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It remains controversial who would benefit from adjuvant chemotherapy (ACT) in patients with early-stage non-small cell lung cancer (NSCLC). We aim to construct a polygenic hazard score (PHS) to predict prognosis and ACT benefit among NSCLC patients.We conducted a retrospective study including 1,395 stage I-II NSCLC patients. We performed a genome-wide association study (GWAS) on overall survival (OS) in patients treated with ACT (SYSUCC ACT set, n=404), and then developed a PHS using LASSO Cox regression in a random subset (training, n=202) and tested it in the remaining set (test, n=202). The PHS was further validated in two independent datasets (SYSUCC surgery set, n=624; PLCO cohort, n=367).The GWAS-derived PHS consisting of 37 single-nucleotide polymorphisms (SNPs) was constructed to classify patients into high and low PHS groups. For patients treated with ACT, those with low PHS had better clinical outcomes than high PHS (test set: HR =0.21, P0.001; PLCO ACT set: HR =0.33, P=0.260). Similar results were found in the extended validation cohorts including patients with or without ACT (SYSUCC: HR =0.48, P0.001; PLCO: HR =0.60, P=0.033). Within subgroup analysis by treatment or clinical factors, we further observed consistent results for the prognostic value of the PHS. Notably, ACT significantly improved OS in stage II patients with low PHS (HR =0.26, P0.001), while there was no ACT survival benefit among patients with high PHS (HR =0.97, P=0.860).The PHS improved prognostic stratification and could help identify patients who were most likely to benefit from ACT in early-stage NSCLC.

Shared decision making (SDM) activities in Malaysia began around 2010. The rise in the numbers of patients with chronic disease in Malaysia underscores a growing need for doctors to practice patient-centred care and SDM as more Malaysians come into regular contact with health decision-making scenarios. Recent guidelines for medical professionalism have emphasized that options and risks be discussed in consultations, especially for procedures with risk of adverse outcomes. Although SDM is not legally required, principles of SDM are applied in legal judgements on informed consent. Research on SDM has grown to include the adoption of patient and public involvement in research, an increased emphasis on incorporating local cultural values in SDM, and implementation of SDM in Malaysia's health system and organizational culture. While COVID-19 hindered the progress of SDM research, one positive development was that vaccination choices heightened public consciousness about personal decisional autonomy and the need to discuss pros and cons with doctors before making a medical decision.

Background This study aimed to evaluate the implementation of an insulin-choice PDA specifically measuring implementation outcomes.Methods A mixed-methods sequential explanatory design was used. The RE-AIM domains namely “Reach”, “Adoption”, “Implementation”, and “Maintenance” were used to guide evaluation.Results For ‘Reach’, 88.9% (n = 48/54) of doctors and 55% (n = 11/20) of nurses attended the insulin PDA training workshops. This was attributed to their self-motivation and the mandate from the Head of Department. The PDA reached 387 patients and was facilitated by the doctors who delivered the PDA to them and their own desire to know more about insulin. Doctors’ ‘Adoption’ of the PDA was high (83.3%, n = 45/54) due to the positive personal experience with the usefulness of the PDA. Only 65.7% (n = 94/143) of patients who received the PDA read it. The degree of ‘Implementation’ of the PDA varied for different tasks (ranged from 19.2%-84.9%) and was challenged by patient and system barriers. For ‘Maintenance’, 80% of the doctors were willing to continue using the PDA due to its benefits.Conclusion This study highlighted that PDA implementation is promising. Addressing the issues of social hierarchy, and HCPs’ roles and responsibilities can further improve implementation outcomes.

