Streptomyces virginiae XDS1-5, an antagonistic actinomycete, as a biocontrol to peach brown rot caused by Monilinia fructicola.

BACKGROUND: Peach brown rot, caused by the pathogen Monilinia fructicola, represents a significant postharvest infectious disease affecting peach fruit. This disease is responsible for a substantial increase in fruit decay rates, leading to significant economic losses, often exceeding 50%. Currently, there is a growing interest in identifying biocontrol agents to mitigate peach brown rot, with a predominant interest in Bacillus species. RESULTS: In this investigation, we isolated 410 isolates of actinomycetes from non-farmland ecosystem soil samples. Subsequently, 27 isolates exhibiting superior inhibitory capabilities were selected. Among these, strain XDS1-5 demonstrated the most robust fungistatic effect against brown rot disease, achieving an 80% inhibition rate in vitro and a 66% inhibition rate in vivo. XDS1-5 was identified as belonging to the Streptomyces virginiae species. Furthermore, a fermentation filtrate of XDS1-5 exhibited the ability to metabolize 34.21% of the tested carbon sources and 7.37% of the tested nitrogen sources. Particularly noteworthy was its capacity to disrupt the cell membrane structure directly, leading to increased cell membrane permeability and cytoplasmic leakage. Additionally, our investigation indicated that indoline, a metabolite produced by XDS1-5, played a pivotal role in inhibiting the growth of M. fructicola. CONCLUSION: In summary, our study has identified a biocontrol actinomycete, XDS1-5, with the potential to effectively inhibit postharvest brown rot disease in peaches. This finding holds great significance for the biological control of peach brown rot, offering promising prospects for mitigating the economic losses associated with this devastating disease. © 2024 Society of Chemical Industry.

An integrated multi-omics analysis reveals osteokines involved in global regulation.

Bone secretory proteins, termed osteokines, regulate bone metabolism and whole-body homeostasis. However, fundamental questions as to what the bona fide osteokines and their cellular sources are and how they are regulated remain unclear. In this study, we analyzed bone and extraskeletal tissues, osteoblast (OB) conditioned media, bone marrow supernatant (BMS), and serum, for basal osteokines and those responsive to aging and mechanical loading/unloading. We identified 375 candidate osteokines and their changes in response to aging and mechanical dynamics by integrating data from RNA-seq, scRNA-seq, and proteomic approaches. Furthermore, we analyzed their cellular sources in the bone and inter-organ communication facilitated by them (bone-brain, liver, and aorta). Notably, we discovered that senescent OBs secrete fatty-acid-binding protein 3 to propagate senescence toward vascular smooth muscle cells (VSMCs). Taken together, we identified previously unknown candidate osteokines and established a dynamic regulatory network among them, thus providing valuable resources to further investigate their systemic roles.

Executive function, perceived stress and eating behaviours among Chinese young adults.

Young adults in a transitional period may experience more stress and, hence, suffer from an increased risk of unhealthy eating. Executive function (EF) involves not only inhibitory control and mental flexibility (the 'cool' facet) to facilitate resistance to immediate temptations, but also affective decision making (the 'hot' facet) that helps to regulate emotional eating. The effects of different facets of EF and their interactions with perceived stress on eating behaviours remained underexplored. In this study, 594 young adults in their graduation year of post-secondary education were included. We used latent profile analysis to identify major patterns of eating behaviours and analysed their associations with perceived stress, and both the 'cool' and 'hot' facets of EF using multinominal logistic regression models. Latent profile analysis identified three clusters of eating patterns: non-approaching moderate eaters (N = 312, 52.5%), approaching eaters (N = 229, 38.6%), and approaching-and-avoidant eaters (N = 53, 8.9%). Logistic regression models found that the approaching-and-avoidant eating pattern was associated with higher perceived stress (OR = 3.16, p value = 0.007) and poorer affective decision-making (OR = 0.97, p value = 0.006). Stratified analysis further revealed that higher perceived stress was significantly associated with approaching-and-avoidant eating only among individuals with poorer affective decision-making. These findings suggest that individuals with poorer emotional regulation may face greater difficulties in regulating eating behaviours when experiencing higher stress. Interventions for people with a mixed pattern of approaching-and-avoidance eating should focus on providing support to regulate emotion-related eating.

