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Abstract Diverse post-translational modifications have been shown to play important roles in regulating protein function in eukaryotes. By contrast, the roles of post-translational modifications in bacteria are not so well understood, particularly as they relate to pathogenesis. Here, we demonstrate post-translational protein modification by covalent addition of lactate to lysine residues (lactylation) in the human pathogen Staphylococcus aureus. Lactylation is dependent on lactate concentration and specifically affects alpha-toxin, in which a single lactylated lysine is required for full activity and virulence in infection models. Given that lactate levels typically increase during infection, our results suggest that the pathogen can use protein lactylation as a mechanism to increase toxin-mediated virulence during infection.

Abstract Background Neuromelanin is mostly located in dopaminergic neurons in the substantia nigra (SN) pars compacta, and can be detected by magnetic resonance imaging (MRI). It is a promising imaging-base biomarker for neurological diseases. We previously developed a melanin-specific probe N-(2-(diethylamino)-ethyl)-18F-5-fluoropicolinamide (18F-P3BZA), which was initially developed for the imaging of melanoma. 18F-P3BZA exhibited high levels of binding to the melanin in vitro and in vivo with high retention and favorable pharmacokinetics. In this study we further investigated whether 18F-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques. Results 18F-P3BZA exhibited desired hydrophobicity with estimated log Know 5.08 and log D7.4 1.68. 18F-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 ± 8 µL g-1s-1. 18F-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. Binding of 18F-P3BZA to B16F10 cells was much higher than to SKOV3 cells at 60 min (6.17 ± 0.53%IA and 0.24 ± 0.05%IA, respectively). In the biodistribution study, 18F-P3BZA had higher accumulation in B16F10 tumors (6.31 ± 0.99%IA/g) than in SKOV3 tumors (0.25 ± 0.09%IA/g). Meanwhile, 18F-P3BZA uptake in B16F10 tumors could be blocked by excess cold 19F-P3BZA (0.81 ± 0.02%IA/g, 88% inhibition, p

Abstract As a Brassica crop, Brassica napus typically has single flowers that contain four petals. The double-flower phenotype of rapeseed has been a desirable trait in China because of its potential commercial value in ornamental tourism. However, few double-flowered germplasms have been documented in B. napus, and knowledge of the underlying genes is limited. Here, B. napus D376 was characterized as a double-flowered strain that presented an average of 10.92 ± 1.40 petals and other normal floral organs. F1, F2 and BC1 populations were constructed by crossing D376 with a single-flowered line reciprocally. Genetic analysis revealed that the double-flower trait was a recessive trait controlled by multiple genes. To identify the key genes controlling the double-flower trait, bulk segregant analysis sequencing (BSA-seq) and RNA-seq analyses were conducted on F2 individual bulks with opposite extreme phenotypes. Through BSA-seq, one candidate interval was mapped at the region of chromosome C05: 14.56–16.17 Mb. GO and KEGG enrichment analyses revealed that the DEGs were significantly enriched in carbohydrate metabolic processes, notably starch and sucrose metabolism. Interestingly, five and thirty-six DEGs associated with floral development were significantly up- and down-regulated, respectively, in the double-flowered plants. A combined analysis of BSA-seq and RNA-seq data revealed that five genes were candidates associated with the double flower trait, and BnaC05.ERS2 was the most promising gene. These findings provide novel insights into the breeding of double-flowered varieties and lay a theoretical foundation for unveiling the molecular mechanisms of floral development in B. napus.

Abstract Background Triglyceride-glucose (TyG) index is linked to a poor prognosis for cardiovascular condition and is a valid indicator of insulin resistance. This study evaluated the potential predicting usefulness of the TyG index for all-cause mortality, both short- and long-term, for those concerning critical coronary artery disease (CAD). Methods In this study, information from 5452 critically-ill individuals with CAD in intensive care units were gathered from the Medical Information Marketplace in Intensive Care (MIMIC-IV) database. Depending on the TyG index degree, the patients were categorized into three categories. Clinical outcomes included short-term (30-day) and long-term (365-day) all-cause mortality. The corresponding relationships involving the TyG index and clinical outcomes were examined by deploying restricted cubic spline (RCS) regression analysis and Cox proportional risk regression. Results An increased TyG index was associated with increased 30-day (Tertile 1: 6.1%, Tertile 2: 7.3%, Tertile 3: 9.2%, P = 0.001) and 365-day (Tertile 1: 15.2%, Tertile 2: 17.0%, Tertile 3: 19.6%, P = 0.002) death rates across all causes. Cox regression with multiple variables indicates that higher TyG indices were linked to higher all-caused mortality hazard ratios throughout the short and long terms, with a larger predictive value for the former. RCS regression analyses suggested that the risk of death was notably and linearly that is associated with TyG index. Conclusions The TyG index is a reliable predictor of all-cause mortality at different stages in critically ill CAD patients, with a higher predictive ability for short-term mortality. Early intervention in patients with elevated TyG index may improve their survival outcomes. Future research should delve into understanding its pathophysiological mechanisms and develop intervention strategies based on the TyG index, providing new insights and strategies to enhance the outlook for critically ill CAD patients.

Background: Cardiovascular disease (CVD) remains a leading cause of mortality globally. Environmental pollutants, specifically volatile organic compounds (VOCs), have been identified as significant risk factors. This study aims to develop a machine learning (ML) model to predict CVD risk based on VOC exposure and demographic data using SHapley Additive exPlanations (SHAP) for interpretability. Methods: We utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018, comprising 5098 participants. VOC exposure was assessed through 15 urinary metabolite metrics. The dataset was split into a training set (70 %) and a test set (30 %). Six ML models were developed, including Random Forest (RF), Light Gradient Boosting Machine (LightGBM), Decision Tree (DT), Extreme Gradient Boosting (XGBoost), Multi-Layer Perceptron (MLP), and Support Vector Machines (SVM). Model performance was evaluated using the Area Under the Receiver Operating Characteristic Curve (AUROC), accuracy, balanced accuracy, F1 score, J-index, kappa, Matthew's correlation coefficient (MCC), positive predictive value (PPV), negative predictive value (NPV), sensitivity (sens), specificity (spec) and SHAP was applied to interpret the best-performing model. Results: The RF model exhibited the highest predictive performance with an ROC of 0.8143. SHAP analysis identified age and ATCA as the most significant predictors, with ATCA showing a protective effect against CVD, particularly in older adults and those with hypertension. The study found a significant interaction between ATCA levels and age, indicating that the protective effect of ATCA is more pronounced in older individuals due to increased oxidative stress and inflammatory responses associated with aging. E-values analysis suggested robustness to unmeasured confounders. Conclusions: This study is the first to utilize VOC exposure data to construct an ML model for predicting CVD risk. The findings highlight the potential of combining environmental exposure data with demographic information to enhance CVD risk prediction, supporting the development of personalized prevention and intervention strategies.