Background: Over-the-counter (OTC) drugs facilitates residents self-medication. However, inappropriate self-medications have become a serious problem in China and even all over the world.Objectives: To make an investigation on the current status of Chinese residents’ self-medication behaviors and important considerations, and to explore the factors related to the considerations of drug efficacy and safety.Design: A quantitative, cross-sectional study.Methods: Multi-stage sampling was used to conduct a cross-sectional investigation in China 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government. State that an interviewer-administrated questionnaire, was used for data collection. The questionnaire that was used in the investigation included demographic sociological characteristics, health literacy scale-short form (HLS-SF), the 10-item Big Five Inventory (BFI-10), the EuroQol-5D visual analogue scale (EQ-5D VAS), self-medication status and important considerations when self-medicating. Descriptive statistics were performed, and the Chi-square test was used for univariate analysis. Log-binomial regression was used for multivariate analysis on whether residents regard drug efficacy or safety as an important consideration.Results: 9256 respondents were included in the data analysis. The self-medication rate of Chinese adults was as high as 99.1%. Paracetamol and other analgesics were the most common types of OTC medication that respondents purchased, followed by vitamins/minerals. Medical staff recommendations, drug safety and efficacy were the top three important considerations. The residents in the east, central and western regions who consider safety is 63.5%, 61.5%, and 66.8% respectively. The proportion of curative effect was 60.2%, 55.7%, and 61.4% respectively. Log-binomial regression showed that western respondents, retired people, those who mainly used ways including basic medical insurance for employees, commercial medical insurance, free medical treatment to cover their medical cost, respondents with high neuroticism, high health literacy were more likely to consider drug safety as an important factor (p < 0.05). Eastern respondents, employed, main way of medical expenses borne was Out-of-pocket Payment, those with chronic disease were more likely to consider drug efficacy as an important factor (p < 0.05). Female, respondents with high levels of agreeableness, conscientiousness, openness, and self-rated health status were more likely to regard both drug safety and efficacy as important considerations (p < 0.05).Conclusion: Self-medication is practiced by most Chinese adults. Whether Chinese adults take drug efficacy or safety as an important consideration is related to their demographic and sociological characteristics, Big Five personality characteristics, health literacy and self-assessed health status. There is a need to strengthen the management of OTC drugs and public education about self-medication.

EBV is classified as the group I human carcinogen and is associated with multiple cancers, including NPC. The interplays between the microbiota and oncovirus in cancer development remain largely unknown.

To investigated the mechanisms underlying the effects of modified Kaixin San(MKXS) on improving memory and synaptic damage of Alzheimer's disease(AD) mouse model with conditional presenilin 1/2 conditional double knockout(PS cDKO). Specifically, 60 PS cDKO mice(3-3.5 months old) and their age-matched wild-type(WT) littermates were randomized into three groups: WT group(n=20), PS cDKO group(n=20), and PS cDKO+MKXS group(n=20). Mice in WT and PS cDKO groups were fed with standard chow and those in PS cDKO+MKXS group were given chow containing MKXS(at 2.55 g·kg~(-1)) for 60 days. Novel object reco-gnition task was employed to detect the recognition memory of mice, and Western blot to detect the protein levels of synapse-associated proteins in the hippocampus(HPC) of mice, such as NR1, NR2 A, NR2 B, p-αCaMKⅡ, tau, and p-tau. Microglial morphology in the HPC CA1 of mice was observed based on immunohistochemistry. Quantitative real time-PCR(qRT-PCR) was employed to detect the mRNA levels of the pro-inflammatory factors and synapse-associated proteins in the HPC of mice, including COX-2, iNOS, IL-1β, IL-6, TNF-α, PSD95, NR1, NR2 A, NR2 B, and MAP2. The protein levels of IL-1β, TNF-α, and IL-6 were tested by enzyme-linked immunosorbent assay(ELISA). The interaction between PSD95 and αCaMKⅡ and between PSD95 and p-αCaMKⅡ was tested by co-immunoprecipitation(Co-IP). The results showed that PS cDKO+MKXS demonstrated significantly higher preference index and recognition index of the new objects, lower protein level of p-tau(ser 396/404) and mRNA levels of COX-2, iNOS, TNF-α, IL-1β, and IL-6 in HPC, higher protein levels of NR1, NR2 A, NR2 B, and p-αCaMKⅡ and mRNA levels of NR1, NR2 A, NR2 B, PSD95, and MAP2, and stronger interaction of αCaMKⅡ with PSD95 and interaction of p-αCaMKⅡ with PSD95 than the PS cDKO group. Immunohistoche-mical staining showed that MKXS inhibited the activation of microglia. In conclusion, MKXS improves memory and synaptic damage in mice with AD by modulating αCaMKⅡ-PSD95 protein binding through inhibition of neuroinflammation.