Marine polysaccharides: Biological activities and applications in drug delivery systems.

The ocean is the common home of a large number of marine organisms, including plants, animals, and microorganisms. Researchers can extract thousands of important bioactive components from the oceans and use them extensively to treat and prevent diseases. In contrast, marine polysaccharide macromolecules such as alginate, carrageenan, Laminarin, fucoidan, chitosan, and hyaluronic acid have excellent physicochemical properties, good biocompatibility, and high bioactivity, which ensures their wide applications and strong therapeutic potentials in drug delivery. Drug delivery systems (DDS) based on marine polysaccharides and modified marine polysaccharide molecules have emerged as an innovative technology for controlling drug distribution on temporal, spatial, and dosage scales. They can detect and respond to external stimuli such as pH, temperature, and electric fields. These properties have led to their wide application in the design of novel drug delivery systems such as hydrogels, polymeric micelles, liposomes, microneedles, microspheres, etc. In addition, marine polysaccharide-based DDS not only have smart response properties but also can combine with the unique biological properties of the marine polysaccharide base to exert synergistic therapeutic effects. The biological activities of marine polysaccharides and the design of marine polysaccharide-based DDS are reviewed. Marine polysaccharide-based responsive DDS are expected to provide new strategies and solutions for disease treatment.

Photoinduced Radical Desulfurative C(sp3)-C(sp2) Coupling via Electron Donor-Acceptor Complexes.

Herein, we disclose a radical desulfurative C-C coupling protocol for the synthesis of 4-alkylpyridines. A variety of substituents on both benzyl thiols and 4-cyanopyridines are tolerated. The reaction is carried out under mild and photocatalyst- and transition-metal-free conditions. Preliminary mechanistic studies show that an electron donor-acceptor complex is formed between benzyl thiols and 4-cyanopyridines under alkaline conditions. Then, a variety of 1°, 2°, and 3° C(sp3)-centered radicals was formed by cleavage of the C-S bond, and the 4-alkylpyridines were achieved through a radical-radical coupling with the pyridyl radical anion.

Clinical Value of Detecting Fecal Calprotectin by Using Colloidal Gold Assay in Screening or Diagnosing Crohn's Disease.

Background: Crohn's disease (CD) is a chronic inflammatory disease, and its incidence is gradually increasing. Thus, the use of a simple and convenient examination method to detect CD in the natural population as early as possible is crucial. This study is aimed at using the colloidal gold semiquantitative assay to detect fecal calprotectin (FCP) and determine whether it is helpful in screening or diagnosing CD. Methods: Using a prospectively maintained database, 59 patients with CD were analyzed using FCP measurement. Subsequently, 76 patients and 89 healthy individuals were assigned to the gastrointestinal dysfunction and control groups, respectively. To aid in the screening or diagnosis of CD, the receiver operating characteristic curve was used to determine the diagnostic efficacy of FCP thresholds. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were presented with 95% confidence intervals (CIs). Results: Patients with CD showed significantly higher FCP levels. Compared with the healthy population, when the FCP level cut-off was 15 µg/g and 60 µg/g, the sensitivity, specificity, PPV, and NPV for CD diagnosis were 98.3% (CI, 95.0%-100%) and 78.0% (CI, 67.4-88.6%), 84.3% (CI, 76.7%-91.8%) and 98.9% (CI, 96.7%-100%), 80.6% (CI, 71.5%-89.7%) and 97.9% (CI, 93.7%-100%), and 98.7% (CI, 96.2%-100%) and 87.1% (CI, 80.6%-93.6%), respectively. The AUCs were 0.969 (CI, 0.941-0.997). Compared with the gastrointestinal dysfunction group, using the same FCP level cut-off, the sensitivity, specificity, PPV, and NPV for CD diagnosis were 98.3% (CI, 95.0%-100%) and 78.0% (CI, 67.4%-88.6%), 71.1% (CI, 60.9%-81.3%) and 89.5% (CI, 82.3%-96.7%), 72.5% (CI, 62.7%-82.3%) and 85.2% (CI, 75.7%-94.7%), and 98.1% (CI, 94.5%-100%) and 84.0% (CI, 76.0%-92.0%), respectively. The AUCs were 0.908 (CI, 0.856-0.960). Conclusion: Detecting FCP by using the colloidal gold semiquantitative assay can be effective in screening and adjunct diagnosing of CD.

