Exploring the recycled water acceptance based on the technological perspective of UTAUT2: a hybrid analytical approach.

Introduction: The development of advanced sewage technologies empowers the industry to produce high-quality recycled water, which greatly influences human's life and health. Thus, this study investigates the mechanism of individuals' adoption of recycled water from the technology adoption perspective. Methods: Employing the mixed method of structural equation modeling and artificial neural network analysis, we examined a research model developed from the extended Unified Theory of Acceptance and Use of Technology (UTAUT2) framework. To examine the research model, this study employs a leading web-survey company (Sojump) to collect 308 valid samples from the residents in mainland China. Results: The structural equation modeling results verified the associations between the six predictors (performance expectancy, effort expectancy, social influence, facilitating conditions, environmental motivation, and price value), individuals' cognitive and emotional attitudes, and acceptance intention. The artificial neural network analysis validates and complements the structural equation modeling results by unveiling the importance rank of the significant determinants of the acceptance decisions. Discussion: The study provides theoretical implications for recycled water research and useful insights for practitioners and policymakers to reduce the environmental hazards of water scarcity.

Exploring the Role of Neutrophil-Related Genes in Osteosarcoma via an Integrative Analysis of Single-Cell and Bulk Transcriptome.

BACKGROUND: The involvement of neutrophil-related genes (NRGs) in patients with osteosarcoma (OS) has not been adequately explored. In this study, we aimed to examine the association between NRGs and the prognosis as well as the tumor microenvironment of OS. METHODS: The OS data were obtained from the TARGET-OS and GEO database. Initially, we extracted NRGs by intersecting 538 NRGs from single-cell RNA sequencing (scRNA-seq) data between aneuploid and diploid groups, as well as 161 up-regulated differentially expressed genes (DEGs) from the TARGET-OS datasets. Subsequently, we conducted Least Absolute Shrinkage and Selection Operator (Lasso) analyses to identify the hub genes for constructing the NRG-score and NRG-signature. To assess the prognostic value of the NRG signatures in OS, we performed Kaplan-Meier analysis and generated time-dependent receiver operating characteristic (ROC) curves. Gene enrichment analysis (GSEA) and gene set variation analysis (GSVA) were utilized to ascertain the presence of tumor immune microenvironments (TIMEs) and immunomodulators (IMs). Additionally, the KEGG neutrophil signaling pathway was evaluated using ssGSEA. Subsequently, PCR and IHC were conducted to validate the expression of hub genes and transcription factors (TFs) in K7M2-induced OS mice. RESULTS: FCER1G and C3AR1 have been identified as prognostic biomarkers for overall survival. The findings indicate a significantly improved prognosis for OS patients. The effectiveness and precision of the NRG signature in prognosticating OS patients were validated through survival ROC curves and an external validation dataset. The results clearly demonstrate that patients with elevated NRG scores exhibit decreased levels of immunomodulators, stromal score, immune score, ESTIMATE score, and infiltrating immune cell populations. Furthermore, our findings substantiate the potential role of SPI1 as a transcription factor in the regulation of the two central genes involved in osteosarcoma development. Moreover, our analysis unveiled a significant correlation and activation of the KEGG neutrophil signaling pathway with FCER1G and C3AR1. Notably, PCR and IHC demonstrated a significantly higher expression of C3AR1, FCER1G, and SPI1 in Balb/c mice induced with K7M2. CONCLUSIONS: Our research emphasizes the significant contribution of neutrophils within the TIME of osteosarcoma. The newly developed NRG signature could serve as a good instrument for evaluating the prognosis and therapeutic approach for OS.

Chemerin in caudal division of nucleus tractus solitarius increases sympathetic activity and blood pressure.