Abstract Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5’-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

BackgroundLewy body dementia (LBD) is a neurodegenerative disorder characterized by the accumulation of Lewy bodies, which primarily composed of misfolded alpha-synuclein (αS). The development of LBD and APOE4 subtypes is thought to be associated with disorders of lipid metabolism. In this study, we investigated the causal relationship between serum lipids, liposomes and LBD using a two-sample Mendelian randomization (TSMR) method.MethodsA TSMR analysis of genome-wide association study (GWAS) data for 8 serum lipids, 179 lipidomes components, LBD and its subtypes was performed, using inverse variance weighted as the primary outcome. To ensure robustness, the sensitivity analyses including MR Pleiotropy RESidual Sum and Outlier, Cochran’s test, leave-one-out method and funnel plots were performed.ResultsIn this study, we found that low-density lipoprotein cholesterol (LDL-C) (OR=1.45, 95% CI=1.19-1.77, P

PurposeFibroblast activation protein (FAP) is highly expressed in the mesenchyme of most malignant epithelial tumors, while its expression is low in normal tissues. FAP inhibitors (FAPIs) bind specifically to FAP and are used for tumor-targeted diagnosis and therapy. The aim of this study was to radiosynthesize a novel molecular probe 131I-FAPI and evaluate its in-vitro targeting and biological characteristics.MethodsThe structurally modified FAPI was labelled with 131I through the chloramine-T method. The radiolabeling rate was then detected by thin-layer chromatography (TLC). The stability of 131I-FAPI was determined at PBS (room temperature) and serum (37°C). Its hydrophilicity was calculated by measuring its lipid-water partition coefficient. Pancreatic cancer PANC-1 cell line and glioma U87 cell line were cultured in vitro. Cell uptake assay was used to show the binding ability of 131I-FAPI. The CCK-8 assay was used to calculate the inhibitory effects of 131I-FAPI at different time points (4h, 8h, 12h, 24h, 48h) after comparing with the 131I and FAPI. The before-and-after-24h scratch areas of the two cells were determined in order to verify the effect of 131I-FAPI on the migration ability of the cells.ResultsThe radiolabeling rate was (84.9 ± 1.02) %. The radiochemical purity of 131I-FAPI remained over 80% in both 25°C PBS and 37°C serum. The value of the lipid-water partition coefficient was -0.869 ± 0.025, indicating the hydrophilic of the probe. The cellular uptake assay showed that U87 cells had a specific binding capacity for 131I-FAPI. In cell inhibition assays, the inhibitory effect of 131I-FAPI on U87 cells increased with time. The results of cell scratch assay showed that 131I-FAPI had the strongest inhibitory effect on the migratory ability of U87 cells compared with 131I and FAPI (P

Abstract Funduscopic diseases, including diabetic retinopathy (DR) and age‐related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti‐vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next‐generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally.

Parkinson’s disease is a common neurodegenerative disorder. Here we present a human induced pluripotent stem cells (iPSCs) derived from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female patient diagnosed with sporadic Parkinson’s disease using the sendai virus. Generated iPSCs maintain normal karyotype, exhibit pluripotent stem cell markers, and possess differentiation potential. The iPSCs allows for differentiation into various cell subtypes, providing conditions for the research of the pathogenesis and drug development of Parkinson’s disease.

Background: Influenza vaccination is an important prevention strategy for flu illness. However, the vaccination rate is still low in Guangzhou, China. This study aimed to understand the status of knowledge, the attitude towards the vaccines’ reliability and safety, and other aspects associated with the willingness and practice of influenza vaccines in the pediatric and adult populations of Guangzhou city. Methods: This study was performed in eleven districts in Guangzhou between November 2020 and December 2020, including the Yuexiu, Liwan, Haizhu, Tianhe, Baiyun, Panyu, Huadu, Nansha, Huangpu, Zengcheng, and Conghua districts. The parents of children and teenagers under the age of eighteen in Guangzhou were surveyed using self-administered questionnaires in four domains: demographic information, the knowledge status and perception of influenza vaccination, the willingness and attitude towards influenza vaccination, and previous vaccine uptake. A multivariable logistic regression was employed to assess the possible determinants of willingness and practice to receive influenza vaccination, calculating the odds ratios (ORs) and 95% confidence interval (CI). A two-sided p-value < 0.05 was deemed statistically significant. Results: A total of 13,213 valid questionnaires were collected (validity rate 98.8%). Out of these participants, 42.62% (5631 participants) expressed a willingness to receive the influenza vaccine, while 55.40% (7320 participants) reported that their children and teenagers had been vaccinated against the flu. Furthermore, 40.44% of the respondents (5343 participants) or other family members had received the influenza vaccine. Logistic regression indicated that factors such as being female (OR = 1.395, 95% CI: 1.278–1.522), being involved in the work of COVID-19 prevention and control (1.551, 1.396–1.724), affirming the preventive effects of vaccination (2.474, 2.106–2.906), knowing about annual influenza vaccination (2.756, 2.540–2.992), and understanding prioritized influenza vaccination populations (1.464, 1.343–1.596) were all positively associated with vaccination willingness. Conversely, middle-aged persons (aged 40–49 years old) (0.726, 0.617–0.853), higher educational levels (undergraduate versus middle school) (0.858, 0.768–0.959), heightened concerns about vaccine safety (considering side effects are obvious versus considering it is safe and basically no side effects) (0.284, 0.188–0.429) and lower knowledge scores (0.813, 0.701–0.942) were adversely linked with vaccination willingness. Conclusion: These findings provide essential insights for altering the perception of influence and influenza vaccination, as well as enhancing health communication strategies to improve influenza vaccine uptake among Guangzhou residents.

Cotton fiber, the mainstay of the world’s textile industry, is formed by the differentiation of epidermal cells on the outer peridium of the ovule. The TBL gene family is involved in the regulation of epidermal hair development as well as response to abiotic stress. However, the function of TBL genes in cotton has not been systematically studied yet. Here, we identified 131 and 130 TBL genes in TM-1 (Gossypium hirsutum) and Hai7124 (Gossypium barbadense), respectively. Phylogenetic, gene structure, expression pattern and cis-element of promoter analysis were performed and compared. Single gene association analysis indicated that more TBL genes related to fiber quality traits were found in G. barbadense, whereas more genes associated with yield traits were found in G. hirsutum. One gene, GhTBL84 (GH_D04G0930), was induced by treatment at 4°C for 12 and 24 h in G. hirsutum and silencing of the GhTBL84 gene by VIGS technology in TM-1 can significantly improve the resistance of cotton seedlings to low temperature stress. In sum, our study conducted a genome-wide identification and comparative analysis of TBL family genes in G. hirsutum and G. barbadense and demonstrated a group of TBL genes significantly associated with fiber quality and excavated cold stress responsive gene, such as GhTBL84, providing a theoretical basis for further improving cotton agronomic traits.

