Search

Abstract Nucleoli are fundamentally essential sites for ribosome biogenesis in cells and formed by liquid-liquid phase separation (LLPS) for a multilayer condensate structure. How the nucleoli integrity is maintained remains poorly understood. Here, we reveal that METTL3/METTL14, the typical methyltransferase complex catalyzing N6-methyladnosine (m6A) on mRNAs maintain nucleoli integrity in human embryonic stem cells (hESCs). METTL3/METTL14 deficiency impairs nucleoli and leads to the complete loss of self-renewal in hESCs. We further show that SUV39H1/H2 protein, the methyltransferases catalyzing H3K9me3 were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. Together, these findings uncover a previously unknown role of METTL3/METTL14 to maintain nucleoli integrity by facilitating SUV39H1/H2 degradation in human cells.

Abstract Hydrochar from waste biomass is a promising material for removing emerging contaminants (e.g., antibiotics) in water/soil environment. Abundant small-sized hydrochar particles (HPs) with a high content of reactive functional groups and high mobility are easily released into ecosystems through hydrochar applications. However, the photodegradation ability and corresponding structures of HPs are largely unknown, which hinder accurate estimation of the remediation effect of hydrochar in ecosystems. Herein, photodegradation performance of HP towards targeted norfloxacin (NOR, a typical antibiotic) under light irradiation (visible and UV light) were investigated after adsorption processes upon release into soil/water, and its reactive species and photoactive structures were clarified and compared with those of residual bulk hydrochar (BH) comprehensively. The results showed that: (1) photodegradation percentages of HPs were 4.02 and 4.48 times higher than those of BHs under UV and visible light, in which reactive species of both HPs and BHs were ·OH and ·O2 −; (2) density functional theory (DFT) results identified that the main photoactive structure of graphitic-N decreased the energy gap (Eg) of HPs, and C=O, COOH groups improved electron donating ability of BHs; (3) well-developed graphitization structure of HP resulted from higher polymerization reaction was an significant photoactive structure involving its superior photodegradation ability relative to that of BH. The distinct heterogeneities of photodegradation ability in HP and BH and underlying photoactive structures provide an in-depth understanding of hydrochar application for removing emerging contaminants in soil/water environment. Identifying photoactive structures is helpful to predict photodegradation ability of hydrochar according to their abundance. Graphical Abstract

ObjectiveTo explore the reasonable dietary trajectory of elderly people in the community and to test the correlation between different dietary trajectories and body mass index (BMI) of the elderly people in the community to provide a reference for these individuals to formulate scientific interventions and cultivate healthy living habits.MethodsThe data of The Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018 were used to evaluate the dietary status of elderly people in the community according to their diet, and body mass index was calculated according to height and weight. The latent variable growth mixed (LGMM) model was used to analyze the development trajectory of diet in elderly people, and the multivariate logistic regression model was used to test the relationship between different dietary development trajectories and BMI changes as well as to test the correlation between different dietary trajectories and BMI of the elderly people in the community.ResultsThe LGMM fit four dietary trajectories of elderly individuals: the continuous reasonable diet group (37.81%), the dietary behavior decline group (28.84%), the continuous unreasonable diet group (20.16%), and the dietary behavior improvement group (13.19%). The results showed that factors including male sex, rural setting, being spouseless, nonformal education status, not being wealthy, living alone, and having tooth loss were more likely to be classified as the “persistently unreasonable diet group” (p

Abstract Aims There are few studies on the treatment of heart failure by injecting stem cells into the pericardial cavity. Can the cells injected into the pericardial cavity migrate through the epicardium to the myocardial tissue? Whether there is therapeutic effect and the mechanism of therapeutic effect are still unclear. This study investigated the therapeutic efficacy and evidence of cell migration of adipose‐derived stem cells (ADSCs) injected into the pericardial cavity in rat heart failure. The aim of this study is to demonstrate the effectiveness and mechanism of treating heart failure by injecting stem cells into the pericardial cavity, laying an experimental foundation for a new approach to stem cell therapy for heart disease in clinical practice. Methods and results The inguinal adipose tissue of male SD rats aged 4–6 weeks was taken, ADSCs were isolated and cultured, and their stem cell surface markers were identified. Forty rats aged 6–8 weeks were divided into sham operation group, heart failure group, and treatment group; there were 15 rats in the heart failure group and 15 rats in the treatment group. The heart failure model was established by intraperitoneal injection of adriamycin hydrochloride. The heart function of the three groups was detected by small animal ultrasound. The model was successful if the left ventricular ejection fraction

Abstract Fluorescent‐patterned materials are widely used in information storage and encryption. However, preparing a patterned fluorescent display on a matrix currently requires a time‐consuming (hours or even days) and complex multi‐step process. Herein, a rapid and mild technique developed for the in‐situ controllable synthesis of fluorescent nitrogen‐doped carbon dots (NCDs) on eco‐friendly transparent wood films (TEMPO‐oxidized carboxyl wood film [TOWF]) within a few minutes was developed. A wood skeleton was employed as the carbon precursor for NCD synthesis as well as the matrix for the uniform and controlled distribution of NCDs. Moreover, the in‐situ synthesis mechanism for preparing NCDs in TOWF was proposed. The resulting fluorescent wood films have excellent tensile strength (310.00 ± 15.57 MPa), high transmittance (76.2%), high haze (95.0%), UV‐blocking properties in the full ultraviolet (UV) range, and fluorescent performance that can be modified by changing the heating parameters. Fluorescent patterning was simply achieved by regulating the in‐situ NCD synthesis regions, and the fluorescent patterns were formed within 10 s. These fluorescent‐patterned wood films can effectively store and encrypt information, and they can interact with external information through a transparent matrix. This work provides a green and efficient strategy for fabricating fluorescent information storage and encryption materials.

IntroductionEmerging proof suggests that Apocynum venetum flowers polysaccharide (AVFP) has immunomodulatory effects in vitro. However, the action mechanism of AVFA is still unclear in vivo. The purpose of this study is to probe into the potential mechanism of AVFA in immunosuppressed mice by investigating organ index, cytokine levels, anti-oxidative stress capacity, transcriptomics, and gut microbiota.MethodsImmunocompromised mice induced by cyclophosphamide (CTX) were divided into six groups. The enzyme-labeled method, hematoxylin and eosin, transcriptomics, and high-throughput sequencing were used to detect the regulatory effects of AVFP on immunocompromised mice and the function of AVFP on the concentration of short-chain fatty acids (SCFAs) by high-performance liquid chromatography (HPLC) analysis. The Spearman correlation analysis was used to analyze the correlation between the intestinal microbiota and biochemical indexes.ResultsThe experimental results illustrated that AVFP has protective effects against CTX-induced immunosuppression in mice by prominently increasing the organ index and levels of anti-inflammatory factors in serum in addition to enhancing the antioxidant capacity of the liver. Meanwhile, it could also signally decrease the level of pro-inflammatory cytokines in serum, the activity of transaminase in serum, and the content of free radicals in the liver, and alleviate the spleen tissue damage induced by CTX. Transcriptomics results discovered that AVFP could play a role in immune regulation by participating in the NF-κB signaling pathway and regulating the immune-related genes Bcl3, Hp, Lbp, Cebpd, Gstp2, and Lcn2. Gut microbiota results illustrated that AVFP could increase the abundance of beneficial bacteria, reduce the abundance of harmful bacteria, and regulate the metabolic function of intestinal microorganisms while dramatically improving the content of SCFAs, modulating immune responses, and improving the host metabolism. The Spearman analysis further evaluated the association between intestinal microbiota and immune-related indicators.ConclusionThese findings demonstrated that AVFP could enhance the immune effects of the immunosuppressed mice and improve the body’s ability to resist oxidative stress.