Chemerin is an adipokine that contributes to metabolism regulation. Nucleus tractus solitarius (NTS) is the first relay station in the brain for accepting various visceral afferent activities for regulating cardiovascular activity. However, the roles of chemerin in the NTS in regulating sympathetic activity and blood pressure are almost unknown. This study aimed to determine the role and potential mechanism of chemerin in the NTS in modulating sympathetic outflow and blood pressure. Bilateral NTS microinjections were performed in anaesthetized adult male Sprague-Dawley rats. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were continuously recorded. Chemerin and its receptor chemokine-like receptor 1 (CMKLR1) were highly expressed in caudal NTS (cNTS). Microinjection of chemerin-9 to the cNTS increased RSNA, MAP and HR, which were prevented by CMKLR1 antagonist α-NETA, superoxide scavenger tempol or N-acetyl cysteine, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium or apocynin. Chemerin-9 increased superoxide production and NADPH oxidase activity in the cNTS. The increased superoxide production induced by chemerin-9 was inhibited by α-NETA. The effects of cNTS microinjection of chemerin-9 on the RSNA, MAP and HR were attenuated by the pretreatment with paraventricular nucleus (PVN) microinjection of NMDA receptor antagonist MK-801 rather than AMPA/kainate receptor antagonist CNQX. These results indicate that chemerin-9 in the NTS increases sympathetic outflow, blood pressure and HR via CMKLR1-mediated NADPH oxidase activation and subsequent superoxide production in anaesthetized normotensive rats. Glutamatergic inputs in the PVN are needed for the chemerin-9-induced responses.

Transcriptome and metabolome analyses reveal chlorogenic acid accumulation in pigmented potatoes at different altitudes.

Pigmented potato tubers are abundant in chlorogenic acids (CGAs), a metabolite with pharmacological activity. This article comprehensively analyzed the transcriptome and metabolome of pigmented potato Huaxingyangyu and Jianchuanhong at four altitudes of 1800 m, 2300 m, 2800 m, and 3300 m. A total of 20 CGAs and intermediate CGA compounds were identified, including 3-o-caffeoylquinic acid, 4-o-caffeoylquinic acid, and 5-o-caffeoylquinic acid. CGA contents in Huaxinyangyu and Jianchuanhong reached its maximum at an altitude of 2800 m and slightly decreased at 3300 m. 48 candidate genes related to the biosynthesis pathway of CGAs were screened through transcriptome analysis. Weighted gene co-expression network analysis (WGCNA) identified that the structural genes of phenylalanine deaminase (PAL), coumarate-3 hydroxylase (C3H), cinnamic acid 4-hydroxylase (C4H) and the transcription factors of MYB and bHLH co-regulate CGA biosynthesis. The results of this study provide valuable information to reveal the changes in CGA components in pigmented potato at different altitudes.

The impact of CYP3A4 genetic polymorphism on crizotinib metabolism and drug-drug interactions.

To elucidate the impact of CYP3A4 activity inhibition and genetic polymorphism on the metabolism of crizotinib. Enzymatic incubation systems for crizotinib were established, and Sprague-Dawley rats were utilized for in vivo experiments. Analytes were quantified using LC-MS/MS. Upon screening 122 drugs and natural compounds, proanthocyanidins emerged as inhibitor of crizotinib metabolism, exhibiting a relative inhibition rate of 93.7%. The IC50 values were 24.53 ± 0.32 µM in rat liver microsomes and 18.24 ± 0.12 µM in human liver microsomes. In vivo studies revealed that proanthocyanidins markedly affected the pharmacokinetic parameters of crizotinib. Co-administration led to a significant reduction in the AUC(0-t), Cmax of PF-06260182 (the primary metabolite of crizotinib), and the urinary metabolic ratio. This interaction is attributed to the mixed-type inhibition of liver microsome activity by proanthocyanidins. CYP3A4, being the principal metabolic enzyme for crizotinib, has its genetic polymorphisms significantly influencing crizotinib's pharmacokinetics. Kinetic data showed that the relative metabolic rates of crizotinib across 26 CYP3A4 variants ranged from 13.14% (CYP3A4.12, 13) to 188.57% (CYP3A4.33) when compared to the wild-type CYP3A4.1. Additionally, the inhibitory effects of proanthocyanidins varied between CYP3A4.12 and CYP3A4.33, when compared to the wild type. Our findings indicate that proanthocyanidins coadministration and CYP3A4 genetic polymorphism can significantly influence crizotinib metabolism.

