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Cardiovascular diseases rank the highest incidence and mortality worldwide. As the most common type of cardiovascular disease, myocardial infarction causes high morbidity and mortality. Recent studies have revealed that extracellular vesicles, including exosomes, show great potential as a promising cell-free therapy for the treatment of myocardial infarction. However, low heart-targeting efficiency and short plasma half-life have hampered the clinical translation of extracellular vesicle therapy. Currently, four major types of strategies aiming at enhancing target efficiency have been developed, including modifying EV surface, suppressing non-target absorption, increasing the uptake efficiency of target cells, and utilizing a hydrogel patch. This presented review summarizes the current research aimed at EV heart targeting and discusses the challenges and opportunities in EV therapy, which will be beneficial for the development of effective heart-targeting strategies.

Pseudogenes are important resources for investigation of genome evolution and genomic diversity because they are nonfunctional but have regulatory effects that influence plant adaptation and diversification. However, few systematic comparative analyses of pseudogenes in closely related species have been conducted. Here, we present a turnip (Brassica rapa ssp. rapa) genome sequence and characterize pseudogenes among diploid Brassica species/subspecies. The results revealed that the number of pseudogenes was greatest in Brassica oleracea (CC genome), followed by B. rapa (AA genome) and then Brassica nigra (BB genome), implying that pseudogene differences emerged after species differentiation. In Brassica AA genomes, pseudogenes were distributed asymmetrically on chromosomes because of numerous chromosomal insertions/rearrangements, which contributed to the diversity among subspecies. Pseudogene differences among subspecies were reflected in the flavor-related glucosinolate (GSL) pathway. Specifically, turnip had the highest content of pungent substances, probably because of expansion of the methylthioalkylmalate synthase-encoding gene family in turnips; these genes were converted into pseudogenes in B. rapa ssp. pekinensis (Chiifu). RNA interference-based silencing of the gene encoding 2-oxoglutarate-dependent dioxygenase 2, which is also associated with flavor and anticancer substances in the GSL pathway, resulted in increased abundance of anticancer compounds and decreased pungency of turnip and Chiifu. These findings revealed that pseudogene differences between turnip and Chiifu influenced the evolution of flavor-associated GSL metabolism-related genes, ultimately resulting in the different flavors of turnip and Chiifu.

Elucidating the nature of topological magnets is at quantum frontier. Here the authors report a topological charge-entropy relation in TbMn6Sn6 that goes beyond conventional electron behavior and points to a transport visualization of Chern gapped Dirac fermions.

Abstract Background Legionellosis remains a public health problem. The most common diagnostic method to detect Legionella pneumophila (L. pneumophila) is culture. Polymerase chain reaction (PCR) is a fast and accurate method for this detection in environmental samples. Methods Four databases were searched for studies that evaluated the detection efficiency of PCR in L. pneumophila. The quality evaluation was conducted using Review Manager 5.3. We used Meta-DiSc 1.4 software and the Stata 15.0 software to create forest plots, a meta-regression, a bivariate boxplot and a Deeks’ funnel plot. Results A total of 18 four-fold tables from 16 studies were analysed. The overall pooled sensitivity and specificity of PCR was 94% and 72%, respectively. The positive likelihood ratio (RLR) and negative likelihood ratio (NLR) was 2.73 and 0.12, respectively. The result of the diagnostic odds ratio (DOR) was 22.85 and the area under the curve (AUC) was 0.7884. Conclusion Establishing a laboratory diagnostic tool for L. pneumophila detection is important for epidemiological studies. In this work, PCR demonstrated a promising diagnostic accuracy for L. pneumophila.

Abstract Background Opportunistic Candida species causes severe infections when the human immune system is weakened, leading to high mortality. Methods In our study, bioinformatics analysis was used to study the high-throughput sequencing data of samples infected with four kinds of Candida species. And the hub genes were obtained by statistical analysis. Results A total of 547, 422, 415 and 405 differentially expressed genes (DEGs) of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis groups were obtained, respectively. A total of 216 DEGs were obtained after taking intersections of DEGs from the four groups. A protein–protein interaction (PPI) network was established using these 216 genes. The top 10 hub genes (FOSB, EGR1, JUNB, ATF3, EGR2, NR4A1, NR4A2, DUSP1, BTG2, and EGR3) were acquired through calculation by the cytoHubba plug-in in Cytoscape software. Validated by the sequencing data of peripheral blood, JUNB, ATF3 and EGR2 genes were significant statistical significance. Conclusions In conclusion, our study demonstrated the potential pathogenic genes in Candida species and their underlying mechanisms by bioinformatic analysis methods. Further, after statistical validation, JUNB, ATF3 and EGR2 genes were attained, which may be used as potential biomarkers with Candida species infection.

