Association of COVID-19 vaccination with risks of hospitalization due to cardiovascular and other diseases: a study using data from the UK Biobank.

OBJECTIVES: To explore whether COVID-19 vaccination protects against hospital admission by preventing infections and severe disease. METHODS: We leveraged the UK-Biobank(UKBB) 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). Multivariable Cox, Poisson regression, propensity score matching(PSM) and inverse probability treatment weighting(IPTW) analyses were performed. We also performed adjustment using prescription-time distribution matching(PTDM) and prior-event rate ratio(PERR). RESULTS: We observed that COVID-19 vaccination(at least one dose), when compared to no vaccination, was associated with reduced short-term risks of hospitalizations from stroke(hazard ratio[HR]=0.178, 95%CI:0.127-0.250,P=1.50e-23), venous thromboembolism(VTE) (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(NCP) (HR=0.108,CI:0.080-0.145;P=2.20e-49), coronary artery disease(CAD) (HR=0.563,CI:0.416-0.762;P=2.05e-4), chronic obstructive pulmonary disease(COPD) (HR=0.212,CI:0.126-0.357;P=4.92e-9), type-2 diabetes(T2DM) (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 above results, reduced hospitalizations for stroke, heart failure, NCP and dementia were consistently observed across regression, PSM/IPTW, PTDM, and PERR. The results for 2-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.

Macrophage membrane-coated nanoparticles for the treatment of infectious diseases.

Infectious diseases threaten human health severely, and traditional treatment techniques face multiple limitations. Macrophages as the important component of immune cells, display the 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 improvement of 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 enlightenment on how to fight against 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. In the end of this review, a look forward to the challenges of this aspect is presented.

A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children.

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 r2 = 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 (r2 > 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.

Combined GWAS and eGWAS reveals the genetic basis underlying drought tolerance in emmer wheat (Triticum turgidum L.).

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.

Amphiphilic nanofibrillated cellulose/polyurethane composites with antibacterial, antifouling and self-healing properties for potential catheter applications.

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.

Versatile Peptide-Based Nanosystems for Photodynamic Therapy.

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.

Uptake and effect of carboxyl-modified polystyrene microplastics on cotton plants.

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.

YouTube Video Analytics for Patient Education: An Exploratory Clustering of Obstructive Sleep Apnea Videos.

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.

Non-operating revenue is an important source of funding for rural hospitals, especially those that are government-owned.

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.

Saponins from Chenopodium quinoa Willd. husks alleviated high-fat-diet-induced hyperlipidemia via modulating the gut microbiota and multiple metabolic pathways.

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 ß-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.

Response time characteristics of a transmissive uniformly doped GaAsP photocathode.

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.

Effects of Block Copolymer Terminal Groups on Toughening Epoxy-Based Composites: Microstructures and Toughening Mechanisms.

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.

An ultrasmall organic synapse for neuromorphic computing.

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 PBFCL10 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 PBFCL10 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.

Development and performance validation of a low-cost algorithms-based hyperspectral imaging system for radiodermatitis assessment.

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.

Discovery of a SHP2 Degrader with In Vivo Anti-Tumor Activity.

Src homology 2 domain-containing phosphatase 2 (SHP2) is an attractive target for cancer therapy due to its multifaceted roles in both tumor and immune cells. Herein, we designed and synthesized a novel series of proteolysis targeting chimeras (PROTACs) using a SHP2 allosteric inhibitor as warhead, with the goal of achieving SHP2 degradation both inside the cell and in vivo. Among these molecules, compound P9 induces efficient degradation of SHP2 (DC50 = 35.2 ± 1.5 nM) in a concentration- and time-dependent manner. Mechanistic investigation illustrates that the P9-mediated SHP2 degradation requires the recruitment of the E3 ligase and is ubiquitination- and proteasome-dependent. P9 shows improved anti-tumor activity in a number of cancer cell lines over its parent allosteric inhibitor. Importantly, administration of P9 leads to a nearly complete tumor regression in a xenograft mouse model, as a result of robust SHP2 depletion and suppression of phospho-ERK1/2 in the tumor. Hence, P9 represents the first SHP2 PROTAC molecule with excellent in vivo efficacy. It is anticipated that P9 could serve not only as a new chemical tool to interrogate SHP2 biology but also as a starting point for the development of novel therapeutics targeting SHP2.

Resistive Sensing of Seed Cotton Moisture Regain Based on Pressure Compensation.

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 (R2) 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.

Regioselective Synthesis of N-Vinyl Pyrazoles from Vinyl Sulfonium Salts with Diazo Compounds.

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.

Safety evaluation of rare ginsenosides of stems and leaves from American ginseng: 90-day exposure toxicity study combined with intestinal flora analysis and metabonomics in rats.

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.

Development of a two-beveled-fiber polarized fiber-optic Raman probe coupled with a ball lens for in vivo superficial epithelial Raman measurements in endoscopy.

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.