GLP-1 in the Hypothalamic Paraventricular Nucleus Promotes Sympathetic Activation and Hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension.

Predictive and Prognostic Potentials of Lymphocyte-C-Reactive Protein Ratio Upon Hospitalization in Adult Patients with Acute Pancreatitis.

Purpose: In this study, our objective was to investigate the potential utility of lymphocyte-C-reactive protein ratio (LCR) as a predictor of disease progression and a screening tool for intensive care unit (ICU) admission in adult patients with acute pancreatitis (AP). Methods: We included a total of 217 adult patients with AP who were admitted to the First Affiliated Hospital of Harbin Medical University between July 2019 and June 2022. These patients were categorized into three groups: mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), based on the presence and duration of organ dysfunction. Various demographic and clinical data were collected and compared among different disease severity groups. Results: Height, diabetes, lymphocyte count (LYMPH), lymphocyte percentage (LYM%), platelet count (PLT), D-Dimer, albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), glucose (GLU), calcium ion (Ca2+), C-reactive protein (CRP), procalcitonin (PCT), hospitalization duration, ICU admission, need for BP, LCR, sequential organ failure assessment (SOFA) score, bedside index for severity in AP (BISAP) score, and modified Marshall score showed significant differences across different disease severity groups upon hospitalization. Notably, there were significant differences in LCR between the MAP group and the MSAP and SAP combined group, and the MAP and MSAP combined group and the SAP group, and adult AP patients with ICU admission and those without ICU admission upon hospitalization. Conclusion: In summary, LCR upon hospitalization can be utilized as a simple and reliable predictor of disease progression and a screening tool for ICU admission in adult patients with AP.

Effects and mechanisms of anti-diabetic dietary natural products: an updated review.

Diabetes is a global public health issue, characterized by an abnormal level of blood glucose. It can be classified into type 1, type 2, gestational, and other rare diabetes. Recent studies have reported that many dietary natural products exhibit anti-diabetic activity. In this narrative review, the effects and underlying mechanisms of dietary natural products on diabetes are summarized based on the results from epidemiological, experimental, and clinical studies. Some fruits (e.g., grape, blueberry, and cherry), vegetables (e.g., bitter melon and Lycium barbarum leaves), grains (e.g., oat, rye, and brown rice), legumes (e.g., soybean and black bean), spices (e.g., cinnamon and turmeric) and medicinal herbs (e.g., Aloe vera leaf and Nigella sativa), and vitamin C and carotenoids could play important roles in the prevention and management of diabetes. Their underlying mechanisms include exerting antioxidant, anti-inflammatory, and anti-glycation effects, inhibiting carbohydrate-hydrolyzing enzymes, enhancing insulin action, alleviating insulin resistance, modulating the gut microbiota, and so on. This review can provide people with a comprehensive knowledge of anti-diabetic dietary natural products, and support their further development into functional food to prevent and manage diabetes.

Polarization Effect and Improvement of the Electroinduced Formation Efficiency of a Highly Viscous Liquid Bridge.

In the electroinduced formation of a highly viscous liquid bridge, improving the efficiency of formation is important for industrial applications. This paper presents the preregulation method of the polarization status to shorten the formation time of a liquid bridge. The hindering effect of high viscosity on the polarization of liquid suspensions was investigated. The formation time of the liquid bridge is shortened, and stability is improved by prepolarizing the initial liquid film, with a maximum reduction in the average and standard deviation of times by 12.65 and 2.52 s, respectively. These effects are confirmed at different viscosities and voltages. In addition, this method has no obvious influence on the shape of the liquid bridge. This study provides an approach to improve the electroinduced formation.

Preparation, Antioxidant Activities and Bioactive Components of Kombucha Beverages from Golden-Flower Tea (Camellia petelotii) and Honeysuckle-Flower Tea (Lonicera japonica).