The Influencing Factors of "Post-African Swine Fever" Pig Farm Biosecurity: Evidence from Sichuan Province, China.

Effective biosecurity measures are crucial in controlling and preventing major pig diseases, ultimately ensuring farm income and social stability. This study extracted data from 205 farmer surveys in Sichuan Province, China, to construct a biosecurity index system for pig farms. The biosecurity levels of pig farms were evaluated using a projection pursuit method to identify weak areas. The Tobit model was then utilized to determine the factors that influenced the biosecurity levels. The results indicated that the overall biosecurity levels of the pig farms were low. The study found that the average biosecurity score among farms was 0.61, with a minimum score of 0.37 and a maximum score of 0.89 (on a scale of 0 to 1). These results suggest that there are significant differences in biosecurity levels among the farms. The study also found that the scores for first-level indicators related to breeding environment management, as well as second-level indicators related to personnel management and awareness of African swine fever prevention and control, were significantly lower than scores for other indicators in the farmers' biosecurity systems. This study investigated the factors influencing biosecurity on farms and found that technical training, farm size, income share, production organization, and government inspections had a significant impact on the level of biosecurity implemented. This study emphasizes the significance of biosecurity in enhancing pig farm biosecurity and its role in improving farm resilience to major animal diseases like African swine fever. It also provides valuable insights for policymakers to make informed decisions regarding related policies.

Analysis of factors with low positive predictive value in the diagnosis of urinary tract infection by flow cytometry.

PURPOSE: Culture-negative urine specimens can be rapidly screened by urine flow cytometry (UFC), while low positive predictive value (PPV) limits the clinical application. We explored the factors associated with a low PPV. METHODS: A total of 5095 urine specimens were analyzed with UFC and culture. Diagnostic performance of leukocytes, bacteria, and BACT-info flags was evaluated by sensitivity, specificity, PPV, and negative predictive value (NPV). The association of contaminated culture and squamous epithelial cell count and BACT-info flag was performed by logistic regression analysis. RESULTS: The NPVs of parallel combination of bacteria and leucocytes were 98.9% in males and 97.9% in females, and PPVs of serial combination were 86.6% and 77.8% in men and women, respectively. The PPV of Gram-negative flag was higher than that of Gram-positive flag. The proportions of contamination in the urine culture results of false positive specimens were 86.9% in males and 98.5% in females at the cutoff points of the serial combination, and these parameters were 53.2% in males and 85.6% in females for the Gram-positive flag. There was a statistically significant association between contaminated cultures and squamous epithelial cells count in females, but not in males. Associations between contaminated cultures and Gram-positive flags or Gram-pos/-neg flags were statistically significant, but there was no association between contaminated cultures and Gram-negative flags. CONCLUSIONS: A serial combination of leukocytes and bacteria may maximize PPV in the diagnosis of bacterial urinary tract infection by urine flow cytometry, and contamination is the main reason for a low PPV.

Deep eutectic solvents combined with beta-cyclodextrin derivatives for chiral separation of typical adrenergic receptor agonists by capillary electrophoresis with amperometric detection.