Breast cancer is a complex and multifactorial disease which stems significantly from both environmental and genetic factors. A growing number of epidemiological studies have suggested that ambient air pollution (AAP) exposure may play an important role in breast cancer development. However, no consistency has been reached concerning whether high levels of air pollutant exposure were related to increased breast cancer risk among the current evidence. To further clarify such association of long-term AAP exposure with risk of breast cancer, a systematic review and meta-analysis of available evidence was performed. An extensive literature search in 3 academic databases was conducted before March 10, 2020. The risk of bias (RoB) for each individual study was evaluated with a domain-based assessment tool, developed by the National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT). Meta-estimates for air pollutant–breast cancer combinations were calculated for a standardized increment in exposure by random-effect models. The confidence level in the body of evidence and the certainty of evidence was also assessed for each air pollutant–breast cancer combination. The initial search identified 5446 studies, and 18 of them were eligible. The pooled analysis found an increased risk of breast cancer was associated with an increase in each 10 μg/m3 in nitrogen dioxide (NO2) exposure (hazard ratio (HR) = 1.02, 95% confidence interval (CI) = 1.01, 1.04), while particulate matter with aerodynamic diameters ≤ 2.5 μm and 10 μm (PM2.5, PM10) revealed no statistically significant associations with breast cancer risk. Our evaluation on the certainty of evidence indicates that there was a “moderate level of evidence” in the body of evidence for an association of NO2 exposure with an increased breast cancer risk and an “inadequate level of evidence” in the body of evidence for an association of PM2.5 and PM10 exposure with an increased breast cancer risk. Our study suggests long-term exposure to NO2 is related to an increased risk of breast cancer. However, in consideration of the limitations, further studies, especially performed in developing countries, with improvements in exposure assessment, outcome ascertainment, and confounder adjustment, are needed to draw a definite evidence of a causal relationship.

Background Distant metastasis is the leading cause of death for esophageal squamous cell carcinoma (ESCC) with limited treatment options and unsatisfactory effectiveness. Bromodomain (BRD) containing proteins are emerging targets for cancer therapy with promising effects. As a unique member of BRD family, the function and molecular mechanism of ATAD2 in cancer development is seldomly investigated. Methods The clinical impact of ATAD2 was assessed both at RNA and protein level in 75 and 112 ESCC patients separately. The biological function of ATAD2 was investigated in vitro and in vivo. Signaling pathway and downstream effectors of ATAD2 were identified by RNA sequencing, luciferase reporter, co-immunoprecipitation, chromatin immunoprecipitation, immunofluorescence and western blot assay. Results We found that elevated ATAD2 expression was significantly associated with lymph node metastasis, advanced clinical stage as well as poor survival of ESCC patients. Silencing ATAD2 significantly suppressed ESCC cell migration and invasion in vitro, and inhibited tumor growth and lung metastasis in vivo. Mechanically, we identified a new cofactor, C/EBPβ. ATAD2 directly interacted with C/EBPβ and promoted its nuclear translocation, which directly bound to the promoter region of TGF-β1 and activated its expression. Further, we demonstrated that TGF-β1 activated its downstream effectors in a Smad3 dependent manner. In addition, we further found that ATAD2 promoted ESCC metastasis through TGF-β signaling induced Snail expression and the subsequent epithelial-mesenchymal transition. Conclusion Our findings demonstrated the pro-metastatic function of ATAD2 and uncovered the new molecular mechanism by regulating C/EBPβ/TGF-β1/Smad3/Snail signaling pathway, thus providing a potential target for the treatment of ESCC metastasis.

Background PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone. Methods A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca2+]i, a Fluo-3/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells). Results PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K+-induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME/ODQ or K+ channel blockers (Gli/TEA). PFI-3 abolished Ca2+-induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca2+-free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca2+-induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60 mM) in Ca2+-free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques. Conclusions PFI-3 blunted PE and high K+-induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs).

This study focuses on the compatibility and thermal reactivity of blends of aviation kerosene JET A-1 with four kinds of butanol. This prospective research predicts a suitable ratio of butanol isomers that can be added to JET A-1 for turbojets. Thus, this study was performed to establish the physical stability of different blending ratios at low temperature, high-temperature gasification stability, gas expansion enthalpy, and heat of combustion of blended aviation fuel. The blend proportion compatibility and thermal reactive stability of the low- and high-temperature physical characteristics and the combustion properties were studied by conducting refrigerated cooling system-differential scanning calorimetry (RCS90-DSC) and oxygen bomb calorimetry. We obtained two kinds of butanol isomers, n-butanol and sec-butanol, with the highest and best ratio of addition of 20% to JET A-1, they include the compatibility parameters, such as the onset temperature of freezing characteristics, the onset gasification temperature, the expansion enthalpy (selected nonthermal heating rate of 4 °C min−1), and heat values are −73.23 and −64.87 °C, 58.61 and 22.92 °C, 52.42 and.52.99 kJ kg−1, and 43.46 and 42.98 MJ kg−1, respectively. This research was developed to preliminarily assess the feasibility and compatibility of the suitable addition of bio-oil or bio-butanol to aviation fuel for use in aircraft engines to reduce engine testing and energy consumption.

