A Mixed Effect Similarity Matrix Regression Model (SMRmix) for Integrating Multiple Microbiome Datasets at Community Level and its Application in HIV.

Recent studies have highlighted the importance of human microbiota in our health and diseases. However, in many areas of research, individual microbiome studies often offer inconsistent results due to the limited sample sizes and the heterogeneity in study populations and experimental procedures. Integrative analysis of multiple microbiome datasets is necessary. However, statistical methods that incorporate multiple microbiome datasets and account for the study heterogeneity are not available in the literature. In this paper, we develop a mixed effect similarity matrix regression (SMRmix) approach for identifying community level microbiome shifts between outcomes. SMRmix has a close connection with the microbiome kernel association test, one of the most popular approaches for such a task but is only applicable when we have a single study. Via extensive simulations, we show that SMRmix has well-controlled type I error and higher power than some potential competitors. We also applied SMRmix to data from the HIV-reanalysis consortium, a collective effort that obtained all publicly available data on gut microbiome and HIV at December 2017, and obtained consistent associations of gut microbiome with HIV infection, and with MSM status (i.e. men who have sex with men).

Study on the antidepressive effects and mechanism of raw and fried Ziziphi Spinosae Semen via metabolomics and gut microbiota analysis.

Ziziphi Spinosae Semen (ZSS) and fried ZSS (FZSS) have been used for treating insomnia and depression in China. However, the potential influence of chemical variations on their efficacy remains unclear. This study demonstrated that compared with ZSS, FZSS exhibited an increase in the content of seven compounds, while the fatty oil content decreased. Both ZSS and FZSS exhibited antidepressive effects in a chronic unpredictable mild stress rat model, indicating a synergistic regulation of deficiencies in 5-hydroxytryptamine in the brain and the hyperactivation of severe peripheral inflammation. ZSS demonstrated a superior modulatory effect compared with FZSS, as indicated by integrated pharmacodynamic index, metabolic profile, and relative distance value. The potential mechanism underlying their antidepressive effects involved the modulation of gut microbiota structure to alleviate excessive inflammatory responses and imbalanced tryptophan metabolism. Correlation analysis indicated that the higher fatty oil contents should be comprehensively considered as the main reason for ZSS's superior antidepressive effects, achieved through the regulation of pyroglutamic acid levels.

iso-BAI Guided Surface Recrystallization for Over 14% Tin Halide Perovskite Solar Cells.

Tin-based perovskite solar cells (PSCs) are promising environmentally friendly alternatives to their lead-based counterparts, yet they currently suffer from much lower device performance. Due to variations in the chemical properties of lead (II) and tin (II) ions, similar treatments may yield distinct effects resulting from differences in underlying mechanisms. In this work, a surface treatment on tin-based perovskite is conducted with a commonly employed ligand, iso-butylammonium iodide (iso-BAI). Unlike the passivation effects previously observed in lead-based perovskites, such treatment leads to the recrystallization of the surface, driven by the higher solubility of tin-based perovskite in common solvents. By carefully designing the solvent composition, the perovskite surface is effectively modified while preserving the integrity of the bulk. The treatment led to enhanced surface crystallinity, reduced surface strain and defects, and improved charge transport. Consequently, the best-performing power conversion efficiency of FASnI3 PSCs increases from 11.8% to 14.2%. This work not only distinguishes the mechanism of surface treatments in tin-based perovskites from that of lead-based counterparts, but also underscores the critical role in designing tailor-made strategies for fabricating efficient tin-based PSCs.

Endothelium-targeted Ddx24 conditional knockout exacerbates ConA-induced hepatitis in mice due to vascular hyper-permeability.