Pianyanzi gold deposit is located in the Daduhe metallogenic belt at the northern end of the Kangyan-Yunnan axis. It is a rare flummagnesite type gold deposit in the world. Produced in the upper sinian dengying formation, the mineral composition is relatively rich, up to 50 kinds of minerals have been identified. The ore type is mainly flummagnesite-quartz type, and the ore body is controlled by both strata and structure. By means of EPMA and SEM, it is found that the gold minerals are mainly fluobesite, pyrite, tetrahedrite and so on. According to the chemical state of gold, the occurrence state of gold can be divided into three categories: independent minerals, complex complexes and lattice gold. According to the distribution relationship between gold and carrier minerals, it can be divided into three categories: encapsulated gold, fissure gold and intergranular gold. The granularity of gold has a large span, mainly concentrated in 2 ~ 10 μm, and belongs to the crystallized gold and microscopic gold.

Abstract Purposes In addition to its role in cellular progression and cancer, SIRT6, a member of nicotinamide adenine dinucleotide (NAD+)-dependent class III deacylase sirtuin family, serves a variety of roles in the body's immune system. In this study, we sought to determine the relationship between the expression of SIRT6 and the clinicopathological outcomes of patients with solid tumours by conducting a meta-analysis of the available data. Methods The databases PubMed and ISI Web of Science were searched for relevant literature, and the results were presented here. Using Stata16.0, a meta-analysis was conducted to determine the impact of SIRT6 on clinicopathological characteristics and prognosis in malignancy patients. The results were published in the journal Cancer Research. The dataset from the Cancer Genome Atlas (TCGA) was used to investigate the prognostic significance of SIRT6 in various types of tumors. Results The inclusion and exclusion criteria were met by 15 studies. In patients with solid tumours, reduced SIRT6 expression was found to be related with improved overall survival (OS) (HR = 0.66, 95% CI = 0.45–0.97, P

H7 avian influenza viruses (AIVs) normally circulated among birds before. From 1996 to 2012, human infections with H7 AIVs (H7N2, H7N3, and H7N7) were reported in Canada, Italy, Mexico, the Netherlands, the United Kingdom and the USA. Until March 2013, human infections with H7N9 AIVs were reported in China. Since then, H7N9 AIVs have continued to circulate in both humans and birds. Therefore, the detection of antibodies against the H7 subtype of AIVs has become an important topic. In this study, a competitive enzyme-linked immunosorbent assay (cELISA) method for the detection of antibody against H7 AIVs was established. The optimal concentration of antigen coating was 5 μg mL−1, serum dilution was 1/10, and enzyme-labeled antibody was 1/3 000. To determine the cut-off value of cELISA, percent inhibition (PI) was determined by using receiver operating characteristic (ROC) curve analysis in 178 AIVs negative samples and 368 AIVs positive serum samples (n=546). When PI was set at 40%, the specificity and sensitivity of cELISA were 99.4 and 98.9%, respectively. This method could detect the antibodies against H7Nx (N1–N4, N7–N9) AIVs, and showed no reaction with AIVs of H1–H6 and H8–H15 subtypes or common avian viruses such as Newcastle disease virus (NDV), Infectious bronchitis virus (IBV) and Infectious bursal disease virus (IBDV), exhibiting good specificity. This method showed a coincidence rate of 98.56% with hemagglutinin inhibition (HI) test. And the repeatability experiment revealed that the coefficients of variation (CV) of intra- and inter-batch repetition were all less than 12%. The data indicated that the cELISA antibody-detection method established in this study provided a simple and accurate technical support for the detection of a large number of antibody samples of H7-AIV.