IntroductionSocial media platforms serve as a valuable resource for users to share health-related information, aiding in the monitoring of adverse events linked to medications and treatments in drug safety surveillance. However, extracting drug-related adverse events accurately and efficiently from social media poses challenges in both natural language processing research and the pharmacovigilance domain.MethodRecognizing the lack of detailed implementation and evaluation of Bidirectional Encoder Representations from Transformers (BERT)-based models for drug adverse event extraction on social media, we developed a BERT-based language model tailored to identifying drug adverse events in this context. Our model utilized publicly available labeled adverse event data from the ADE-Corpus-V2. Constructing the BERT-based model involved optimizing key hyperparameters, such as the number of training epochs, batch size, and learning rate. Through ten hold-out evaluations on ADE-Corpus-V2 data and external social media datasets, our model consistently demonstrated high accuracy in drug adverse event detection.ResultThe hold-out evaluations resulted in average F1 scores of 0.8575, 0.9049, and 0.9813 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively. External validation using human-labeled adverse event tweets data from SMM4H further substantiated the effectiveness of our model, yielding F1 scores 0.8127, 0.8068, and 0.9790 for detecting words of adverse events, words in adverse events, and words not in adverse events, respectively.DiscussionThis study not only showcases the effectiveness of BERT-based language models in accurately identifying drug-related adverse events in the dynamic landscape of social media data, but also addresses the need for the implementation of a comprehensive study design and evaluation. By doing so, we contribute to the advancement of pharmacovigilance practices and methodologies in the context of emerging information sources like social media.

Digital transformation is conducive to food security. This paper constructed an index system of the digitization level of the grain industry chain based on the panel data of 30 provinces in China from 2011 to 2022. It adopted the entropy method to measure it and analyzed the law of its spatial–temporal evolution. It was found that the digitization level of China’s grain industry chain has shown a year-on-year growth trend, and, at the same time, there are spatial spillover effects and spatial heterogeneity. Analyzed by Theil’s index, there were evident differences among the four major regions and three major grain functional areas in China, and the differences mainly originated from within the region, and there was a phenomenon of “digital divide”. The digitalization level of China’s grain industry chain has shown a decreasing trend of “East-Middle-West”. In conclusion, this paper proposes practical countermeasures to facilitate the digitization level of the grain industry chain in China, thereby providing developing countries with a reference value for the digital transformation of the grain industry chain. Therefore, we should promote the construction of digital infrastructure, increase the cultivation of digital talents, coordinate regional development, and accelerate the digital transformation of the grain industry chain.

Numerous studies have discussed the therapeutic outcomes of using cell therapy or acupuncture to treat peripheral artery disease (PAD). However, there are no long-term studies on the safety and efficacy of transplanting peripheral blood mononuclear cells (PBMNCs) via acupoints to treat PAD. We first reviewed the short-term and long-term clinical results of PAD patients treated with PBMNCs through intramuscular non-acupoint transplantation (control group; n = 45) or intramuscular acupoint transplantation (acupoint group; n = 45) at a single university hospital general medical center between December 2002 and September 2022. Pain intensity (assessed with the verbal rating scale [VRS] score) in the acupoint group was considerably lower than that in the control group at month 1 (mean ± standard deviation [SD]: 1.29 ± 0.96 vs 1.76 ± 0.82; P = 0.016) and month 3 (mean ± SD: 1.27 ± 0.90 vs 1.61 ± 0.86; P = 0.042). We observed significant improvement of VRS score (P < .001 for all) and ankle-brachial index (ABI; P < .001 for all) from baseline in both groups at months 1, 3, 6, 12, 36, and 60. The 10-year cumulative rate of major amputation–free survival (MAFS) was higher in the acupoint group as compared to the control group (81.9%, 95% confidence interval [CI]: 71.3%–94.1% vs 78.5%, 95% CI: 66.7%–92.3%; P = 0.768). Compared with the routine injection method, intramuscular transplantation of PBMNCs via selected acupoints could significantly decrease the short-term pain intensity in patients with PAD, which remains an option for consideration.

The opioid crisis in the United States is a significant public health issue, with a nearly threefold increase in opioid-related fatalities between 1999 and 2014. In response to this crisis, society has made numerous efforts to mitigate its impact. Recent advancements in understanding the structural intricacies of the κ opioid receptor (KOR) have improved our knowledge of how opioids interact with their receptors, triggering downstream signaling pathways that lead to pain relief. This review concentrates on the KOR, offering crucial structural insights into the binding mechanisms of both agonists and antagonists to the receptor. Through comparative analysis of the atomic details of the binding site, distinct interactions specific to agonists and antagonists have been identified. These insights not only enhance our understanding of ligand binding mechanisms but also shed light on potential pathways for developing new opioid analgesics with an improved risk-benefit profile.

The origin of agricultural products is crucial to their quality and safety. This study explored the differences in chemical composition and structure of rice from different origins using fluorescence detection technology. These differences are mainly affected by climate, environment, geology and other factors. By identifying the fluorescence characteristic absorption peaks of the same rice seed varieties from different origins, and comparing them with known or standard samples, this study aims to authenticate rice, protect brands, and achieve traceability. The study selected the same variety of rice seed planted in different regions of Jilin Province in the same year as samples. Fluorescence spectroscopy was used to collect spectral data, which was preprocessed by normalization, smoothing, and wavelet transformation to remove noise, scattering, and burrs. The processed spectral data was used as input for the long short-term memory (LSTM) model. The study focused on the processing and analysis of rice spectra based on NZ-WT-processed data. To simplify the model, uninformative variable elimination (UVE) and successive projections algorithm (SPA) were used to screen the best wavelengths. These wavelengths were used as input for the support vector machine (SVM) prediction model to achieve efficient and accurate predictions. Within the fluorescence spectral range of 475–525 nm and 665–690 nm, absorption peaks of nicotinamide adenine dinucleotide (NADPH), riboflavin (B2), starch, and protein were observed. The origin tracing prediction model established using SVM exhibited stable performance with a classification accuracy of up to 99.5%.The experiment demonstrated that fluorescence spectroscopy technology has high discrimination accuracy in tracing the origin of rice, providing a new method for rapid identification of rice origin.