Chlamydia psittaci is an important pathogen that causes chronic and atypical pneumonia in humans. Autophagy and the unfolded protein response (UPR) are important mechanisms for regulating the growth of infectious parasitic pathogens in living cells. Here, we explored whether C. psittaci infection induced autophagy via the UPR and the effect of these cellular responses on the survival and replication of C. psittaci in human bronchial epithelial cells (HBEs). Not only were the numbers of autophagosomes and the expression of LC3-II and Beclin1 increased following C. psittaci infection of HBEs, but also the expression of p62 (also called sequestosome-1) was downregulated. Moreover, after C. psittaci infection, the UPR and UPR sensors PERK/eIF2α and IRE1α/XBP1 were activated, but not the ATF6 pathway. When either Bip siRNA was used to block normal initiation of the UPR, or activation of the PERK and IER1α pathways was blocked with specific inhibitors GSK2606414 and 4μ8C, the level of autophagy caused by C. psittaci infection was significantly inhibited. Furthermore, blocking activation of the UPR and associated pathways significantly reduced the number of C. psittaci inclusions. Our research suggests that the UPR, via the PERK and IRE1α, but not ATF6 signaling pathways, regulates HBE-cell autophagy induced by C. psittaci infection and the replication of C. psittaci.

The dysbiosis of oral microbiota is linked to numerous diseases and is associated with personal lifestyles, such as alcohol drinking. However, there is inadequate data to study the effect of alcohol drinking on oral microbiota from the Chinese population. Here, we profiled the oral microbiota of 150 healthy subjects in the Chinese population by 16S rRNA gene sequencing. The results showed that drinkers had significantly higher alpha diversity than non-drinkers. A significant difference in overall microbiota composition was observed between non-drinkers and drinkers. Additionally, using DESeq analysis, we found genus Prevotella and Moryella, and species Prevotella melaninogenica and Prevotella tannerae were significantly enriched in drinkers; meanwhile, the genus Lautropia, Haemophilus and Porphyromonas, and species Haemophilus parainfluenzae were significantly depleted in drinkers. PICRUSt analysis showed that significantly different genera were mainly related to metabolism pathways. The oxygen-independent pathways, including galactose, fructose and mannose metabolism pathways, were enriched in drinkers and positively associated with genera enriched in drinkers; while the pyruvate metabolism pathway, an aerobic metabolism pathway, was decreased in drinkers and negatively associated with genera enriched in drinkers. Our results suggested that alcohol drinking may affect health by altering oral microbial composition and potentially affecting microbial functional pathways. These findings may have implications for better understanding the potential role those oral bacteria play in alcohol-related diseases.

Background Nasopharyngeal carcinoma (NPC) is closely associated with genetic factors and Epstein-Barr virus infection, showing strong familial aggregation. Individuals with a family history suffer elevated NPC risk, requiring effective genetic counseling for risk stratification and individualized prevention. Methods We performed whole-exome sequencing on 502 familial NPC patients and 404 unaffected relatives and controls. We systematically evaluated the established cancer predisposition genes and investigated novel NPC susceptibility genes, making comparisons with 21 other familial cancers in the UK biobank (N = 5218). Results Rare pathogenic mutations in the established cancer predisposition genes were observed in familial NPC patients, including ERCC2 (1.39%), TP63 (1.00%), MUTYH (0.80%), and BRCA1 (0.80%). Additionally, 6 novel susceptibility genes were identified. RAD54L, involved in the DNA repair pathway together with ERCC2, MUTYH, and BRCA1, showed the highest frequency (4.18%) in familial NPC. Enrichment analysis found mutations in TP63 were enriched in familial NPC, and RAD54L and EML2 were enriched in both NPC and other Epstein-Barr virus–associated cancers. Besides rare variants, common variants reported in the studies of sporadic NPC were also associated with familial NPC risk. Individuals in the top quantile of common variant-derived genetic risk score while carrying rare variants exhibited increased NPC risk (odds ratio = 13.47, 95% confidence interval = 6.33 to 28.68, P = 1.48 × 10–11); men in this risk group showed a cumulative lifetime risk of 24.19%, much higher than those in the bottom common variant-derived genetic risk score quantile and without rare variants (2.04%). Conclusions This study expands the catalog of NPC susceptibility genes and provides the potential for risk stratification of individuals with an NPC family history.

