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Competing Interests: The authors have no funding or conflicts of interest to disclose.

A stable isotope dilution-liquid chromatography-tandem mass spectrometry method based on a derivatisation strategy involving an N,N'-carbonylimidazole solution (CDI) with 4-(dimethylamino)-benzenemethanamine was developed for the determination of 11 free fatty acids (FFAs) in human blood samples. Serum samples were subjected to liquid‒liquid extraction and centrifuged, and the supernatant was collected for a two-step derivatisation reaction with a CDI and 4-(dimethylamino)-aniline acetonitrile solution. The derivatised solution was separated on a ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) column with a mobile phase consisting of water-acetonitrile in gradient elution and then detected by tandem mass spectrometry using electrospray ionisation (ESI) and multiple reaction monitoring (MRM) in positive ion mode and quantified using the isotope internal standard method. The effects of the derivatisation reaction time, temperature and concentration of derivatisation reagents on the response values of the analytes were investigated. The optimal conditions were as follows: 1.0 mg mL -1 CDI acetonitrile solution at 25 °C for 25 min, followed by a reaction with a 1.0 mg mL -1 4-(dimethylamino)-benzenemethanamine acetonitrile solution at 70 °C for 30 min. Under the optimal conditions, the limits of detection (LODs) of the 11 FFAs were in the range of 3.0-14.0 ng mL -1 ; the limits of quantification (LOQs) were in the range of 8.0-45.0 ng mL -1 ; and the mean recoveries ranged from 83.4 to 112.8%, with intraday and interday precisions ranging from 0.7 to 9.1% and 3.7-9.5%, respectively. The experimental method is simple in terms of the pretreatment operation, accurate and reliable, and can be applied to the sensitive determination of FFAs in human blood samples., Competing Interests: Declaration of competing interest All authors have accepted responsibility for the entire content of this manuscript and approved its submission. 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. All authors have accepted responsibility for the entire content of this manuscript and approved its submission., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To explore whether COVID-19 vaccination protects against hospital admission by preventing infections and severe disease., Methods: We leveraged the UK Biobank and studied associations of COVID-19 vaccination (BioNTech-BNT162b2 or Oxford-AstraZeneca-ChAdOx1) with hospitalizations from cardiovascular and other selected diseases (N = 393,544; median follow-up = 54 days among vaccinated individuals). Multivariable Cox, Poisson regression, propensity score matching, and inverse probability treatment weighting analyses were performed. We also performed adjustment using prescription-time distribution matching, and prior event rate ratio., Results: We observed that COVID-19 vaccination (at least one dose), compared with no vaccination, was associated with reduced short-term risks of hospitalizations from stroke (hazard ratio [HR] = 0.178, 95% confidence interval [CI]: 0.127-0.250, P = 1.50e-23), venous thromboembolism (HR = 0.426, CI: 0.270-0.673, P = 2.51e-4), dementia (HR = 0.114, CI: 0.060-0.216; P = 2.24e-11), non-COVID-19 pneumonia (HR = 0.108, CI: 0.080-0.145; P = 2.20e-49), coronary artery disease (HR = 0.563, CI: 0.416-0.762; P = 2.05e-4), chronic obstructive pulmonary disease (HR = 0.212, CI: 0.126-0.357; P = 4.92e-9), type 2 diabetes (HR = 0.216, CI: 0.096-0.486, P = 2.12e-4), heart failure (HR = 0.174, CI: 0.118-0.256, P = 1.34e-18), and renal failure (HR = 0.415, CI: 0.255-0.677, P = 4.19e-4), based on standard Cox regression models. Among the previously mentioned results, reduced hospitalizations for stroke, heart failure, non-COVID-19 pneumonia, and dementia were consistently observed across regression, propensity score matching/inverse probability treatment weighting, prescription-time distribution matching, and prior event rate ratio. The results for two-dose vaccination were similar., Conclusions: Taken together, this study provides further support to the safety and benefits of COVID-19 vaccination, and such benefits may extend beyond reduction of infection risk or severity per se. However, causal relationship cannot be concluded and further studies are required., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Ischemic heart disease (IHD) remains a leading cause of mortalities worldwide, necessitating timely reperfusion to reduce acute mortality. Paradoxically, reperfusion can induce myocardial ischemia/reperfusion (I/R) injury, which is primarily characterized by mitochondrial dysfunction. Translocator protein (TSPO) participates in multiple cellular events; however, its role in IHD, especially in the process of myocardial I/R injury, has not been well determined. The aim of the present study was to investigate the functional role of TSPO in myocardial I/R injury and dissect the concomitant cellular events involved. This study utilized small interfering RNA (siRNA) technology to knock down TSPO expression. The I/R process was simulated using an anoxia/reoxygenation (A/R) model. The role of TSPO in H9c2 cardiomyocytes was assessed using various techniques, such as Western blotting, Flow cytometry, Reverse transcription-quantitative PCR (RT-qPCR), Immunofluorescence, Co-immunoprecipitation (co-IP) and similar methods. It was found that A/R markedly upregulated the expression of TSPO in cardiomyocytes. Inhibition of TSPO improved myocardial cell apoptosis and damage following A/R stimulation. Additionally, targeting TSPO alleviated mitochondrial damage, reduced mitochondrial ROS release and enhanced ATP synthesis following A/R stimulation. It was further confirmed that A/R stimulation induced a significant increase in the expression of pivotal markers [phosporylated-PKR-like ER kinase (PERK)/PERK, activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1] involved in the adaptive unfolded protein response, which is accompanied by downstream signaling during endoplasmic reticulum (ER) stress. Notably, TSPO knockdown increased the expression of the aforementioned markers and, subsequently, TSPO was confirmed to interact with ATF6, suggesting that TSPO might play a role in ER stress during myocardial I/R injury. Finally, inhibition of TSPO upregulated mitophagy, as indicated by further decreases in P62 and increases in Parkin and PINK1 levels following A/R stimulation. Together, the results suggest that TSPO plays a multifaceted role in myocardial I/R injury. Understanding TSPO-induced cellular responses could inform targeted therapeutic strategies for patients with IHD., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Wen et al.)

Background: At present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear., Objective: To explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD., Methods: We performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction., Results: Among the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients' ipsilateral MCA-PI were less than 0.614, and another one's MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009)., Conclusions: A lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages., (© 2024. The Author(s).)

Drought is one of the major environmental constraints for wheat production world-wide. As the progenitor and genetic reservoir of common wheat, emmer wheat is considered as an invaluable gene pool for breeding drought-tolerant wheat. Combining GWAS and eGWAS analysis of 107 accessions, we identified 86 QTLs, 105 462 eQTLs as well as 68 eQTL hotspots associating with drought tolerance (DT) in emmer wheat. A complex regulatory network composed of 185 upstream regulator and 2432 downstream drought-responsive candidates was developed, of which TtOTS1 was found to play a negative effect in determining DT through affecting root development. This study sheds light on revealing the genetic basis underlying DT, which will provide the indispensable genes and germplasm resources for elite drought tolerance wheat improvement and breeding., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

Infectious diseases severely threaten human health, and traditional treatment techniques face multiple limitations. As an important component of immune cells, macrophages display unique biological properties, such as biocompatibility, immunocompatibility, targeting specificity, and immunoregulatory activity, and play a critical role in protecting the body against infections. The macrophage membrane-coated nanoparticles not only maintain the functions of the inner nanoparticles but also inherit the characteristics of macrophages, making them excellent tools for improving drug delivery and therapeutic implications in infectious diseases (IDs). In this review, we describe the characteristics and functions of macrophage membrane-coated nanoparticles and their advantages and challenges in ID therapy. We first summarize the pathological features of IDs, providing insight into how to fight them. Next, we focus on the classification, characteristics, and preparation of macrophage membrane-coated nanoparticles. Finally, we comprehensively describe the progress of macrophage membrane-coated nanoparticles in combating IDs, including drug delivery, inhibition and killing of pathogens, and immune modulation. At the end of this review, a look forward to the challenges of this aspect is presented., (© 2024 IOP Publishing Ltd.)