BACKGROUND: Acute hepatitis is a progressive inflammatory disorder that can lead to liver failure. Endothelial permeability is the vital pathophysiological change involved in infiltrating inflammatory factors. DDX24 has been implicated in immune signaling. However, the precise role of DDX24 in immune-mediated hepatitis remains unclear. Here, we investigate the phenotype of endothelium-targeted Ddx24 conditional knockout mice with Concanavalin A (ConA)-induced hepatitis. METHODS: Mice with homozygous endothelium-targeted Ddx24 conditional knockout (Ddx24flox/flox; Cdh5-Cre+) were established using the CRISPR/Cas9 mediated Cre-loxP system. We investigated the biological functions of endothelial cells derived from transgenic mice and explored the effects of Ddx24 in mice with ConA-induced hepatitis in vivo. The mass spectrometry was performed to identify the differentially expressed proteins in liver tissues of transgenic mice. RESULT: We successfully established mice with endothelium-targeted Ddx24 conditional knockout. The results showed migration and tube formation potentials of murine aortic endothelial cells with DDX24 silencing were significantly promoted. No differences were observed between Ddx24flox/flox; Cdh5-Cre+ and control regarding body weight and length, pathological tissue change and embryogenesis. We demonstrated Ddx24flox/flox; Cdh5-Cre+ exhibited exacerbation of ConA-induced hepatitis by up-regulating TNF-α and IFN-γ. Furthermore, endothelium-targeted Ddx24 conditional knockout caused vascular hyper-permeability in ConA-injected mice by down-regulating vascular integrity-associated proteins. Mechanistically, we identified Ddx24 might regulate immune-mediated hepatitis by inflammation-related permeable barrier pathways. CONCLUSION: These findings prove that endothelium-targeted Ddx24 conditional knockout exacerbates ConA-induced hepatitis in mice because of vascular hyper-permeability. The findings indicate a crucial role of DDX24 in regulating immune-mediated hepatitis, suggesting DDX24 as a potential therapeutic target in the disorder.

Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Fine particulate matter contributes to COPD-like pathophysiology: experimental evidence from rats exposed to diesel exhaust particles.

BACKGROUND: Ambient fine particulate matter (PM2.5) is considered a plausible contributor to the onset of chronic obstructive pulmonary disease (COPD). Mechanistic studies are needed to augment the causality of epidemiologic findings. In this study, we aimed to test the hypothesis that repeated exposure to diesel exhaust particles (DEP), a model PM2.5, causes COPD-like pathophysiologic alterations, consequently leading to the development of specific disease phenotypes. Sprague Dawley rats, representing healthy lungs, were randomly assigned to inhale filtered clean air or DEP at a steady-state concentration of 1.03 mg/m3 (mass concentration), 4 h per day, consecutively for 2, 4, and 8 weeks, respectively. Pulmonary inflammation, morphologies and function were examined. RESULTS: Black carbon (a component of DEP) loading in bronchoalveolar lavage macrophages demonstrated a dose-dependent increase in rats following DEP exposures of different durations, indicating that DEP deposited and accumulated in the peripheral lung. Total wall areas (WAt) of small airways, but not of large airways, were significantly increased following DEP exposures, compared to those following filtered air exposures. Consistently, the expression of α-smooth muscle actin (α-SMA) in peripheral lung was elevated following DEP exposures. Fibrosis areas surrounding the small airways and content of hydroxyproline in lung tissue increased significantly following 4-week and 8-week DEP exposure as compared to the filtered air controls. In addition, goblet cell hyperplasia and mucus hypersecretions were evident in small airways following 4-week and 8-week DEP exposures. Lung resistance and total lung capacity were significantly increased following DEP exposures. Serum levels of two oxidative stress biomarkers (MDA and 8-OHdG) were significantly increased. A dramatical recruitment of eosinophils (14.0-fold increase over the control) and macrophages (3.2-fold increase) to the submucosa area of small airways was observed following DEP exposures. CONCLUSIONS: DEP exposures over the courses of 2 to 8 weeks induced COPD-like pathophysiology in rats, with characteristic small airway remodeling, mucus hypersecretion, and eosinophilic inflammation. The results provide insights on the pathophysiologic mechanisms by which PM2.5 exposures cause COPD especially the eosinophilic phenotype.

MIDASim: a fast and simple simulator for realistic microbiome data.