Enantioseparation has always been one of the research hotspots and difficulties in the field of modern separation science. In this work, a binary chiral electrophoretic separation system was constructed using deep eutectic solvents (DESs) coupled with beta-cyclodextrin derivatives based on capillary electrophoresis with amperometric detection system, and five groups of typical adrenergic receptor agonists (adrenaline, salbutamol, isoproterenol, norepinephrine and terbutaline) were selected as the model enantiomers. The effects of additive types and contents of DESs and cyclodextrins, and the pH value and concentration of the running buffer on the resolution of the selected chiral compounds were investigated in detail. The mechanism of DESs improving separation was explored preliminarily by means of UV spectrophotometry, which was further verified based on the comparison of single and mixed components of choline chlorine-urea DES. Under the optimum conditions, the relative standard deviations for inter-day and intra-day repeatability of the migration time, peak area and resolution for adrenaline and salbutamol were within 8.7%, and the limits of detection reached 0.030 µg mL-1 (S/N = 3). The recovery data were in the range of 96.3-118.7%. The developed methods have been applied for the analyses of (+)-adrenaline hydrochloride injection and (±)-salbutamol aerosol. This binary chiral electrophoretic separation system by CE-AD has high detection sensitivity and low analytical cost, providing an alternative for the separation and analysis of chiral drugs.

Defining indicators for the scoping stage of health impact assessment to evaluate tobacco control policy in the city of Beijing.

INTRODUCTION: Beijing initiated the nation's most comprehensive tobacco control program that adheres to the WHO Framework Convention on Tobacco Control. This study aimed to identify a set of indicators for the scoping of an Health Impact Assessment (HIA) to assess this policy. METHODS: This study used a modified Delphi process. It proposed a tobacco control health impact framework based on the Driving forces- Pressure- State- Exposure- Effect- Action model and the Determinants of Health Theory. After a review of current surveillance system and literature, a working group of 13 experts with multidisciplinary background was established to formulate indicator evaluation criteria and conduct indicator scoring. Each indicator was scored by experts according to four evaluation criteria chosen. Indicators that obtained a total score above 80% and with standard error less than 5 were selected as the final set of indicators. Kendall's coefficient of concordance was calculated. RESULTS: Twenty-three out of 36 indicators were selected. Smoking prevalence, mortality rate, hospital admission rate, tobacco consumption and hospital admission fees of smoking related diseases achieved more than 90% of total scores and ranked as the top five. Kendall's concordance coefficient was 0.218 for all indicators. For all model composition, Kendall's concordance coefficients were statistically significant. CONCLUSION: This study identified a set of twenty-three indicators for scoping of HIA of a comprehensive tobacco control policy in Beijing based on a tobacco control health impact conceptual framework. The set of indicators achieved high scores and statistically significant consistency and has great potential to promote the evaluation of tobacco control policy in a global city. Further study might use the set of indicators for HIA on tobacco control policy to analyze empirical data.

The delayed clearance of Talaromyces marneffei in blood culture may be associated with higher MIC of voriconazole after antifungal therapy among AIDS patients with talaromycosis.

OBJECTIVES: This study aimed to investigate the influencing factors of delayed clearance of Talaromyces marneffei (T. marneffei) in blood culture of patients with acquired immune deficiency syndrome (AIDS) complicated with talaromycosis after antifungal therapy. METHODS: The patients with AIDS complicated with talaromycosis were retrospectively enrolled, and divided into two groups according to the blood T. marneffei culture results in two weeks after antifungal therapy. The baseline clinical data were collected and the antifungal susceptibility of T. marneffei was tested. RESULTS: A total of 190 patients with AIDS and talaromycosis were enrolled, of whom 101 cases remained positive for T. marneffei (Pos-group) while the other 89 cases were negative in blood culture (Neg-group) after two weeks' antifungal treatment. The Pos-group had a higher baseline Aspartate aminotransferase (AST, 78.5 vs. 105 U/L; P = 0.073) and lower CD4+ T cells level (11 vs. 7 cells/µl; P = 0.061). The percentage of isolates with higher MICs of voriconazole (VOR) and fluconazole (FLU) in the Pos-group were significantly higher than those in the Neg-group (χ2 = 12.623, P < 0.001 and χ2 = 9.356, P = 0.002, respectively). By multivariate logistic regression, the MIC value for VOR was identified as the prognostic variable that may influence the clearance of T. marneffei in blood culture after antifungal therapy among AIDS patients with talaromycosis. CONCLUSIONS: The delayed negative conversion of blood T. marneffei-culture may be associated with some factors especially higher MIC of VOR, indicating the possibility of drug resistance of T. marneffei.