Lightweight and high-strength insulation materials have important application prospects in the aerospace, metallurgical, and nuclear industries. In this study, a highly porous silica fiber reinforced phenolic resin matrix composite was prepared by vacuum impregnation and atmospheric drying using quartz fiber needled felt as reinforcement and anhydrous ethanol as a pore-making agent. The effects of curing agent content on the structure, composition, density, and thermal conductivity of the composite were studied. The mechanical properties of the composite in the xy direction and z direction were analyzed. The results showed that this process can also produce porous phenolic resin (PR) with a density as low as 0.291 g/cm 3 , where spherical phenolic resin particles are interconnected to form a porous network structure with a particle size of about 5.43 μm. The fiber-reinforced porous PR had low density (0.372~0.397 g/cm 3 ) and low thermal conductivity (0.085~0.095 W/m·K). The spherical phenolic resin particles inside the composite were well combined with the fiber at the interface and uniformly distributed in the fiber lap network. The composite possessed enhanced mechanical properties with compressive strength of 3.5-5.1 MPa in the xy direction and appeared as gradual compaction rather than destruction as the strain reached 30% in the z direction. This research provides a lightweight and high-strength insulation material with a simple preparation process and excellent performance.

Compared to traditional methods, using machine learning to assess or predict the odor of molecules can save costs in various aspects. Our research aims to collect molecules with coffee odor and summarize the regularity of these molecules, ultimately creating a binary classifier that can determine whether a molecule has a coffee odor. In this study, a total of 371 coffee-odor molecules and 9,700 non-coffee-odor molecules were collected. The Knowledge-guided Pre-training of Graph Transformer (KPGT), support vector machine (SVM), random forest (RF), multi-layer perceptron (MLP), and message-passing neural networks (MPNN) were used to train the data. The model with the best performance was selected as the basis of the predictor. The prediction accuracy value of the KPGT model exceeded 0.84 and the predictor has been deployed as a webserver PredCoffee., Competing Interests: 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., (© 2024 The Author(s).)

This study focuses on enhancing interventional medical devices, specifically catheters, using a novel composite material. Challenges like corrosion and contamination in vivo, often caused by body fluids' pH, bacteria, and proteins, lead to mechanical damage, bacterial colonization, and biofilm formation on devices like catheters. The objective of this study was to prepare a versatile composite (HFs) by designing polyurethanes (HPU) with an ionic chain extender (HIID) and blending them with amphiphilic nanofibrillated cellulose (Am-CNF). The composite leverages dynamic interactions such as hydrogen bonding and electrostatic forces, as evidenced by Molecular Mechanics (MM) calculations. The H4F0.75 composite exhibited exceptional properties: 99 % length recovery post 600 stretching cycles at 100 % strain, rapid self-healing in artificial urine, high bactericidal activity, and excellent cell viability. Moreover, mechanical aging tests and UV-vis spectral analysis confirmed the material's durability and safety. These findings suggest that the HFs composite holds significant promise for improving catheters' performance in medical applications., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Dyslexia and developmental language disorders are important learning difficulties. However, their genetic basis remains poorly understood, and most genetic studies were performed on Europeans. There is a lack of genome-wide association studies (GWAS) on literacy phenotypes of Chinese as a native language and English as a second language (ESL) in a Chinese population. In this study, we conducted GWAS on 34 reading/language-related phenotypes in Hong Kong Chinese bilingual children (including both twins and singletons; total N = 1046). We performed association tests at the single-variant, gene, and pathway levels. In addition, we tested genetic overlap of these phenotypes with other neuropsychiatric disorders, as well as cognitive performance (CP) and educational attainment (EA) using polygenic risk score (PRS) analysis. Totally 5 independent loci (LD-clumped at r 2  = 0.01; MAF > 0.05) reached genome-wide significance (p < 5e-08; filtered by imputation quality metric Rsq>0.3 and having at least 2 correlated SNPs (r 2  > 0.5) with p < 1e-3). The loci were associated with a range of language/literacy traits such as Chinese vocabulary, character and word reading, and rapid digit naming, as well as English lexical decision. Several SNPs from these loci mapped to genes that were reported to be associated with EA and other neuropsychiatric phenotypes, such as MANEA and PLXNC1. In PRS analysis, EA and CP showed the most consistent and significant polygenic overlap with a variety of language traits, especially English literacy skills. To summarize, this study revealed the genetic basis of Chinese and English abilities in a group of Chinese bilingual children. Further studies are warranted to replicate the findings., (© 2024. The Author(s).)

4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) is a flavor compound widely found in natural products and is used in food as a flavor-enhancing agent. Quinone oxidoreductase (QOR) was verified as a key enzyme to synthesize HDMF in strawberry, while its impact on HDMF production by Zygosaccharomyces rouxii was still unknown. The QOR gene was cloned and overexpressed in Z. rouxii , and its impact on HDMF production by Z. rouxii was then further analyzed. At the same time, it is expected to obtain engineered strains of Z. rouxii with high HDMF production. The results showed that the engineered strains of Z. rouxii exhibit different levels of QOR gene expression and HDMF production; among them, the QOR6 strain exhibiting the highest gene expression level and HDMF production was named as ZrQOR . The HDMF production of the ZrQOR strain was significantly higher than that of wild-type Z. rouxii at 3 and 5 days of culture, with 1.41-fold and 1.08-fold increases, respectively. At 3 days of fermentation, the highest HDMF yield of ZrQOR strain was obtained (2.75 mg/L), 2 days ahead of the reported highest HDMF production by Z. rouxii . At 3, 5, and 7 days, QOR gene expression was 4.8-fold, 3.3-fold, and 5.6-fold higher in the ZrQOR strain than in the wild-type Z. rouxii , respectively. Therefore, overexpression of the QOR gene facilitates HDMF synthesis. The genetic stability of the 0-20 generation ZrQOR strain was stable, and there was no significant difference in colony shape, QOR expression, or HDMF production compared to the wild type. In this study, the genetic engineering Z. rouxii strain was used to improve HDMF production. This research has laid the groundwork for further industrial production of HDMF via microbial synthesis., 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., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Background: Hyperlipidemia is characterized by abnormally elevated blood lipids. Quinoa saponins (QS) have multiple pharmacological activities, including antitumor, bactericidal and immune-enhancing effects. However, the lipid-lowering effect and mechanisms of QS in vivo have been scarcely reported., Methods: The effect of QS against hyperlipidemia induced by high-fat diet in rats was explored based on gut microbiota and serum non-targeted metabolomics., Results: The study demonstrated that the supplementation of QS could reduce serum lipids, body weight, liver injury and inflammation. 16S rRNA sequencing demonstrated that QS mildly increased alpha-diversity, altered the overall structure of intestinal flora, decreased the relative richness of Firmicutes, the ratio of Firmicutes/Bacteroidetes (P < 0.05) and increased the relative richness of Actinobacteria, Bacteroidetes, Bifidobacterium, Roseburia and Coprococcus (P < 0.05). Simultaneously, metabolomics analysis showed that QS altered serum functional metabolites with respect to bile acid biosynthesis, arachidonic acid metabolism and taurine and hypotaurine metabolism, which were closely related to bile acid metabolism and fatty acid β-oxidation. Furthermore, QS increased protein levels of farnesoid X receptor, peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase 1, which were related to the screened metabolic pathways. Spearman correlation analysis showed that there was a correlation between gut microbiota and differential metabolites., Conclusion: QS could prevent lipid metabolism disorders in hyperlipidemic rats, which may be closely associated with the regulation of the gut microbiota and multiple metabolic pathways. This study may provide new evidence for QS as natural active substances for the prevention of hyperlipidemia. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Microplastics (MPs) have emerged as a significant global environmental concern, particularly within agricultural soil systems. The extensive use of plastic film mulching in cotton cultivation has led to the alarming presence of MP pollution in cotton fields. However, the uptake and effects of MPs on the growth of cotton plants are poorly understood. In this study, we conducted a comprehensive analysis of hydroponically cultured cotton seedlings at the phenotypic, transcriptional, and metabolic levels after exposure to carboxyl-modified polystyrene microplastics (PS-COOH). Treatment with three concentrations of PS-COOH (100, 300, and 500 mg/L) resulted in notable growth inhibition of treated plants and exhibited a dose-dependent effect. And, PS-COOH can invade cotton roots and be absorbed through the intercellular spaces via apoplastic uptake, with accumulation commensurate with treatment duration. Transcriptomic analysis showed significant up-regulation of genes associated with antioxidant activity in response to 300 mg/L PS-COOH treatment, suggesting the induction of oxidative stress. In addition, the PS-COOH treatment activated the phenylpropanoid biosynthesis pathway, leading to lignin and flavonoid accumulation, and altered sucrose catabolism. These findings illustrate the absorption and effects of MPs on cotton seedlings and offer valuable insights into the potential toxicity of MPs to plants in soil mulched with plastic film., 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.)