One undescribed benzofuran derivative (illiciumphenolicacid A, 1) and one new phenolic glycoside (illiciumphenolicacid B, 2), together with six known compounds (3–8) were isolated from the leaves of Illicium dunnianum Tutcher. Their structures were elucidated by detailed spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR). In addition, we determined the α-glucosidase inhibitory activity of the isolates in vitro using spectrophotometric methods. Compared with the positive control acarbose (IC50 306.2 ± 4.1 μM), compounds 1–8 were shown to be moderate potential α-glucosidase inhibitory activity with IC50 values in the range 380–655 μM. [ABSTRACT FROM AUTHOR]

An iron(III)‐promoted radical fluoroalkylation of o‐alkenylaryl isocyanides has been developed using readily available perfluoroalkyl iodides as fluoroalkyl source. This cyclization reaction features broad substrate scope and provides a simple and efficient approach for regioselective construction of biologically important 2‐fluoroalkylated quinolines in 38–81 % yields. [ABSTRACT FROM AUTHOR]

With the acceleration of urbanization in China, high density has become a significant feature of urban development. Although high-density development provides convenience, it also results in numerous environmental and climatic problems, such as the urban heat island effect, haze and extreme weather. These issues have reduced the comfort levels of the urban outdoor environment, led to increased energy consumption and had serious impacts on social development and the lives of residents. Improving the comfort of the outdoor urban environment is vital, especially in the current tendency for high-density urban developments. This paper focuses on a typical urban district in Shanghai, where we have gathered ambient meteorological data and human thermal sensation votes during spring and summer through monitoring and questionnaire research. Correlation analysis was conducted to examine the relationship between thermal sensation votes and comfort indexes (PET, UTCI). The findings indicated that the neutral PET during spring and summer was 22.30 °C and 24.55 °C, respectively, whilst the neutral UTCI was 18.75 °C and 26 °C, respectively, with the neutral temperature in summer being significantly higher than that in spring. Upon comparing the evaluation indices, it was found that the correlation between the UTCI and average thermal sensation votes was stronger; thus, the UTCI better represents people’s thermal sensation in the Shanghai area. Finally, regression analysis demonstrated that the acceptable PET range for 90% of cases during both seasons in Shanghai is between 25.0 °C and 32.1 °C, and the UTCI range is between 24.2 °C and 27.7 °C. This study presents theoretical criteria for evaluating environmental thermal comfort, laying the foundation for practical paths to optimize urban design for climate responsiveness in high-density urban areas.

Overconsumption of high-fat foods increases the risk of fatty liver disease (FLD) and liver cancer with long pathogenic cycles. It is also known that the intake of the chemical poison nitrosamine and its nanopreparations can promote the development of liver injuries, such as FLD, and hepatic fibrosis, and significantly shorten the formation time of the liver cancer cycle. The present work confirmed that the coexposure of a high-fat diet (HFD) and nano-diethylnitrosamine (nano-DEN) altered the tumor microenvironment and studied the effect of this coexposure on the progression of fatty liver malignant transformation into liver cancer. Gene transcriptomics and immunostaining were used to evaluate the tumor promotion effect of the coexposure in mice. After coexposure treatment, tumor nodules were obviously increased, and inflammation levels were elevated. The liver transcriptomics analysis showed that the expression levels of inflammatory, fatty, and fibrosis-related factors in the coexposed group were increased in comparison with the nano-DEN- and high-fat-alone groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that coexposure aggravated the high expression of genes related to the carcinomatous pathway and accelerated the formation of the tumor microenvironment. The immunohistochemical staining results showed that the coexposure significantly increased the abnormal changes in proteins related to inflammation, proliferation, aging, and hypoxia in mouse liver tissues. The coexposure of high fat and nano-DEN aggravated the process of steatosis and carcinogenesis. In conclusion, the habitual consumption of pickled foods containing nitrosamines in a daily HFD significantly increases the risk of liver pathology lesions progressing from FLD to liver cancer.

This paper employs the discrete element method (DEM) to study the mechanical properties of artificial crushed stone. Different grain shapes and gradations are considered, and three types of 3D artificial stone models are generated based on the statistical conclusions in the relevant literature and the observed data. Concurrently, the 3D models of the artificial stones are divided into three groups by their shape parameters (elongation index and flatness index). Furthermore, three types of gradation with different Cu (coefficient of uniformity) and Cc (coefficient of curvature) are also considered. Then, several 3D triaxial compression tests are conducted with the numerical methods to determine the relationship between the grain shapes and their mechanical characteristics. The test results showed that there was a positive correlation between a particles’ angularities and the maximum deviatoric stress in the triaxial compression tests when there were obvious distinctions between the particles. In addition, gradations had a conspicuous impact on the stiffness of the sample. The stress–strain curve possessed a larger slope when the coefficient of curvature was bigger. In terms of shear strength, the results in this paper align well with the traditional shear strength envelope which are convincing for the dependability of the methods used in this paper. The radial deformation capacity and volume strain of the specimen during the triaxial compression tests are also examined. It is believed that there were great differences in deformability between different samples. At the mesoscopic level, the change in coordination number is identified as the fundamental reason for the change in volume strain trend.

