFTSV. Then we used other RNA viruses, including VSV-GFP, SeV, EV71, and ZIKV, to repeat the experiment and demonstrated the same results as SFTSV in all tested RNA viruses. By knocking out the hnRNPA2B1 gene, SFTSV RNA replication was inhibited, and overexpression of hnRNPA2B1 restored RNA levels of SFTSV and other tested RNA viruses. We revealed a novel mechanism where the SFTSV nucleoprotein interacts with hnRNPA2B1, retaining it in the cytoplasm. This interaction promotes viral RNA replication by binding to the 5' UTR of SFTSV RNA. The findings suggest that targeting hnRNPA2B1 could be a potential strategy for developing broad-spectrum antiviral therapies, given its conserved role across different RNA viruses. This research provides significant insights into the replication mechanisms of RNA viruses and highlights potential targets for antiviral interventions., Competing Interests: The authors declare no conflict of interest.

Tetracyclines (TCs) rank second globally in the use of animal infection therapy and animal husbandry as growth promoters among all antibiotics. However, large amounts of TCs residue in food products and more than 75% of TCs are excreted into the environment, causing adverse effects on the ecological system and human health. It has been challenging to simultaneously realize low-cost, rapid, and highly selective detection of TCs. Here, inspired by the fluorogenic reactions between resorcinol and catecholamines, we find the fluorescence quenching ability of tetracycline (TC) and firstly propose a fluorescent "turn-off" detection of TC using dopamine and 4-fluororesorcinol. The optimal reaction condition for the fluorescent assay is investigated and the optimized probe showed a good limit of detection (LOD of 1.7 µM) and a wide linear range (10 µM to 350 µM). Moreover, this fluorescent assay proved to be an effective tool for detecting TC in river, Sprite, and beer samples, which represent the aquatic environments and food and may contain tetracyclines residues. Finally, the high selectivity of the method for TC has been confirmed by eliminating the interference from common substances. The proposed strategy provides a high-efficiency and selective solution for the detection of TCs in environment and food and the application fields of this fluorescent assay could be further expanded in the future., (© 2024. The Author(s).)

Phosphorus is regarded as a promising material for high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity, appropriate lithiation potential, and low lithium-ion diffusion barrier. Phosphorus/carbon composites (PC) are engineered to serve as high-capacity high-rate anodes; the interaction between phosphorus and carbon, long-term capacity retention, and safety problems are important issues that must be well addressed simultaneously. Herein, an in situ polymerization approach to fabricate a poly-melamine-hybridized (pMA) phosphorus/carbon composite (pMA-PC) is employed. The pMA hybridization enhances the density and electrical conductivity of the PC, improves the structural integrity, and facilitates stable electron transfer within the pMA-PC composite. Moreover, the pMA-PC composite exhibits efficient adsorption of lithium polysulfides, enabling stable transport of Li + ions. Therefore, the pMA-PC anode demonstrates a high specific charging capacity of 1,381 mAh g -1 at 10 A g -1 , and a great capacity retention of 86.7% at 1 A g -1 over 500 cycles. The synergistic effect of phosphorus and nitrogen further confers excellent flame retardant properties to the pMA-PC anode, including self-extinguishing in 2.5 s, and a much lower combustion temperature than PC. The enhanced capacity and safety performance of pMA-PC show potential in future high-capacity and high-rate LIBs., (© 2024 Wiley‐VCH GmbH.)

Graphene field-effect transistors (GFETs) are widely used in biosensing due to their excellent properties in biomolecular signal amplification, exhibiting great potential for high-sensitivity and point-of-care testing in clinical diagnosis. However, difficulties in complicated fabrication steps are the main limitations for the further studies and applications of GFETs. In this study, a modular fabrication technique is introduced to construct microfluidic GFET biosensors within 3 independent steps. The low-melting metal electrodes and intricate flow channels are incorporated to maintain the structural integrity of graphene and facilitate subsequent sensing operations. The as-fabricated GFET biosensor demonstrates excellent long-term stability, and performs effectively in various ion environments. It also exhibits high sensitivity and selectivity for detecting single-stranded nucleic acids at a 10 fm concentration. Furthermore, when combined with the CRISPR/Cas12a system, it facilitates amplification-free and rapid detection of nucleic acids at a concentration of 1 fm. Thus, it is believed that this modular-fabricated microfluidic GFET may shed light on further development of FET-based biosensors in various applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Severe fever with thrombocytopenia syndrome virus (SFTSV) nonstructural protein (NSs) is an important viral virulence factor that sequesters multiple antiviral proteins into inclusion bodies to escape the antiviral innate immune response. However, the mechanism of the NSs restricting host innate immunity remains largely elusive. Here, we found that the NSs induced complete macroautophagy/autophagy by interacting with the CCD domain of BECN1, thereby promoting the formation of a BECN1-dependent autophagy initiation complex. Importantly, our data showed that the NSs sequestered antiviral proteins such as TBK1 into autophagic vesicles, and therefore promoted the degradation of TBK1 and other antiviral proteins. In addition, the 8A mutant of NSs reduced the induction of BECN1-dependent autophagy flux and degradation of antiviral immune proteins. In conclusion, our results indicated that SFTSV NSs sequesters antiviral proteins into autophagic vesicles for degradation and to escape antiviral immune responses.