Purpose: Non-operating revenue (NOR), derived from investments, contributions, government appropriations, and medical space rentals, can contribute to financial stability of hospitals by offsetting operating losses and improving profitability. NOR might benefit rural hospitals that often face intense financial pressures. However, little is known about how much rural hospitals rely on NOR and if certain organizational characteristics are associated with differences in NOR., Methods: Healthcare Cost Report Information System data from 2011 to 2019 were used to analyze sources of revenue among Critical Access Hospitals (CAHs) and Rural Prospective Payment System (R-PPS) hospitals through descriptive statistics and regression models. Reliance on NOR was measured by the percentage of total revenue from non-operating sources., Findings: Results indicate that both CAHs and R-PPS hospitals rely on NOR; however, CAHs have a higher percentage of total revenue derived from non-operating sources (3.2%) as compared to R-PPS hospitals (1.9%) (p < 0.001). Government-owned hospitals have significantly higher reliance on NOR than other ownership types. System affiliation also influences reliance on NOR. Lastly, results suggest that NOR may play a role in improving overall profit margins., Conclusions: As rural hospitals disproportionately face challenges related to declining profitability and the risk for closure, they may rely on NOR to continue to strengthen financial performance and provide health care to their communities. However, NOR is not guaranteed, and reliance on NOR further reiterates the value of stable, adequate reimbursement to guard against fluctuations in NOR., (© 2023 National Rural Health Association.)

Photodynamic therapy (PDT) has become an important therapeutic strategy because it is highly controllable, effective, and does not cause drug resistance. Moreover, precise delivery of photosensitizers to tumor lesions can greatly reduce the amount of drug administered and optimize therapeutic outcomes. As alternatives to protein antibodies, peptides have been applied as useful targeting ligands for targeted biomedical imaging, drug delivery and PDT. In addition, other functionalities of peptides such as stimuli responsiveness, self-assembly, and therapeutic activity can be integrated with photosensitizers to yield versatile peptide-based nanosystems for PDT. In this article, we start with a brief introduction to PDT and peptide-based nanosystems, followed by more detailed descriptions about the structure, property, and architecture of peptides as background information. Finally, the most recent advances in peptide-based nanosystems for PDT are emphasized and summarized according to the functionalities of peptide in the system to reveal the design and development principle in different therapeutic circumstances. We hope this review could provide useful insights and valuable reference for the development of peptide-based nanosystems for PDT.

With the growing popularity of content-sharing platforms, patients are increasingly using the Internet as a critical source of health information. As one of the most popular video-sharing sites, YouTube provides easy access to health information seekers, but it is difficult and time-consuming to identify and retrieve high-quality videos that may serve as engaging patient education materials. This paper reports on an exploratory analysis of 317 YouTube videos on Obstructive Sleep Apnea (OSA) to better understand some key features of the videos and the relationships between them to facilitate subsequent video classification and recommendation. Features intrinsic to a video, such as video duration, and extrinsic, such as the number of views, are analyzed using unsupervised clustering methods and the Sankey diagram to discover the relationship between the clusters and their significance across different clusters, providing promising insights for the assessment of video quality.

Background: Posterior oropharyngeal saliva (POS) is increasingly recognized as an alternative specimen for detecting respiratory pathogens. The accuracy of Xpert® MTB/RIF Ultra (X-Ultra), when performed on POS obtained from patients with paucibacillary pulmonary tuberculosis (TB) is unclear., Methods: We consecutively recruited adults with symptoms suggestive of pulmonary TB who were negative by both smear microscopy and Xpert MTB/RIF (X-Classic). Each participant was required to provide one bronchoalveolar lavage fluid (BALF) and one POS specimen, respectively. Diagnostic performances of X-Ultra and X-Classic on POS were compared against clinical and mycobacterial reference standards., Findings: 686 participants meeting inclusion criteria were consecutively enrolled into the study. The overall diagnostic sensitivities of X-Ultra and X-Classic on POS samples were 78.9% [95% confidence interval (CI): 72.8-83.8] and 56.4% (95% CI: 49.7-62.9), respectively; the specificities were 96.6% (95% CI: 94.3-98.1) for X-Ultra and 97.6 (95CI: 95.5-98.8) for X-Classic in POS specimens. Notably, the sensitivity of X-Ultra on POS was as sensitive as X-Classic on BALF against microbiological reference standard (78.9% VS 73.1%). Against clinical diagnosis as a reference standard, the sensitivities of X-Ultra and X-Classic on POS were 55.9% (95% CI: 50.5-61.2; 193/345) and 40.0% (95% CI: 34.8-45.4; 138/345), respectively. The risk of negative results with POS was dramatically increased with decreasing bacterial loads., Conclusions: The testing of POS using X-Ultra shows promise as a tool to identify patients with paucibacillary TB. Considering that bronchoscopy is a semi-invasive procedure, POS testing ahead of bronchoscopy, may decrease the need for bronchoscopic procedures, and the cost of care.

High-performance organic neuromorphic devices with miniaturized device size and computing capability are essential elements for developing brain-inspired humanoid intelligence technique. However, due to the structural inhomogeneity of most organic materials, downscaling of such devices to nanoscale and their high-density integration into compact matrices with reliable device performance remain challenging at the moment. Herein, based on the design of a semicrystalline polymer PBFCL 10 with ordered structure to regulate dense and uniform formation of conductive nanofilaments, we realize an organic synapse with the smallest device dimension of 50 nm and highest integration size of 1 Kb reported thus far. The as-fabricated PBFCL 10 synapses can switch between 32 conductance states linearly with a high cycle-to-cycle uniformity of 98.89% and device-to-device uniformity of 99.71%, which are the best results of organic devices. A mixed-signal neuromorphic hardware system based on the organic neuromatrix and FPGA controller is implemented to execute spiking-plasticity-related algorithm for decision-making tasks., (© 2023. The Author(s).)

In this paper, the matrix difference method is used to calculate the photoelectron continuity equation and the outgoing electron flux density equation. The effects of the GaAsP/AlGaAsP recombination rate, electron diffusion coefficient, and activation layer thickness on the time-resolved characteristics and quantum efficiency of a GaAsP photocathode are systematically studied, and the accuracy of the theoretical calculation is verified by experiments. The response speed and quantum efficiency of the GaAsP photocathode can be greatly improved by adjusting the thickness of the GaAsP activation layer reasonably.