PM2.5 was sampled in four seasons of 2021 in Nanchang. Organic carbon (OC), elemental carbon (EC), and water-soluble ions were the main chemical compositions in PM2.5. The annual average of OC/PM2.5 and EC/PM2.5 was 17.1% and 2.1%, respectively, while nine water-soluble ions were 56.7%. The order of each ion percentage in PM2.5 was NO3− > SO42− > K+ > Na+ > NH4+ > Cl− > NO2− > Ca2+ > Mg2+. The OC/EC (6.54, 13.17, 8.95, 7.99) and Char-EC/Soot-EC (0.88, 0.64, 1.32, 3.74) indicated that the carbon aerosols mainly originated from coal combustion, biomass combustion, and motor-vehicle emissions. High concentrations of Cl− and Ca2+ in spring were associated with dust sources. A good correlation between Na+, SO42−, and NO3− suggests the formation of Na2SO4 and NaNO3. The results of PM2.5 source apportionment by positive matrix factorisation (PMF) showed five main sources: motor-vehicle sources (18–33%), secondary sources (16–36%), coal combustion sources (16–30%), biomass-combustion sources (10–28%), and dust sources (5–7%). Backward trajectory clustering analysis showed PM2.5 in spring and autumn were more influenced by medium distance and local air but mainly influenced by local sources in winter.

Heterocyclic skeleton (Azoles) and different energetic groups containing high performing explosives are highly emerged in recent years to meet the challenging requirements of energetic materials in both military and civilian applications with improved performance. For this purpose tetrazole (Azole) is identified as an attractive heterocyclic backbone with energetic functional groups nitro (-NO2), nitrato (-ONO2), nitrimino (-NNO2), and nitramino (–NH–NO2) to replace the traditionally used high performing explosives. The tetrazole based compounds having these energetic functional groups demonstrated advanced energetic performance (detonation velocity and pressure), densities, and heat of formation (HOF) and became a potential replacement of traditional energetic compounds such as RDX. This review presents a summary of the recently reported nitro-tetrazole energetic compounds containing poly-nitro, di/mono-nitro, nitrato/nitramino/nitrimino, bridged/bis/di tetrazole and nitro functional groups, describing their preparation methods, advance energetic properties, and further applications as high-performing explosives, especially those reported in the last decade. This review aims to provide a fresh concept for designing nitro-tetrazole based high performing explosives together with major challenges and perspectives.

Abstract Nonlinear activation is a crucial building block of most machine-learning systems. However, unlike in the digital electrical domain, applying a saturating nonlinear function in a neural network in the analog optical domain is not as easy, especially in integrated systems. In this paper, we first investigate in detail the photodetector nonlinearity in two main readout schemes: electrical readout and optical readout. On a 3-bit-delayed XOR task, we show that optical readout trained with backpropagation gives the best performance. Furthermore, we propose an additional saturating nonlinearity coming from a deliberately non-ideal voltage amplifier after the detector. Compared to an all-optical nonlinearity, these two kinds of nonlinearities are extremely easy to obtain at no additional cost, since photodiodes and voltage amplifiers are present in any system. Moreover, not having to design ideal linear amplifiers could relax their design requirements. We show through simulation that for long-distance nonlinear fiber distortion compensation, using only the photodiode nonlinearity in an optical readout delivers BER improvements over three orders of magnitude. Combined with the amplifier saturation nonlinearity, we obtain another three orders of magnitude improvement of the BER.