BackgroundBlood counts and biochemical markers are among the most common tests performed in hospitals and most readily accepted by patients, and are widely regarded as reliable biomarkers in the literature. The aim of this study was to assess the causal relationship between blood counts, biochemical indicators and pulmonary arterial hypertension (PAH).MethodsA two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between blood counts and biochemical indicators with PAH. The genome-wide association study (GWAS) for blood counts and biochemical indicators were obtained from the UK Biobank (UKBB), while the GWAS for PAH were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the primary analysis method, supplemented by three sensitivity analyses to assess the robustness of the results. And we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 2003–2018 to verify the relationship.ResultsThe MR analysis primarily using the IVW method revealed genetic variants of platelet count (OR=2.51, 95% CI 1.56-4.22, P

Members of the Malvaceae family, including Corchorus spp., Gossypium spp., Bombax spp., and Ceiba spp., are important sources of natural fibers. In the past decade, the genomes of several Malvaceae species have been assembled; however, the evolutionary history of Malvaceae species and the differences in their fiber development remain to be clarified. Here, we report the genome assembly and annotation of two natural fiber plants from the Malvaceae, Bombax ceiba and Ceiba pentandra, whose assembled genome sizes are 783.56 Mb and 1575.47 Mb, respectively. Comparative analysis revealed that whole-genome duplication and Gypsy long terminal repeat retroelements have been the major causes of differences in chromosome number (2n = 14 to 2n = 96) and genome size (234 Mb to 2676 Mb) among Malvaceae species. We also used comparative genomic analyses to reconstruct the ancestral Malvaceae karyotype with 11 proto-chromosomes, providing new insights into the evolutionary trajectories of Malvaceae species. MYB-MIXTA-like 3 is relatively conserved among the Malvaceae and functions in fiber cell-fate determination in the epidermis. It appears to perform this function in any tissue where it is expressed, i.e. in fibers on the endocarp of B. ceiba and in ovule fibers of cotton. We identified a structural variation in a cellulose synthase gene and a higher copy number of cellulose synthase-like genes as possible causes of the finer, less spinnable, weaker fibers of B. ceiba. Our study provides two high-quality genomes of natural fiber plants and offers insights into the evolution of Malvaceae species and differences in their natural fiber formation and development through multi-omics analysis.

Objective To determine the optimal process conditions for efficiently extracting human prothrombin complex concentrates from human plasma. Methods Using human plasma as the materials and the yield of prothrombin complex concentrates as the evaluation standard, the preparation process parameters were studied and optimized through design of exporement(DOE), orthogonal experiments, and single factor experiments. Results The optimal process conditions were as follows: DEAE Sephadex A50 gel was selected, which balanced to pH 7.6, and then the amount of 1.7-2.5 g/L of plasma weight is added into the cryoprecipitate supernatant for adsorption for 40 minutes; Washing solution (0.15-0.175 mol/L sodium chloride) with 3 times the volume of gel was washed 3 times, and eluent (0.5-2.0 mol/L sodium chloride) was washed 3 to 5 times; Add stabilizer (heparin 35 IU, sodium chloride 0.1 mol/L) for ultrafiltration dialysis. Conclusion By using the optimized process mentioned above, the yield(measured by human coagulation factor IX)can reach 620 000 to 630 000 IU/ton of plasma, which is suitable for large-scale production.

Because of their tolerance to root rot and many abiotic stresses, rootstocks are generally required for commercial avocado production. However, cutting and air-layering, which are popular methods of vegetative propagation for producing large numbers of uniform and genetically identical plants, have been unsuccessful for years. To develop a practical and efficient rooting procedure for selected avocado clonal rootstocks, the present research investigated the effects of various factors on rooting cutting. Shoots were divided into three groups (air layering, direct cutting, and stem-buried etiolation) and treated with different combinations (plant growth regulators, PGRs; soaking time; and culture media), in which orthogonal or randomized-block designs were used. The rooting rate, average root length, average root number, average root dry weight, and rooting quality (Q value) were used as evaluation indicators. The results show that etiolation treatment of the mother shoot is the requisite condition for avocado shoot rooting. In addition, the rooting effect of etiolated cuttings was strongly impacted by PGR type, concentration, and soaking time, whereas no significant differences were detected among the culture media. Among these factors, the roots and the survival rates of etiolated cuttings of two hard-to-root varieties were optimal under the following conditions: indolebutyric acid concentration of 2500 mg/L, dipping duration for 5 s, and perlite:vermiculite culture at 1:1. The rooting rate of ‘Dusa’ was generally greater than that of ‘Duke 7’ and reached 82%.

ObjectiveTo investigate the diagnostic efficiency and prognostic value of 68Ga-Pentixafor PET/CT in comparison with adrenal vein sampling (AVS) for functional lateralization in primary aldosteronism (PA). Histology and long-term clinical follow-up normally serve as the gold standard for such diagnosis.MethodsWe prospectively recruited 26 patients diagnosed with PA. All patients underwent 68Ga-Pentixafor PET/CT and AVS. Postsurgical biochemical and clinical outcomes of patients with unilateral primary aldosteronism (UPA), as diagnosed by PET/CT or AVS, were assessed by applying standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Immunohistochemistry (IHC) was performed to detect the expression of aldosterone synthase (CYP11B2) and CXCR4.ResultsOn total, 19 patients were diagnosed with UPA; of these, 13 patients were lateralized by both PET/CT and AVS, four patients were lateralized by PET-only, and two by AVS-only. Seven subjects with no lateralization on AVS and PET received medical therapy. All patients achieved complete biochemical success except one with nodular hyperplasia lateralized by AVS alone. The consistency between PET/CT and AVS outcomes was 77% (20/26). Moreover, CYP11B2-positive nodules were all CXCR4-positive and showed positive findings on PET. Patients who achieved complete biochemical and clinical success had a higher uptake on PET as well as stronger expression levels of CXCR4 and CYP11B2.ConclusionOur analysis showed that 68Ga-Pentixafor PET/CT could enable non-invasive diagnosis in most patients with PA and identify additional cases of unilateral and surgically curable PA which could not be classified by AVS. 68Ga-Pentixafor PET/CT should be considered as a first-line test for the future classification of PA.