Despite the considerable research attention paid to block copolymer (BCP)-toughened epoxy resins, the effects of their terminal groups on their phase structure are not thoroughly understood. This study fills this gap by closely examining the effects of amino and carboxyl groups on the fracture toughness of epoxy resins at different temperatures. Through the combination of scanning electron microscopy and digital image correlation (DIC), it was found that the amino-terminated BCP was capable of forming a stress-distributing network in pure epoxy resin, resulting in better toughening effects at room temperature. In a 60 wt.% silica-filled epoxy composite system, the addition of a carboxyl-terminated BCP showed little toughening effect due to the weaker filler/matrix interface caused by the random dispersion of the microphase of BCPs and distributed silica. The fracture toughness of the epoxy system at high temperatures was not affected by the terminal groups, regardless of the addition of silica. Their dynamic mechanical properties and thermal expansion coefficients are also reported in this article.

The measurement of seed cotton moisture regain (MR) during harvesting operations is an open and challenging problem. In this study, a new method for resistive sensing of seed cotton MR measurement based on pressure compensation is proposed. First, an experimental platform was designed. After that, the change of cotton bale parameters during the cotton picker packaging process was simulated through the experimental platform, and the correlations among the compression volume, compression density, contact pressure, and conductivity of seed cotton were analyzed. Then, support vector regression (SVR), random forest (RF), and a backpropagation neural network (BPNN) were employed to build seed cotton MR prediction models. Finally, the performance of the method was evaluated through the experimental platform test. The results showed that there was a weak correlation between contact pressure and compression volume, while there was a significant correlation ( p < 0.01) between contact pressure and compression density. Moreover, the nonlinear mathematical models exhibited better fitting performance than the linear mathematical models in describing the relationships among compression density, contact pressure, and conductivity. The comparative analysis results of the three MR prediction models showed that the BPNN algorithm had the highest prediction accuracy, with a coefficient of determination (R 2 ) of 0.986 and a root mean square error (RMSE) of 0.204%. The mean RMSE and mean coefficient of variation (CV) of the performance evaluation test results were 0.20% and 2.22%, respectively. Therefore, the method proposed in this study is reliable. In addition, the study will provide a technical reference for the accurate and rapid measurement of seed cotton MR during harvesting operations.

Objective: To investigate the efficacy of STA-MCA double-anastomosis and single-anastomosis in patients with cerebral hypoperfusion caused by chronic internal carotid artery occlusion(CICAO)., Methods: In this retrospective study, data were collected from 19 patients with CICAO who underwent STA-MCA anastomosis at our hospital between January 2016 and January 2022, and they were divided into single anastomosis group and double anastomosis group according to the surgical method. The study collected general clinical data from both groups, including age, sex, lipid levels, blood pressure, glucose levels, smoking and alcohol consumption. Additionally, pre- and postoperative neurological function, cerebral hemodynamic parameters, and postoperative ischemic events were also recorded. By combining our study findings with the existing literature, a comparative analysis of the efficacy of single- and double-anastomosis in patients with CICAO was conducted., Results: Prior to surgical treatment，there were no statistically significant differences in cerebral hemodynamic parameters, including rob (0.65 ± 0.09 VS. 0.62 ± 0.04), rut (1.73 ± 0.40 VS. 1.99 ± 0.53), and rTMax (2.02 ± 0.49 VS. 1.72 ± 0.46), as well as neurofunctional scores, including modified Rankin Scale (MRS) (2.8 ± 1.03 VS. 2.4 ± 0.88) and National Institutes of Health Stroke Scale (NIHSS) (9.1 ± 5.08 VS. 8.3 ± 4.09) between the two groups. After operation, rCBF (single: 0.65 ± 0.09 VS.0.84 ± 0.08, p = 0.007; double: 0.62 ± 0.04 VS.1.08 ± 0.20, p = 0.001) were significantly increased in both groups, but the rMTT (1.99 ± 0.53 VS.1.27 ± 0.42, p = 0.0447) and rTMax (1.72 ± 0.46 VS.1.16 ± 0.16, p = 0.038) showed significant differences postoperatively only in the double-anastomosis group. The MRS (single: 1.8 ± 1.23, double: 1.7 ± 0.9) in both groups and the NIHSS (7.2 ± 5.11) in single-anastomosis group were not improved after surgery, while the NIHSS (8.3 ± 4.09 VS.4.4 ± 3.08, p = 0.037) in double-anastomosis group was improve significantly. In summary, the double-anastomosis group showed better improvement in rCBF and NIHSS scores compared to the single-anastomosis group.(ΔrCBF: 0.19±0.09 VS. 0.45±0.18, p=0.02, ΔNIHSS: 1.9±0.56 VS. 4±1.73, p=0.002). The cases were followed up for 20.3 ± 18.6 months, and there were no ischemic events in either group during the follow-up period., Conclusion: STA-MCA revascularization can improve CBF in patients with hypoperfusion caused by CICAO, and prevent the reoccurrence of ischemic stroke effectively. Compared with single-anastomosis, double-anastomosis can provide more CBF and improve neurologic dysfunction., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rare ginsenosides have already been widely applied in many fields, including health food and bio-medicine. The human being can expose to rare ginsenosides directly or indirectly increasingly. However, there are few studies on the safety assessment of rare ginsenoside mixtures. In the present study, the sub-chronic toxicity of rare ginsenosides for 90 days on SD rats was performed by combining the intestinal flora analysis and urine metabonomics aiming to illustrate the safety of long-term consumption of rare ginsenosides and the potential damage for liver and intestinal. 48 adult rats were divided into four groups: control (0 mg/kg), low-dose (60 mg/kg), medium-dose (200 mg/kg), and high-dose (600 mg/kg). Rats in the high-dose group showed inflammatory changes in their livers and intestines. The strong bactericidal effect of rare ginsenosides caused intestinal flora disorder and changed the structure of intestinal flora in rats, thus inducing intestinal damage in rats. In the high-dose group, levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (AKP) increased significantly. As a result of the high-dose treatment, certain metabolic pathways were altered, such as vitamin B6 metabolism, methionine metabolism, glutathione metabolism, and others. These results indicated that high doses of rare ginsenosides induced liver injury by affecting the above metabolic pathways. Rare ginsenosides with no observed adverse effect level (NOAEL) were below 200 mg/kg/day in vivo. Thus, this present study provides insight into the rational use of rare ginsenosides., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Flour products played a vital role in the global diet structure. With the increasing demand for dietary health and food standardization, the staple food of flour products made from coarse grains due to its unique flavor and rich nutrition has become a trend and is favored by consumers. However, the lack of gluten protein in the raw materials prevented the formation of a stable gluten network structure, leading to the deterioration of the quality of flour products. Ultrasonic treatment, as an innovative food processing technology, generated energy during the action of ultrasonic waves that had a positive impact on the texture, organizational structure, or flavor characteristics of food. That was of great significance for improving food production efficiency, improving food processing quality, and extending food shelf life. This article applied ultrasonic technology to the processing of flour products from the perspective of promoting fermentation and improving production efficiency of flour products. The cavitation effect of ultrasound promoted the formation of gluten network structure, improved the rheology properties of dough and the quality of flour products by promoting protein cross-linking, improving the foaming and emulsifying stability of gluten protein, and promoting the growth and reproduction of yeast. All reviewed studies indicate that ultrasound would be a promising technology for producing high-quality surface products under appropriate conditions., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ultrasonic humidifiers are commonly used in households to maintain indoor humidity and generate a large number of droplets or spray aerosols. However, there have been various health concerns associated with humidifier use, largely due to aerosols generated during operation. Here, we investigated the size distribution, chemical composition, and charged fraction of aerosol particles emitted from commercial ultrasonic humidifiers. Heavy metals in water used for humidifiers were found to be highly enriched in the ultrasonic humidifier aerosols (UHA), with the enrichment factors ranging from 10 2 to 10 7 . This enrichment may pose health concerns for the building occupants, as UHA concentrations of up to 10 6 particles/cm 3 or 3 mg/m 3 were observed. Furthermore, approximately 90% of UHA were observed to be electrically charged, for the first time according to our knowledge. Based on this discovery, we proposed and tested a new method to remove UHA by using a simple electrical field. The designed electrical field in this work can efficiently remove 81.4% of UHA. Therefore, applying this electrical field could be an effective method to significantly reduce the health risks by UHA., 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 © 2023. Published by Elsevier B.V.)