Abstract Risk factors of lung cancer unrelated to smoking are not well-studied, especially among women. Family history has been shown to play a role in predisposing individuals to lung cancer, but this relationship has not been investigated in the Southeast Asian population. A total of 1159 women were recruited in a case–control study conducted in public hospitals in Singapore from 2005 to 2008. After excluding participants with incomplete family history information, 374 cases and 785 controls remained in the final analysis. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusting for potential confounders. Overall, family history of lung cancer was associated with a higher risk for lung cancer (aOR 2.08, 95% CI 1.25–3.47). When stratified by smoking status, a significant association was observed among never-smokers (aOR 2.78, 95% CI 1.57–4.90). Further stratification by fruit consumption identified a significant association between family history of lung cancer and higher risk of lung cancer among never-smokers who had low fruit consumption (aOR 3.09, 95% CI 1.37–7.01). Our findings suggest that family history of lung cancer is a significant risk factor for lung cancer in Singaporean Chinese women, especially among never-smokers.

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major challenge for clinical management worldwide with limited antimicrobial options. Phages are considered an alternative option. Here, we isolated and identified a phage able to lyse ST11-K64 CRKP, the major type in China. This phage has a narrow host range, only lysing ST11-K64 CRKP, and inhibits the growth of host strains for 3 h forming large clear plaques (3.0 to 6.0 mm in diameter) with a surrounding halo. This phage exhibited excellent stability in different temperatures and pH and did not contain any virulence, lysogenic, antimicrobial resistance genes nor tRNA, meeting the criteria for phage therapy. Genomic analysis revealed that it represents a novel species of the Przondovirus genus according to ICTV standards. However, phage-resistant bacterial mutants emerged after 4-h exposure. Compared to the parental strain, phage-resistant mutants showed nonmucoid appearance and exhibited significantly reduced virulence for Galleria mellonella larva. Three randomly selected phage-resistant mutants were genome sequenced. Interruption of capsular polysaccharide biosynthesis-associated gene wcaJ or wbaZ by IS903B alone or an IS903-formed composite transposon was identified. Interruption of wcaJ is a known phage resistant mechanism, while that of wbaZ is not. By complementing the intact wbaZ, the phage susceptibility was restored, confirming the role of wbaZ interruption in phage resistance. This highlights that alteration in the capsular polysaccharide biosynthesis gene cluster, which could be due to transposable elements, is a major mechanism for resistance to Przondovirus phages in CRKP. Noncapsule-targeting phages may be combined for improving phage therapy against CRKP. IMPORTANCE Phage therapy is an alternative approach against multidrug resistant microorganisms such as carbapenem-resistant Klebsiella pneumoniae (CRKP), which represents a major challenge for treatment due to very limited options of antimicrobial agents. For optimizing phage therapy, more new lytic phages are needed. Here, we isolated and characterized a phage of a novel species able to rapidly lyse a major type of CRKP without carrying any virulence, lysogenic, antimicrobial resistance genes. This phage is therefore suitable for clinical treatment. However, phage-resistant mutants of CRKP strains were observed after exposure. We found a new mechanism, i.e., interruption of a capsular polysaccharide biosynthesis gene wbaZ by an insertion sequence-formed composite transposon. Our study demonstrates the capsular polysaccharide biosynthesis gene cluster as a major source of resistance to certain lytic phages in CRKP. This requires more studies to counter phage resistance. Our studies also highlight the critical role of insertion sequences in phage resistance.

BackgroundEpstein-Barr virus-associated gastric cancer (EBVaGC) exhibits unique histological characteristics within the immune-cell-rich microenvironment, but the role of tertiary lymphoid structure (TLS) in EBVaGC is not yet fully understood.MethodsWe retrospectively identified EBVaGC from 8517 consecutive GC cases from the two top cancer centers in China. Furthermore, we evaluated the prognostic value of TLS in 148 EBVaGC patients from our institute and then validated it in an external cohort (76 patients). TLS was quantified and its relationships with overall survival (OS) and therapeutic response were further analyzed. Multiplex immunofluorescence staining and targeted sequencing were used to characterize the composition of TLS and the genomic landscape, respectively.ResultsIn our study, EBVaGC was observed in 4.3% (190/4436) and 2.6% (109/4081) of GCs in the training and validation cohorts, respectively. TLS was identified in the intratumor (94.6%) and peritumor (77.0%) tissues with lymphoid aggregates, primary and secondary (i.e., mature TLSs) follicles in EBVaGC. Kaplan-Meier analysis showed that mature TLS in intratumoral tissues was associated with a favorable OS in the training and validation cohorts (p < 0.0001; p = 0.0108). Multivariate analyses demonstrated that intratumoral TLS maturation, pTNM, and PD-L1 expression were independent prognostic factors for OS (p < 0.05). Furthermore, the mature TLS was significantly associated with a good response to treatment in EBVaGC patients. Interestingly, the mutation frequency of SMARCA4 was significantly lower in the mature TLS groups.ConclusionsIntratumoral mature TLS was associated with a favorable prognosis and good therapeutic response, suggesting that it is a potential prognostic biomarker and predicts a good therapeutic response in EBVaGC patients.