Background: Secondary unilateral cleft lip nasal deformity is a prevalent condition in the world, and surgical repair remains a formidable challenge. The objective of the study is to investigate functionally and aesthetically outcomes of a new technique using a complex of autologous costal cartilage and fascia grafts to repair the secondary unilateral cleft lip nasal deformity., Methods: First, the autologous costal cartilage and fascia were harvested from a total of 34 patients with secondary unilateral cleft lip nasal deformity, who were undergoing treatments at the First Affiliated Hospital of Xi'an Jiaotong University from April 2020 to June 2023. Then, the cartilage was sub-divided into 6 pieces and placed on the depressed alar base, nasal columella, lower lateral cartilage, and nasal tip. At the same time, the fascia was trimmed to cover the nasal tip cap graft and augment the dorsum of the nose. Patient outcomes were assessed through subjective evaluation and objective anthropometric measurements. In addition, associated complications were also examined., Results: All were primary healing incisions, and no patients were encountered with any clinical complications. We found that the overall mean score of the Independent Rhinoplasty Outcome Score (IROS) was very good during the subjective assessment. Also, the objective measurements indicated an excellent nasal symmetry. Furthermore, both functionally and aesthetically satisfactory outcomes were obtained in all the patients during long-time follow-up., Conclusions: Secondary rhinoplasty using the complex of autologous costal cartilage and fascia grafts is a safe and effective approach for unilateral cleft lip nasal deformity repair., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Phosphorus anode has shown great potential for the high-rate and high-energy-density lithium-ion batteries. Nevertheless, it still suffers from possible electrode cracking, ion-transport restrictions, and active-particle decomposition resulting from repeated alloying/de-alloying. To address the aforementioned issues, a nitrogen-doped flower-like porous phosphorus (f-P) sphere has been developed. The abundant micro-mesopores facilitate ion diffusion and enhance the internal bonding strength of the electrode. Concurrently, the doped nitrogen promotes the generation of a favorable solid electrolyte interphase constructed by fast-ion-conductors. As a result, the f-P exhibits a high-rate capacity of 735mAh g -1 at 20 A g -1 and maintains high Coulombic efficiencies over 900 cycles at 10 A g -1 . Furthermore, coin full-cells comprising the f-P anode and lithium cobalt oxide cathode demonstrate stable operation at a high current density of 6 mA cm -2 . The combination of a porous structure and doping strategy represents a viable approach for strengthening the durability of electrodes and optimizing the ion transport kinetics of advanced alloy anode materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the relationship between aromatic amino acids (AAAs), - phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) - and coronary artery disease (CAD) in a prospective study involving 2970 participants undergoing coronary angiography at Beijing Hospital. Serum levels of Phe, Tyr and Trp were analysed. The cross-sectional data revealed that serum Tyr and Trp levels were significantly and inversely associated with CAD. During a median follow-up period of 44 months, 343 major adverse cardiovascular events (MACEs) and 138 all-cause deaths were recorded. MACE included myocardial infarction, stroke, revascularisation and all-cause mortality. Low serum Trp levels predicted an increased risk of MACE and death. High serum Phe levels were linked to an increased risk of MACE, while low Tyr levels were associated with a higher risk of death. Collectively, our findings underscore a close correlation between AAAs and CAD, as well as their potential predictive value for adverse cardiovascular outcomes.

Lithium difluoro(oxalate) borate (LiDFOB) contributes actively to cathode-electrolyte interface (CEI) formation, particularly safeguarding high-voltage cathode materials. However, LiNi x Co z Mn y O 2 -based batteries benefit from the LiDFOB and its derived CEI only with appropriate electrolyte design while a comprehensive understanding of the underlying interfacial mechanisms remains limited, which makes the rational design challenging. By performing ab initio calculations, the CEI evolution on the LiNi 0.8 Co 0.1 Mn 0.1 O 2 has been investigated. The findings demonstrate that LiDFOB readily adheres to the cathode via semidissociative configuration, which elevates the Li deintercalation voltage and remains stable in solvent. Electrochemical processes are responsible for the subsequent cleavage of B-F and B-O bonds, while the B-F bond cleavage leading to LiF formation is dominant in the presence of adequate Li + with a substantial Li intercalation energy. Thus, impregnation is established as an effective method to regulate the conversion channel for efficient CEI formation, which not only safeguards the cathode's structure but also counters electrolyte decomposition. Consequently, in comparison to utilizing LiDFOB as an electrolyte additive, employing LiDFOB impregnation in the NCM811/Li cell yields significantly improved cycling stability for over 2000 h.

