Ergone Derivatives from the Deep-Sea-Derived Fungus Aspergillus terreus YPGA10 and 25,28-Dihydroxyergone-Induced Apoptosis in Human Colon Cancer SW620 Cells.

Ten new ergone derivatives (1-10) and five known analogues (11-15) were isolated from the deep-sea-derived fungus Aspergillus terreus YPGA10. The structures including the absolute configurations were established by detailed analysis of the NMR spectroscopic data, HRESIMS, ECD calculation, and coupling constant calculation. All the structures are characterized by a highly conjugated 25-hydroxyergosta-4,6,8(14),22-tetraen-3-one nucleus. Structurally, compound 2 bearing a 15-carbonyl group and compounds 5-7 possessing a 15ß-OH/OCH3 group are rarely encountered in ergone derivatives. Bioassay results showed that compounds 1 and 11 demonstrated cytotoxic effects on human colon cancer SW620 cells with IC50 values of 8.4 and 3.1 µM, respectively. Notably, both compounds exhibited negligible cytotoxicity on the human normal lung epithelial cell BEAS-2B. Compound 11 was selected for preliminary mechanistic study and was found to inhibit cell proliferation and induce apoptosis in human colon cancer SW620 cells. In addition, compound 1 displayed cytotoxic activity against five human leukemia cell lines with IC50 values ranging from 5.7 to 8.9 µM. Our study demonstrated that compound 11 may serve as a potential candidate for the development of anticolorectal cancer agents.

AtERF13 and AtERF6 double knockout fine-tunes growth and the transcriptome to promote cadmium tolerance in Arabidopsis.

The toxic heavy metal cadmium (Cd) restricts plant growth. However, how plants fine-tune their growth to modulate Cd resistance has not been determined. Ethylene response factors (ERFs) are key regulators of Cd stress, and Arabidopsis thaliana ERF13 and ERF6 (AtERF13 and AtERF6) negatively regulate growth. We previously demonstrated that AtERF13 is a transcriptional activator that binds a Cd-responsive element. Herein, we report that Arabidopsis plants improve Cd tolerance by repressing AtERF13 and AtERF6. We found that AtERF13 and AtERF6 were strongly downregulated by Cd stress and that AtERF6 weakly bound Cd-responsive elements. Moreover, AtERF13 physically interacted with AtERF6. Importantly, AtERF13 and AtERF6 double knockout mutants, but not single mutants or overexpression lines, grew better, tolerated more Cd and had higher Cd contents than did the wild type. Comparative transcriptome analysis revealed that the double mutants regulate the defense response to cope with Cd toxicity. Accordingly, we propose that, upon Cd stress, Arabidopsis plants repress AtERF13 and AtERF6 to relieve their growth inhibition effects and adjust the transcriptome to adapt to Cd stress, leading to increased Cd tolerance. Our findings thereby provide deep mechanical insights into how dual-function transcription factors fine-tune growth and the transcriptome to promote Cd tolerance in plants.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

The UAF1-USP1 Deubiquitinase Complex Stabilizes cGAS and Facilitates Antiviral Responses.

Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) detects cytoplasmic microbial DNA and self-DNA from genomic instability, initiates innate immunity, and plays fundamental roles in defense against viruses and the development of various diseases. The cellular cGAS level determines the magnitude of the response to DNA. However, the underlying mechanisms of the control of cGAS stability, especially its feedback regulation during viral infection, remain largely unknown. In this study, we show that viral infection induces the expression of the UAF1-USP1 deubiquitinase complex in primary peritoneal macrophages (PMs) of C57BL/6J mice. UAF1-USP interacts with cGAS, selectively cleaves its K48-linked polyubiquitination, and thus stabilizes its protein expression in PMs and HEK293T cells. Concordantly, the UAF1-USP1 deubiquitinase complex enhances cGAS-dependent type I IFN responses in PMs. Uaf1 deficiency and ML323 (a specific inhibitor of UAF1-USP1 deubiquitinase complex) attenuates cGAS-triggered antiviral responses and facilitates viral replication both in vitro and in vivo. Thus, our study uncovers a positive feedback mechanism of cGAS-dependent antiviral responses and suggests the UAF1-USP1 complex as a potential target for the treatment of diseases caused by aberrant cGAS activation.

Gestational exposure to 1-NP induces ferroptosis in placental trophoblasts via CYP1B1/ERK signaling pathway leading to fetal growth restriction.