Biodegradable plastics such as poly(lactic acid) (PLA) are gaining considerable interest as promising substitutes for conventional petroleum-based plastics due to ecological, health, and environmental concerns. PLA possesses good biodegradability and biocompatibility but is limited by its slow crystallization rate, low impact resistance, and high costs. In this study, a small amount of natural wood fiber (WF) was incorporated into PLA to improve mechanical and crystallization properties as well as cost reduction. The effects of WF size (20–40, 80–100, and 140–160 mesh) and loading content (0.5–8 wt%) on the mechanical and crystallization properties were investigated and compared. Results indicated that WF of 80–100 mesh (WF80-100) exhibited a better reinforcement effect on PLA than the other two sizes of WF. The optimal loading content for WF80-100 was 1 wt%, at which the flexural and tensile strength increased by about 18% compared to neat PLA, and the elongation at break increased by 27%. Moreover, the degree of crystallinity and crystallization rate significantly increased with the addition of WF80-100. Polarized optical microscopy observation revealed that the number of spherulites increased in 1WF80-100/PLA composite and the spherulite size decreased compared to neat PLA. These findings confirmed that WF, even at a low addition level, could act as both a reinforcement material and an efficient nucleating agent for PLA, which is closely related to its size.

BackgroundCombined epidural-general anesthesia (GA + EA) has been recommended as a preferred technique for both thoracic and abdominal surgery. The epidural anesthesia on the general anesthetic (GA) requirements has not been well investigated. Therefore, we conducted the present study to explore the predicted effect-site concentration of propofol (Ceprop) required for achieving the loss of consciousness (LOC) in 50% of patients (EC50) with or without epidural anesthesia.MethodsSixty patients scheduled for gastrectomy were randomized into the GA + EA group or GA alone group to receive general anesthesia alone. Ropivacaine 0.375% was used for epidural anesthesia to achieve a sensory level of T4 or above prior to the induction of general anesthesia. The EC50 of predicted Ceprop for LOC was determined by the up–down sequential method. The consumption of anesthetics, emergence time from anesthesia, and postoperative outcomes were also recorded and compared.ResultsThe EC50 of predicted Ceprop for LOC was lower in the GA + EA group than in the GA alone group [2.97 (95% CI: 2.63–3.31) vs. 3.36 (95% CI: 3.19–3.53) μg mL−1, (p = 0.036)]. The consumption of anesthetics was lower in the GA + EA group than in the GA alone group (propofol: 0.11 ± 0.02 vs. 0.13 ± 0.02 mg kg−1 min−1, p = 0.014; remifentanil: 0.08 ± 0.03 vs. 0.14 ± 0.04 μg kg−1 min−1, p

Hawthorn leaves also known as crataegi foilum, are a combination of botanical drugs used commonly in Traditional Chinese Medicine. Hawthorn, the plant from which hawthorn leaves are prepared, is distributed in Northeast China, North China, and other regions in China. Hawthorn leaves are known to activate blood circulation and eliminate stasis, invigorating Qi, eliminating turbidity, and reducing the levels of lipids. So far, over a hundred compounds have been isolated from hawthorn leaves, including flavonoids, terpenoids, lignans, organic acids, and nitrogenous compounds. Hawthorn leaves are used for the treatment of hypertension, protecting against ischemic injury, angina, hyperglycemia, hyperlipidemia, and certain other conditions. Several of the currently available clinical preparations also use hawthorn leaves as raw materials, such as Yixintong capsules, Xinan capsules, etc. The present report systematically reviews the chemical composition, biological activities, and quality standards of hawthorn leaves, to provide a scientific basis and reference for detailed research on hawthorn leaves.

The Omicron variant of SARS-CoV-2 has rapidly become the dominant strain worldwide due to its high transmissibility, although it appears to be less pathogenic than previous strains. However, individuals with hematological malignancy (HM) and COVID-19 remain susceptible to severe infection and mortality, especially those with chronic lymphocytic leukemia (CLL) and those undergoing chimeric antigen receptor T-cell (CAR-T) treatment. Hematologists should thoroughly assess the severity of the patient’s hematological disease and the potential risk of SARS-CoV-2 infection before initiating chemotherapy or immunosuppressive treatment. Vaccination and booster doses are strongly recommended and patients with a poor vaccine response may benefit from long-acting COVID-19 neutralizing monoclonal antibodies (such as Evusheld). Early use of small molecule antiviral drugs is recommended for managing mild COVID-19 in HM patients and those with severe immunodeficiency may benefit from SARS-CoV-2 neutralizing monoclonal antibody therapy and high-titer COVID-19 convalescent plasma (CCP). For moderate to severe cases, low-dose glucocorticoids in combination with early antiviral treatment can be administered, with cytokine receptor antagonists or JAK inhibitors added if the condition persists or worsens. In the treatment of hematological malignancies, delaying chemotherapy is preferable for CLL, acute leukemia (AL), and low-risk myelodysplastic syndrome (MDS), but if the disease progresses, appropriate adjustments in dosage and frequency of treatment are required, with the avoidance of anti-CD20 monoclonal antibody, CAR-T and hematopoietic stem cell transplantation (HSCT). Patients with chronic myelocytic leukemia (CML) and myeloproliferative neoplasms (MPNs) can continue current treatment. What’s more, non-drug protective measures, the development of new vaccines and antiviral drugs, and monitoring of mutations in immunocompromised populations are particularly important.

Mitochondria dynamically change their morphology via fusion and fission, a process called mitochondrial dynamics. Dysregulated mitochondrial dynamics respond rapidly to metabolic cues, and are linked to the initiation and progression of diverse human cancers. Metabolic adaptations significantly contribute to tumor development and escape from tissue homeostatic defenses. In this work, we identified oroxylin A (OA), a dual GLUT1/mitochondrial fusion inhibitor, which restricted glucose catabolism of hepatocellular carcinoma cells and simultaneously inhibited mitochondrial fusion by disturbing SIRT1/PDK2/PARL axis. Based the dual action of OA in metabolic regulation and mitochondrial dynamics, further results revealed that mitochondrial functional status and spare respiratory capacity (SRC) of cancer cells had a close correlation with mitochondrial metabolic plasticity, and played important roles in the susceptibility to cancer therapy aiming at glucose restriction. Cancer cells with healthy mitochondria and high SRC exhibit greater metabolic flexibility and higher resistance to GLUT1 inhibitors. This phenomenon is attributed to the fact that high SRC cells fuse mitochondria in response to glucose restriction, enhancing tolerance to energy deficiency, but undergo less mitochondrial oxidative stress compared to low SRC cells. Thus, inhibiting mitochondrial fusion breaks mitochondrial metabolic plasticity and increases cancer cell susceptibility to glucose restriction therapy. Collectively, these finding indicate that combining a GLUT1 inhibitor with a mitochondrial fusion inhibitor can work synergistically in cancer therapy and, more broadly, suggest that the incorporations of mitochondrial dynamics and metabolic regulation may become the targetable vulnerabilities bypassing the genotypic heterogeneity of multiple malignancies.