Background: Bladder cancer (BLCA) is the sixth most common cancer in men, with an increasing incidence of morbidity and mortality. Necroptosis is a type of programmed cell death and plays a critical role in the biological processes of bladder cancer (BLCA). However, current studies focusing on long noncoding RNA (lncRNA) and necroptosis in cancer are limited, and there is no research about necroptosis-related lncRNAs (NRLs) in BLCA.Methods: We obtained the RNA-seq data and corresponding clinical information of BLCA from The Cancer Genome Atlas (TCGA) database. The seven determined prognostic NLRs were analyzed by several methods and verified by RT-qPCR. Then, a risk signature was established based on the aforementioned prognostic NLRs. To identify it, we evaluated its prognostic value by Kaplan–Meier (K-M) survival curve and receiver operating characteristics (ROC) curve analysis. Moreover, the relationships between risk signature and clinical features, functional enrichment, immune landscape, and drug resistance were explored as well.Results: We constructed a signature based on seven defined NLRs (HMGA2-AS1, LINC02489, ETV7-AS1, EMSLR, AC005954.1, STAG3L5P-PVRIG2P-PILRB, and LINC02178). Patients in the low-risk cohort had longer survival times than those in the high-risk cohort, and the area under the ROC curve (AUC) value of risk signature was higher than other clinical variables. Functional analyses, the infiltrating level of immune cells and functions, ESTIMATE score, and immune checkpoint analysis all indicated that the high-risk group was in a relatively immune-activated state. In terms of treatments, patients in the high-risk group were more sensitive to immunotherapy, especially anti-PD1/PD-L1 immunotherapy and conventional chemotherapy.Conclusion: The novel NLR signature acts as an invaluable tool for predicting prognosis, immune microenvironment, and drug resistance in muscle-invasive bladder cancer (MIBC) patients.

BackgroundPrevious studies have reported differential associations of certain dietary factors such as soy consumption by epidermal growth factor receptor mutant (EGFR +) subtype of non-small cell lung cancer (NSCLC). However, whether the other dietary factors including meat, fruits, and vegetables have differential risks on different histological and molecular subtypes of lung cancer remains unclear. Therefore, we conducted a case-control study to evaluate these associations.MethodsA total of 3,170 cases and 4,238 controls from three different studies (Genes and Environment in Lung Cancer Study, Lung Cancer Consortium Singapore Study, and Multi-ethnic Cohort Study) were included. Information on demographics, lifestyle, and dietary consumption was obtained using questionnaires. Diet was assessed by using the number of standard servings of each item consumed per week. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between meat, vegetables, and fruits consumption with lung cancer risk after adjusting for potential confounders.ResultsWe identified a significant inverse association between higher consumption of fruits and the risk of lung cancer (2nd tertile: OR = 0.54, 95%CI = 0.46–0.65; 3rd tertile: OR = 0.77, 95%CI = 0.65–0.91), compared with the lower (1st tertile) consumption of fruits. Higher vegetable consumption was significantly associated with a lower risk of EGFR + lung cancer (OR = 0.69, 95% CI = 0.54–0.88), however, this association was not significant among EGFR wild-type (−) lung cancer. Conversely, higher consumption of total meat (OR = 2.10, 95%CI = 1.58–2.79) was significantly associated with higher lung cancer risk, as compared with the lower consumption group.ConclusionsDifferential associations between vegetable consumption with EGFR mutation status in NSCLC were found. Further prospective studies are warranted to assess this association and elucidate the biological mechanisms.