Potential roles and molecular mechanisms of bioactive ingredients in Curcumae Rhizoma against breast cancer.

BACKGROUND: Breast cancer is the most prevalent cancer worldwide, with high morbidity and mortality. Despite great advances in the therapeutic strategies, the survival rate in the past decades of patients with breast cancer remains unsatisfactory. Growing evidence has demonstrated that Curcumae Rhizoma, called Ezhu in Chinese, showed various pharmacological properties, including anti-bacterial, anti-oxidant, anti-inflammatory and anti-tumor activities. It has been widely used in Chinese medicine to treat many types of human cancer. PURPOSE: To comprehensively summarize and analyze the effects of active substances in Curcumae Rhizoma on breast cancer malignant phenotypes and the underlying mechanisms, as well as discuss its medicinal value and future perspectives. METHOD: We used "Curcumae Rhizoma" or the name of crude extracts and bioactive components in Curcumae Rhizoma in combination with "breast cancer" as key words. Studies focusing on their anti-breast cancer activities and mechanisms of action were extracted from Pubmed, Web of Science and CNKI databases up to October 2022. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guideline was followed. RESULTS: Crude extracts and 7 main bioactive phytochemicals (curcumol, ß-elemene, furanodiene, furanodienone, germacrone, curdione and curcumin) isolated from Curcumae Rhizoma have shown many anti-breast cancer pharmacological properties, including inhibiting cell proliferation, migration, invasion and stemness, reversing chemoresistance, and inducing cell apoptosis, cycle arrest and ferroptosis. The mechanisms of action were involved in regulating MAPK, PI3K/AKT and NF-κB signaling pathways. In vivo and clinical studies demonstrated that these compounds exhibited high anti-tumor efficacy and safety against breast cancer. CONCLUSION: These findings provide strong evidence that Curcumae Rhizoma acts as a rich source of phytochemicals and has robust anti-breast cancer properties.

A Novel Derivative of Curcumol, HCL-23, Inhibits the Malignant Phenotype of Triple-Negative Breast Cancer and Induces Apoptosis and HO-1-Dependent Ferroptosis.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype of breast cancer. Curcumol, as a natural small molecule compound, has potential anti-breast cancer activity. In this study, we chemically synthesized a derivative of curcumol, named HCL-23, by structural modification and explored its effect on and underlying mechanism regarding TNBC progression. MTT and colony formation assays demonstrated that HCL-23 significantly inhibited TNBC cells proliferation. HCL-23 induced G2/M phase cell cycle arrest and repressed the capability of migration, invasion, and adhesion in MDA-MB-231 cells. RNA-seq results identified 990 differentially expressed genes including 366 upregulated and 624 downregulated genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that these differentially expressed genes were obviously enriched in adhesion, cell migration, apoptosis, and ferroptosis. Furthermore, HCL-23 induced apoptosis via the loss of mitochondrial membrane potential and the activation of the caspase family in TNBC cells. In addition, HCL-23 was verified to trigger ferroptosis through increasing cellular reactive oxygen species (ROS), labile iron pool (LIP), and lipid peroxidation levels. Mechanistically, HCL-23 markedly upregulated the expression of heme oxygenase 1 (HO-1), and the knockdown of HO-1 could attenuate ferroptosis induced by HCL-23. In animal experiments, we found that HCL-23 inhibited tumor growth and weight. Consistently, the upregulation of Cleaved Caspase-3, Cleaved PARP, and HO-1 expression was also observed in tumor tissues treated with HCL-23. In summary, the above results suggest that HCL-23 can promote cell death through activating caspases-mediated apoptosis and HO-1-dependent ferroptosis in TNBC. Therefore, our findings provide a new potential agent against TNBC.