Abstract Objective: In the field of nutritional epidemiology, principal component analysis (PCA) has been used extensively in identifying dietary patterns. Recently, compositional data analysis (CoDA) has emerged as an alternative approach for obtaining dietary patterns. We aimed to directly compare and evaluate the ability of PCA and principal balances analysis (PBA), a data-driven method in CoDA, in identifying dietary patterns and their associations with the risk of hypertension. Design: Cohort study. A 24-h dietary recall questionnaire was used to collect dietary data. Multivariate logistic regression analysis was used to analyse the association between dietary patterns and hypertension. Setting: 2004 and 2009 China Health and Nutrition Survey. Participants: A total of 3892 study participants aged 18–60 years were included as the subjects. Results: PCA and PBA identified five patterns each. PCA patterns comprised a linear combination of all food groups, whereas PBA patterns included several food groups with zero loadings. The coarse cereals pattern identified by PBA was inversely associated with hypertension risk (highest quintile: OR = 0·74 (95 % CI 0·57, 0·95); P for trend = 0·037). None of the five PCA patterns was associated with hypertension. Compared with the PCA patterns, the PBA patterns were clearly interpretable and accounted for a higher percentage of variance in food intake. Conclusions: Findings showed that PBA might be an appropriate and promising approach in dietary pattern analysis. Higher adherence to the coarse cereals dietary pattern was associated with a lower risk of hypertension. Nevertheless, the advantages of PBA over PCA should be confirmed in future studies.

Summary: Chimeric antigen receptor (CAR) T cell therapy lacks persistent efficacy with “on-target, off-tumor” toxicities for treating solid tumors. Thus, an antibody-guided switchable CAR vector, the chimeric Fc receptor CD64 (CFR64), composed of a CD64 extracellular domain, is designed. T cells expressing CFR64 exert more robust cytotoxicity against cancer cells than CFR T cells with high-affinity CD16 variant (CD16v) or CD32A as their extracellular domains. CFR64 T cells also exhibit better long-term cytotoxicity and resistance to T cell exhaustion compared with conventional CAR T cells. With trastuzumab, the immunological synapse (IS) established by CFR64 is more stable with lower intensity induction of downstream signaling than anti-HER2 CAR T cells. Moreover, CFR64 T cells exhibit fused mitochondria in response to stimulation, while CARH2 T cells contain predominantly punctate mitochondria. These results show that CFR64 T cells may serve as a controllable engineered T cell therapy with prolonged persistence and long-term antitumor activity.

Microplastics (MPs) were considered as emerging pollutants in soil. Cadmium (Cd) is the typical heavy metal contaminant in paddy soil in China. It was not unraveled that the effects of the existence of MPs on soil properties and Cd adsorption after rice growth in paddy soil, one of the most important soil types in China. In this study, several typical MPs in dosage of 0.5% (w/w) with different particle sizes, including polyethylene (PE, 200μm), polyacrylonitrile (PAN, 200μm), and polyethylene terephthalate (PET, 200 and 10μm), were selected and aged for a rice season (∼6 months) in paddy soil by column experiments. Some essential physicochemical properties of paddy soil collected from different treatments and the adsorption performance of typical metal contaminants (cadmium, Cd) in paddy soil with MPs coexisting were compared. The results indicated that the 6-month existence of 200μmMPs increased water content (15.94% to 26.08-30.30%), pH value (7.05 to 7.16–7.33), organic matter (OM) content (15.1 gkg −1 to 18.2–22.9 gkg −1), the percentage of soil sand and Cd adsorption capacity of paddy soil, whereas decreased soil cation exchange capacity (CEC), the percentage of soil clay and silt. The adsorption experiments of Cd in soil showed that the adsorption behavior was consistent with the pseudo-second order and Langmuir isotherm model, and the addition of MPs would increase the adsorption capacity of Cd in soil. Besides, the particle size of MPs was found to be one of the dominant factors, in which MPs with smaller particle size (10μm) favored the increase of water content, pH, OM content, CEC, and adsorption performance with Cd. The results of this study could provide a supplemental understanding of the effect of MPs input on the paddy soil ecosystem, including the soil properties and the bioavailability and transport of metal in paddy soil.

Home-purchase limit is a unique administrative housing policy of China and has non-negligible influences on the housing price. The objective of this study is to analyze the spillover effect of home-purchase limit policy on housing prices in 35 large and medium-sized cities. The panel data of these cities and the spatial Durbin model are employed in this study. The results indicate that the spillover effect of home-purchase limit policy is positive and significant in all of 35 cities. However, when we categorize these cities into high-risk, medium-risk, and low-risk based on housing price characteristics, the spillover effect of home-purchase limit policy is different. It is not significant in high-risk cities, is negatively significant in medium-risk cities, and is positively significant in low-risk cities. This paper suggests that local governments can pay more attention to the precise design and implementation of home-purchase limit policy, and maintain policy continuity to avoid further spillover fluctuations in housing prices.

IntroductionSARS-CoV-2 nucleocapsid (N) protein plays a key role in multiple stages of the viral life cycle such as viral replication and assembly. This protein is more conserved than the Spike protein of the virus and can induce both humoral and cell-mediated immune responses, thereby becoming a target for clinical diagnosis and vaccine development. However, the immunogenic characteristics of this protein during natural infection are still not completely understood.MethodsPatient-derived monoclonal antibodies (mAbs) against SARS-CoV-2 N protein were generated from memory B cells in the PBMCs using the antigen-specific B cell approach. For epitope mapping of the isolated hmAbs, a panel of series-truncated N proteins were used , which covered the N-terminal domain (NTD, aa 46-174 ) and C-terminal domain (CTD, aa 245-364 ), as well as the flanking regions of NTD and CTD. NTD- or CTD-specific Abs in the plasma from COVID-19 patients were also tested by ELISA method. Cross-binding of hmAbs or plasma Abs in COVID-19 patients to other human β-CoV N proteins was determined using the capture ELISA.ResultsWe isolated five N-specific monoclonal antibodies (mAbs) from memory B cells in the peripheral blood of two convalescent COVID-19 patients. Epitope mapping revealed that three of the patient-derived mAbs (N3, N5 and N31) targeted the C-terminal domain (CTD), whereas two of the mAbs (N83 and 3B7) targeted the N-terminal domain (NTD) of SARS-CoV-2 N protein. All five patient-derived mAbs were cross-reactive to the N protein of SARS-CoV but showed little to no cross-reactivity to the N proteins of other human beta coronaviruses (β-CoVs). We also tested 52 plasma samples collected from convalescent COVID-19 patients for Abs against the N proteins of human β-CoVs and found that 78.8% of plasma samples showed detectable Abs against the N proteins of SARS-CoV-2 and SARS-CoV. No plasma sample had cross-reactive Abs to the N protein of MERS-CoV. Cross-reactive Abs to the N proteins of OC43 and HKU1 were detected in 36.5% (19/52) and 19.2% (10/52) of plasma samples, respectively.DiscussionThese results suggest that natural SARS-CoV-2 infection elicits cross-reactive Abs to the N protein of SARS-CoV and that the five patient-derived mAbs to SARS-CoV-2 N protein NTD and CTD cross-react with their counterparts of SARS-CoV, but not other human β-CoVs. Thus, these five patient-derived mAbs can potentially be used for developing the next generation of COVID-19 At-Home Test kits for rapid and specific screening of SARS-CoV-2 infection.

Abstract Background Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.

Myocardial remodeling is a key pathophysiological basis of heart failure, which seriously threatens human health and causes a severe economic burden worldwide. During chronic stress, the heart undergoes myocardial remodeling, mainly manifested by cardiomyocyte hypertrophy, apoptosis, interstitial fibrosis, chamber enlargement, and cardiac dysfunction. The NADPH oxidase family (NOXs) are multisubunit transmembrane enzyme complexes involved in the generation of redox signals. Studies have shown that NOXs are highly expressed in the heart and are involved in the pathological development process of myocardial remodeling, which influences the development of heart failure. This review summarizes the progress of research on the pathophysiological processes related to the regulation of myocardial remodeling by NOXs, suggesting that NOXs-dependent regulatory mechanisms of myocardial remodeling are promising new therapeutic targets for the treatment of heart failure.