Commensal enterococci with pathogenic potential often facilitate the growth of diverse pathogens, thereby exacerbating infections. However, there are few effective therapeutic strategies to prevent and intervene in enterococci-mediated polymicrobial infections. Here, we find that enterococci at high density drive the expansion and pathogenicity of enteric Salmonella enterica serotype Typhimurium (S. Tm). Subsequently, we show that the driving role of enterococci in such infections is counteracted by dietary coumarin glycosides in vivo. Enterococci, which are tolerant of iron-deficient environments, produce β-glucosidases to hydrolyze coumarin glycosides into bioactive aglycones, inhibiting S. Tm growth and ameliorating the severity of S. Tm-induced symptoms by inducing iron limitation. Overall, we demonstrate that coumarin glycosides as a common diet effectively reverse enterococci-facilitated enteric infections, providing an alternative intervention to combat polymicrobial infections.

Background. Endothelial barrier disruption of human pulmonary vascular endothelial cells (HPVECs) is an important pathogenic factor for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Mesenchymal stem cells-exosome (MSCs-Exo) represents an ideal carrier for cell-free therapy. The therapeutic implication and underlying mechanism of human placental MSCs-Exo (HPMSCs-Exo) in ALI/ARDS need to be further explored. Materials and Methods. HPMSCs-Exo was extracted from HPMSCs and characterized. Then, the therapeutic effects of exosomes were evaluated in ALI mice and HPVECs. RNA-sequencing was applied to reveal the miRNA profile of HPMSCs-Exo and differentially expressed genes (DEGs) in HPMSCs-Exo-pretreated HPVECs. The targets of miRNAs were predicted by bioinformatics methods and correlated to DEGs. Finally, the role of hsa-miR-148a-3p/ROCK1 pathway in HPVECs has been further discussed. Results. The results showed that HPMSCs-Exo could downregulate Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), upregulate the expression of zonula occludens-1 (ZO-1) and F-actin, promote HPVECs migration and tube formation, reduce cytoskeletal disorders and cell permeability, and thus improve ALI/ARDS. RNA-sequencing revealed the DEGs were mainly enriched in cell junction, angiogenesis, inflammation, and energy metabolism. HPMSCs-Exo contains multiple miRNAs which are associated with cytoskeletal function; the expression abundance of hsa-miR-148a-3p is the highest. Bioinformatic analysis identified ROCK1 as a target of hsa-miR-148a-3p. The overexpression of hsa-miR-148a-3p in HPMSCs-Exo promoted the migration and tube formation of HPVECs and reduced ROCK1 expression. However, the overexpression of ROCK1 on HPVECs reduced the therapeutic effect of HPMSCs-Exo. Conclusions. HPMSCs-Exo represents a protective regimen against endothelial barrier disruption of HPVECs in ALI/ARDS, and the hsa-miR-148a-3p/ROCK1 pathway plays an important role in this therapeutics implication.

Abstract In conjunction with previous studies, we have noted that ferroptosis, as an emerging mode of regulated cell death (RCD), is intimately related to anthracycline pharmacotherapy. Not only does ferroptosis significantly modulate tumour resistance and drug toxicity, which are core links of the relevant chemotherapeutic process, but it also appears to play a conflicting role that has yet to be appreciated. By targeting the dual role of ferroptosis in anthracycline-based chemotherapy, this review aims to focus on the latest findings at this stage, identify the potential associations and provide novel perspectives for subsequent research directions and therapeutic strategies.

Abstract Sarcopenia is a syndrome characterized by progressive loss of skeletal muscle mass, strength and function, which is one of the most important clinical features of cancer malnutrition, representing a poor prognostic indicator in oncology. Sarcopenia is commonly assessed by measuring the skeletal muscle index (SMI) of the third lumbar spine (L3) using computed tomography (CT). The primary aim of this meta‐analysis was to study the association between low SMI and comprehensive clinicopathological characteristics as well as prognosis in patients with ovarian cancer. Data were searched in PubMed, EMBASE and Cochrane databases from inception to 10 June 2022. Studies evaluating the prognostic effect of SMI on ovarian cancer survival or chemotherapy‐related side effects were included. The risk of bias and study quality were assessed via the Newcastle–Ottawa Scale (NOS). The search strategy yielded 1286 hits in all three databases combined. Thirteen studies were included for qualitative and quantitative analysis, comprising 1814 patients. Our meta‐analysis revealed the significant association between low SMI and progression‐free survival (PFS) [P = 0.02; hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.06–1.85], as well as 5‐year overall survival (OS) [P = 0.02; odds ratio (OR): 1.35, 95% CI: 1.05–1.74]. Low SMI was also obviously associated with body mass index (BMI)

With the growing significance of green chemistry in organic synthesis, electrochemical oxidation has seen rapid development. Compounds undergo oxidation–reduction reactions through electron transfer at the electrode surface. This article proposes the use of electrochemical methods to achieve cleavage of the benzyl C–N bond. This method selectively oxidatively cleaves the C–N bond without the need for metal catalysts or external oxidants. Additionally, primary, secondary, and tertiary amines exhibit good adaptability under these conditions, utilizing water as the sole source of oxygen.

An iodophor-catalyzed direct disulfenylation of amino naphthalenes with aryl sulfonyl hydrazines in water was developed. A series of aryl sulfides were obtained in moderate to excellent yields. The advantages of this green protocol were the simple reaction conditions (metal-free, water as the solvent, under air), the odorless and easily available sulfur reagent, the broad substrate scope, and gram-scale synthesis. Moreover, the potential application of aryl sulfides was exemplified by further transformations.

Excessive nitrogen application is a common phenomenon in rice production in China, which will lead to a low nitrogen utilization rate and increase farmers’ production costs. In Jingzhou, Hubei Province, for two consecutive years (2021, 2022), rice was planted with nursery-box total fertilization (NBTF) technology to provide technical support for rice seedling box contact fertilization technology. The results showed that, compared with the conventional treatment, the seedling emergence rate decreased by 7.70–11.87%, but the seedling quality significantly improved and the plant height significantly increased by 4.38–6.06% in the full-heading stage after the aforementioned treatments. The leaf area index significantly increased by 16.75–34.55%, 10.04–19.30%, and 12.13–18.60% in the tiller, booting, and full-heading stages, respectively, whereas the photosynthetic rate significantly increased by 3.80–5.25% in the booting stage. The rice yield under the 50% CRU and 50% CRU + S treatments was the same as that under the FFP treatment. The rice yield under 50% CRU + BT and 50% CRU + BT + S treatments was 7.50–10.61% higher than that under the FFP treatment; nitrogen partial factor productivity increased by 96.15–123.63%. NBTF combined with Boxingtanzhuang (in Chinese) seedling trays showed an increase in yield, whereas normal seedling trays showed a stable yield. It is suggested that the seedling tray and fertilizer should be specialized in the rice seedling box, and the height of the seedling tray should be increased by 3–5 cm. At the same time, special controlled-release urea should be selected to ensure less N release before emergence and improve the seedling emergence rate so as to popularize NBTF technology in a large area.