Environmentally adaptive polysaccharide-based hydrogels and their applications in extreme conditions: A review.

Polysaccharide hydrogels are one of the most promising hydrogel materials due to their inherent characteristics, including biocompatibility, biodegradability, renewability, and easy modification, and their structure and functional designs have been widely researched to adapt to different application scenarios as well as to broaden their application fields. As typical wet-soft materials, the high water content and water-absorbing ability of polysaccharide-based hydrogels (PHs) are conducive to their wide biomedical applications, such as wound healing, tissue repair, and drug delivery. In addition, along with technological progress, PHs have shown potential application prospects in some high-tech fields, including human-computer interaction, intelligent driving, smart dressing, flexible sensors, etc. However, in practical applications, due to the poor ability of PHs to resist freezing below zero, dehydration at high temperature, and acid-base/swelling-induced deformation in a solution environment, they are prone to lose their wet-soft peculiarities, including structural integrity, injectability, flexibility, transparency, conductivity and other inherent characteristics, which greatly limit their high-tech applications. Hence, reducing their freezing point, enhancing their high-temperature dehydration resistance, and improving their extreme solution tolerance are powerful approaches to endow PHs with multienvironmental adaptability, broadening their application areas. This report systematically reviews the study advances of environmentally adaptive polysaccharide-based hydrogels (EAPHs), comprising anti-icing hydrogels, high temperature/dehydration resistant hydrogels, and acid/base/swelling deformation resistant hydrogels in recent years. First, the construction methods of EAPHs are presented, and the mechanisms and properties of freeze-resistant, high temperature/dehydration-resistant, and acid/base/swelling deformation-resistant adaptations are simply demonstrated. Meanwhile, the features of different strategies to prepare EAPHs as well as the strategies of simultaneously attaining multienvironmental adaptability are reviewed. Then, the applications of extreme EAPHs are summarized, and some meaningful works are well introduced. Finally, the issues and future outlooks of PH environment adaptation research are elucidated.

MicrobiotaProcess: A comprehensive R package for deep mining microbiome.

The data output from microbiome research is growing at an accelerating rate, yet mining the data quickly and efficiently remains difficult. There is still a lack of an effective data structure to represent and manage data, as well as flexible and composable analysis methods. In response to these two issues, we designed and developed the MicrobiotaProcess package. It provides a comprehensive data structure, MPSE, to better integrate the primary and intermediate data, which improves the integration and exploration of the downstream data. Around this data structure, the downstream analysis tasks are decomposed and a set of functions are designed under a tidy framework. These functions independently perform simple tasks and can be combined to perform complex tasks. This gives users the ability to explore data, conduct personalized analyses, and develop analysis workflows. Moreover, MicrobiotaProcess can interoperate with other packages in the R community, which further expands its analytical capabilities. This article demonstrates the MicrobiotaProcess for analyzing microbiome data as well as other ecological data through several examples. It connects upstream data, provides flexible downstream analysis components, and provides visualization methods to assist in presenting and interpreting results.

Zinc deficiency associated with cutaneous toxicities induced by epidermal growth factor receptor tyrosine kinase inhibitor therapy in patients with lung adenocarcinoma.