Cryogenic detection technology is essential to ensure safety and effectiveness in fields such as medical refrigeration, cold chain transport, and cryogenic bioengineering. In this paper, a time-responsive visual cryogenic detection strategy is developed based on the storage properties of CaZnOS: Pb 2+ , Pr 3+ phosphors with shallow traps. Since the carrier release rate from the trap center receives the influence of ambient temperature and storage time, the storage time of the temperature-sensitive product can be determined by the different optical signals of CaZnOS: Pb 2+ , Pr 3+ phosphors obtained under 980 nm laser irradiation. In addition, CaZnOS: Pb 2+ , Pr 3+ phosphors with multimode luminescence enable time-responsive visual detection of ambient temperature under extreme conditions. This work not only demonstrates the potential of CaZnOS: Pb 2+ , Pr 3+ phosphors for visual detection of temperature and time but also paves the way for the development of various applications relying on cryogenic monitoring.

The hypothalamus is an important component of the hypothalamic-pituitary-adrenal axis and an important brain region of the limbic system. Twenty-four first depressive episode(FDE) patients and 25 healthy controls were recruited for this study. The hypothalamus was used as a seed to observe the characteristics of resting state and dynamic functional connectivity (FC) changes in FDE patients, and further observed the correlation between the different brain regions and clinical symptoms. The results found that compared with the HC group, the FDE group showed sFC was increased of the left hypothalamus with right superior parietal gyrus and right middle temporal gyrus, and dFC was increased of the left hypothalamus with left inferior occipital gyrus. And sFC was increased of the right hypothalamus with right orbital part of inferior frontal gyrus, right supplementary motor area, and right middle temporal gyrus, and the dFC was also increased of right hypothalamus with right superior parietal gyrus and left middle temporal gyrus. In addition,there was a negative correlation between dFC values of the right hypothalamus with the right superior parietal gyrus and clinical symptoms in the FDE group. This study provides new insights into understanding the altered neuropathological mechanisms of the hypothalamic circuit in FDE., Competing Interests: Declaration of competing interest All authors of this study declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Denosumab has recently become an important part of the treatment regime for spinal giant cell tumors of the bone (GCTB). Its use has significantly reduced the risk of surgery and postoperative complications in patients with spinal GCTB. However, the use of denosumab has not yet been optimized to reap the maximum benefits. Here, we have reported the case of a patient who was treated with denosumab in combination with excision and scraping for GCTB of the T10 vertebrae, which achieved good tumor control and no recurrence at the 2-year postoperative follow-up. We have also reviewed the case in the light of relevant literature as well as presented our ideas and recommendations for the optimal use of denosumab., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Miao, Han, Zheng, Xu, Yu, Han and Yu.)

The turnover and stabilization of soil organic carbon are tightly associated with the properties of litter input. Due to the complexity of litter decomposition and the high heterogeneity of forest soils, there are considerable uncertainties about how soil minerals, microorganisms, and environmental factors jointly regulate the transformation and stability of litter-derived soil organic carbon. Here, we present an overview of the "microbial efficiency-matrix stabilization" framework centered on microbial metabolism and organic carbon transformation, as well as the new "microbial carbon pump" and "mineral carbon pump" theories in forest soil organic carbon transformation and stabilization. We specifically highlighted a differential mechanism of "organo-organic interfaces" from the "organo-mineral interfaces" in the effects on soil organic carbon accumulation. We further expounded the transformation processes and stability of soil organic carbon based on the "carbon material cycling" and "energy fluxes", aiming to provide theoretical support for the research on carbon sequestration in forest soils.