Kombucha is a fermented tea known for its health benefits. In this study, golden-flower tea (Camellia petelotii) and honeysuckle-flower tea (Lonicera japonica) were first used as raw materials to prepare kombucha beverages. The antioxidant activities, total phenolic contents, concentrations of bioactive components, and sensory scores of two kombucha beverages were assessed. Additionally, effects of fermentation with or without tea residues on kombucha beverages were compared. The results found that two kombucha beverages possessed strong antioxidant activities and high scores of sensory analysis. In addition, fermentation with golden-flower tea residues could remarkably enhance the antioxidant activity (maximum 2.83 times) and total phenolic contents (3.48 times), while fermentation with honeysuckle tea residues had a minor effect. Furthermore, concentrations of several bioactive compounds could be increased by fermentation with golden-flower tea residues, but fermentation with honeysuckle-flower tea residues had limited effects. Moreover, the fermentation with or without tea residues showed no significant difference on sensory scores of golden-flower tea kombucha and honeysuckle-flower tea kombucha, and golden-flower tea kombucha had higher sensory scores than honeysuckle-flower tea kombucha. Therefore, it might be a better strategy to produce golden-flower tea kombucha by fermentation with tea residues, while honeysuckle-flower tea kombucha could be prepared without tea residues.

Functional evaluation of CYP2C19 and CYP3A4 gene polymorphism on ibuprofen metabolism.

AIM: Ibuprofen is the most commonly used analgesic. CYP polymorphisms are mainly responsible for the differences in drug metabolism among individuals. Variations in the ability of populations to metabolize ibuprofen can lead to drug exposure events. The aim of this study was to evaluate the effects of CYP2C19 and CYP3A4 polymorphisms on ibuprofen metabolism in a Chinese population. METHODS: First, 31 CYP2C19 and 12 CYP3A4 microsomal enzymes were identified using an insect expression system. Then, variants were evaluated using a mature incubation system. Moreover, ibuprofen metabolite content was determined via ultra-performance liquid chromatography-tandem mass spectrometry analysis. Finally, kinetic parameters of CYP2C19 and CYP3A4 genotypes were determined via Michaelis-Menten curve fitting. RESULTS: Most variants exhibited significantly altered intrinsic clearance compared to the wild type. In the CYP2C19 metabolic pathway, seven variants exhibited no significant alterations in intrinsic clearance (CLint), six variants exhibited significantly high CLint (121-291%), and the remaining 15 variants exhibited substantially reduced CLint (1-71%). In the CYP3A4 metabolic pathway, CYP3A4*30 was not detected in the metabolite content due to the absence of activity, and 10 variants exhibited significantly reduced CLint. CONCLUSION: To the best of our knowledge, this is the first study to assess the kinetic characteristics of 31 CYP2C19 and 12 CYP3A4 genotypes on ibuprofen metabolism. However, further studies are needed on poor metabolizers as they are more susceptible to drug exposure. Our findings suggest that the kinetic characteristics in combination with artificial intelligence to predict the toxicity of ibuprofen and reduce any adverse drug reactions.

Ferulic acid, ligustrazine, and tetrahydropalmatine display the anti-proliferative effect in endometriosis through regulating Notch pathway.

AIMS: With an ambiguous anti-proliferative mechanism, the combination of ferulic acid, ligustrazine, and tetrahydropalmatine (FLT) shows good anti-endometriosis (EMS) activity. In EMS, the expression of Notch pathway and its role in proliferation are not yet unclear. In this study, we sought to uncover the role of Notch pathway's effect and FLT's anti-proliferative mechanism on EMS proliferation. MAIN METHODS: In autograft and allograft EMS models, the proliferating markers (Ki67, PCNA), Notch pathway, and the effect of FLT on them were detected. Then, the anti-proliferative influence of FLT was measured in vitro. The proliferating ability of endometrial cells was investigated with a Notch pathway activator (Jagged 1 or VPA) or inhibitor (DAPT) alone, or in combination with FLT separately. KEY FINDINGS: FLT presented the inhibitory effect on ectopic lesions in 2 EMS models. The proliferating markers and Notch pathway were promoted in ectopic endometrium, but FLT showed the counteraction. Meantime, FLT restrained the endometrial cell growth and clone formation along with a reduction in Ki67 and PCNA. Jagged 1 and VPA stimulated the proliferation. On the contrary, DAPT displayed the anti-proliferating effect. Furthermore, FLT exhibited an antagonistic effect on Jagged 1 and VPA by downregulating Notch pathway and restraining proliferation. FLT also displayed a synergistic effect on DAPT. SIGNIFICANCE: This study indicated that the overexpressing Notch pathway induced EMS proliferation. FLT attenuated the proliferation by inhibiting Notch pathway.