PURPOSE: Cutaneous toxicities are common adverse effects following epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Zinc deficiency causes diverse diseases, including skin toxicities. Therefore, this study aimed to investigate the role of zinc deficiency in patients with EGFR-TKI-induced skin toxicities. EXPERIMENTAL DESIGN: This retrospective study enrolled 269 patients with diverse skin disorders who visited our hospital between January 2016 and December 2017. The skin toxicity severities and plasma zinc levels of 101 EGFR-TKI-treated cancer patients were analysed and compared with those of 43 non-EGFR-TKI-treated cancer patients and 125 patients without cancer but presenting cutaneous manifestations. Additionally, the role of zinc in erlotinib-induced skin eruptions was established in a 14-day-murine model. Clinical features were further evaluated following systemic zinc supplementation in EGFR-TKI-treated cancer patients. RESULTS: EGFR-TKI-treated patients demonstrated severe cutaneous manifestations and a significant decrease in plasma zinc levels than those of the control groups. The serum zinc level and Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading of EGFR-TKI-induced skin toxicities showed a significant negative correlation (r = -0.29; p < 0.0001). Moreover, erlotinib treatment decreased the plasma zinc levels and induced periorificial dermatitis in rats confirming zinc deficiency following EGFR-TKI treatment. Zinc supplementation to the EGFR-TKI-treated cancer patients showed a significant decrease in the CTCEA grading (p < 0.0005 for mucositis and p < 0.0.0001 for all other cases) after 8 weeks. CONCLUSIONS: Skin impairment following EGFR-TKI therapy could be ameliorated through zinc supplementation. Thus, zinc supplementation should be considered for cancer patients undergoing EGFR-TKI therapy.

Comparing critical source areas for the sediment and nutrients of calibrated and uncalibrated models in a plateau watershed in southwest China.

Controlling non-point source pollution is often difficult and costly. Therefore, focusing on areas that contribute the most, so-called critical source areas (CSAs), can have economic and ecological benefits. CSAs are often determined using a modelling approach, yet it has proved difficult to calibrate the models in regions with limited data availability. Since identifying CSAs is based on the relative contributions of sub-basins to the total load, it has been suggested that uncalibrated models could be used to identify CSAs to overcome data scarcity issues. Here, we use the SWAT model to study the extent to which an uncalibrated model can be applied to determine CSAs. We classify and rank sub-basins to identify CSAs for sediment, total nitrogen (TN), and total phosphorus (TP) in the Fengyu River Watershed (China) with and without model calibration. The results show high similarity (81%-93%) between the identified sediment and TP CSA number and locations before and after calibration both on the yearly and seasonal scale. For TN alone, the results show moderate similarity on the yearly scale (73%). This may be because, in our study area, TN is determined more by groundwater flow after calibration than by surface water flow. We conclude that CSA identification with the uncalibrated model for TP is always good because its CSA number and locations changed least, and for sediment, it is generally satisfactory. The use of the uncalibrated model for TN is acceptable, as its CSA locations did not change after calibration; however, the TN CSA number changed by over 60% compared to the figures before calibration on both yearly and seasonal scales. Therefore, we advise using an uncalibrated model to identify CSAs for TN only if water yield composition changes are expected to be limited. This study shows that CSAs can be identified based on relative loading estimates with uncalibrated models in data-deficient regions.

Inhaled platelet vesicle-decoyed biomimetic nanoparticles attenuate inflammatory lung injury.

Acute lung injury (ALI) is an inflammatory response which causes serious damages to alveolar epithelia and vasculature, and it still remains high lethality and mortality with no effective treatment. Based on the inflammatory homing of platelets and cell membrane cloaking nanotechnology, in this study we developed a biomimetic anti-inflammation nanoparticle delivery system for ALI treatment. PM@Cur-RV NPs were designed by combining the poly (lactic-co-glycolic acid) nanoparticles (NPs) coated with platelet membrane vesicles (PM) for the purpose of highly targeting delivery of curcumin (Cur) and resveratrol (RV) to inflammatory lungs. PM@Cur-RV NPs showed good biocompatibility and biosafety both in vitro and in vivo. Accumulation of NPs into lung tract was observed after inhaled NPs. Remarkably, the inhalation of PM@Cur-RV NPs effectively inhibited lung vascular injury evidenced by the decreased lung vascular permeability, and the reduced proinflammatory cytokine burden in an ALI mouse model. The analysis of infiltrated macrophages in the lungs showed that the Cur-RV-modulated macrophage polarized towards M2 phenotype and the decreased histone lactylation might contribute to their anti-inflammation effects. Together, this work highlights the potential of inhalation of biomimetic nanoparticle delivery of curcumin and resveratrol for the treatment of pulmonary diseases.