With China's economic development, air pollution has become increasingly serious. Studying the concentration of PM2.5, as the main component of haze, is the key to control air quality. Extent research lacks spatiotemporal correlations and full regional coverage. Therefore, a fine-grained prediction method was developed for continuous prediction of station-specific and regional PM2.5 concentrations over 24 h that comprise two parts: a site prediction model (TSRT model) and a grid prediction model. The TSRT model includes a long short-term memory-based temporal predictor that uses temporally related features as inputs, a Long Short-Term Memory-based spatial predictor that requires spatially related features as inputs, and a regression model based on regression-tree algorithm to aggregate the predictions of temporal and spatial predictors. The grid concentration prediction model based on a fully connected back-propagation neural network with grid characteristics as inputs achieved a PM2.5 regional prediction with 1-km2 non-overlapping grids across the study area. The approach was evaluated with data from 101 monitoring stations in the Beijing-Tianjin-Hebei area. The results imply that: (1) the forecasting performance of TSRT models is better than other possible methods with average R2 = 0.9 and average MAE = 10.35 μg/m3, (2) R2 and MAE values of the grid prediction model are 0.77 and 21.87 μg/m3, supporting the advantages of our method over well-known interpolation models, such as kriging interpolation, and (3) the method provides appropriate PM2.5 concentration prediction in the next 24 h. Therefore, this novel method may improve PM2.5 prediction, benefiting people's daily lives and influencing policies.

Nasopharyngeal carcinoma (NPC), the most common head and neck cancer, is characterized by distinct geographic distribution and familial aggregation. Multiple risk factors, including host genetics, environmental factor and EBV infection, have been linked to the development of NPC, particularly in the familial clustering cases. However, the cause of NPC endemicity remains enigmatic due possibly to the complicated interplay between these risk factors. Recently, positive Epstein-Barr virus (EBV) DNA loads at nasopharyngeal (NP) cavity has been found to reflect NPC development and applied in NPC screening. To examine whether the increased NP EBV loads could aggregate in the families and be affected by host genetics and environmental factor, EBV loads were obtained by 510 NP brushing samples from eligible unaffected individuals, who have 2 or more relatives affected with NPC, in 116 high-risk NPC families. The correlation of relative pairs was estimated using S.A.G.E. (version 6.4, 2016), and host heritability of NP EBV loads was calculated with variance component models using SOLAR (version 8.4.2, 2019). In result, significant correlations of EBV loads were observed between parent-offspring pairs and sibling-sibling pairs (P

Heparan sulfate (HS) is a kind of cellular adhesion receptor that mediates the attachment and internalization of virus infection. Herein, to mimic the cell surface receptor, mercaptoethane sulfonate (MES), an analogue of HS, was used as the surface modifier to synthesize bovine serum albumin (BSA)-coated tellurium nanoparticles (Te/BSA NPs) with a unique triangular star shape (Te/BSA nanostars). Using porcine reproductive and respiratory syndrome virus (PRRSV), which utilizes HS as a cellular receptor, as a model of arterivirus, we found that Te/BSA nanostars suppressed virus infection mainly by inhibiting the virus internalization process. Interestingly, Te/BSA nanostars exhibited much higher antiviral activity than the spherical Te/BSA NPs (Te/BSA nanospheres), the Te/BSA NPs were synthesized with GSH as a substitute of MES, suggesting that both MES modification and the novel shapes of Te/BSA NPs enhance their antiviral activity. Finally, the antiviral effect of Te/BSA nanostars on porcine epidemic diarrhea virus (PEDV), a model of coronavirus, was also demonstrated, indicating the potential broad-spectrum antiviral property of Te/BSA nanostars.