Background: Advances in sequencing technology has led to the discovery of associations between the human microbiota and many diseases, conditions, and traits. With the increasing availability of microbiome data, many statistical methods have been developed for studying these associations. The growing number of newly developed methods highlights the need for simple, rapid, and reliable methods to simulate realistic microbiome data, which is essential for validating and evaluating the performance of these methods. However, generating realistic microbiome data is challenging due to the complex nature of microbiome data, which feature correlation between taxa, sparsity, overdispersion, and compositionality. Current methods for simulating microbiome data are deficient in their ability to capture these important features of microbiome data, or can require exorbitant computational time. Methods: We develop MIDASim ( MI crobiome DA ta Sim ulator), a fast and simple approach for simulating realistic microbiome data that reproduces the distributional and correlation structure of a template microbiome dataset. MIDASim is a two-step approach. The first step generates correlated binary indicators that represent the presence-absence status of all taxa, and the second step generates relative abundances and counts for the taxa that are considered to be present in step 1, utilizing a Gaussian copula to account for the taxon-taxon correlations. In the second step, MIDASim can operate in both a nonparametric and parametric mode. In the nonparametric mode, the Gaussian copula uses the empirical distribution of relative abundances for the marginal distributions. In the parametric mode, an inverse generalized gamma distribution is used in place of the empirical distribution. Results: We demonstrate improved performance of MIDASim relative to other existing methods using gut and vaginal data. MIDASim showed superior performance by PER-MANOVA and in terms of alpha diversity and beta dispersion in either parametric or nonparametric mode. We also show how MIDASim in parametric mode can be used to assess the performance of methods for finding differentially abundant taxa in a compositional model. Conclusions: MIDASim is easy to implement, flexible and suitable for most microbiome data simulation situations. MIDASim has three major advantages. First, MIDASim performs better in reproducing the distributional features of real data compared to other methods at both presence-absence level and relative-abundance level. MIDASim-simulated data are more similar to the template data than competing methods, as quantified using a variety of measures. Second, MIDASim makes few distributional assumptions for the relative abundances, and thus can easily accommodate complex distributional features in real data. Third, MIDASim is computationally efficient and can be used to simulate large microbiome datasets.

How Photogenerated I2 Induces I-Rich Phase Formation in Lead Mixed Halide Perovskites.

Bandgap tunability of lead mixed halide perovskites (LMHPs) is a crucial characteristic for versatile optoelectronic applications. Nevertheless, LMHPs show the formation of iodide-rich (I-rich) phase under illumination, which destabilizes the semiconductor bandgap and impedes their exploitation. Here, it is shown that how I2 , photogenerated upon charge carrier trapping at iodine interstitials in LMHPs, can promote the formation of I-rich phase. I2 can react with bromide (Br- ) in the perovskite to form a trihalide ion I2 Br- (Iδ- -Iδ+ -Brδ- ), whose negatively charged iodide (Iδ- ) can further exchange with another lattice Br- to form the I-rich phase. Importantly, it is observed that the effectiveness of the process is dependent on the overall stability of the crystalline perovskite structure. Therefore, the bandgap instability in LMHPs is governed by two factors, i.e., the density of native defects leading to I2 production and the Br- binding strength within the crystalline unit. Eventually, this study provides rules for the design of chemical composition in LMHPs to reach their full potential for optoelectronic devices.

Postdeposition Halide Exchange for Achieving Deep-Blue Perovskite Light-Emitting Diodes: The Role of the Organic Cations in the Chloride Source.

Postdeposition halide exchange has been a popular strategy for tuning the emission wavelength of metal halide perovskites and is particularly attractive in achieving deep-blue perovskite light-emitting diodes (PeLEDs), where the quality of the emissive layer is largely limited by the low solubility of chlorides in perovskite precursor solution. In this work, the halide exchange strategy is examined for deep-blue PeLEDs, with a focus on understanding the role of the organic cations of the halide salt (i.e., the chloride source for ion exchange) in modifying the properties of the perovskite films and consequently the PeLED performances. By comparatively investigating the treatment effects of two model systems, namely phenethylammonium chloride and 2,2-diphenylethylammonium chloride (DPEACl), it is found that although the two chlorides produce highly similar photoluminescence properties of the perovskite films, they create different landscapes for current flow in the PeLEDs. In particular, the bulky branch-structured DPEA cations exhibit minimal disturbance to the perovskite grains while providing highly effective inter-grain void filling and thus leakage current blocking, leading to 3D perovskite-based PeLEDs with a record high peak external quantum efficiency of 6.4% at 462 nm. The study highlights the importance of organic cation selection in the halide exchange processes for PeLEDs.

Comparison of endovenous microwave ablation versus radiofrequency ablation for lower limb varicose veins.