Immunogenicity and safety of heterologous immunisation with Ad5-nCOV in healthy adults aged 60 years and older primed with an inactivated SARS-CoV-2 vaccine (CoronaVac): a phase 4, randomised, observer-blind, non-inferiority trial.

Background: People over 60 have been found to develop less protection after two doses of inactivated COVID-19 vaccines than younger people. Heterologous immunisation could potentially induce more robust immune responses compared to homologous immunisation. We aimed to assess the immunogenicity and safety of a heterologous immunisation with an adenovirus type 5-vectored vaccine (Ad5-nCOV, Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) previously. Methods: We did a randomised, observer-blinded, non-inferiority trial in healthy adults aged 60 years and older in Lianshui County (Jiangsu, China) between August 26, 2021 and May 15, 2022. 199 eligible participants who had received two doses of CoronaVac in the past 3-6 months were randomised (1:1) to receive a third dose of Convidecia (group A, n = 99) or CoronaVac (group B, n = 100), while 100 participants primed with one dose of CoronaVac in the past 1-2 months were randomised equally to receive a second dose of Convidecia (group C, n = 50) or CoronaVac (group D, n = 50). Participants and investigators were masked to the vaccine received. Primary outcomes were the geometric mean titers (GMTs) of neutralising antibodies against live SARS-CoV-2 virus 14 days after boosting and 28-day adverse reactions. This study was registered with ClinicalTrials.govNCT04952727. Findings: A heterologous third dose of Convidecia resulted in a 6.2-fold (GMTs: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralising antibodies against SARS-CoV-2 wild-type, delta (B.1.617.2) and omicron (BA.1.1) 14 days post boosting, respectively, compared with the homologous boost. The heterologous booster with Convidecia induced significantly higher neutralsing activities, with up to 91% inhibition in binding of Spike to ACE2 for BA.4 and BA.5 variants, compared with 35% inhibition induced by three doses of CoronaVac. For participants primed with one dose of CoronaVac, a heterologous dose of Convidecia induced higher neutralising antibodies against wild-type than two doses of CoronaVac (GMTs: 70.9 vs 9.3, p < 0.0001), but not for that against variants of concern (GMTs against delta: 5.0 vs 4.0, p = 0.4876; GMTs against omicron: 4.8 vs 3.7, p = 0.4707). Adverse reactions were reported by 8 (8.1%) participants in group A and 4 (4.0%) in group B (p ＞ 0.05), and 8 (16.0%) in group C and 1 (2.0%) in group D (p = 0.031). Interpretation: In elderly individuals primed with two doses of CoronaVac, the heterologous immunisation with Convidecia induced strong antibodies against SARS-CoV-2 wildtype and variants of concern, which could be an alternative regimen for enhancing protection in this vulnerable population. Funding: National Natural Science Foundation of China, Jiangsu Provincial Key Research and Development Program, and Jiangsu Science Fund for Distinguished Young Scholars Program.

Brain structure underlying the empathizing-systemizing difference in children with autism spectrum disorder.