The aim of this study was to investigate the anti-ferroptotic effect of resveratrol (RSV) on retinal Müller cells (RMCs) in the early stages of diabetic retinopathy (DR) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4)/prostaglandin-endoperoxide synthase 2 (PTGS2). The retina was obtained from normal and diabetic Sprague-Dawley rats or wild-type and Nrf2 knockout (KO) diabetic mice, with or without RSV (10 mg/kg/d) treatment for 12 weeks. RMCs transfected with or without SiNrf2 were cultured with high glucose and RSV (20 mM). The retinal neurofunctional changes were measured by electroretinogram (ERG). The retinal inner nuclear layer cell mitochondrial morphological changes were detected by transmission electron microscopy. The cell viabilities were measured by cell counting kit-8 (CCK-8) assay. The levels of Fe 2+ , malonic dialdehyde (MDA), and glutathione (GSH) were measured by colorimetric method. The expression of Nrf2, GPx4, and PTGS2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry. In vivo, RSV inhibited retinal neurofunctional changes and mitochondrial morphological changes; decreased Fe 2+ , MDA, and PTGS2; and increased GSH, Nrf2, and GPx4 in retina of DM rats. In vitro, RSV decreased MDA and PTGS2 and increased cell viability, GSH, Nrf2, and GPx4. In vivo and vitro, the role of Nrf2-regulated signaling pathway in anti-ferroptosis by RSV was further confirmed using Nrf2 KO mice and pre-transfected SiNrf2 in RMCs. These findings indicated that RSV is a potential therapeutic option for DR and that Nrf2/GPx4/PTGS2 plays a role in the anti-ferroptosis mechanism of RSV on RMCs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Severe fever with thrombocytopenia syndrome is an emerging viral hemorrhagic fever caused by a tick-borne bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), with a high case fatality. We previously found that SFTSV nucleoprotein (NP) induces macroautophagy/autophagy to facilitate virus replication. However, the role of NP in antagonizing host innate immunity remains unclear. Mitophagy, a selected form of autophagy, eliminates damaged mitochondria to maintain mitochondrial homeostasis. Here, we demonstrate that SFTSV NP triggers mitophagy to degrade MAVS (mitochondrial antiviral signaling protein), thereby blocking MAVS-mediated antiviral signaling to escape the host immune response. Mechanistically, SFTSV NP translocates to mitochondria by interacting with TUFM (Tu translation elongation factor, mitochondrial), and mediates mitochondrial sequestration into phagophores through interacting with LC3, thus inducing mitophagy. Notably, the N-terminal LC3-interacting region (LIR) motif of NP is essential for mitophagy induction. Collectively, our results demonstrated that SFTSV NP serves as a novel virulence factor, inducing TUFM-mediated mitophagy to degrade MAVS and evade the host immune response. Abbreviation: 3-MA: 3-methyladenine; ACTB: actin beta; co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI: 4',6-diamidino-2-phenylindole, dihydrochloride; DMSO: dimethyl sulfoxide; FCCP: carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; GFP: green fluorescent protein; HTNV: Hantan virus; IAV: influenza A virus; IFN: interferon; LAMP1: lysosomal associated membraneprotein 1; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule associatedprotein 1 light chain 3 beta; MAVS: mitochondrial antiviral signaling protein; Mdivi-1: mitochondrial division inhibitor 1; MOI: multiplicity of infection; MT-CO2/COXII: mitochondrially encoded cytochrome C oxidase II; NP: nucleoprotein; NSs: nonstructural proteins; poly(I:C): polyinosinic:polycytidylic acid; RIGI: RNA sensor RIG-I; RLR: RIGI-like receptor; SFTSV: severe fever withthrombocytopenia syndrome virus; TCID50: 50% tissue culture infectiousdose; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20:translocase of outer mitochondrial membrane 20; TUFM: Tu translation elongationfactor, mitochondrial.

Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases., (© 2024. The Author(s).)