OBJECTIVE: Endovenous microwave ablation (EMA) is a recently developed thermal ablation technique used in the treatment of lower limb varicose veins. However, its efficacy and safety have been largely understudied. In the present study, we sought to explore the clinical results of EMA and radiofrequency ablation (RFA) in treating lower limb varicose veins. METHODS: Patients who underwent EMA (n = 65) or RFA (n = 46) at our institute from September 2018 to September 2020 were included in this retrospective investigation. The clinical results and complications were evaluated at 1, 3, 6, and 12 months after the procedure. The effects on disease severity and quality of life were evaluated using the venous clinical severity score and chronic venous insufficiency questionnaire (CIVIQ). RESULTS: The technical success rate was 100% for both experimental groups. Although the operative time between the two groups was comparable, the EMA technique was associated with lower direct costs (P < .001), although also with prolonged hospitalization (P < .001). We found that the use of EMA correlated with more pain at 48 hours postoperatively. Except for the visual analog scale scores, no statistically significant variations were observed in the occurrence of postoperative complications within the first 48 hours postoperatively between the EMA and RFA groups, including paresthesia, ecchymosis, induration, and phlebitis (P > .05). At 4 weeks postoperatively, significantly less pigmentation was observed in the RFA group than in the EMA group (13.04% vs 32.31%; P = .020). However, the pigmentation had resolved in all patients by 12 months postoperatively. The two groups had a reduction in the venous clinical severity scores and an increase in the CIVIQ scores after the procedure. However, the CIVIQ scores within the RFA group had increased more than had those within the EMA group (P < .05). No significant differences were found in recurrence between the two groups (EMA group, 1.54%; RFA group, 2.17%; P = .804). CONCLUSIONS: Both ablation techniques are safe and effective. RFA is associated with relatively higher treatment costs but shorter hospitalization and better quality of life improvement.

In-Plane Chemical Ordering (Mo2/3 R1/3 )2 AlB2 (R = Tb, Dy, Ho, Er, Tm, and Lu) i-MAB Phases and their Two-Dimensional Derivatives (MBene): Synthesis, Structure, Magnetic, and Supercapacitor Performance.

A family of hexagonal in-plane chemical ordering (Mo2/3 R1/3 )2 AlB2 (R = Tb, Dy, Ho, Er, Tm, and Lu) i-MAB phases are synthesized with R-3m hexagonal structure. The i-MAB phases with R = Tb to Tm are considered to have a nonlinear ferromagnetic-like coupling magnetic ground state with gradually weakened magnetocrystalline anisotropy due to variant R-R distances and 4f electrons. Their 2D derivatives (2D-MBene) with rare-earth (R) atom vacancies are obtained by chemical etching. The delamination solvent, surface functional terminations, and chemical bond of 2D-MBene can be modified by one-step nitridation in environment-friendly nitrogen instead of ammonia. A phase conversion is caused by nitridation at 973 K from 2D-MBene to Mo2 N, leading to the optimized specific capacitance of 229 F g-1 . Besides exploring more rare-earth-containing laminated boride systems, this work also demonstrates the promising application of their 2D derivatives with R vacancies in supercapacitors.

Citrus peel extract protects against diesel exhaust particle-induced chronic obstructive pulmonary disease-like lung lesions and oxidative stress.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and characterized by emphysema, small airway remodeling and mucus hypersecretion. Citrus peels have been widely used as food spices and in traditional Chinese medicine for chronic lung disease. Given that citrus peels are known for containing antioxidants and anti-inflammatory compounds, we hypothesize that citrus peel intake can suppress oxidative stress and inflammatory response to air pollution exposure, thereby alleviating COPD-like pathologies. This study aimed to investigate the efficacy of citrus peel extract, namely Guang Chenpi (GC), in preventing the development of COPD induced by diesel exhaust particles (DEPs) and its potential mechanism. DEP-induced COPD-like lung pathologies, inflammatory responses and oxidative stress with or without GC treatment were examined in vivo and in vitro. Our in vivo study showed that GC was effective in decreasing inflammatory cell counts and inflammatory mediator (IL-17A and TNF-α) concentrations in bronchoalveolar lavage fluid (BALF). Pretreatment with GC extract also significantly decreased oxidative stress in the serum and lung tissue of DEP-induced COPD rats. Furthermore, GC pretreatment effectively reduced goblet cell hyperplasia (PAS positive cells) and fibrosis of the small airways, decreased macrophage infiltration as well as carbon loading in the peripheral lungs, and facilitated the resolution of emphysema and small airway remodeling in DEP-induced COPD rats. An in vitro free radical scavenging assay revealed robust antioxidant potential of GC in scavenging DPPH free radicals. Moreover, GC demonstrated potent capacities in reducing ROS production and enhancing SOD activity in BEAS-2B cells stimulated by DEPs. GC treatment significantly attenuated the increased level of IL-8 and MUC5AC from DEP-treated BEAS-2B cells. Mechanistically, GC treatment upregulated the protein level of Nrf-2 and could function via MAPK/NF-κB signaling pathways by suppressing the phosphorylation of p38, JNK and p65. Citrus peel extract is effective in decreasing oxidative stress and inflammatory responses of the peripheral lungs to DEP exposure. These protective effects further contributed to the resolution of COPD-like pathologies.