The phenomenon of climate change has become a global challenge that affects human activities in many ways. Exploring the sustainability and innovativeness of digital education is an important reference for the further implementation of science and education strategies and positive effects on climate change mitigation. This study designed two questionnaires for basic and tertiary education to address variability in education and collected 523 samples for basic education and 412 samples for tertiary education respectively. Using digital teaching practices and digital teaching quality as mediators, structural equation modelling (SEM) was used to examine the impact of digital education on sustainability and innovation in education. Research shows that digital teaching and learning in basic and higher education can significantly contribute to the two-way development of educational sustainability and innovation, through digital teaching and learning practices. Digital teaching practice and digital teaching quality in higher education play a complete mediating role, while basic education only plays a partial mediating role. Higher education emphasizes digital teaching and learning practice processes and teaching quality, and most students hope that online teaching and learning can be further integrated with offline education to form a new model of education. This study will help government departments understand the pedagogical reality of digital education at a deeper level and provide ideas for the subsequent sustainable development and educational innovation of digital teaching. It can also provide new ideas for climate change mitigation and sustainable development.

Abstract Osteosarcoma (OS) is the most common primary solid malignant tumour of bone, with rapid progression and a very poor prognosis. Iron is an essential nutrient that makes it an important player in cellular activities due to its inherent ability to exchange electrons, and its metabolic abnormalities are associated with a variety of diseases. The body tightly regulates iron content at the systemic and cellular levels through various mechanisms to prevent iron deficiency and overload from damaging the body. OS cells regulate various mechanisms to increase the intracellular iron concentration to accelerate proliferation, and some studies have revealed the hidden link between iron metabolism and the occurrence and development of OS. This article briefly describes the process of normal iron metabolism, and focuses on the research progress of abnormal iron metabolism in OS from the systemic and cellular levels.

Abstract Backgroud With the reform of medical system in China, Beijing municipal hospitals explored a new pharmaceutical care model and set up medication therapy management services (MTMs) in ambulatory care since 2019. We were one of the first hospitals to set up this service in China. At the present, there were relatively few reports about the effect of MTMs in China. In this study, we summarized the implementation of MTMs in our hospital, explore the feasibility of pharmacist-led MTMs in ambulatory care and the impact of MTMs on patients’ medical costs. Methods A retrospective study was conducted in a university-affiliated, tertiary comprehensive hospital in Beijing, China. The patients who received at least one MTMs and with complete medical records and pharmaceutical documents from May 2019 to February 2020 were included. Pharmacists provided pharmaceutical care for patients according to the MTMs standards issued by the American Pharmacists Association, identified the numbers and classification of the patients’ perceived medication-related demands, identified medication-related problems (MRPs), and developed the medication-related action plans (MAPs). All MRPs found by pharmacists, pharmaceutical interventions, and resolving recommendations were documented, and calculate the cost of treatment drugs that patients can reduce. Results A total of 112 patients received MTMs in ambulatory care, among them 81 cases with the completed record were included in this study. 67.9% of patients had five or more diseases, 83% of them co-took over 5 drugs. While performing MTMs, 128 patients’ perceived medication-related demands were recorded in all, monitoring and judgment of adverse drug reaction (ADR) (17.19%) was the most common demand. 181 MRPs were found, with an average of 2.55 MPRs per patient. Nonadherence (38%), excessive drug treatment (20%), and adverse drug events (17.12%) were the top three MRPs. Pharmaceutical care (29.77%), adjustment of drug treatment plan (29.10%) and referral to the clinical department (23.41%) were the top three MAPs. Whereby the MTMs provided by pharmacists, the cost-saving of each patient was about $ 43.2 monthly. Conclusion By participating in the MTMs of outpatients, the pharmacists could identify more MRPs and develop personalized MAPs timely for patients, thereby promoting rational drug use and reducing medical expenses.

BackgroundArsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. ObjectiveTo investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. MethodsSeventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results(1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P

Abstract The distribution of Haptoglobin (HP) subtypes differs according to race and geography. It was also confirmed that the serum HP concentration was substantially affected by the HP subtypes. This study aimed to investigate the HP subtypes in northern Chinese and to establish reference intervals for the major HP subtypes using the BN II system. 1195 individuals were included in the study, grouped by haptoglobin subtype, and tested for concentrations by BN II System. Analysis of reference range was performed according to the EP28-A3c guideline. The need to establish reference ranges for subtype, gender, and age groupings was confirmed by the Z-test. The 2.5th and 97.5th percentiles were used as the upper and lower limits of the reference interval, respectively. In the population we investigated, the HP2-2 subtype had the highest proportion, accounting for 49.3%, followed by HP2-1 (38.0%), HP1-1 (7.2%). In addition, about 5.5% of individuals had HP del -related subtypes. The concentrations of the major subtypes (HP1-1, HP2-1, HP2-2) were significantly different, and it was necessary to establish reference ranges by grouping according to the results of the Z-test. The reference intervals were as follows: HP1-1, 0.37–2.19 g/L; HP2-1, 0.38–2.12 g/L; HP2-2, 0.12–1.51 g/L. Significant differences in HP concentrations between genders and ages were found, however, it was not necessary to establish separate reference interval since the results of the Z-test was negative. We have established reference ranges of serum haptoglobin concentrations based on subtypes, which are necessary for the clinical application of haptoglobin.

Abstract Background Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19) may have suppressed the transmission of other infectious diseases. This study aimed to evaluate the impact of different degrees of NPIs during the COVID-19 pandemic on hand, foot and mouth disease (HFMD) in Guangzhou, China. Methods Weekly reported HFMD cases and pathogens information during 2015–2021 in Guangzhou were collected from the China National Notifiable Disease Reporting System. The observed number of HFMD cases in 2020 and 2021 was compared to the average level in the same period during 2015–2019. Then, an interrupted time-series segmented regression analysis was applied to estimate the impact of NPIs on HFMD, such as social distancing, suspension of schools, community management and mask wearing. The effects across different subgroups stratified by gender, children groups and enterovirus subtype of HFMD were also examined. Results A total of 13,224 and 36,353 HFMD cases were reported in 2020 and 2021, which decreased by 80.80% and 15.06% respectively compared with the average number of cases in the same period during 2015–2019. A significant drop in the number of HFMD cases during time when strict NPIs were applied (relative change: 69.07% [95% confidence interval (CI): 68.84%–69.30%]). The HFMD incidence rebounded to historical levels in 2021 as the lockdown eased. The slightest reduction of HFMD cases was found among children at kindergartens or childcare centres among the three children groups (children at kindergartens or childcare centres: 55.50% [95% CI: 54.96%–56.03%]; children living at home: 72.64% [95% CI: 72.38%–72.89%]; others: 74.06% [95% CI: 73.19%–74.91%]). Conclusions The strong NPIs during the COVID-19 epidemic may have a significant beneficial effect on mitigating HFMD. However, the incidence of HFMD rebounded as the NPIs became less stringent. Authorities should consider applying these NPIs during HFMD outbreaks and strengthening personal hygiene in routine prevention.