Herein, we develop a base-promoted regioselective synthesis of N -vinyl pyrazoles from vinyl sulfonium salts with diazo compounds. This metal-free synthetic protocol provides an efficient and practical approach to diverse N -vinyl pyrazoles in good to excellent yields under mild conditions. The reaction appears to experience a [3 + 2] annulation of vinyl sulfonium salts and diazo anions rather than diazo compounds, followed by N -vinylation.

We report on the development of a two-beveled-fiber polarized (TBFP) fiber-optic Raman probe coupled with a ball lens for in vivo superficial epithelial Raman measurements in endoscopy. The two-beveled fibers positioned symmetrically along a ball lens, in synergy with paired parallel-polarized polarizers integrated between the fibers and the ball lens, maximize the Raman signal excitation and collection from the superficial epithelium where gastrointestinal (GI) precancer arises. Monte Carlo (MC) simulations and two-layer tissue phantom experiments show that the probe developed detects ∼90% of the Raman signal from the superficial epithelium. The suitability of the probe developed for rapid (<3 s) superficial epithelial Raman measurements is demonstrated on fresh swine esophagus, stomach, and colon tissues, followed by their differentiation with high accuracies (92.1% for esophagus [sensitivity: 89.3%, specificity: 93.2%], 94.1% for stomach [sensitivity: 86.2%, specificity: 97.2%], and 94.1% for colon [sensitivity: 93.2%, specificity: 94.7%]). The presented results suggest the great potential of the developed probe for enhancing in vivo superficial epithelial Raman measurements in endoscopy.

Polyethylene microplastics have been detected in farmland soil, irrigation water, and soil organisms in agroecosystems, while plastic mulching is suggested as a crucial source of microplastic pollution in the agroecosystem. Plastic mulch can be broken down from plastic mulch debris to microplastics through environmental aging and degradation process in farmlands, and the colonization of polyethylene-degrading microorganisms on polyethylene microplastics can eventually enzymatically depolymerize the polyethylene molecular chains with CO 2 release through the tricarboxylic acid cycle. The selective colonization of microplastics by soil microorganisms can cause changes in soil microbial community composition, and it can consequently elicit changes in enzyme activities and nutrient element content in the soil. The biological uptake of polyethylene microplastics and the associated disturbance of energy investment are the main mechanisms impacting soil-dwelling animal development and behavior. As polyethylene microplastics are highly hydrophobic, their presence among soil particles can contribute to soil water repellency and influence soil water availability. Polyethylene microplastics have been shown to cause impacts on crop plant growth, as manifested by the effects of polyethylene microplastics on soil properties and soil biota in the agroecosystems. This review reveals the degradation process, biological impacts, and associated mechanisms of polyethylene microplastics in agroecosystems and could be a critical reference for their risk assessment and management., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Herein, we disclose a visible-light-induced oxy-alkynylation of diazo compounds with ethynylbenziodoxolones. The efficient protocol provides a mild and metal-free methodology to synthesize propargylic esters in moderate to good yields. Notably, this metal-free carbene transfer reaction appears to involve an oxonium ylide intermediate, followed by intramolecular ligand exchange and reductive elimination.

It is necessary to detect cadmium ions in seawater with high sensitivity because the pollution of cadmium ions seriously endangers the health and life of human beings. Nano-Fe 3 O 4 /MoS 2 /Nafion modified glassy carbon electrode was prepared by a drop coating method. The electrocatalytic properties of Nano-Fe 3 O 4 /MoS 2 /Nafion were measured by Cyclic Voltammetry (CV). Differential Pulse Voltammetry (DPV) was used to study the stripping Voltammetry response of the modified electrode to Cd 2+ . The optimal conditions were determined: In 0.1 mol/L HAc-NaAc solution, the solution pH was 4.2, the deposition potential was - 1.0 V, and the deposition time was 720 s, the membrane thickness was 8 μL. Under the optimum condition, the linear relation of Cd 2+ concentration was found in the range of 5-300 μg/L, and the detection limit was 0.053 μg/L. The recovery of Cd 2+ in seawater ranged from 99.2 to 102.9%. A composite material with simple operation, rapid response and high sensitivity was constructed for the determination of Cd 2+ in seawater., (© 2023. The Author(s).)

Whilst radiotherapy (RT) is widely used for cancer treatment, radiodermatitis caused by RT is one most common severe side effect affecting 95% cancer patients. Accurate radiodermatitis assessment and classification is essential to adopt timely treatment, management and monitoring, which all depend on reliable and objective tools for radiodermatitis grading. We therefore, in this work, reported the development and grading performance validation of a low-cost (∼2318.2 CNY) algorithms-based hyperspectral imaging (aHSI) system for radiodermatitis assessment. The low-cost aHSI system was enabled through Monte Carlo (MC) simulations conducted on multi-spectra acquired from a custom built low-cost multispectral imaging (MSI) system, deriving algorithms-based hyper-spectra with spectral resolution of 1 nm. The MSI system was based on sequentially illuminated narrow-band light-emitting diodes (LEDs) and a CMOS camera. Erythema induced artificially on healthy volunteers was measured by the aHSI system developed, with algorithms-based hyper-spectra and skin layer resolved physiological parameters (i.e., the blood volume fraction (BVF) and the oxygen saturation of hemoglobin in blood, et. al.) derivation using MC simulations. The MC simulations derived BVF and the oxygen saturation of hemoglobin in blood showed significant (P < 0.001, analysis of variance: ANOVA) increase with erythema. Further 1D-convolution neural network (CNN) implemented on the algorithms-based hyper-spectra leads to an overall classification accuracy of 93.1%, suggesting the great potential of low-cost aHSI system developed for radiodermatitis assessment., Competing Interests: Ying Xiong initiated the hardware design of the MSI system developed. Shicheng Hao further optimized the system hardware, and was in charge of the system software development as reported in this work., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Ultra-low molecular weight (ULMW) CO 2 -polyols with well-defined hydroxyl end groups represent useful soft segments for the preparation of high-performance polyurethane foams. However, owing to the poor proton tolerance of catalysts towards CO 2 /epoxide telomerization, it remains challenging to synthesize ULMW yet colorless CO 2 -polyols. Herein, we propose an immobilization strategy of constructing supported catalysts by chemical anchoring of aluminum porphyrin on Merrifield resin. The resulting supported catalyst displays both extremely high proton tolerance (≈8000 times the equivalents of metal centers) and independence of cocatalyst, affording CO 2 -polyols with ULMW (580 g mol -1 ) and high polymer selectivity (>99 %). Moreover, the ULMW CO 2 -polyols with various architectures (tri-, quadra-, and hexa-arm) can be obtained, suggesting the wide proton universality of supported catalysts. Notably, benefiting from the heterogeneous nature of the supported catalyst, colorless products can be facilely achieved by simple filtration. The present strategy provides a platform for the synthesis of colorless ULMW polyols derived from not only CO 2 /epoxides, but also lactone, anhydrides etc. or their combinations., (© 2023 Wiley-VCH GmbH.)