BACKGROUND: Behavioral research has shown that children with autism spectrum disorder (ASD) have a higher empathizing-systemizing difference (D score) than normal children. However, there is no research about the neuroanatomical mechanisms of the empathizing-systemizing difference in children with ASD. METHODS: Participants comprised 41 children with ASD and 39 typically developing (TD) children aged 6‒12 years. Empathizing-systemizing difference was estimated using the D score from the Chinese version of Children's Empathy Quotient and Systemizing Quotient. We quantified brain morphometry, including global and regional brain volumes and surface-based cortical measures (cortical thickness, surface area, and gyrification) via structural magnetic resonance imaging. RESULTS: We found that the D score was significantly negatively associated with amygdala gray matter volume [ß = -0.16; 95% confidence interval (CI): -0.30, -0.02; P value = 0.030] in children with ASD. There was a significantly negative association between D score and gyrification in the left lateral occipital cortex (LOC) in children with ASD (B = -0.10; SE = 0.03; cluster-wise P value = 0.006) and a significantly positive association between D score and gyrification in the right fusiform in TD children (B = 0.10; SE = 0.03; cluster-wise P value = 0.022). Moderation analyses demonstrated significant interactions between D score and diagnosed group in amygdala gray matter volume (ß = 0.19; 95% CI 0.04, 0.35; P value = 0.013) and left LOC gyrification (ß = 0.11; 95% CI 0.05, 0.17; P value = 0.001) but not in right fusiform gyrification (ß = 0.08; 95% CI -0.02, 0.17; P value = 0.105). CONCLUSIONS: Neuroanatomical variation in amygdala volume and gyrification of LOC could be potential biomarkers for the empathizing-systemizing difference in children with ASD but not in TD children. Large-scale neuroimaging studies are necessary to test the replicability of our findings.

Renal herb formula protects against hyperuricemic nephropathy by inhibiting apoptosis and inflammation.

BACKGROUND: Hyperuricemic nephropathy may be induced by the elevation and accumulation of uric acid in kidney after hyperuricemia, which leads to kidney residential cells apoptosis and inflammation. Renal herb formula (RHF) is a self-designed formula based on traditional Chinese medicine theory and clinical practice in kidney disease treatment. In the literature available currently, there is not yet research article reporting the reno-protective effect of RHF against hyperuricemic nephropathy. PURPOSE: This study was performed to analyze the bioactive compound profiles of RHF, evaluate its protective effects against hyperuricemic nephropathy, and investigate the mechanisms of actions regarding apoptosis and inflammation. METHODS: Ultra-performance liquid chromatography with a diode-array detector was applied to establish fingerprint and chemical composition of RHF. Potassium oxonate was used to induce hyperuricemic nephropathy in mice, and uric acid was used to stimulate apoptosis and inflammatory response in HK-2 cells, while the mice and cells were treated with RHF to explore its reno-protective effects and mechanisms. RESULTS: It was found that chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A-C may be the characteristic components of RHF. RHF treatment could improve kidney functions in mice with hyperuricemic nephropathies, such as decreasing urine protein, uric acid, and creatinine and serum uric acid, creatinine, and urea nitrogen. Histopathological observations showed that RHF treatment ameliorated kidney glomerular hypotrophy, tubular damage, and inflammatory infiltration. Mechanism studies revealed that RHF inhibited kidney residential cell apoptosis and inflammatory response by targeting the p53-associated intrinsic apoptosis pathway and NF-κB-mediated inflammatory pathway. CONCLUSION: Taken together, it could be concluded that RHF exerted reno-protective effects against hyperuricemic nephropathy through reducing apoptosis and inflammation. RHF and the bioactive compounds chlorogenic acid analogs as promising candidates may be developed into novel and effective drugs for hyperuricemic nephropathy treatment and management.

Stretching breakup of a conical liquid bridge with a moving contact line.

The stretching breakup of a conical liquid bridge is the core process of micro-dispensing. To precisely control the droplet loading and improve the dispensing resolution, a detailed study of bridge breakup with a moving contact line is required. A conical liquid bridge is established by an electric field and stretching breakup is investigated here. The effect of contact line state is investigated by examining the pressure at the symmetry axis. Compared to the pinned case, the moving contact line causes a shift of the pressure maximum from the bridge neck to top, and it facilitates the evacuation of the bridge top. For the moving case, factors affecting the contact line motion are then considered. The results show that the increase of the stretching velocity U and the decrease of the initial top radius R top accelerate the contact line motion. And the amount of contact line movement is basically constant. To analyze the influence of the moving contact line on bridge breakup, neck evolution is tracked under different U. An increase of U decreases the breakup time and increases the breakup position. Based on the breakup position and the remnant radius, the influences of U and R top on remnant volume V d are examined. It is found that V d decreases with an increase of U and increases with an increase of R top. Accordingly, different sizes of remnant volume can be obtained by adjusting U and R top. This is helpful for the optimization of liquid loading for transfer printing.