Importance: Integrating routine SARS-CoV-2 testing in dialysis facilities may benefit patients receiving dialysis by mitigating risks of serious illness and reducing transmission. Patient acceptance of nonmandatory testing is unknown., Objective: To evaluate the acceptance of 2 SARS-CoV-2 testing strategies among patients in hemodialysis facilities nationwide., Design, Setting, and Participants: This nationwide cluster (dialysis facility-level) randomized trial investigated the acceptance of SARS-CoV-2 testing among patients receiving maintenance hemodialysis at facilities located in 22 states., Intervention: Anterior nares real-time reverse transcriptase-polymerase chain reaction tests offered once every 2 weeks (static testing facilities) vs offered once a week, once every 2 weeks, or once a month depending on county COVID-19 infection prevalence (dynamic testing facilities). Facilities were randomized by county, and tests were offered for 3 months between February 4 and July 24, 2023., Main Outcomes and Measures: The primary outcome was test acceptance. Secondary outcomes included the proportion of patients who accepted at least 1 test., Results: In total, 62 hemodialysis facilities were randomized and 57 participated. Among 2389 participating patients, the median age was 64 (IQR, 54-74) years, 1341 (56%) were male, 138 (6%) were categorized as American Indian, 60 (3%) Asian, 885 (37%) Black, 75 (3%) Native Hawaiian or Pacific Islander, 338 (14%) Hispanic, and 876 (37%) White; and 1603 (67%) had diabetes. A median of 6 (IQR, 6-6) tests were offered per patient in the static arm and 4 (3-6) tests in the dynamic arm. Test acceptance was low: 8% of offered tests were accepted in each of the test arms. Among 503 patients who accepted at least 1 test, the median percentage of offered tests that were accepted was 16% (IQR, 17%-42%) using the static testing strategy and 50% (IQR, 33%-75%) using the dynamic testing strategy (P < .001). Older patients (odds ratio [OR], 1.08 [95% CI, 1.01-1.16] per 5-year age increment), patients with (vs without) diabetes (OR, 1.59 [95% CI, 1.18-2.16]), and women compared with men (OR, 1.30 [95% CI, 0.98-1.73]) were more likely to accept multiple tests. Patients designated in the electronic health record as Hispanic were more likely than patients designated as White (OR, 1.78 [95% CI, 1.15-2.76]) to accept at least 1 test, whereas patients living in zip codes electing Republican representatives to Congress were less likely than patients living in zip codes electing Democratic representatives (OR, 0.34 [95% CI, 0.17-0.69]) to accept multiple tests., Conclusions and Relevance: In this cluster randomized trial evaluating 2 SARS-CoV-2 testing strategies in dialysis facilities, test acceptance was low, and a dynamic testing strategy anchored to COVID-19 infection prevalence did not outperform a static testing strategy of every 2 weeks., Trial Registration: ClinicalTrials.gov Identifier: NCT05225298.

Background: To quantify conjunctival microvascular characteristics obtained by optical coherence tomographic angiography (OCTA) and investigate their relationship with the presence and severity of coronary artery disease (CAD)., Methods: This cross-sectional study included 103 consecutive CAD patients confirmed by coronary angiography and 125 non-CAD controls. The temporal conjunctivas along the limbus of each participant were scanned using OCTA. Quantification of conjunctival microvasculature was performed by AngioTool software. The severity of the disease was evaluated using SYNTAX and Gensini scores., Results: Compared to the controls, the CAD group exhibited significantly lower vessel area density (30.22 ± 3.34 vs. 26.70 ± 4.43 %, p < 0.001), lower vessel length density (6.39 ± 0.77 vs. 5.71 ± 0.89/m, p < 0.001), lower junction density (3.44 ± 0.56 vs. 3.05 ± 0.63/m, p < 0.001), and higher lacunarity (0.11 ± 0.03 vs. 0.14 ± 0.05, p < 0.001). Among all participants, lower vessel area density, lower vessel length density, lower junction density, and higher lacunarity were associated with greater odds of having CAD; the adjusted ORs (95 % confidence intervals) per one SD decrease were 2.71 (1.71, 4.29), 2.51(1.61, 3.90), 2.06 (1.39, 3.05), and 0.36 (0.23, 0.58), respectively. Among CAD patients, junction density was negatively associated with the Gensini score (r = -0.359, p = 0.037) and the Syntax score (r = -0.350, p = 0.042) in women but not in men (p > 0.05)., Conclusions: Conjunctival microvascular characteristics were significantly associated with the presence of CAD. Junction density significantly associated with the severity of CAD among women patients., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of the paper., (Copyright © 2024. Published by Elsevier Inc.)