In this study, water hyacinth was adopted to prepare biochar followed by modification using KMnO4. And the modified biochars were applied in Cd contaminated soil, exploring the effects of water hyacinth biochar on lettuce growth, Cd enrichment, soil enzyme activities and microbial changes by pot experiments. Modified biochar application significantly reduced the Cd accumulation in lettuce shoots and roots. Compared to the control, the application of water hyacinth biochar at 1% rate resulted in significant reduction of Cd contents by 40.7% and 33.7% in the shoots and roots of lettuce. Also, the reduction was 33.3% and 20.8% compared with the application rate of unmodified biochar. With the increase of biochar application, the amount of Cd was absorbed by lettuce shoots and roots showing significant reduction of plant Cd accumulation in response to the biochar application rate. Additionally, the lowest available Cd concentration in soil (1.34 mg kg−1) was obtained with the application of modified biochar at 1% rate, which might be the main reason for the lower Cd concentration in lettuce shoot and root parts. Furthermore, structural analysis showed that Cd was fixed on the modified biochar, in a passivated state, by larger specific surface area, more active sites and more stable covalent binding complexes leading to a strong decrease of the available Cd in the soil. Moreover, it was concluded that the increment of the enzyme activities in the soil was up to 2.51 times significantly following the application of modified water hyacinth biochar with 3% amount. Lastly, 16sRNA sequencing showed that biochar addition may lead to changes of microbial structure and abundance in soil.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which was rapidly declared a pandemic by the World Health Organization (WHO). Early clinical symptomatology focused mainly on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are now well-documented. To experimentally determine whether SARS-CoV-2 could replicate in and affect human brain cells, we infected iPSC-derived human brain organoids. Here, we show that SARS-CoV-2 can productively replicate and promote death of neural cells, including cortical neurons. This phenotype was accompanied by loss of excitatory synapses in neurons. Notably, we found that the U.S. Food and Drug Administration (FDA)-approved antiviral Sofosbuvir was able to inhibit SARS-CoV-2 replication and rescued these neuronal alterations in infected brain organoids. Given the urgent need for readily available antivirals, these results provide a cellular basis supporting repurposed antivirals as a strategic treatment to alleviate neurocytological defects that may underlie COVID-19- related neurological symptoms. This study shows that SARS-CoV-2 virus can infect human brain cortical organoids, inducing cell death and synapse loss; application of Sofosbuvir, an FDA-approved antiviral, rescues these neuronal alterations in infected brain organoids.

Recently, the excessive propagation of water hyacinth has led to serious ecological and environmental problems; thereby, its treatment and disposal are of great significance. Moreover, the remediation of heavy metals in soil is a hot topic at present. Thus, water hyacinth was adopted to prepare biochar to investigate its effect on Cd accumulation in lettuce by pot experiments in this study. The optimal application amount of water hyacinth biochar was 1% (30 t ha−1), considering the Cd absorption and yield of lettuce plants. Compared with those of control, the application of biochar prepared at 700°C for 2 h with an amount of 3% (90 t ha−1) resulted in a reduction in Cd by 73.6% and 38.1%, respectively, in the shoots and roots of lettuce. Within a certain carbonization time (0.5~2 h) and carbonization temperature (300°C~700°C), the content of available Cd in the soil decreases with the increase of the carbonization temperature and time, which might be the main reason for the lower Cd concentration in lettuce after applying the biochar. Furthermore, scanning electron microscopy (SEM) and energy-dispersive X-ray fluorescence spectroscopy (EDS) analyses showed that Cd was fixed on the biochar in a state of passivation, leading to a sharp decrease in the available Cd in the soil. Moreover, it was concluded that the application of biochar brings with it an obvious increase in the enzyme activity increment in the soil up to 2.3 times. Lastly, 16sRNA sequencing has shown that biochar addition leads to variations in microbial structure and abundance in soil. Accordingly, biochar prepared by water hyacinth can increase lettuce yield and reduce the concentration of heavy metals in lettuce.

Insulin resistance, a pathological response to insulin hormone in insulin-dependent cells, is characterized by the presence of high glucose and insulin concentrations. The homeostasis model of insulin resistance (HOMA-IR) is one of the most used indexes to estimate insulin resistance by assessing the fasting glucose and insulin levels. An association was observed between vitamin D levels and insulin resistance, which varied in different ethnic groups, and there is some evidence that vitamin D supplementation could contribute to the improvement of insulin resistance. This study assessed the association between 25-hydroxyvitamin D (25[OH]D) concentration and HOMA-IR in American adults aged 20 years and older, without diabetes and other chronic diseases that can influence insulin resistance. The data from the National Health and Nutrition Examination Survey (NHANES) 2007–2014 were used by exploiting the free and publicly-accessible web datasets. Linear regression models were performed to evaluate the association between serum 25(OH)D concentration and HOMA-IR, and a negative association was observed, which remained significant following the adjustment for age, gender, race/ethnicity, education, body mass index (BMI), physical activity, the season of examination, current smoking, hypertension, the use of drugs which can influence insulin resistance, serum bicarbonates, triglycerides, and calcium and phosphorus levels. Only in non-Hispanic Blacks was this inverse association between vitamin D and HOMA-IR not observed in the fully adjusted model. Further studies are needed to explain the mechanisms of the observed ethnic/racial differences in the association of vitamin D levels with HOMA-IR.