Abstract Launching the intermolecular through‐space charge transfer (TSCT) from a bicomponent assembly for photophysical property manipulation is of great significance in fluorescence probe design. Here, we demonstrate the elaborate control of droplet evaporation dynamics for intermolecular TSCT can facilitate the ultrasensitive detection of JWH‐018, a representative synthetic cannabinoid. Driven by diverse intermolecular interactions, the probe, and JWH‐018 assemble in a closely stacked manner to emit strong fluorescence at 477 nm, ascribing to the intermolecular TSCT at the S2 state. The strategy realizes an ultra‐low limit of detection of 11 nmol/mL and great selectivity towards JWH‐018. The practicability is further verified by constructing a sensing chip for JWH‐018 aerosol detection, which facilitates the on‐site drug abuser screening with the naked eye. Moreover, the proposed assembly‐enabled TSCT is expected to find a variety of applications for optoelectronic materials design and photophysical mechanism‐dominated molecular recognition.

Objective To study the removal effect of fibronectin(Fn) from von willebrand factor(vWF) by ion-exchange chromatography through processing human coagulation factor Ⅷ chromatographic washing products, in order to select a method that can effectively reduce Fn without compromising the activity yield. Methods In a multi-batch process development experiment, Fractogel® EMD TMAE(M) strong anion filler produced by Merck(Germany) was used to conduct chromatography to investigate vWF ristomycins titer (vWF: RCof), vWF recovery, protein content and Fn content. Results During the development of vWF pilot purification process, the content of Fn in the samples can be effectively reduced by ion-exchange chromatography, with removal rate more than 87%, titer recovery of vWF more than 80%, and no significant change in other quality indexes. Conclusion The use of ion-exchange chromatography to purify vWF can effectively reduce the content of Fn, which has positive significance for developing new product process and improving the product quality of blood products manufacturers.

Abstract Successive failure propagating through a power system, typically caused by extreme weather such as storm and lightning, can cause blackouts by means of a variety of processes. To address this issue, this paper proposes preventive control for successive failures of power system to mitigate the consequences of successive failures in extreme weather. First, based on the Poisson process theory, the authors model the successive failure propagation, and present the confidence interval estimation for the time interval between successive failures. Then, a failure pre‐control methodology that quantifies the grid regulating ability and actions is developed to make decisions for system operators on mitigating overloads of transmission lines. Furthermore, a systematic pre‐control framework for successive failures is first proposed to detect latent risks, eliminate predictable consequential outages, and secure power system stability. Results from IEEE‐9 bus and IEEE‐39 bus standard systems as well as a real‐world system show the feasibility and effectiveness of the proposed method. The proposed preventive control framework can provide a systematic pre‐control action scheme for system operators, and realize enhancement of stability and resilience to power system failures.

Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic resistance. The current lack of antibiotic discovery and development urgently calls for new strategies to combat multidrug-resistant (MDR) bacteria, especially those that survive in host cells. Functional nanoparticles are promising intracellular drug delivery systems whose advantages include their high biocompatibility and tunable surface modifications. Inspired by the fact that the rigidity of nanoparticles potentiates their cellular uptake, rigidity-functionalized nanoparticles (RFNs) coated with bacteria-responsive phospholipids were fabricated to boost endocytosis, resulting in the increased accumulation of intracellular antibiotics. Precise delivery and high antibacterial efficacy were demonstrated by the clearing of 99% of MDR bacteria in 4 h using methicillin-resistant Staphylococcus aureus (MRSA) and pathogenic Bacillus cereus as models. In addition, the subcellular distribution of the RFNs was modulated by altering the phospholipid composition on the surface, thereby adjusting the electrostatic effects and reprograming the intracellular behavior of the RFNs by causing them to accurately target lysosomes. Finally, the RFNs showed high efficacy against MRSA-associated infections in animal models of wound healing and bacteremia. These findings provide a controllable rigidity-regulated delivery platform with responsive properties for precisely reprograming the accumulation of cytosolic antibiotics, shedding light on precision antimicrobial therapeutics against intracellular bacterial pathogens in the future.

油脂氧化是导致乳化食品变质的主要原因。油脂中的不饱和脂肪酸发生氧化，不仅会降低乳化食品的营养价值，还会产生不良风味、有害成分，进而影响乳化食品货架期和食用安全。相对于纯油体系，以乳化形式存在的油脂在高油-水界面比下极易发生氧化，缩短乳化食品的货架期。为明确乳化食品中油脂氧化分析以及其货架期评价方法，在介绍乳化食品中油脂氧化的基本过程的基础上，综述了乳化食品中油脂氧化分析方法（过氧化值、共轭二烯值、硫代巴比妥酸值、茴香胺值、挥发性物质含量）以及货架期的评价方法，为乳化食品中油脂氧化程度分析及其货架期预测提供参考。 Oil oxidation is the critical factor for the deterioration of emulsified foods. The oxidation of unsaturated fatty acids in oil not only reduces the nutritional value of emulsified foods, but also produce undesirable flavors and harmful components, and affect the shelf-life and safety. Moreover, compared with the pure oil system, the high oil-water interfacial ratio further makes the emulsified oil highly prone to oxidation, which greatly shortens the shelf-life. Therefore, in order to clarify the oil oxidation analysis and the shelf-life evaluation methods of emulsified foods, based on the introduction of the basic process of oil oxidation in emulsified foods， the analysis method of oil oxidation of emulsified foods (peroxide value, conjugated diene value, thiobarbituric acid value, p-anisidine value, volatile campound content) and the evaluation methods of shelf-life were reviewed. It may provide guidelines for the analysis of oxidation degree and the prediction of shelf-life of emulsified foods.

Purpose: Proximal femoral replacement (PFR) for oncology patients is gaining interest as a limb salvage operation due to its obvious advantages. However, almost all hip replacement surgeries including PFR, are faced with the challenge of how to reconstruct the functional musculature in an optimal way. To address the challenge, we have developed an innovative eggshell procedure and through this study we aim to investigate the specific efficacy of the procedure. Methods: A total of 44 tumor patients with PFR surgery were incorporated into the study, including 12 who underwent the eggshell procedure and 32 who did not. General characteristics, short-term indicators, long-term indicators and complication outcomes were compared successively between the two groups of patients. Results: No significant differences were identified in general characteristics between the two groups. Overall, in terms of both short-term and long-term indicators, the patients with eggshell procedure performed significantly superior to the patients without it. Moreover, the eggshell procedure significantly reduced the incidence of associated complications, including prosthesis dislocation and hip pain. Conclusions: Our eggshell procedure is convenient and accessible. On the one hand, it can reduce surgical side injuries without adding additional complications, and on the other it allows to improve joint mobility and life quality while diminishing the incidence of prosthesis dislocation and hip pain. Despite it may still remain limitations, we have reasons to believe that this procedure can be further promoted and applied.