Abstract Coronavirus disease 2019 (COVID-19) is an ongoing pandemic and there is an urgent need for safe and effective drugs for COVID-19 treatment. Since developing a new drug is time consuming, many approved or investigational drugs have been repurposed for COVID-19 treatment in clinical trials. Therefore, selection of safe drugs for COVID-19 patients is vital for combating this pandemic. Our goal was to evaluate the safety concerns of drugs by analyzing adverse events reported in post-market surveillance. We collected 296 drugs that have been evaluated in clinical trials for COVID-19 and identified 28,597,464 associated adverse events at the system organ classes (SOCs) level in the FDA adverse events report systems (FAERS). We calculated Z-scores of SOCs that statistically quantify the relative frequency of adverse events of drugs in FAERS to quantitatively measure safety concerns for the drugs. Analyzing the Z-scores revealed that these drugs are associated with different significantly frequent adverse events. Our results suggest that this safety concern metric may serve as a tool to inform selection of drugs with favorable safety profiles for COVID-19 patients in clinical practices. Caution is advised when administering drugs with high Z-scores to patients who are vulnerable to associated adverse events.

Emerging evidence suggests that exit from pluripotency is a regulated, rather than passive process. Here the authors identify a requirement for SS18-mediated Brg/Brahma-associated factors (BAF) chromatin remodeling complex assembly during exit from pluripotency, and that SS18 promotes BAF assembly through liquidliquid phase separation.

Reproductive toxicity is one of the prominent endpoints in the risk assessment of environmental and industrial chemicals. Due to the complexity of the reproductive system, traditional reproductive toxicity testing in animals, especially guideline multigeneration reproductive toxicity studies, take a long time and are expensive. Therefore, machine learning, as a promising alternative approach, should be considered when evaluating the reproductive toxicity of chemicals. We curated rat multigeneration reproductive toxicity testing data of 275 chemicals from ToxRefDB (Toxicity Reference Database) and developed predictive models using seven machine learning algorithms (decision tree, decision forest, random forest, k-nearest neighbors, support vector machine, linear discriminant analysis, and logistic regression). A consensus model was built based on the seven individual models. An external validation set was curated from the COSMOS database and the literature. The performances of individual and consensus models were evaluated using 500 iterations of 5-fold cross-validations and the external validation data set. The balanced accuracy of the models ranged from 58% to 65% in the 5-fold cross-validations and 45%–61% in the external validations. Prediction confidence analysis was conducted to provide additional information for more appropriate applications of the developed models. The impact of our findings is in increasing confidence in machine learning models. We demonstrate the importance of using consensus models for harnessing the benefits of multiple machine learning models (i.e., using redundant systems to check validity of outcomes). While we continue to build upon the models to better characterize weak toxicants, there is current utility in saving resources by being able to screen out strong reproductive toxicants before investing in vivo testing. The modeling approach (machine learning models) is offered for assessing the rat multigeneration reproductive toxicity of chemicals. Our results suggest that machine learning may be a promising alternative approach to evaluate the potential reproductive toxicity of chemicals.

Abstract Background Mutations in the DMD gene encoding dystrophin—a critical structural element in muscle cells—cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. Methods In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46–54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. Results Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan. Conclusions We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

Salt stress is an important environmental factor limiting plant growth and crop production. Plant adaptation to salt stress can be improved by chemical pretreatment. This study aims to identify whether hydrogen peroxide (H2O2) pretreatment of seedlings affects the stress tolerance of Arabidopsis thaliana seedlings. The results show that pretreatment with H2O2 at appropriate concentrations enhances the salt tolerance ability of Arabidopsis seedlings, as revealed by lower Na+ levels, greater K+ levels, and improved K+/Na+ ratios in leaves. Furthermore, H2O2 pretreatment improves the membrane properties by reducing the relative membrane permeability (RMP) and malonaldehyde (MDA) content in addition to improving the activities of antioxidant enzymes, including superoxide dismutase, and glutathione peroxidase. Our transcription data show that exogenous H2O2 pretreatment leads to the induced expression of cell cycle, redox regulation, and cell wall organization-related genes in Arabidopsis, which may accelerate cell proliferation, enhance tolerance to osmotic stress, maintain the redox balance, and remodel the cell walls of plants in subsequent high-salt environments.

Infrared detection technology has important applications in laser ranging, imaging, night vision, and other fields. Furthermore, recent studies have proven that hot carriers which are generated by surface plasmon decay can be exploited for photodetection to get beyond semiconductors’ bandgap restriction. In this study, silicon nanopillars (NPs) and gold film at the top and bottom of silicon nanopillars were designed to generate surface plasmon resonance and Fabry–Perot resonance to achieve perfect absorption. The absorption was calculated using the Finite Difference Time Domain (FDTD) method, and factors’ effects on resonance wavelength and absorption were examined. Here we demonstrate how this perfect absorber can be used to achieve near-unity optical absorption using ultrathin plasmonic nanostructures with thicknesses of 15 nm, smaller than the hot electron diffusion length. Further study revealed that the resonance wavelength can be redshifted to the mid-infrared band (e.g., 3.75 μm) by increasing the value of the structure parameters. These results demonstrate a success in the study of polarization insensitivity, detection band adjustable, and efficient perfect absorption infrared photodetectors.

Abstract Background Stem cell therapies have gained great attention for providing novel solutions for treatment of various injuries and diseases due to stem cells’ self-renewal, ability to differentiate into various cell types, and favorite paracrine function. Nevertheless, the low retention of transplanted stem cell still limits their clinical applications such as in wound healing in view of an induced harsh microenvironment rich in reactive oxygen species (ROS) during inflammatory reactions. Methods Herein, a novel chitosan/acellular dermal matrix (CHS/ADM) stem cell delivery system is developed, which is of great ROS scavenging activity and significantly attenuates inflammatory response. Result Under ROS microenvironment, this stem cell delivery system acts as a barrier, effectively scavenging an amount of ROS and protecting mesenchymal stem cells (MSCs) from the oxidative stress. It notably regulates intracellular ROS level in MSCs and reduces ROS-induced cellular death. Most importantly, such MSCs delivery system significantly enhances in vivo transplanted stem cell retention, promotes the vessel growth, and accelerates wound healing. Conclusions This novel delivery system, which overcomes the limitations of conventional plain collagen-based delivery system in lacking of ROS-environmental responsive mechanisms, demonstrates a great potential use in stem cell therapies in wound healing.