Despite the good biocompatibility and antibacterial activity of zinc sulfide nanoparticles (ZnS NPs), whether they possess antiviral activity is still unclear. Here, GSH-modified ZnS NPs (GSH-ZnS NPs) were synthesized and their significant antiviral activity was demonstrated using the

Background: Most traditional intent recognition methods are to recognizing the movement of lower limb prosthesis through statistical features, which are unstable in short-term signals. The another key problem with recognition of lower limb prosthesis motion intent is to explore the instantaneous change between the two difffferent steady modes. Based on the above considerations, the one-dimensional dual-tree complex wavelet transform(1D-DTCWT) is introduced for motion intent recognition in intelligent prosthesis. Methods: 1D-DTCWT adopts two-way complex wavelet transforms with a binary tree structure as functional data analysis (FDA) method that preserves the time-frequency local analysis capabilities of wavelet transforms while maintaining translation invariance and direction selection. Therefore, the 1D-DTCWT can amplify the instantaneous change information hidden in the data while retaining the continuity of the motion behavior, so as to better recognize the motion intention. Furthermore, the feature vector composed of low-frequency wavelet coeffiffifficients decomposed by 1D-DTCWT is classifified and recognized by support vector machine (SVM), which can effffectively classify and recognize the motion intent of the unilateral lower limb amputees. Results: The data of the experiment comes from ten able-bodied subjects and one amputee subject to analyze 5 steady modes, 8 transitional modes, and 13 total motion modes adopting user-dependent and user-independent methods. The experimental results from the user-dependent methods show that the recognition rate for able-bodied subjects reached 98.91%, 98.92%, and 97.27% for the movement modes of steady modes, transitional modes, and total motion modes, respectively. The recognition rate of the amputee subject reached 100%, 91.16%, and 89.27%, respectively, for the three modes. Conclusions: The method in this paper can effffectively solve the problem of short-term signal instability reflflected by traditional statistical feature recognition of motion intent and explore the instantaneous change information of transitional modes while retaining the continuity of the motion behavior.

Ferrous sulfide nanoparticles (FeS NPs) are widely applied to environmental remediation, catalysis, energy storage and medicine because of their high reactivity, large specific surface area and low cost, arousing great interest of researchers. However, there is no literature reported on its application in the antiviral field. In the study, gelatin stabilized FeS nanoparticles (Gel-FeS NPs) were synthesized by co-precipitation of Fe2+ and S2‒ in the aqueous phase with continuous stirring under anaerobic conditions. The as-prepared Gel-FeS NPs were good stabilization and dispersibility with the size distribution of 77.7 ± 16.4 nm, as determined by UV-Vis spectrometer, TEM, FTIR, XRD and XPS. We reported for the first time the virucidic and antiviral activity of Gel-FeS NPs. The Gel-FeS NPs with good dispersibility and biocompatibility were synthesized, and they exhibited effective inhibition on the proliferation of PRRSV by blocking the PRRSV outside the host cells. Moreover, the Fe2+ from degraded ferrous sulfide still displayed an antiviral effect, demonstrating the advantage as an antiviral nanomaterial of Gel-FeS NPs compared to other nanomaterials. This work highlighted the antiviral effect of Gel-FeS NPs, broaden the applications of iron-based nanoparticles for combating the virus.

Background Colorectal cancer (CRC) is the leading cause of cancer death worldwide. Screening is a confirmed way to reduce the incidence and mortality rates of CRC. This study aimed to identify a fecal-based, noninvasive, and accurate method for detection of colorectal cancer (CRC) and advanced adenoma (AA). Methods Through detection in tissue (n = 96) and fecal samples (n = 88) and tested in an independent group of fecal samples (n = 294), the methylated DNA marker ITGA4 and bacterial markers Fusobacterium nucleatum (Fn) and Pepetostreptococcusanaerobius (Pa) were identified from the candidate biomarkers for CRC and AA detection. A prediction score (pd-score) was constructed using the selected markers and fecal immunochemical test (FIT) for distinguishing AA and CRC from healthy subjects by logistic regression method. The diagnostic performance of the pd-score was compared with FIT and validated in the external validation cohort (n = 117) and in a large CRC screening cohort. Results The pd-score accurately identified AA and CRC from healthy subjects with an area under the curve (AUC) of 0.958, at a specificity of 91.37%; the pd-score showed sensitivities of 95.38% for CRC and 70.83% for AA, respectively. In the external validation cohort, the sensitivities of the pd-score for CRC and AA detection were 94.03% and 80.00%, respectively. When applied in screening, the pd-score identified 100% (11/11) of CRC and 70.83% (17/24) of AA in participants with both colonoscopy results and qualified fecal samples, showing an improvement by 41.19% compared to FIT. Conclusions The current study developed a noninvasive and well-validated approach for AA and CRC detection, which could be applied widely as a diagnostic and screening test.