Polycystic ovary syndrome (PCOS) is characterized by reproductive, endocrine, and metabolic disorders. Icariin has been shown to regulate endocrine and metabolic imbalances. This study aimed to determine the therapeutic effect and pharmacological mechanism of icariin in PCOS rats. Rats were fed a high-fat diet and gavaged with letrozole to induce PCOS. Thirty-six female rats were randomly divided into four groups: control, model, low-dose, and high-dose icariin. After 30 days of treatment, we evaluated the therapeutic effects on weight and diet, sex hormone levels, ovarian morphology, estrous cycle, inflammatory factors, and indicators of glucolipid metabolism. Combined with the ovarian transcriptome, we verified the key markers of apoptosis and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway by RT-qPCR for mRNA level, western blot, and immunohistochemistry for protein expression. Icariin significantly improved ovarian function and reproductive endocrine disorders by regulating sex hormones, restoring the estrous cycle, and reducing ovarian morphological damage in PCOS rats. Icariin-treated rats had lower weight gain and reduced triglycerides, fasting insulin, HOMA-IR, TNF-α, and interleukin-6 with higher high-density lipoprotein cholesterol levels than PCOS rats. TUNEL staining showed icariin improved apoptosis in the ovaries. This was supported by an increase in Bcl2 and a decrease in Bad and Bax. Icariin decreased the ratios of p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3, and p-STAT5a/STAT5a, decreased IL-6, gp130 expression, and increased cytokine-inducible SH2-containing protein (CISH) and suppressor of cytokine signaling 1 (SOCS1) expression. The pharmacological mechanism may be related to the reduction in ovarian apoptosis and inhibition of the IL-6/gp130/JAK2/STATs pathway., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Solar-driven interfacial evaporation is considered an efficient way to get fresh water from seawater. However, the low evaporation rate, surface salt crystallization, and low energy collection of the photothermal evaporation layer limit its further application in an outdoor freshwater field. And the aggregate structure design of the material itself is often ignored in solar-driven water evaporation. Black soil (BS), with a unique soil aggregate structure, is rich in tubular pores, which can be used for multilevel sunlight utilization and good capillary water transport. Based on the extraordinary photothermal properties and pumping capacity of BS, a reasonable unidirectional salt-collecting device is designed, which can realize long-term collection of mineral salts and continuous evaporation of seawater and generate electric energy in the continuous evaporation. Inspired by the unique aggregate structure, the photothermal material doping of halloysite and nigrosin will simulate the generation of this aggregate structure and retain a good water transport effect while obtaining multistage utilization of sunlight. The solar-driven evaporation rate of a nigrosin-halloysite solar steam generator is 1.75 kg m -2 h -1 under 1 kW m -2 mimic solar radiation; it can achieve stable salt leaching-induced voltage generation of 240 mV. This work demonstrates not only a solar evaporator that can continuously achieve desalination but also the design strategy of BS-like aggregate photothermal materials, which promotes the development of low-cost resource recovery and energy generation for practical outdoor seawater desalination.

Dissemination of antibiotic resistance genes (ARGs) is a huge challenge worldwide. Information regarding underlying mechanisms of conjugation transfer of sublethal ARGs under photoreactivation is still lacking. In this study, experimental exploration and model prediction were conducted to evaluate the effects of photoreactivation on conjugation transfer of plasma-induced sublethal ARGs. The experimental results showed that reactive species (O 2 - •, 1 O 2 , and •OH) generated in the plasma process led to 0.32, 1.45, 3.21, 4.10, and 3.96-log removal for tetC, tetW, bla TEM -1, aac(3)-II, and intI1 after 8 min treatment at 18 kV, respectively. Their attacks led to breakage and mineralization of ARGs-containing DNA and disturbance of bacterial metabolism. The conjugation transfer frequency increased by 0.58-fold after 48 h of photoreactivation compared with the plasma treatment, as well as the abundances of ARGs and reactive oxygen species levels. The alleviation effects of photoreactivation were independent of cell membrane permeability, but related to promotion of intercellular contact. Ordinary differential equation model predicted that the stabilization time of long-term transfer of ARGs significantly increased by 50 % after photoreactivation compared with the plasma treatment, and the conjugation transfer frequency also increased. This study firstly revealed the mechanisms of conjugation transfer of sublethal ARGs under photoreactivation., Competing Interests: Declaration of Competing Interest There is no conflict of interest between the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Top oil temperature (TOT) is an important parameter to evaluate the running state of a transformer. According to the variation trend of TOT, the internal thermal state of transformers can be predicted so as to arrange operation and maintenance reasonably and prevent the occurrence of accidents. However, due to the complex working environment in the field, there are often a large number of missing values in online monitoring data, which seriously affects the prediction of TOT. At the same time, it is affected by various factors such as load, ambient temperature, wind speed, and solar radiation, which cause the information of different time scales to be mixed in its monitoring data. Therefore, it is difficult to achieve the desired accuracy with a single model. In this article, a model for predicting TOT based on data quality enhancement is proposed. First, the Markov model is used to complete the online monitoring data containing missing values to obtain a complete and continuous time series. Then, using the ensemble empirical modal decomposition method, the time series of TOT is decomposed into multiple time series components to eliminate the interaction between different time scales of information, thus reducing the prediction difficulty. Finally, the sub-prediction model of the extreme learning machine is constructed, and the prediction results of all the sub-models are reconstructed to obtain the final prediction results of TOT. In order to verify the effectiveness of the model, the TOT of an operating transformer for the next two days is predicted in the article, and its mean absolute percentage error (MAPE) is 5.27% and its root mean square error (RMSE) is 2.46. Compared with the BP neural network model and the support vector machines (SVM) model, the MAPE is reduced by 69.56% and 61.92%, respectively, and the RMSE is reduced by 67.02% and 59.87%. The results of this study will provide important support for the fault diagnosis of the top oil temperature online monitoring system., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Copper-based nanoinks are emerging as promising low-cost alternatives to widely used silver nanoinks in electronic printing. However, the spontaneous oxidation of copper under ambient conditions poses significant challenges to its broader application. To address this issue, this paper presents an economical, large-scale, and environmentally friendly method for fabricating Cu@Ag nanoparticles (Cu@Ag NPs). The as-prepared nanoparticles exhibit a narrow size distribution of approximately 100 nm and can withstand ambient exposure for at least 60 days without significant oxidation. The Cu@Ag-based ink, with a 60 wt% loading, was screen-printed onto a flexible polyimide substrate and subsequently heat-treated at 290 °C for 15 minutes under a nitrogen atmosphere. The sintered pattern displayed a low electrical resistivity of 25.5 μΩ·cm (approximately 15 times the resistivity of bulk copper) along with excellent reliability and mechanical fatigue strength. The innovative Cu@Ag NPs fabrication method holds considerable potential for advancing large-scale applications of copper-based inks in flexible electronics.

Rationale: Tobacco smoking and air pollution are primary causes of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop COPD. The mechanisms underlying the defense against nitrosative/oxidative stress in nonsusceptible smokers to COPD remain largely unresolved. Objectives: To investigate the defense mechanisms against nitrosative/oxidative stress that possibly prevent COPD development or progression. Methods: Four cohorts were investigated: 1 ) sputum samples (healthy, n  = 4; COPD, n  = 37), 2 ) lung tissue samples (healthy, n  = 13; smokers without COPD, n  = 10; smoker+COPD, n  = 17), 3 ) pulmonary lobectomy tissue samples (no/mild emphysema, n  = 6), and 4 ) blood samples (healthy, n  = 6; COPD, n  = 18). We screened 3-nitrotyrosine (3-NT) levels, as indication of nitrosative/oxidative stress, in human samples. We established a novel in vitro model of a cigarette smoke extract (CSE)-resistant cell line and studied 3-NT formation, antioxidant capacity, and transcriptomic profiles. Results were validated in lung tissue, isolated primary cells, and an ex vivo model using adeno-associated virus-mediated gene transduction and human precision-cut lung slices. Measurements and Main Results: 3-NT levels correlate with COPD severity of patients. In CSE-resistant cells, nitrosative/oxidative stress upon CSE treatment was attenuated, paralleled by profound upregulation of heme oxygenase-1 (HO-1). We identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a negative regulator of HO-1-mediated nitrosative/oxidative stress defense in human alveolar type 2 epithelial cells (hAEC2s). Consistently, inhibition of HO-1 activity in hAEC2s increased the susceptibility toward CSE-induced damage. Epithelium-specific CEACAM6 overexpression increased nitrosative/oxidative stress and cell death in human precision-cut lung slices on CSE treatment. Conclusions: CEACAM6 expression determines the hAEC2 sensitivity to nitrosative/oxidative stress triggering emphysema development/progression in susceptible smokers.