Abstract The epigenetic abnormality is generally accepted as the key to cancer initiation. Epigenetics that ensure the somatic inheritance of differentiated state is defined as a crucial factor influencing malignant phenotype without altering genotype. Histone modification is one such alteration playing an essential role in tumor formation, progression, and resistance to treatment. Notably, changes in histone acetylation have been strongly linked to gene expression, cell cycle, and carcinogenesis. The balance of two types of enzyme, histone acetyltransferases (HATs) and histone deacetylases (HDACs), determines the stage of histone acetylation and then the architecture of chromatin. Changes in chromatin structure result in transcriptional dysregulation of genes that are involved in cell-cycle progression, differentiation, apoptosis, and so on. Recently, HDAC inhibitors (HDACis) are identified as novel agents to keep this balance, leading to numerous researches on it for more effective strategies against cancers, including glioblastoma (GBM). This review elaborated influences on gene expression and tumorigenesis by acetylation and the antitumor mechanism of HDACis. Besdes, we outlined the preclinical and clinical advancement of HDACis in GBM as monotherapies and combination therapies.

Abstract Density reduction has become a topical issue in wood composite materials for application in building and furniture. In this study, lightweight wood–polyurethane (W–PU) composite foams with the addition of 30 wt% wood particles were prepared. Industrial kraft lignin was used as bio-polyol to substitute partial petroleum-based diethylene glycol (DEG) to synthesize rigid W–PU foams. The effect of varying lignin contents (5, 10, 15 and 20 wt% based on DEG mass) on the reactivity, morphology, density, compressive properties, water absorption and thermal stability of the foams was evaluated. Fourier transform infrared (FTIR) analysis confirmed the formation of characteristic urethane linkages in all the foam samples. With the incorporation of lignin, the foam cellular shape became irregular with formation of large cells. W–PU foams exhibited poor cellular structures with a larger number of open cells. The density of W–PU foams increased from 47 to 96 kg/m3 as the lignin content increased from 0 to 20%. Although the foam reactivity was decreased by the incorporation of lignin, both the compressive strength and modulus were increased upon the incorporation of lignin. Furthermore, the specific compressive strength and modulus of W–PU foams increased by 55% and 48% with lignin content increasing from 0 to 20%, and the 20-day water absorption decreased by 38%. Thermal gravimetric analysis showed that the incorporation of lignin did not significantly affect the thermal degradation behaviour of foam, but it rather increased the mass of char residue. This study provides a promising method for value-added utilization of technical lignin in W–PU lightweight composites.

Nanostructure engineering has proven to be one of the most effective strategies to improve the efficiency of photoelectric devices. Herein, we numerically investigate and experimentally demonstrate a self-assembled silicon-based nanopillars and nanoholes structures, to improve the light absorption of photoelectric devices by an antireflection enhancement. The nanopillars and nanoholes structures are fabricated by the air–liquid interface self-assembly method based on polystyrene (PS) nanospheres. Additionally, the tunable antireflective properties with the different operation wavelength and nanostructures parameters have been discussed based on the Finite-Difference Time-Domain (FDTD) method. The experimental result shows that the self-assembled silicon-based nanopillars and nanoholes structures can achieve the lowest reflectivity of 1.42% (nanopillars) and 5.83% (nanoholes) in the wavelength range of 250–800 nm, which reduced 95.97% and 84.83%, respectively, compared with the plane silicon. The operation mechanism of the tunable antireflective property of self-assembled nanopillars and nanoholes structures is also analyzed in the simulation. Our study suggests that the self-assembled nanopillars and nanoholes structures are potentially attractive as improving efficiency of photoelectric devices.

Metal–organic frameworks (MOFs), a class of porous nanomaterials, have been widely used in gas adsorption-based applications due to their high porosities and chemical tunability. To facilitate the discovery of high-performance MOFs for different applications, a variety of machine learning models have been developed to predict the gas adsorption capacities of MOFs. Most of the predictive models are developed using traditional machine learning algorithms. However, the continuously increasing sizes of MOF datasets and the complicated relationships between MOFs and their gas adsorption capacities make deep learning a suitable candidate to handle such big data with increased computational power and accuracy. In this study, we developed models for predicting gas adsorption capacities of MOFs using two deep learning algorithms, multilayer perceptron (MLP) and long short-term memory (LSTM) networks, with a hypothetical set of about 130,000 structures of MOFs with methane and carbon dioxide adsorption data at different pressures. The models were evaluated using 10 iterations of 10-fold cross validations and 100 holdout validations. The MLP and LSTM models performed similarly with high prediction accuracy. The models for predicting gas adsorption at a higher pressure outperformed the models for predicting gas adsorption at a lower pressure. The deep learning models are more accurate than the random forest models reported in the literature, especially for predicting gas adsorption capacities at low pressures. Our results demonstrated that deep learning algorithms have a great potential to generate models that can accurately predict the gas adsorption capacities of MOFs.

Incorporation of short wood fillers such as wood flour (WF) into polypropylene (PP) often results in a marked reduction of toughness, which is one of the main shortcomings for WF/PP composites. This research reports a facile approach to achieve toughening of WF/PP composites via introducing self-assembling β-nucleating agents into PP matrix. The effect of two kinds of nucleating agents, an aryl amide derivative (TMB5) and a rare earth complex (WBG II), at varying concentrations on the crystallization and mechanical properties of WF/PP composites was comparatively investigated. The results showed that both nucleating agents were highly effective in inducing β-crystal for WF/PP, with β-crystal content (kβ) value reaching 0.8 at 0.05 wt% nucleating agent concentration. The incorporation of TMB or WBG significantly decreased the spherulite size, increased the crystallization temperature and accelerated the crystallization process of WF/PP. As a result of PP crystalline modification, the toughness of composites was significantly improved. Through introducing 0.3 wt% TMB or WBG, the notched impact strength and strain at break of WF/PP increased by approximately 28% and 40%, respectively. Comparatively, although WF/PP-WBG had slightly higher Kβ value than WF/PP-TMB at the same concentration, WF/PP/TMB exhibited more uniform crystalline morphology with smaller spherulites. Furthermore, the tensile strength and modulus of WF/PP-TMB were higher than WF/PP-WBG. This matrix crystalline modification strategy provides a promising route to prepare wood filler/thermoplastic composites with improved toughness and accelerated crystallization.

Gynura procumbens (GP) is a perennial herbal medicine and food homologous plant, which has been reported to have a good hypoglycemic effect. However, its active components and underlying mechanism of action are not clear. Here, we aimed to confirm the effects of GP on type 2 diabetes (T2DM) from several different aspects. We used UPLC/Q-TOF MS to analyze the metabolic patterns, which included blood samples of clinical subjects and db/db mice to screen for serum metabolic markers and metabolic pathways. We also used network pharmacology to study GP targets in the treatment of T2DM. Data from endogenous metabolites in plasma showed that two common pathways, including glycerol phosphate metabolism and retinol metabolism, were identified in plasma samples of the groups. Finally, Western blot analysis was used to verify the expression of proteins in the PI3K/AKT and AGE–RAGE signaling pathways. The protein expression of AKT, eNOS, iNS, and MAPK was significantly upregulated, and the expression of caspase-8 and caspase-3 was significantly downregulated. Thus, our findings indicated that GP could alleviate insulin resistance by regulating biometabolic markers and key proteins in the PI3K/AKT and AGE–RAGE signaling pathways to treat T2DM.