Identification of Human Body Fluid Stains and Non-Biological Stains by Three-Dimensional Fluorescence Spectroscopy.

OBJECTIVES: To establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy. METHODS: The collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types. RESULTS: According to the results of data training and comparison, all the recognition accuracies of Fanta®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy. CONCLUSIONS: Three-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.

Safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster following three doses of CoronaVac: a multicentre, open-label, phase 4, randomised trial.

BACKGROUND: Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster. METHODS: This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 1011 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 1011 viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group vs homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing. FINDINGS: Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% vs 9% and 14%, respectively; p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7-837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0-672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 [48·0-71·4]; p<0·0001). INTERPRETATION: A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac. FUNDING: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan.

Application of transcriptome in time analysis and donor characterization in blood samples.

As an effective supplement to the current forensic DNA typing and one of the research hotpots in forensic science, the in-depth mining and characterization of biological evidence can provide rich and reliable clues for case investigation. In this study, the time-dependent variations of transcriptome were confirmed in in vitro blood samples within 0-168 days and a random forest model was established to realize the classification of blood samples with different TSD (time since deposition). Meanwhile, significant differences were observed in the transcripts of blood samples with different smoking habits and genders within a certain time period. HLA-DRB1, HLA-DQB1 and HLA-DQA2 were identified as markers for smoking habit identification, while the transcripts for RPS4Y1 and EIF1AY from the non-recombining region of the Y chromosome (NRY) were identified as markers for male sex identification. Thus, this study provides a theoretical foundation and experimental strategy for establishing a transcriptome-based method for characterizing blood sample retention time and donor characteristics in the field of forensic investigation.

The coverage of SARS-CoV-2 vaccination and the willingness to receive the SARS-CoV-2 variant vaccine among employees in China.

BACKGROUND: COVID-19, which is caused by SARS-CoV-2, is a major global health threat. The dominant variant of SARS-CoV-2 has changed over time due to continuous evolution. We aimed to evaluate the coverage of SARS-CoV-2 vaccination among employees in China, explore their willingness to receive the SARS-CoV-2 variant vaccine and examine the potential factors influencing vaccination coverage and willingness. METHODS: A cross-sectional epidemiological survey was conducted online from January 1, 2022, to January 30, 2022. The information collected in the survey included sociodemographic characteristics, lifestyle habits, vaccination coverage, willingness to be vaccinated against SARS-CoV-2 variants and the reasons for vaccination and willingness. Multivariable logistic regression models were used to assess the associations of potential factors with the rate of vaccination and the willingness to be vaccinated. RESULTS: Among 62,395 eligible participants, the coverage of SARS-CoV-2 vaccination was 98.9% for at least one dose and 70.1% for a booster. The great majority of vaccinated individuals (94.4%) voluntarily received the vaccine. A total of 60,694 respondents (97.7%) were willing to be vaccinated against SARS-CoV-2 variants, mainly due to confidence in the effectiveness of vaccines (92.8%). A total of 1431 respondents were unwilling to be vaccinated, mainly because of concerns about the adverse effects of vaccines (77.6%). Longer education duration was associated with a higher rate of SARS-CoV-2 vaccination and willingness to be vaccinated. General or poor health status and having no history of influenza vaccination were associated with a lower rate of SARS-CoV-2 vaccination and willingness to be vaccinated. Additionally, we observed a significant positive association of abuse experience with the willingness to be vaccinated. CONCLUSION: Although the rate of SARS-CoV-2 vaccination and the willingness to be vaccinated were relatively high in the study population, there were still some respondents with vaccine hesitancy. Relevant strategies based on significant related factors should be developed and implemented to encourage vaccination.