Anticancer peptides (ACPs), naturally occurring molecules with remarkable potential to target and kill cancer cells. However, identifying ACPs based solely from their primary amino acid sequences remains a major hurdle in immunoinformatics. In the past, several web-based machine learning (ML) tools have been proposed to assist researchers in identifying potential ACPs for further testing. Notably, our meta-approach method, mACPpred, introduced in 2019, has significantly advanced the field of ACP research. Given the exponential growth in the number of characterized ACPs, there is now a pressing need to create an updated version of mACPpred. To develop mACPpred 2.0, we constructed an up-to-date benchmarking dataset by integrating all publicly available ACP datasets. We employed a large-scale of feature descriptors, encompassing both conventional feature descriptors and advanced pre-trained natural language processing (NLP)-based embeddings. We evaluated their ability to discriminate between ACPs and non-ACPs using eleven different classifiers. Subsequently, we employed a stacked deep learning (SDL) approach, incorporating 1D convolutional neural network (1D CNN) blocks and hybrid features. These features included the top seven performing NLP-based features and 90 probabilistic features, allowing us to identify hidden patterns within these diverse features and improve the accuracy of our ACP prediction model. This is the first study to integrate spatial and probabilistic feature representations for predicting ACPs. Rigorous cross-validation and independent tests conclusively demonstrated that mACPpred 2.0 not only surpassed its predecessor (mACPpred) but also outperformed the existing state-of-the-art predictors, highlighting the importance of advanced feature representation capabilities attained through SDL. To facilitate widespread use and accessibility, we have developed a user-friendly for mACPpred 2.0, available at https://balalab-skku.org/mACPpred2/., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Haizao, Sargassum, is widely used to treat goiter. Gancao, Glycyrrhizae radix et rhizome, is renowned for reducing toxicity or increasing effects in traditional Chinese medicine. As a classic herb pair, Haizao-Gancao (HG) is a commonly used and effective combined therapy for goiter. The underlying biological mechanisms of HG on goiter is still unclear., Aim of the Study: To explore the effect of HG on goiter, employing molecular docking combined with experimental validation to elucidate the molecular mechanism., Materials and Methods: The rat goiter model was created by gavageing propylthiouracil (PTU) intragastrically for a duration of 14 days. The rats had been separated into six groups: control, model, euthyrox, HG high-dose (HG-H), medium-dose (HG-M) and low-dose (HG-L) group. Based on general observations (such as the rats' living status, body weight, and rectal temperature), the relative weight of the thyroid, thyroid function, hematoxylin-eosin (HE) staining, and transmission electron microscopy (TEM) to view the pathological variations of the thyroid glands, the effect of HG was evaluated. Discovered the chemical composition of HG by UPLC-MS/MS and the possible targets were predicted adopting several databases. Next, we explored their pharmacological mechanisms using molecular docking and validated key targets using western blotting (WB) and co-immunoprecipitation (Co-IP)., Results: HG significantly increased the levels of triiodothyronine(T3), free triiodothyronine (FT3), free thyroxine (FT4), gained body weight and reduced tumescent thyroid glands in PTU-induced rats. The model group pathological changes such as uneven size, irregular shape and disordered arrangement of follicular epithelial cells occurred. However, HG groups thyroid follicles and epithelial cells appeared apparently normal. A variety of characteristic changes of autophagic vesicles appeared in the HG groups as opposed to the model group. In conclusion, the HG-L showed the best therapeutic effect. By UPLC-MS/MS, the major chemical components of HG were identified. The result revealed that HG contained flavonoids, alkaloids, organic acids, phenolic acidsand and terpenoids, etc. The molecular docking results of formononetin and naringenin and Beclin1 protein showed a high interaction of -5.38 kcal/mol and -5.25 kcal/mol. This implies that formononetin and naringenin may have a therapeutic effect in goiter rats by controlling the Beclin1-mediated autophagy. Western Blot (WB) and co-immunoprecipitation (Co-IP) results showed that HG can disrupt Beclin1/class III phosphatidylinositol 3-kinase(PI3KC3) binding and promote Beclin1/B-cell leukemia/lymphoma-2(Bcl-2) complex formation. Taken together, results demonstrate that autophagy inhibition via reducing Beclin1/PI3KC3 formation and increasing Beclin1/Bcl-2 binding activity., Conclusions: HG ameliorates propylthiouracil-induced goiter by regulating the Beclin1-mediated autophagy, thus promoting the autophagy of thyroid cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters., Methods: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD., Results: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm 3 [125.67, 189.41] vs 90.55 cm 3 [66.80, 119.84], p  < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio ( p  < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p  = 0.011). If the cut-point of EATV was set as 139.252 cm 3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively., Conclusion: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

Phenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.

Current strategies for simultaneously achieving high thermoelectric performance and high light absorption efficiency still suffer from complex steps and high costs. Herein, two kinds of amorphous thermoelectric films of n-type Bi 2 Te 3 and p-type Bi 0.5 Sb 1.5 Te 3 with high Seebeck coefficients were prepared by pulsed laser deposition (PLD) technology. In addition, C-decorated films with excellent light absorption efficiency at the junction of the thermoelectric legs were prepared by simple drop coating and reactive ion etching (RIE) method. The TE/C-RIE composite device exhibits excellent photodetection performance under the conditions of simulated natural light, monochromatic light, and high-frequency chopping. The maximum responsivity and specific detectivity of the device can reach 153.58 mV W -1 and 6.97 × 10 6 cm Hz 1/2 W -1 (under simulated natural light), respectively. This represents an improvement rate of 85.91% compared to that of the pure TE device. Benefiting from the excellent photodetection efficiency of the device and integration advantage of PLD technology, the composite structure can be expanded into integrated photoimaging devices. The accurate identification of patterned light sources with letters (T, J, and U) and digitals (0-9) was successfully realized by associating the response electrical signals of each electrode with the position coordinates. This work provides valuable guidance for the design and fabrication of wide-spectrum photodetectors and complex optical imaging devices.