Quasi-2D Dion-Jacobson phase perovskites as a promising material platform for stable and high-performance lasers.

Metal halide perovskites have shown outstanding optoelectronic and nonlinear optical properties; yet, to realize wafer-scale high-performance perovskite-integrated photonics, the materials also need to have excellent ambient stability and compatibility with nanofabrication processes. In this work, we introduce Dion-Jacobson (D-J) phase perovskites for photonic device applications. By combining self-assembled monolayer-assisted film growth with thermal pressing, we obtain a series of compact and extremely smooth D-J phase perovskite thin films that exhibit excellent stability during electron-beam lithography, solvent development, and rinse. Combining spectroscopic and morphological characterizations, we further demonstrate how organic spacers can be used to fine-tune the photophysical properties and processability of the perovskite films. The distributed-feedback lasers based on the D-J phase perovskites exhibit a low lasing threshold (5.5 µJ cm-2 pumped with nanosecond laser), record high Q factor (up to 30,000), and excellent stability, with an unencapsulated device demonstrating a T90 beyond 60 hours in ambient conditions (50% relative humidity).

High-Mobility and Bias-Stable Field-Effect Transistors Based on Lead-Free Formamidinium Tin Iodide Perovskites.

Electronic devices based on tin halide perovskites often exhibit a poor operational stability. Here, we report an additive engineering strategy to realize high-performance and stable field-effect transistors (FETs) based on 3D formamidinium tin iodide (FASnI3) films. By comparatively studying the modification effects of two additives, i.e., phenethylammonium iodide and 4-fluorophenylethylammonium iodide via combined experimental and theoretical investigations, we unambiguously point out the general effects of phenethylammonium (PEA) and its fluorinated derivative (FPEA) in enhancing crystallization of FASnI3 films and the unique role of fluorination in reducing structural defects, suppressing oxidation of Sn2+ and blocking oxygen and water involved defect reactions. The optimized FPEA-modified FASnI3 FETs reach a record high field-effect mobility of 15.1 cm2/(V·s) while showing negligible hysteresis. The devices exhibit less than 10% and 3% current variation during over 2 h continuous bias stressing and 4200-cycle switching test, respectively, representing the best stability achieved so far for all Sn-based FETs.

Characterizing current noise of commercial constant-current sources by using an optically pumped rubidium atomic magnetometer.

This paper introduces a method for characterizing the current noise of commercial constant-current sources (CCSs) using a free-induction-decay (FID) type optically pumped rubidium atomic magnetometer driven by a radio frequency magnetic field. We convert the sensitivity of the atomic magnetometer into the current noise of CCS by calibrating the coil constant. At the same time, the current noise characteristics of six typical commercial low-noise CCSs are compared. The current noise level of the Keysight model B2961A is the lowest among the six tested CCSs, which is 36.233 ± 0.022 nA/Hz1/2 at 1-25 Hz and 133.905 ± 0.080 nA/Hz1/2 at 1-100 Hz. The sensitivity of the atomic magnetometer is dependent on the current noise level of the CCS. The CCS with low noise is of great significance for high-sensitivity atomic magnetometers. This research provides an important reference for promoting the development of high precision CCS, metrology, and basic physics research.

Identification of potential genetic Loci and polygenic risk model for Budd-Chiari syndrome in Chinese population.

Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow obstruction, posing life-threatening risks in severe cases. Reported risk factors include inherited and acquired hypercoagulable states or other predisposing factors. However, many patients have no identifiable etiology, and causes of BCS differ between the West and East. This study recruited 500 BCS patients and 696 normal individuals for whole-exome sequencing and developed a polygenic risk scoring (PRS) model using PLINK, LASSOSUM, BLUP, and BayesA methods. Risk factors for venous thromboembolism and vascular malformations were also assessed for BCS risk prediction. Ultimately, we discovered potential BCS risk mutations, such as rs1042331, and the optimal BayesA-generated PRS model presented an AUC >0.9 in the external replication cohort. This model provides particular insights into genetic risk differences between China and the West and suggests shared genetic risks among BCS, venous thromboembolism, and vascular malformations, offering different perspectives on BCS pathogenesis.

Association Between Online Health Information-Seeking Behaviors by Caregivers and Delays in Pediatric Cancer: Mixed Methods Study in China.