Objectives: An outbreak of the SARS-CoV-2 Delta variant occurred in Guangzhou in 2021. This study aimed to identify the transmission dynamics and epidemiological characteristics of the Delta variant outbreak to formulate an effective prevention strategy. Methods: A total of 13102 close contacts and 69 index cases were collected. The incubation period, serial interval, and time interval from the exposure of close contacts to the symptom onset of cases were estimated. Transmission risks based on the exposure time and various characteristics were also assessed. Results: The mean time from exposure to symptom onset among non-household presymptomatic transmission was 3.83 ± 2.29 days, the incubation period was 5 days, and the serial interval was 3 days. The secondary attack rate was high within 4 days before onset and 4–10 days after symptom onset. Compared with other contact types, household contact had a higher transmission risk. The transmission risk increased with the number and frequency of contact with index cases. Cycle threshold (Ct) values were associated with lower transmission risk (adjusted odds ratio [OR] 0.93 [95% CI 0.88–0.99] for ORF 1ab gene; adjusted OR 0.91 [95% CI 0.86–0.97] for N gene). Conclusion: The contact tracing period may need to be extended to 4 days before symptom onset. The low Ct value of index cases, the high number and frequency of contact with index cases, and household contacts were associated with a higher transmission risk of SARS-CoV-2 Delta.

Purpose: Fibroblast activation protein (FAP) is highly expressed in the mesenchyme of most malignant epithelial tumors, while its expression is low in normal tissues. FAP inhibitors (FAPIs) bind specifically to FAP and are used for tumor-targeted diagnosis and therapy. The aim of this study was to radiosynthesize a novel molecular probe 131I-FAPI and evaluate its in-vitro targeting and biological characteristics. Methods: The structurally modified FAPI was labelled with 131I through the chloramine-T method. The radiolabeling rate was then detected by thin-layer chromatography (TLC). The stability of 131I-FAPI was determined at PBS (room temperature) and serum (37°C). Its hydrophilicity was calculated by measuring its lipid-water partition coefficient. Pancreatic cancer PANC-1 cell line and glioma U87 cell line were cultured in vitro. Cell uptake assay was used to show the binding ability of 131I-FAPI. The CCK-8 assay was used to calculate the inhibitory effects of 131I-FAPI at different time points (4h, 8h, 12h, 24h, 48h) after comparing with the 131I and FAPI. The before-and-after-24h scratch areas of the two cells were determined in order to verify the effect of 131I-FAPI on the migration ability of the cells. Results: The radiolabeling rate was (84.9 ± 1.02) %. The radiochemical purity of 131I-FAPI remained over 80% in both 25°C PBS and 37°C serum. The value of the lipid-water partition coefficient was -0.869 ± 0.025, indicating the hydrophilic of the probe. The cellular uptake assay showed that U87 cells had a specific binding capacity for 131I-FAPI. In cell inhibition assays, the inhibitory effect of 131I-FAPI on U87 cells increased with time. The results of cell scratch assay showed that 131IFAPI had the strongest inhibitory effect on the migratory ability of U87 cells compared with 131I and FAPI (P<0.001). Conclusion: 131I-FAPI was synthesized with good in-vitro stability and hydrophilic properties. It can be specifically bound by U87 cells. The proliferation and migration of U87 cells can be effectively inhibited. 131I-FAPI is promising to become a therapeutic probe. [ABSTRACT FROM AUTHOR]

MADS-box genes play a crucial role in fruit ripening, yet limited research has been conducted on mango. Based on the conserved domains of this gene family, 84 MADS-box genes were identified in the mango genome, including 22 type I and 62 type II MADS-box genes. Gene duplication analysis revealed that both tandem duplication and segmental replication significantly contributed to the expansion of MADS-box genes in the mango genome, with purifying selection playing a vital role in the segmental duplication events within the MiMADS gene family. Cis-acting element analysis demonstrated that most MiMADS genes were hormonally regulated and participated in the growth, development, and stress resistance of mango fruit. Moreover, through expression pattern analysis and phylogenetic tree construction, we identified six MiMADS genes belonging to the SEP1 subfamily and two belonging to the AG subfamily as potential candidates involved in mango ripening regulation. Notably, Mi08g17750 and Mi04g18430 from the SEP1 subfamily were identified as key regulators inhibiting mango fruit maturation; their interaction network was also analyzed. These findings provide a foundation for further investigation into the regulatory mechanisms underlying mango ripening.

Abstract Osteosarcoma (OS) is the most common bone-derived tumor, and chemoresistance is a pivotal factor in the poor prognosis of patients with OS. Ferroptosis, as an emerging modality of regulated cell death, has demonstrated potential value in tumor chemoresistance studies. Through the gene expression omnibus database in conjunction with the FerrDb database, we identified novel ferroptosis-related differentially expressed genes (DEGs) involving chemoresistance in OS patients. Subsequently, enrichment analysis, protein–protein interaction network analysis and survival analysis were performed sequentially to recognize the hub genes and ultimately to construct a predictive model. The model constructed from the TARGET database was exhibited in a nomogram and assessed by calibration curves. The prognostic value of the model and hub genes was validated separately by an independent cohort. Twenty-two ferroptosis-related DEGs were identified, including 16 up-regulated and 6 down-regulated. Among them, expressions of CBS, COCS1, EGFR, as hub genes, were significantly associated with the prognosis of OS patients and were evidenced as independent prognostic factors. An efficient prognostic model covering hub gene expressions and clinical variables was developed and validated. Combining the results of hub genes in differential analysis, the actions of hub genes in ferroptosis, and the prognostic relevance of hub genes in patients, we revealed that CBS, SOCS1 and EGFR might play essential roles in OS and its chemoresistance with potential research and clinical value.

IntroductionFlavonoids are important secondary metabolites in plants and light is a crucial environmental factor regulating flavonoids biosynthesis. However, effect of light on the different flavonoids compositions accumulation in mango and the relevant molecular mechanism still need to be clarified.MethodsIn this study, green-mature fruits of red mango cultivar ‘Zill’ were subjected to postharvest light treatment, and fruit peel color, total soluble solids content, total organic acid, and firmness of flesh were measured. The flavonoids metabolites profile, and the expression of flavonoids-related genes and light signal pathway genes were also analyzed.ResultsResults showed that light treatment promoted the red coloration of fruit peel and increased the total soluble solids content and firmness of flesh. The concentration of flavonols, proanthocyanidins and anthocyanins, and expression of key flavonoids biosynthetic genes including MiF3H, MiFLS, MiLAR, MiANS, MiUFGT1, and MiUFGT3 were significantly induced by light. The MYBs regulating flavonols and proanthocyanidins, i.e. MiMYB22 and MiMYB12, as well as the key light signal pathway transcription factors (TFs) MiHY5 and MiHYH, were identified in mango. The transcription of MiMYB1, MiMYB12, MiMYB22, MiHY5 and MiHYH was up-regulated by light.DiscussionOur results provide a postharvest technology to improve mango fruit appearance quality, and are helpful to reveal the molecular mechanism of light-induced flavonoids biosynthesis in mango.