The metabolism of L-tryptophan (TRP) regulates homeostasis, immunity, and neuronal function. Altered TRP metabolism has been implicated in the pathophysiology of various diseases of the central nervous system. TRP is metabolized through two main pathways, the kynurenine pathway and the methoxyindole pathway. First, TRP is metabolized to kynurenine, then kynurenic acid, quinolinic acid, anthranilic acid, 3-hydroxykynurenine, and finally 3-hydroxyanthranilic acid along the kynurenine pathway. Second, TRP is metabolized to serotonin and melatonin along the methoxyindole pathway. In this review, we summarize the biological properties of key metabolites and their pathogenic functions in 12 disorders of the central nervous system: schizophrenia, bipolar disorder, major depressive disorder, spinal cord injury, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, multiple sclerosis, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Furthermore, we summarize preclinical and clinical studies, mainly since 2015, that investigated the metabolic pathway of TRP, focusing on changes in biomarkers of these neurologic disorders, their pathogenic implications, and potential therapeutic strategies targeting this metabolic pathway. This critical, comprehensive, and up-to-date review helps identify promising directions for future preclinical, clinical, and translational research on neuropsychiatric disorders.

Background: T cell lymphomas (TCL) are a group of heterogeneous diseases with over 40 subtypes. In this study, we identified a novel TCL subtype which was featured by a unique T cell receptor (TCR) presentation, α, β and γ chains were co-existing in a single malignant T cell., Case Presentation: A 45-year-old male patient was diagnosed T cell lymphoma after 2-month of abdominal distension and liver enlargement. Combining histology review, PET-CT scanning and immunophenotyes, the patient was not classified to any existing TCL subtypes. To better understand this unclassified TCL case, we performed single cell RNA sequencing paired with TCR sequencing on the patient's PBMC and bone marrow samples. To our surprise, we identified that the malignant T cells had a very rare TCR combination, by expressing two α chains, one β chain and one γ chain simultaneously. We further studied the molecular pathogenesis and tumor cell heterogeneity of this rare TCL subtype. A set of potential therapeutic targets were identified from the transcriptome data, such as CCL5, KLRG1 and CD38., Conclusions: We identified the first TCL case co-expressing α, β and γ chains and dissected its molecular pathogenesis, providing valuable information for precision medicine options for this novel TCL subtype., Competing Interests: RZ, LZ, and LL are employees of Innovec Biotherapeutics. CW is the co-founder of Innovec Biotherapeutics. 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 © 2023 Song, Wang, Wang, Liu, Zhang, Zhang, Zhang and Shi.)

Spermatogenesis depends on an orchestrated series of developing events in germ cells and full maturation of the somatic microenvironment. To date, the majority of efforts to study cellular heterogeneity in testis has been focused on single-cell gene expression rather than the chromatin landscape shaping gene expression. To advance our understanding of the regulatory programs underlying testicular cell types, we analyzed single-cell chromatin accessibility profiles in more than 25,000 cells from mouse developing testis. We showed that single-cell sequencing assay for transposase-accessible chromatin (scATAC-Seq) allowed us to deconvolve distinct cell populations and identify cis -regulatory elements (CREs) underlying cell-type specification. We identified sets of transcription factors associated with cell type-specific accessibility, revealing novel regulators of cell fate specification and maintenance. Pseudotime reconstruction revealed detailed regulatory dynamics coordinating the sequential developmental progressions of germ cells and somatic cells. This high-resolution dataset also unveiled previously unreported subpopulations within both the Sertoli and Leydig cell groups. Further, we defined candidate target cell types and genes of several genome-wide association study (GWAS) signals, including those associated with testosterone levels and coronary artery disease. Collectively, our data provide a blueprint of the 'regulon' of the mouse male germline and supporting somatic cells., Competing Interests: HS, SR, AL, RZ, LY, HQ, HS, RH, TL, JL No competing interests declared, (© 2023, Suen et al.)

Background and Objectives: Alzheimer's disease (AD) has an insidious onset, the early stages are easily overlooked, and there are no reliable, rapid, and inexpensive ancillary detection methods. This study analyzes the differences in handwriting kinematic characteristics between AD patients and normal elderly people to model handwriting characteristics. The aim is to investigate whether handwriting analysis has a promising future in AD auxiliary screening or even auxiliary diagnosis and to provide a basis for developing a handwriting-based diagnostic tool., Materials and Methods: Thirty-four AD patients (15 males, 77.15 ± 1.796 years) and 45 healthy controls (20 males, 74.78 ± 2.193 years) were recruited. Participants performed four writing tasks with digital dot-matrix pens which simultaneously captured their handwriting as they wrote. The writing tasks consisted of two graphics tasks and two textual tasks. The two graphics tasks are connecting fixed dots (task 1) and copying intersecting pentagons (task 2), and the two textual tasks are dictating three words (task 3) and copying a sentence (task 4). The data were analyzed by using Student's t -test and Mann-Whitney U test to obtain statistically significant handwriting characteristics. Moreover, seven classification algorithms, such as eXtreme Gradient Boosting (XGB) and Logistic Regression (LR) were used to build classification models. Finally, the Receiver Operating Characteristic (ROC) curve, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Area Under Curve (AUC) were used to assess whether writing scores and kinematics parameters are diagnostic., Results: Kinematic analysis showed statistically significant differences between the AD and controlled groups for most parameters ( p  < 0.05, p  < 0.01). The results found that patients with AD showed slower writing speed, tremendous writing pressure, and poorer writing stability. We built statistically significant features into a classification model, among which the model built by XGB was the most effective with a maximum accuracy of 96.55%. The handwriting characteristics also achieved good diagnostic value in the ROC analysis. Task 2 had a better classification effect than task 1. ROC curve analysis showed that the best threshold value was 0.084, accuracy = 96.30%, sensitivity = 100%, specificity = 93.41%, PPV = 92.21%, NPV = 100%, and AUC = 0.991. Task 4 had a better classification effect than task 3. ROC curve analysis showed that the best threshold value was 0.597, accuracy = 96.55%, sensitivity = 94.20%, specificity = 98.37%, PPV = 97.81%, NPV = 95.63%, and AUC = 0.994., Conclusion: This study's results prove that handwriting characteristic analysis is promising in auxiliary AD screening or AD diagnosis., Competing Interests: XT was employed by the company Cloudbutterfly Technology 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 © 2023 Qi, Zhang, Wei, Zhang, Wang, Lang, Zhang and Tian.)