Loss of phosphatase and tensin homolog (PTEN) has been linked to an immunosuppressive tumor microenvironment, but its underlying mechanisms remain largely enigmatic. Here, we report that PTEN can be secreted by the transmembrane emp24 domain-containing protein 10 (TMED10)-channeled protein secretion pathway. Inhibiting PTEN secretion from tumor cells contributes to immunosuppression and impairs the tumor-suppressive role of PTEN, while intratumoral injection of PTEN protein promotes antitumor immunity and suppresses tumor growth in mice. Mechanistically, extracellular PTEN binds to the plexin domain-containing protein 2 (PLXDC2) on macrophages, triggering subsequent activation of JAK2-STAT1 signaling, which switches tumor-associated macrophages (TAMs) from the immunosuppressive to inflammatory phenotype, leading to enhanced activation of CD8 + T and natural killer cells. Importantly, PTEN treatment also enhances the therapeutic efficacy of anti-PD-1 treatment in mice and reverses the immune-suppressive phenotype of patient-derived primary TAMs. These data identify a cytokine-like role of PTEN in immune activation and tumor suppression and demonstrate the therapeutic potential for extracellular administration of PTEN in cancer immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Low-temperature anticounterfeiting technologies play a crucial role in ensuring the authenticity and integrity of temperature-sensitive products such as vaccines, pharmaceuticals, and food items. In this work, a low-temperature anticounterfeiting route based on the differentiated photoluminescence (PL), PersL, and thermally stimulated luminescence (TSL) behaviors of metal halide perovskite, pure CsCdCl 3 , and CsCdCl 3 :10% Te 4+ is proposed. The CsCdCl 3 host exhibits pronounced color shifts, encompassing PL, PersL, and TSL behaviors, ranging from blue to yellow and orange as the temperature rises from 100 K to room temperature. This color change is attributed to a change in the luminous center (from the D 3d octahedron to the C 3v octahedron). Conversely, the addition of Te 4+ as the luminescence center inhibits the matrix emission, maintains the characteristic orange emission of Te 4+ , and regulates the trap distribution of the matrix at low temperature and the TL luminescence intensity. This work highlights the significant promise of CsCdCl 3 :10% Te 4+ and CsCdCl 3 phosphors as innovative low-temperature anticounterfeiting technologies, especially for cold-chain vaccine safety monitoring.

Background: Mutations in mitochondrial tRNA ( mt-tRNA ) genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus (T2DM). We pre-viously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA Trp A5514G and tRNA Ser(AGY) C12237T variants, however, the effects of these mt-tRNA variants on T2DM progression are largely unknown., Aim: To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic, molecular, and biochemical levels., Methods: Cytoplasmic hybrid (cybrid) cells carrying both m.A5514G and m.C12237T variants, and healthy control cells without these mitochondrial DNA (mtDNA) variants were generated using trans-mitochondrial technology. Mitochondrial features, including mt-tRNA steady-state level, levels of adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mtDNA copy number, nicotinamide adenine dinucleotide (NAD + )/NADH ratio, enzymatic activities of respiratory chain complexes (RCCs), 8-hydroxy-deo-xyguanine (8-OhdG), malondialdehyde (MDA), and superoxide dismutase (SOD) were examined in cell lines with and without these mt-tRNA variants., Results: Compared with control cells, the m.A5514G variant caused an approximately 35% reduction in the steady-state level of mt-tRNA Trp ( P < 0.0001); however, the m.C12237T variant did not affect the mt-tRNA Ser(AGY) steady-state level ( P = 0.5849). Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells: ATP, MMP, NAD + /NADH ratio, enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells ( P < 0.05 for all measures). By contrast, the levels of ROS, 8-OhdG and MDA were significantly increased ( P < 0.05 for all measures), but mtDNA copy number was not affected by m.A5514G and m.C12237T variants ( P = 0.5942)., Conclusion: The m.A5514G variant impaired mt-tRNA Trp metabolism, which subsequently caused mitochondrial dysfunction. The m.C12237T variant did not alter the steady-state level of mt-tRNA Ser(AGY) , indicating that it may be a modifier of the m.A5514G variant. The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: PEDV, Brachyspira hyodysenteriae, and Lawsonia intracellularis , are highly contagious diarrheal pathogens that have caused significant harm to the global swine industry. Co-infections with multiple pathogens are common, making it challenging to identify the actual causative agents depending only on clinical information. It is crucial to develop a reliable method to simultaneously detect and differentiate these pathogens., Methods: Based on the conserved regions of the M gene of PEDV, NADH oxidase gene of B. hyodysenteriae , and the 16S rDNA gene of L. intracellularis , specific probes and primers for the multiplex real-time PCR assay were designed. The concentrations of primers and probes were optimized using a matrix method., Results: The approach demonstrated high specificity and no cross-reactivity with major pathogens related to diarrheal diseases. It showed high sensitivity with a detection limit of 10 copies/μL for B. hyodysenteriae and L. intracellularis , and 100 copies/μL for PEDV, respectively. It also demonstrated high reproducibility and stability with low coefficients of variation. Results from the multiplex real-time PCR method were in complete agreement with the commercial singleplex real-time PCR kit for detecting PEDV, B. hyodysenteriae and L. intracellularis . Clinical data revealed single infection rates of 31.46% for PEDV, 58.43% for B. hyodysenteriae , and 98.6% for L. intracellularis . The co-infection rates were 16.85% for PEDV + B. hyodysenteriae , 31.46% for PEDV + L. intracellularis , 57.86% for B. hyodysenteriae  +  L. intracellularis , and 16.85% for PEDV + B. hyodysenteriae  +  L. intracellularis , respectively., Discussion: The new multiplex real-time PCR method can simultaneously differentiate PEDV, B. hyodysenteriae and L. intracellularis , making it a valuable diagnostic tool for preventing and controlling infectious diseases, as well as aiding in epidemiological investigations., Competing Interests: FL, YL, and XL were employed by the Shandong New Hope Liuhe Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ren, Li, Yu, Li, Li, Sha and Li.)