Abstract Nanomaterials are promising carriers to improve the bioavailability and therapeutic efficiency of drugs by providing preferential drug accumulation at their sites of action, but their delivery efficacy is severely limited by a series of biological barriers, especially the mononuclear phagocytic system (MPS)—the first and major barrier encountered by systemically administered nanomaterials. Herein, the current strategies for evading the MPS clearance of nanomaterials are summarized. First, engineering nanomaterials methods including surface modification, cell hitchhiking, and physiological environment modulation to reduce the MPS clearance are explored. Second, MPS disabling methods including MPS blockade, suppression of macrophage phagocytosis, and macrophages depletion are examined. Last, challenges and opportunities in this field are further discussed.

ObjectivesThe study aimed to identify leisure activity patterns among older adults and explore the differences in the prevalence of mild cognitive impairment (MCI) of these patterns.MethodsA total of 352 older adults aged ≥ 65 years in Shijiazhuang were enrolled in this study from June to September 2021. Their leisure activities and cognition were evaluated. Latent class analysis and logistic regression models were used for analysis. The manuscript was organized according to the STROBE guidelines.ResultsWe identified three latent classes of leisure activities: multidomain activities (MDA) class (55%), self-improvement activities (SIA) class (21%), and family-centered activities (FCA) class (24%). Three latent classes significantly differed in general characteristics (gender, education, and body mass index) and the prevalence of MCI. The prevalence of MCI was 3.694 times higher in older adults in the FCA class than in older adults in the MDA class (OR = 3.694, P < 0.001) and 2.573 times higher in older adults in the SIA class (OR = 2.573, P = 0.036).ConclusionPatterns of low participation in intellectual activities were associated with MCI. Identifying the heterogeneity in leisure activity engagement in later life was critical for tailoring interventions and designing programs that can improve the cognitive function of older adults.

A major challenge to the treatment of advanced prostate cancer (PCa) is the development of resistance to androgen-deprivation therapy (ADT) and chemotherapy. It is imperative to discover effective therapies to overcome drug resistance and improve clinical outcomes. We have developed a novel class of silicon-containing compounds and evaluated the anticancer activities and mechanism of action using cellular and animal models of drug-resistant PCa. Five organosilicon compounds were evaluated for their anticancer activities in the NCI-60 panel and established drug-resistant PCa cell lines. GH1504 exhibited potent in vitro cytotoxicity in a broad spectrum of human cancer cells, including PCa cells refractory to ADT and chemotherapy. Molecular studies identified several potential targets of GH1504, most notably androgen receptor (AR), AR variant 7 (AR-v7) and survivin. Mechanistically, GH1504 may promote the protein turnover of AR, AR-v7 and survivin, thereby inducing apoptosis in ADT-resistant and chemoresistant PCa cells. Animal studies demonstrated that GH1504 effectively inhibited the in vivo growth of ADT-resistant CWR22Rv1 and chemoresistant C4-2B-TaxR xenografts in subcutaneous and intraosseous models. These preclinical results indicated that GH1504 is a promising lead that can be further developed as a novel therapy for drug-resistant PCa.

As the outbreak of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory disease coronavirus 2 (SARS-COV-2), fast, accurate, and economic detection of viral infection has become crucial for stopping the spread. Polymerase chain reaction (PCR) of viral nucleic acids has been the gold standard method for SARS-COV-2 detection, which, however, generally requires sophisticated facilities and laboratory space, and is time consuming. This review presents recent advances in PCR-free nucleic acid detection methods for SARS-CoV-2, including emerging methods of isothermal amplification, nucleic acid enzymes, electrochemistry and CRISPR.

Objective: To assess the cost effectiveness of radium-223 dichloride for patients with metastatic castration-resistant prostate cancer (mCRPC) in China.Materials and methods: A Markov model was developed to estimate the long-term health and economic outcomes of radium-223 plus best standard care (BSC) treatment and BSC only for bone mCRPC patients over a lifetime horizon. The patients and interventions were modeled according to the ALSYMPCA trial. Costs were collected from a Chinese health system perspective. Utility values were derived from the published literature. The base-case model results were quality-adjusted life year (QALY), total cost, and incremental cost-utility ratio (ICUR). Uncertainty analyses were performed to assess the robustness of our conclusions.Results: Compared with the BSC arm, radium-223 achieved an excess 0.344 QALYs with an incremental cost of $29,459, resulting in an ICUR of $85,647 per QALY. The probability of Ra-223 being cost effective for the patients with bone mCRPC was sharply low (

ObjectivesIt is known that high altitude influences the growth metrics of high-altitude residents. Using a WHO-recommended standard, the research aimed to establish growth and development reference values for children of Tibetan ethnicity between the ages of 6 and 17 years old.MethodsThe measurements took place in Jomda County, Tibet with an average altitude of 3,650 m above sea level. A total of 3,955 observations (1,932 boys and 2,023 girls) were utilized to model the centile estimations. Included in the measurements are height, weight, body mass index, heart rate, blood pressure, forced lung capacity, sit and reach, and standing long jump. The measurements were modeled using the generalized additive models for location, scale, and shape (GAMLSS). Models were fitted with suitable distributions and locally smoothed using the P-spline for each GAMLSS hyper-parameter. Using the smallest Schwarz Bayesian criterion, the optimal model for each measurement was selected. After model adjustment, centile estimations were calculated for each model.ResultsCompared to the height reference values at the 50th percentile for multi-ethnic Chinese children residing at low altitudes, Tibetan ethnic children exhibit apparent stunted growth. In terms of forced vital capacity, it is remarkable that Tibetan ethnic children lag behind multi-ethnic Chinese children residing at low altitudes. Heart rate and blood pressure regulation are generally normal. Centile estimations are provided in this article and tabulated centiles (1p, 3p, 5p, 15p, 25p, 50p, 75p, 85p, 95p, 97p, 99p) in Chinese, Tibetic, and English are openly available in FigShare (doi: 10.6084/m9.figshare.20898196.v1).ConclusionThis study established the first GAMLSS based growth and development reference values for Tibetan ethnic children aged 6–17. These reference values have numerous clinical and scientific applications. We offer Chinese policymakers with practical initiatives to further enhance the health of Tibetan ethnic children.