The Incidence of Falls and Related Factors among Chinese Elderly Community Residents in Six Provinces.

This cross-sectional study classified the factors related to falls among residents ≥ 60 years old in China in order to provide evidence for the prevention of falls in the elderly. A total of 2994 participants were enrolled, and the correlations between social demography, physical health, self-health management awareness, family support, and fall risk were analyzed. Factors influencing falls were classified by location, cause, and the activity during falls. Suffering from osteoarthropathy (OR = 1.761, 95% CI: 1.234-2.513, p < 0.05), depression or anxiety (OR = 1.896, 95% CI: 1.331-2.700, p < 0.001), household size > 2 (OR = 1.806, 95% CI: 1.042-3.130, p < 0.05), and poor self-assessed health (OR = 1.478, 95% CI: 1.107-1.972, p < 0.01) were risk factors. Higher participation in community health programs (OR = 0.522, 95% CI: 0.298-0.912, p < 0.05) and spousal support (OR = 0.909, 95% CI: 0.841-0.981, p < 0.05) were protective factors. Falls were divided into the following categories: stairs/hallway (vision, attention problems), bath/toilet (vision, attention problems, slipping), indoor housework (dizziness, leg weakness), and outdoor activities (attention, surface problems). While acknowledging that the personal physical and mental health of the elderly may lead to falls, community support, accelerated transformation of housing, and the construction of barrier-free environments play an important role in reducing the risk of falls.

HIV-infected patients rarely develop invasive fungal diseases under good immune reconstitution after ART regardless high prevalence of pathogenic filamentous fungi carriage in nasopharynx/oropharynx.

Purpose: We aimed to investigate the prevalence and risk factors of filamentous fungi (FF) carriage in human immunodeficiency virus (HIV)-infected patients in Guangdong province, along with its subsequent incidence of invasive fungal disease (IFD). Methods: Seven hundred and sixteen HIV-infected individuals from the outpatient clinic and 293 sex-matched healthy controls were recruited prospectively from May 1 to August 31, 2017. Fungi were isolated from oropharyngeal and nasopharyngeal swabs, then identified by morphological and molecular biological techniques. Logistic regression analysis was used to identify risk factors of pathogenic FF carriage. Pathogenic FF carriers were followed up through the end of 2019. Results: Of the 716 included HIV-infected patients, 602 (84.1%) were male, the median age was 34 (27-42) years, and the median CD4+ count was 385 (254-542) cells/µl. Pathogenic FF were isolated in 119 (16.6%) cases with HIV infection and 40 (13.7%) healthy controls. Mucorales were found in 3 HIV-infected individuals and Talaromyces marneffei in 2 HIV-infected individuals, but not in healthy controls. History of cured opportunistic infections (OIs; OR, 1.97; 95% CI, 1.23-3.13, p = 0.004), and smoking (OR, 1.55; 95%CI, 1.03-2.32, p = 0.035) were independent risk factors of pathogenic FF carriage in HIV-infected individuals. A total of 119 pathogenic FF carriers with HIV infection were followed. During follow-up, 119 (100%) cases received antiretroviral therapy (ART) for at least 28 months, 107 (90%) cases had CD4+ counts>200 cells/µl, and none developed IFD. Discussion: Pathogenic FF carriage is common in HIV-infected individuals but may not develop IFD in those who achieved immune reconstitution. Smoking and cured OIs history increase the risk of pathogenic FF carriage. Smoking abstinence and ART adherence are especially important for these patients.