The COVID-19 pandemic has caused substantial losses worldwide in people's lives, health, and property. Currently, COVID-19 is still prominent worldwide without any specific drug treatment. The SARS-CoV-2 pathogen is the cause of various systemic diseases, mainly acute pneumonia. Within the pathological process, neutrophils are recruited to infected sites, especially in the lungs, for the first stage of removing invading SARS-CoV-2 through a range of mechanisms. Macroautophagy/autophagy, a conserved autodegradation process in neutrophils, plays a crucial role in the neutrophil phagocytosis of pathogens. NETosis refers to neutrophil cell death, while auto-inflammatory factors and antigens release NETs. This review summarizes the latest research progress and provides an in-depth explanation of the underlying mechanisms of autophagy and NETosis in COVID-19. Furthermore, after exploring the relationship between autophagy and NETosis, we discuss potential targets and treatment options. This review keeps up with the latest research on COVID-19 from neutrophil autophagy and NETosis with a new perspective, which can guide the urgent development of antiviral drugs and provide guidance for the clinical treatment of COVID-19. Abbreviations: AKT1: AKT serine/threonine kinase 1; AMPK: AMP-activated protein kinase; AP: autophagosome; ARDS: acute respiratory distress syndrome; ATG: autophagy related; BECN1: beclin 1; cfDNA: cell-free DNA; COVID-19: coronavirus disease 2019; CQ: chloroquine; DMVs: double-membrane vesicles; ELANE/NE: elastase, neutrophil expressed; F3: coagulation factor III, tissue factor; HCQ: hydroxychloroquine; MAP1LC3/LC3: microtubule associated protein 1 light chain of 3; MPO: myeloperoxidase; MTORC1: mechanistic target of rapamycin kinase complex 1; NETs: neutrophil traps; NSP: nonstructural protein; PI3K: class I phosphoinositide 3-kinase; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SKP2: S-phase kinase associated protein 2; TCC: terminal complement complex; ULK1: unc-51 like.

Titanium nanoparticles and pyrethroid pesticides are now being widely used in industrial, agriculture, and biomedical applications. In recent years, their health safety profiles have aroused concerns among health scientists. This study mainly explored the combined effects of titanium dioxide nanoparticles (TiO 2 NPs) and cypermethrin (CYP) on reproductive toxicity in male rats by gavage for 90 days. Thirty-two male Sprague-Dawley rats were assigned to four groups: the control group, the TiO 2 NPs group, the CYP group, and the combined titanium dioxide nanoparticles with cypermethrin (TiO 2 NPs + CYP) group. The results of biochemical analysis on testicular tissue homogenate showed that TiO 2 NPs and CYP mixtures decreased the activities of glutathione peroxidase (GSH-Px) and catalase (CAT) while increasing the activity of malondialdehyde (MDA) and lactate dehydrogenase (LDH). Meanwhile, the results of two-way factorial analysis of variance (ANOVA) showed a significant effect on GSH-Px, CAT, LDH, testicular cell apoptosis, and sperm quality in rats after exposure. Furthermore, the combined exposure group exhibited apoptosis of testicular cells and DNA damage. The results indicated that exposure to a mixture of TiO 2 NPs and CYP had adverse effects on the reproductive status of male rats., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Hepatosplenic T-cell lymphoma (HSTCL), mostly derived from γδ T cells, is a rare but very aggressive lymphoma with poor outcomes. In this study, we generated the first single cell landscape for this rare disease and characterized the molecular pathogenesis underlying the disease progression., Methods: We performed paired single cell RNA-seq and T cell receptor (TCR) sequencing on biopsies from a HSTCL patient pre- and post- chemotherapy treatments. Following by a series of bioinformatics analysis, we investigated the gene expression profile of γδ HSTCS as well as its tumor microenvironment (TME)., Results: We characterized the unique gene expressing signatures of malignant γδ T cells with a set of marker genes were newly identified in HSTCL (AREG, PLEKHA5, VCAM1 etc.). Although the malignant γδ T cells were expanded from a single TCR clonotype, they evolved into two transcriptionally distinct tumor subtypes during the disease progression. The Tumor&#95;1 subtype was dominant in pre-treatment samples with highly aggressive phenotypes. While the Tumor&#95;2 had relative mild cancer hallmark signatures but expressed genes associated with tumor survival signal and drug resistance (IL32, TOX2, AIF1, AKAP12, CD38 etc.), and eventually became the main tumor subtype post-treatment. We further dissected the tumor microenvironment and discovered the dynamically rewiring cell-cell interaction networks during the treatment. The tumor cells had reduced communications with the microenvironment post-treatment., Conclusions: Our study reveals heterogenous and dynamic tumor and microenvironment underlying pathogenesis of HSTCL and may contribute to identify novel targets for diagnosis and treatment of HSTCL in the future., (© 2022. The Author(s).)

(1) Background: Icariin is the main component of the Chinese herb Epimedium. A number of studies have shown that it alleviates abnormal lipid metabolism. However, it is not clear whether and how icariin can ameliorate hepatic steatosis with polycystic ovary syndrome (PCOS). This study was designed to explore the anti-hepatosteatosis effect of icariin in rats with polycystic ovary syndrome. (2) Methods: Female Sprague Dawley(SD)rats were treated with a high-fat diet and letrozole for 21 days to make nonalcoholic fatty liver disease (NAFLD) in the polycystic ovary syndrome model. Then model rats were treated with icariin (by gavage, once daily) for 28 days. Serum hormones and biochemical variables were determined by ELISA or enzyme. RNA-sequence analysis was used to enrich related target pathways. Then, quantitative Real-time PCR (qRT-PCR) and Western blot were performed to verify target genes and proteins. (3) Results: Icariin treatment reduced excess serum levels of Testosterone (T), Estradiol (E2), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), LH/FSH ratio, insulin, triglycerides (TG), and aspartate aminotransferase (AST) in high-fat diet (HFD) and letrozole fed rats. Meanwhile, icariin ameliorated HFD and letrozole-induced fatty liver, as evidenced by a reduction in excess triglyceride accumulation, vacuolization, and Oil Red O staining area in the liver of model rats. Results of RNA-sequencing, western blotting, and qRT-PCR analyses indicated that icariin up-regulated fatty acid translocase (CD36), in mitochondria, and peroxisome proliferator-activated receptor α (PPARα) expression, which led to the enhancement of fatty acid oxidation molecules, such as cytochrome P450, family 4, subfamily a, polypeptide 3 (CYP4A3), carnitine palmitoyltransferase 1 α (CPT1α), acyl-CoA oxidase 1 (ACOX1), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD). Besides, icariin reduced lipid synthesis, which elicited stearoyl-Coenzyme A desaturase 1 (SCD1), fatty acid synthase (FASN), and acetyl-CoA (ACC). (4) Conclusion: Icariin showed an ameliorative effect on hepatic steatosis induced by HFD and letrozole, which was associated with improved fatty acid oxidation and reduced lipid accumulation in the liver.

Titanium dioxide nanoparticles (TiO 2 NPs) and cypermethrin (CPM) are widely used in various fields, and they can enter the environment in different ways. Combined exposure of TiO 2 NPs and CPM may increase the accumulation of pollutants in organisms and affect human health. This study was undertaken to evaluate the oxidative and inflammatory parameters associated with the combined exposure of TiO 2 NPs and CPM in rats. Twenty-four healthy male adult SD rats were randomly divided into four groups. The first group served as the control, while groups 2, 3, and 4 were treated with TiO 2 NPs (450 mg/m 3 ); CPM (6.67 mg/m 3 ) or combined exposure of TiO 2 NPs and CPM by inhalation for 90 days. We investigated the oxidative damage induced through combined exposure of TiO 2 NPs and CPM in rats by evaluating hematology of the rats and determining the blood biochemical index. Our results demonstrated that inhalation of TiO 2 NPs and CPM increased the levels of oxidative stress markers such as malondialdehyde and alkaline phosphatase in the serum of rats. These were accompanied by a decreased glutathione peroxidase and total superoxide dismutase levels. Furthermore, the level of glutathione peroxidase was further decreased while malondialdehyde was increased in the combined exposure of TiO 2 NPs and CPM. Interestingly, pathological sections showed that different degrees of tissue injury could be seen in the liver and lung tissues of each exposure group. In summary, the combined exposure of TiO 2 NPs and CPM can cause increased oxidative damage in rats and damage the tissue structure of the liver and lung.

A visible-light photocatalytic regioselective [2 + 2 + 1] radical annulation reaction of alkenes, tert -butyl nitrite, and gem -dihalides has been developed. The protocol provides an efficient and practical approach to obtain isoxazolines in good yields under mild conditions. Significantly, gem -dihalides serve as C1 synthons, while cheap tert -butyl nitrite acts as an ideal "N-O" synthon.