Perceived social support is positively related to life satisfaction in infertile women. Whereas, the underlying mechanism of this relationship is unclear. The present study aimed to investigate whether self-compassion mediated the relationship of perceived social support with life satisfaction and whether infertility self-efficacy moderated the relationship between perceived social support and self-compassion in infertile women. A total of 290 infertile women in mainland China undergoing treatment completed an online survey assessing perceived social support, life satisfaction, self-compassion, and infertility self-efficacy. The results supported the mediation model that perceived social support was associated with life satisfaction via self-compassion. Besides, infertility self-efficacy moderated the relationship between perceived social support and self-compassion. Specifically, perceived social support displayed a stronger predictive effect on self-compassion when infertile women had higher level of infertility self-efficacy.

Retrograde monosynaptic tracing with EnvA-pseudotyped rabies virus has been employed to identify the afferent and efferent connectivity of transplanted human embryonic stem (hES) cell-derived neurons in animal models. Due to the protracted development of transplanted human neurons in host animals, it is important that those transplanted cells express avian leukosis and sarcoma virus subgroup A receptor (TVA) and rabies glycoprotein G (Rgp) for a period of up to several months to enable identification of the synaptic inputs from host neurons to grafted neurons through this rabies virus-based method. Here, we report the generation of an engineered hES cell line through CRISPR/Cas9-mediated targeting to the AAVS1 locus of an EnvA-pseudotyped rabies virus-based tool for retrograde monosynaptic tracing. This engineered hES cell line, named H1-CAG-GTRgp, expresses GFP, TVA and Rgp. Upon transplantation of H1-CAG-GTRgp-derived neural progenitor cells (NPCs) into the rat brain after traumatic injury, the grafted neurons derived from H1-CAG-GTRgp cells expressed GFP, TVA, and Rgp stably for up to 6 months post-transplantation and received robust synaptic inputs from host neurons in the target regions of the orthotopic neural circuitry. The retrograde monosynaptic tracing hES cell line provides an efficient approach to analyze transplant connectivity for the comprehensive assessment of host-donor cell innervation. Keywords: Neural progenitors, AAVS1 locus, EnvA-pseudotyped rabies virus, Retrograde monosynaptic tracing, Transplantation

CTCF plays key roles in gene regulation, chromatin insulation and organizing the higher-order chromatin architecture of mammalian genomes. Here the authors investigate the function an alternatively spliced shorter CTCF isoform, finding that this isoform antagonizes canonical CTCF occupancy and changes chromatin architecture to promote apoptosis.

Abstract Background Mast cells are being increasingly recognized as critical components in the tumor microenvironment. Protein Kinase D (PKD) is essential for the progression of prostate cancer, but its role in prostate cancer microenvironment remains poorly understood. Methods The expression of PKD, mast cells and microvessel density were examined by IHC. The clinical significance was determined by statistical analyses. The biological function of PKD and the underlying mechanisms were investigated using in vitro and in vivo models. Results PKD2/3 contributed to MCs recruitment and tumor angiogenesis in the prostate cancer microenvironment. Clinical data showed that increased activation of PKD at Ser744/748 in prostate cancer was correlated with mast cell infiltration and microvascular density. PKD2/3 silencing of prostate cancer cells markedly decreased MCs migration and tube formation of HUVEC cells. Moreover, PKD2/3 depletion not only reduced SCF, CCL5 and CCL11 expression in prostate cancer cells but also inhibited angiogenic factors in MCs. Conversely, exogenous SCF, CCL5 and CCL11 reversed the effect on MCs migration inhibited by PKD2/3 silencing. Mechanistically, PKD2/3 interacted with Erk1/2 and activated Erk1/2 or NF-κB signaling pathway, leading to AP-1 or NF-κB binding to the promoter of scf, ccl5 and ccl11. Finally, PKD-specific inhibitor significantly reduced tumor volume and tumor growth in mice bearing RM-1 prostate cancer cells, which was attributed to attenuation of mast cell recruitment and tumor angiogenesis. Conclusions These results demonstrate a novel PKDs function that contributes to tumor angiogenesis and progression through mast cells recruitment in prostate cancer microenvironment.

Abstract Background Reference genome selection is a prerequisite for successful analysis of next generation sequencing (NGS) data. Current practice employs one of the two most recent human reference genome versions: HG19 or HG38. To date, the impact of genome version on SNV identification has not been rigorously assessed. Methods We conducted analysis comparing the SNVs identified based on HG19 vs HG38, leveraging whole genome sequencing (WGS) data from the genome-in-a-bottle (GIAB) project. First, SNVs were called using 26 different bioinformatics pipelines with either HG19 or HG38. Next, two tools were used to convert the called SNVs between HG19 and HG38. Lastly we calculated conversion rates, analyzed discordant rates between SNVs called with HG19 or HG38, and characterized the discordant SNVs. Results The conversion rates from HG38 to HG19 (average 95%) were lower than the conversion rates from HG19 to HG38 (average 99%). The conversion rates varied slightly among the various calling pipelines. Around 1.5% SNVs were discordantly converted between HG19 or HG38. The conversions from HG38 to HG19 had more SNVs which failed conversion and more discordant SNVs than the opposite conversion (HG19 to HG38). Most of the discordant SNVs had low read depth, were low confidence SNVs as defined by GIAB, and/or were predominated by G/C alleles (52% observed versus 42% expected). Conclusion A significant number of SNVs could not be converted between HG19 and HG38. Based on careful review of our comparisons, we recommend HG38 (the newer version) for NGS SNV analysis. To summarize, our findings suggest caution when translating identified SNVs between different versions of the human reference genome.

In order to improve the mechanical properties and toughness of phenolic foams, a reinforcement method using two kinds of bamboo fibers was optimized with respect to the fiber contents. The compressive and flexural properties, thermal stability, friability and morphology of the phenolic foam composites were studied. The mechanical properties of the pristine foam and composites were evaluated by measuring the compressive strength. The results showed that the greatest mechanical properties were achieved by incorporating 2.5wt% of the reinforcement, and the compressive and flexural strengths of the two composites increased by 26.21% and 24.35%, respectively, compared with that of the pristine foam. The results of thermogravimetric testing demonstrated that the addition of bamboo fiber imparted better thermal stability to the phenolic foam, which was mainly attributed to the higher initial thermal decomposition temperature of the bamboo fiber. However, the influences of both reinforcements on the thermal stability of the material were negligible. The incorporation of bamboo fiber decreased the friability of the phenolic foam. Furthermore, the reduction in friability of the foam composites with longer lengths were higher than that in foams with shorter bamboo fibers. Moreover, the morphology and cell sizes of the fiber-reinforced phenolic foams were analyzed by scanning electron microscopy, the results indicated strong bonding between the fibers and phenolic matrix, and the incorporation of the bamboo fibers into the foam resulted in increased cell size of the material. Finally, the thermal conductivity and flame resistance of the phenolic foams reinforced by the bamboo fibers were also measured.

Reliability of nonvolatile resistive switching devices is the key point for practical applications of next-generation nonvolatile memories. Nowadays, nanostructured organic/inorganic heterojunction composites have gained wide attention due to their application potential in terms of large scalability and low-cost fabrication technique. In this study, the interaction between polyvinyl alcohol (PVA) and two-dimensional material molybdenum disulfide (MoS2) with different mixing ratios was investigated. The result confirms that the optimal ratio of PVA:MoS2 is 4:1, which presents an excellent resistive switching behavior. Moreover, we propose a resistive switching model of Ag/ZnO/PVA:MoS2/ITO bilayer structure, which inserts the ZnO as the protective layer between the electrode and the composite film. Compared with the device without ZnO layer structure, the resistive switching performance of Ag/ZnO/PVA:MoS2/ITO was improved greatly. Furthermore, a large resistive memory window up to 104 was observed in the Ag/ZnO/PVA:MoS2/ITO device, which enhanced at least three orders of magnitude more than the Ag/PVA:MoS2/ITO device. The proposed nanostructured Ag/ZnO/PVA:MoS2/ITO device has shown great application potential for the nonvolatile multilevel data storage memory.