BACKGROUND: Pediatric cancer patients in China often present at an advanced stage of disease resulting in lower survival and poorer health outcomes. One factor hypothesized to contribute to delays in pediatric cancer has been the online health information-seeking (OHIS) behaviors by caregivers. OBJECTIVE: This study aims to examine the association between OHIS behaviors by caregivers and delays for Chinese pediatric cancer patients using a mixed methods approach. METHODS: This study used a mixed methods approach, specifically a sequential explanatory design. OHIS behavior by the caregiver was defined as the way caregivers access information relevant to their children's health via the Internet. Delays in pediatric cancer were defined as any one of the following 3 types of delay: patient delay, diagnosis delay, or treatment delay. The quantitative analysis methods included descriptive analyses, Student t tests, Pearson chi-square test, and binary logistic regression analysis, all performed using Stata. The qualitative analysis methods included conceptual content analysis and the Colaizzi method. RESULTS: A total of 303 pediatric cancer patient-caregiver dyads was included in the quantitative survey, and 29 caregivers completed the qualitative interview. Quantitative analysis results revealed that nearly one-half (151/303, 49.8%) of patients experienced delays in pediatric cancer, and the primary type of delay was diagnosis delay (113/303, 37.3%), followed by patient delay (50/303, 16.5%) and treatment delay (24/303, 7.9%). In this study, 232 of the 303 (76.6%) caregiver participants demonstrated OHIS behaviors. When those engaged in OHIS behaviors were compared with their counterparts, the likelihood of patient delay more than doubled (odds ratio=2.21; 95% CI 1.03-4.75). Qualitative analysis results showed that caregivers' OHIS behaviors impacted the cancer care pathway by influencing caregivers' symptom appraisal before the first medical contact and caregivers' acceptance of health care providers' diagnostic and treatment decisions. CONCLUSIONS: Our findings suggest that OHIS among Chinese pediatric caregivers may be a risk factor for increasing the likelihood of patient delay. Our government and society should make a concerted effort to regulate online health information and improve its quality. Specialized freemium consultations provided by health care providers via online health informatic platforms are needed to shorten the time for caregivers' cancer symptom appraisal before the first medical contact.

The 2023 wearable photoplethysmography roadmap.

Photoplethysmography is a key sensing technology which is used in wearable devices such as smartwatches and fitness trackers. Currently, photoplethysmography sensors are used to monitor physiological parameters including heart rate and heart rhythm, and to track activities like sleep and exercise. Yet, wearable photoplethysmography has potential to provide much more information on health and wellbeing, which could inform clinical decision making. This Roadmap outlines directions for research and development to realise the full potential of wearable photoplethysmography. Experts discuss key topics within the areas of sensor design, signal processing, clinical applications, and research directions. Their perspectives provide valuable guidance to researchers developing wearable photoplethysmography technology.

Dicoumarol is an effective post-exposure prophylactic for SARS-CoV-2 Omicron infection in human airway epithelium.

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells (AECs) is a quick way to find novel treatments for COVID-19. Computational screening has found dicoumarol (DCM), a natural anticoagulant, to be a potential SARS-CoV-2 inhibitor, but its inhibitory effects and possible working mechanisms remain unknown. Using air-liquid interface culture of primary human AECs, we demonstrated that DCM has potent antiviral activity against the infection of multiple Omicron variants (including BA.1, BQ.1 and XBB.1). Time-of-addition and drug withdrawal assays revealed that early treatment (continuously incubated after viral absorption) of DCM could markedly inhibit Omicron replication in AECs, but DCM did not affect the absorption, exocytosis and spread of viruses or directly eliminate viruses. Mechanistically, we performed single-cell sequencing analysis (a database of 77,969 cells from different airway locations from 10 healthy volunteers) and immunofluorescence staining, and showed that the expression of NAD(P)H quinone oxidoreductase 1 (NQO1), one of the known DCM targets, was predominantly localised in ciliated AECs. We further found that the NQO1 expression level was positively correlated with both the disease severity of COVID-19 patients and virus copy levels in cultured AECs. In addition, DCM treatment downregulated NQO1 expression and disrupted signalling pathways associated with SARS-CoV-2 disease outcomes (e.g., Endocytosis and COVID-19 signalling pathways) in cultured AECs. Collectively, we demonstrated that DCM is an effective post-exposure prophylactic for SARS-CoV-2 infection in the human AECs, and these findings could help physicians formulate novel treatment strategies for COVID-19.