A novel highly pathogenic avian influenza A(H5N6) clade 2.3.4.4b virus was isolated from a poultry market in China that a person with a confirmed case had visited. Most genes of the avian and human H5N6 isolates were closely related. The virus also exhibited distinct antigenicity to the Re-11 vaccine strain.

Abstract Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks’ continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.

Abstract Background Pancreatic cancer (PC) is one of the most lethal cancer types with high degree of malignancy and poor prognosis. Recent studies have shown that long non-coding RNAs (lncRNAs) were associated with the initiation and progression of pancreatic cancer. In the current study, we have investigated the expression, biological function and mechanism of a lncRNA CTD-3252C9.4 in pancreatic cancer. Methods The expression of CTD-3252C9.4 in pancreatic cancer cells and tissues was measured by qRT-PCR. In vitro and in vivo functional experiments assays were implemented for identifying CTD-3252C9.4 function in pancreatic cancer. Molecular relationships among CTD-3252C9.4, IRF1 and IFI6 were investigated via luciferase reporter assay, pulldown assay and ChIP assays. Results CTD-3252C9.4 was found remarkably decreased in pancreatic cancer cells and tissues. Overexpression of CTD-3252C9.4 suppressed migration, invasion and proliferation, yet facilitated apoptosis of pancreatic cancer cells both in vitro and in vivo. Then, IFI6 was identified as a downstream target that could be down-regulated by CTD-3252C9.4 and IFI6 overexpression could counteract the effects of CTD-3252C9.4 upregulation on the survival and apoptosis of pancreatic cancer cells. Furthermore, mechanism experiments revealed that IRF1 was a transcriptional factor of IFI6 that can be blocked by CTD-3252C9.4 to inhibit IFI6 transcription. Conclusion Our data indicated that CTD-3252C9.4 could promote pancreatic cancer cell apoptosis and restrain cell growth via binding IRF1 and preventing the transcription of IFI6, which may become a potential therapeutic target for pancreatic cancer.

Abstract Background In response to the World Health Organization’s recommendation, policy makers have been adopting evidence-based healthcare approach to promote the development of traditional, complementary and integrative medicine (TCIM) into Hong Kong’s health system. Disseminating synopses of clinical evidence from systematic reviews or randomized trials is regarded as a potentially effective strategy to promote evidence uptake. The study aimed to identify barriers and facilitators to implementing this strategy among Hong Kong Chinese medicine practitioners (CMPs). Methods Twenty-five CMPs aged under 45 years and trained in Hong Kong after reunification with China in 1997 were interviewed individually. Four clinical evidence synopses of randomized trials and systematic reviews on Chinese medicine interventions were presented, and CMPs were asked to comment on their applicability in routine practice. The Consolidated Framework for Implementation Research (CFIR) was applied to guide interview and analysis. Results The barriers included: i) CMPs’ perceived difficulties in applying complex evidence in decision-making and ii) inadequate training and limited consultation time. The facilitators were i) availability of publicly accessible and user-friendly synopses, ii) formation of community of evidence-based practice among CMPs with input from key opinion leaders, iii) opportunity for interprofessional collaborations with conventional healthcare providers, and iv) patients’ demand for evidence-based clinical advice. Besides, i) CMPs’ knowledge and beliefs in evidence-based healthcare approach, ii) presentations of evidence-based information in the synopses, and iii) clinical decision making as influenced by quality of evidence reported acted as both barriers and facilitators. Conclusions This CFIR-based qualitative study investigated how the World Health Organization recommendation of promoting evidence use in routine practice was perceived by CMPs trained in Hong Kong after reunification with China in 1997. Key barriers and facilitators to applying evidence were identified. Such results will inform tailoring of implementation strategies for promoting evidence uptake, in the context of a well-developed health system dominated by conventional medicine.