Surface anti-reflection (AR) with nanometer-scaled texture has shown excellent light trapping performance involving optical devices. In this work, we developed a simple and lithography-free structure replication process to obtain large scale surface cup-shaped nano-pillar (CSNP) arrays for the first time. A method of depositing was used for pattern transfer based on PMMA pre-coated through-hole anodic aluminum oxide (AAO) thin film (~500 nm), and eventually, the uniformity of the transferred nanostructures was guaranteed. From the spectrum (250 nm~2000 nm) dependent measurements, the CSNP nanostructured Si showed excellent AR performance when compared with that of the single-polished Si. Moreover, the CSNP was found to be polarization insensitive and less dependent on incidence angles (≤80°) over the whole spectrum. To further prove the excellent antireflective properties of the CSNP structure, thin film solar cell models were built and studied. The maximum value of Jph for CSNP solar cells shows obvious improvement comparing with that of the cylinder, cone and parabola structured ones. Specifically, in comparison with the optimized Si3N4 thin film solar cell, an increment of 54.64% has been achieved for the CSNP thin film solar cell.

The use of differentiating human induced pluripotent stem cells (hiPSCs) in mini-tissue organoids provides an invaluable resource for regenerative medicine applications, particularly in the field of disease modeling. However, most studies using a kidney organoid model, focused solely on the transcriptomics and did not explore mechanisms of regulating kidney organoids related to metabolic effects and maturational phenotype. Here, we applied metabolomics coupled with transcriptomics to investigate the metabolic dynamics and function during kidney organoid differentiation. Not only did we validate the dominant metabolic alteration from glycolysis to oxidative phosphorylation in the iPSC differentiation process but we also showed that glycine, serine, and threonine metabolism had a regulatory role during kidney organoid formation and lineage maturation. Notably, serine had a role in regulating S-adenosylmethionine (SAM) to facilitate kidney organoid formation by altering DNA methylation. Our data revealed that analysis of metabolic characterization broadens our ability to understand phenotype regulation. The utilization of this comparative omics approach, in studying kidney organoid formation, can aid in deciphering unique knowledge about the biological and physiological processes involved in organoid-based disease modeling or drug screening.

Zika virus (ZIKV) is a mosquito-borne flavivirus that has been linked to congenital microcephaly during recent epidemics. No licensed antiviral drug or vaccine is available.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). As of October 21, 2020, more than 41.4 million confirmed cases and 1.1 million deaths have been reported. Thus, it is immensely important to develop drugs and vaccines to combat COVID-19. The spike protein present on the outer surface of the virion plays a major role in viral infection by binding to receptor proteins present on the outer membrane of host cells, triggering membrane fusion and internalization, which enables release of viral ssRNA into the host cell. Understanding the interactions between the SARS-CoV-2 trimeric spike protein and its host cell receptor protein, angiotensin converting enzyme 2 (ACE2), is important for developing drugs and vaccines to prevent and treat COVID-19. Several crystal structures of partial and mutant SARS-CoV-2 spike proteins have been reported; however, an atomistic structure of the wild-type SARS-CoV-2 trimeric spike protein complexed with ACE2 is not yet available. Therefore, in our study, homology modeling was used to build the trimeric form of the spike protein complexed with human ACE2, followed by all-atom molecular dynamics simulations to elucidate interactions at the interface between the spike protein and ACE2. Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) and in silico alanine scanning were employed to characterize the interacting residues at the interface. Twenty interacting residues in the spike protein were identified that are likely to be responsible for tightly binding to ACE2, of which five residues (Val445, Thr478, Gly485, Phe490, and Ser494) were not reported in the crystal structure of the truncated spike protein receptor binding domain (RBD) complexed with ACE2. These data indicate that the interactions between ACE2 and the tertiary structure of the full-length spike protein trimer are different from those between ACE2 and the truncated monomer of the spike protein RBD. These findings could facilitate the development of drugs and vaccines to prevent SARS-CoV-2 infection and combat COVID-19.

In this study, three-layer low-density (about 400 kg/m3) particleboards consisting of a mixture of wood particles and expanded polystyrene (EPS) were manufactured. EPS bead was incorporated in the core layer as a light filler. The influence of EPS content (0 %, 2,5 %, 5 %, 7,5 %, 10 % and 12,5 %) and press temperature (110 °C and 140 °C) on the microstructure, density profile, bending properties, internal bond and thickness swelling of the panels was investigated. Results showed that incorporation of EPS beads filled in the voids between wood particles, improved the core layer integrity, and generated a more pronounced density profile. Consequently, the bending properties and internal bond of panels adding EPS were remarkably improved, and the thickness swelling was decreased. However, the variation of the amount of EPS from 2,5 % to 12,5 % had no significant effect on the bending properties and thickness swelling. Comparing the two press temperatures, although higher temperature (140 °C) was more favourable in control panels without EPS as filler, it had a negative effect on the properties of panels with addition of EPS filler, especially for high EPS contents (10 % and 12,5 %), attributing to the shrinkage of EPS bead under press temperature that is much higher than its glass transition temperature (104 °C).

Oxygen dependence and anabatic hypoxia are the major factors responsible for the poor outcome of photodynamic therapy (PDT) against cancer. Combining of PDT and hypoxia-activatable bioreductive therapy has achieved remarkably improved antitumor efficacy compared to single PDT modality. However, controllable release and activation of prodrug and safety profiles of nanocarrier are still challenging in the combined PDT/hypoxia-triggered bioreductive therapy. Herein, we developed a near infrared (NIR) light-decomposable nanomicelle, consisting of PEGylated cypate (pCy) and mPEG-polylactic acid (mPEG2k-PLA2k) for controllable delivery of hypoxia-activated bioreductive prodrug (tirapazamine, TPZ) (designated TPZ@pCy), for combating metastatic breast cancer via hypoxia-enhanced phototherapies. TPZ@pCy was prepared by facile nanoprecipitation method, with good colloidal stability, excellent photodynamic and photothermal potency, favorable light-decomposability and subsequent release and activation of TPZ under irradiation. In vitro experiments demonstrated that TPZ@pCy could be quickly internalized by breast cancer cells, leading to remarkable synergistic tumor cell-killing potential. Additionally, metastatic breast tumor-xenografted mice with systematic administration of TPZ@pCy showed notable tumor accumulation, promoting tumor ablation and lung metastasis inhibition with negligible toxicity upon NIR light illumination. Collectively, our study demonstrates that this versatile light-decomposable polymeric micelle with simultaneous delivery of photosensitizer and bioreductive agent could inhibit tumor growth as well as lung metastasis, representing a promising strategy for potent hypoxia-enhanced phototherapies for combating metastatic breast cancer.