Background The infection and spread of porcine reproductive and respiratory syndrome virus (PRRSV) pose a serious threat to the global pig industry, and inhibiting the viral infection process is a promising treatment strategy. Nanomaterials can interact with viruses and have attracted much attention due to their large specific surface area and unique physicochemical properties. Ferrous sulfide nanoparticles (FeS NPs) with the characteristics of high reactivity, large specific surface area, and low cost are widely applied to environmental remediation, catalysis, energy storage and medicine. However, there is no report on the application of FeS NPs in the antiviral field. In this study, gelatin stabilized FeS nanoparticles (Gel-FeS NPs) were large-scale synthesized rapidly by the one-pot method of co-precipitation of Fe2+ and S2‒. Results The prepared Gel-FeS NPs exhibited good stability and dispersibility with an average diameter of 47.3 nm. Additionally, they were characterized with good biocompatibility and high antiviral activity against PRRSV proliferation in the stages of adsorption, invasion, and replication. Conclusions We reported for the first time the virucidal and antiviral activity of Gel-FeS NPs. The synthesized Gel-FeS NPs exhibited good dispersibility and biocompatibility as well as effective inhibition on PRRSV proliferation. Moreover, the Fe2+ released from degraded Gel-FeS NPs still displayed an antiviral effect, demonstrating the advantage of Gel-FeS NPs as an antiviral nanomaterial compared to other nanomaterials. This work highlighted the antiviral effect of Gel-FeS NPs and provided a new strategy for ferrous-based nanoparticles against PRRSV. Graphical Abstract

The mixed species of Staphylococcus aureus and Candida albicans can cause infections on skin, mucosa or bloodstream, however, mechanisms of their cross-kingdom interactions related to pathogenesis and drug resistance are still not clear. Here an increase of S. aureus proliferation and biofilm formation was observed in S. aureus and C. albicans dual-species culture, and the synergistic pathogenic effect was then confirmed in both local (cutaneous abscess) and systemic infection (peritonitis) murine models. According to the transcriptome analysis of the dual-species culture, virulence factors of S. aureus were significantly upregulated. Surprisingly, the beta-lactams and vancomycin-resistant genes in S. aureus as well as azole-resistant genes in C. albicans were also significantly increased. The synergistic effects on drug resistance to both antibacterial and antifungal agents were further proved both in vitro and in cutaneous abscess and peritonitis murine models treated by methicillin, vancomycin and fluconazole. The synergistic interactions between S. aureus and C. albicans on pathogenesis and drug resistance highlight the importance of targeting the microbial interactions in polyspecies-associated infections.

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is a widely used modality for acquiring various target samples, but its efficacy in gallbladder masses is unknown. The aim of this retrospective study was to evaluate the efficacy and safety of EUS-FNB in patients with gallbladder masses.The study samples were composed of patients from March 2015 to July 2019 who needed to identify the nature of gallbladder masses through EUS-FNB. The outcomes of this study were the adequacy of specimens, diagnostic yields, technical feasibility, and adverse events of the EUS-FNB in gallbladder masses.A total of 27 consecutive patients with a median age of 58 years were included in this study. The 22-gauge FNB needle was feasible in all lesions. The median follow-up period of the patients was 294 days. The specimens sufficient for diagnosis account for 89% (24/27) and 93% (25/27) in cytology and histology, respectively. The overall diagnostic yields for malignancy showed the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 95.45% [95% confidence interval (CI): 75.12%-99.76%], 100% (95% CI: 46.29%-100%), 100% (95% CI: 80.76%-100%), 83.33% (95% CI: 36.48%-99.12%), and 96.30% (95% CI: 80.20%-99.99%), respectively. The subgroup analysis revealed that FNB could obtain sufficient specimens and high diagnostic yields in both gallbladder mass20.5 mm group and ≥ 20.5 mm group. One patient experienced mild abdominal pain after the procedure and recovered within one day.EUS-FNB is a reasonable diagnostic tool for the pretreatment diagnosis of patients with gallbladder masses, especially for patients who may miss the opportunity of surgery and need sufficient specimens to identify the pathological type so as to determine chemotherapy regimens. Further large-scale studies are needed to confirm our conclusion.