Molecular imprinting is a promising approach for developing polymeric materials as artificial receptors. However, only a few types of molecularly imprinted polymers (MIPs) are commercially available, and most research on MIP S is still in the experimental phase. The significant limitation has been a challenge for screening imprinting systems, particularly for weak functional target molecules. Herein, a combined method of quantum mechanics (QM) computations and molecular dynamics (MD) simulations was employed to screen an appropriate 2,4-dichlorophenoxyacetic acid (2,4-D) imprinting system. QM calculations were performed using the Gaussian 09 software. MD simulations were conducted using the Gromacs2018.8 software suite. The QM computation results were consistent with those of the MD simulations. In the MD simulations, a realistic model of the 'actual' pre-polymerisation mixture was obtained by introducing numerous components in the simulations to thoroughly investigate all non-covalent interactions during imprinting. This study systematically examined MIP systems using computer simulations and established a theoretical prediction model for the affinity and selectivity of MIPs. The combined method of QM computations and MD simulations provides a robust foundation for the rational design of MIPs.

Denitrification driven by bacteria and fungi is the main source of nitrous oxide （N 2 O） emissions from paddy soil. It is generally believed that biochar reduces N 2 O emissions by influencing the bacterial denitrification process, but the relevant mechanism of its impact on fungal denitrification is still unclear. In this study, the long-term straw carbonization returning experimental field in Changshu Agricultural Ecological Experimental Base of the Chinese Academy of Sciences was taken as the object. Through indoor anaerobic culture and molecular biology technology, the relative contributions of bacteria and fungi to denitrifying N 2 O production in paddy soil and the related microorganism mechanism were studied under different long-term biochar application amounts （blank, 2.25 t·hm -2 , and 22.5 t·hm -2 , respectively, expressed by BC0, BC1, and BC10）. The results showed that compared with that in BC0, biochar treatment significantly reduced N 2 O emission rate, denitrification potential, and cumulative N 2 O emissions, and the contribution of bacterial denitrification was greater than that of fungal denitrification in all three treatments. Among them, the relative contribution rate of bacterial denitrification in BC10 （62.9%） was significantly increased compared to BC0 （50.8%）, whereas the relative contribution rate of fungal denitrification in BC10 （37.1%） was significantly lower than that in BC0 （49.2%）. The application of biochar significantly increased the abundance of bacterial denitrification functional genes （ nirK , nirS , and nosZ ） but reduced the abundance of fungal nirK genes. The contribution rate of fungal denitrification was significantly positively correlated with the N 2 O emission rate and negatively correlated with soil pH, TN, SOM, and DOC. Biochar may have inhibited the growth of denitrifying fungi by increasing pH and carbon and nitrogen content, reducing the abundance of related functional genes, thereby weakening the reduction ability of NO to N 2 O during fungal denitrification process. This significantly reduces the contribution rate of N 2 O production during the fungal denitrification process and the denitrification N 2 O emissions from paddy soil. This study helps to broaden our understanding of the denitrification process in paddy soil and provides a theoretical basis for further regulating fungal denitrification N 2 O emissions.