Fetal growth restriction (FGR) is a prevalent complication in obstetrics, yet its exact aetiology remains unknown. Numerous studies suggest that the degradation of the living environment is a significant risk factor for FGR. 1-Nitropyrene (1-NP) is a widespread environmental pollutant as a representative substance of nitro-polycyclic aromatic hydrocarbons. In this study, we revealed that 1-NP induced FGR in fetal mice by constructing 1-NP exposed pregnant mice models. Intriguingly, we found that placental trophoblasts of 1-NP exposed mice exhibited significant ferroptosis, which was similarly detected in placental trophoblasts from human FGR patients. In this regard, we established a 1-NP exposed cell model in vitro using two human trophoblast cell lines, HTR8/SVneo and JEG-3. We found that 1-NP not only impaired the proliferation, migration, invasion and angiogenesis of trophoblasts, but also induced severe cellular ferroptosis. Meanwhile, the ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively rescued 1-NP-induced trophoblast biological function impairment. Mechanistically, we revealed that 1-NP regulated ferroptosis by activating the ERK signaling pathway. Moreover, we innovatively revealed that CYP1B1 was essential for the activation of ERK signaling pathway induced by 1-NP. Overall, our study innovatively identified ferroptosis as a significant contributor to 1-NP induced trophoblastic functional impairment leading to FGR and clarified the specific mechanism by which 1-NP induced ferroptosis via the CYP1B1/ERK signaling pathway. Our study provided novel insights into the aetiology of FGR and revealed new mechanisms of reproductive toxicity of environmental pollutants.

Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures.

BACKGROUND & AIMS: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. METHODS: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. RESULTS: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). CONCLUSIONS: aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. IMPACT AND IMPLICATIONS: In this multicenter nationwide cohort study, we developed and externally validated two novel hepatocellular carcinoma (HCC) risk prediction models (called aMAP-2 and aMAP-2 Plus scores), using longitudinal discriminant analysis algorithm and longitudinal data (i.e., aMAP and alpha-fetoprotein) with or without the addition of cell-free DNA signatures, based on 13,728 patients from 61 centers across mainland China. Our findings demonstrated that the performance of aMAP-2 and aMAP-2 Plus scores was markedly better than the original aMAP score, and any other existing HCC risk scores across all subsets, especially for patients with cirrhosis. More importantly, the stepwise application of aMAP scores (aMAP -> aMAP-2 -> aMAP-2 Plus) provides an improved enrichment strategy, identifying patients at high risk of HCC, which could effectively guide individualized HCC surveillance.

Influence of RRM, RGG and Potential Phosphorylated Sites in Cold-Inducible Protein RBM3 on its Subcellular Localization and Neuroprotective Effects.

BACKGROUND: As a potent mediator of hypothermic neuroprotection, the cold-inducible protein RBM3 is characterized with one RNA-recognition motifs (RRM) and one arginine-glycine-rich (RGG) domain. It is known that these conserved domains are required for nuclear localization in some RNA-binding proteins. However, little is known about the actual role of RRM and RGG domains in subcellular localization of RBM3. METHODS: To clarify it, various mutants of human Rbm3 gene were constructed. Plasmids were transfected into cells and the localization of RBM3 protein and its varias mutants in cells and role in neuroprotection. RESULTS: In human neuroblastoma SH-SY5Y cells, either a truncation of RRM domain (aa 1-86) or RGG domain (aa 87-157) led to an obvious cytoplasmic distribution, compared to a predominant nuclear localization of whole RBM3 protein (aa 1-157). In contrast, mutants in several potential phosphorylated sites of RBM3, including Ser102, Tyr129, Ser147, and Tyr155, did not alter the nuclear localization of RBM3. Similarly, mutants in two Di-RGG motif sites also did not affect the subcellular distribution of RBM3. Lastly, the role of Di-RGG motif in RGG domains was further investigated. The mutant of double arginines in either Di-RGG motif-1 (Arg87/90) or -2 (Arg99/105) exhibited a higher cytoplasmic localization, indicating that both Di-RGG motifs are required for nucleic localization of RBM3. CONCLUSIONS: Our data suggest that RRM and RGG domains are both required for the nuclear localization of RBM3, with two Di-RGG domain being crucial for nucleocytoplasmic shuttling of RBM3.

Metal-responsive elements confer cadmium response in Arabidopsis.

MAIN CONCLUSION: Molecular, biochemical, and genetic experiments demonstrate that metal-responsive elements (MREs), initially identified in animals, confer the cadmium transcriptional response in Arabidopsis, thus providing deep functional insights of MREs in plants. Cadmium (Cd) is highly toxic to all organisms including plants. Cd-responsive gene transcription is a fundamental aspect of the Cd response, in which Cd stress regulatory cis-acting elements are essential. However, little is known regarding such elements in plants. Metal-responsive elements (MREs, 5'-TGCRCNC-3', R: A or G, N: any base) are essential for transcriptional induction of Cd in animals. MREs are also contained in the promoters of some Cd-regulated plant genes, but whether MREs confer Cd responses in plants is poorly defined. Herein, we used a previously identified MRE of the tobacco feedback-insensitive anthranilate synthase α-2 chain gene as a representative MRE (named as MREa, 5'-TGCACAC-3') to explore the roles of MREs in the transcriptional response to Cd stress in Arabidopsis thaliana. First, we showed that MREa conferred Cd stress responsiveness on a minimal promoter in both concentration- and time-dependent manners, whereas the mutated MREa did not. Second, MREa specifically bound nuclear extracts, displaying a biochemical characteristic of cis-acting elements. We screened and identified four MREa-binding transcription factors, including ethylene response factor 13 (AtERF13). At last, MREa could mediate AtERF13 to activate the ß-glucuronidase (GUS) reporter expression. Overall, these molecular, biochemical, and genetic data suggest that MREa is instrumental in the Cd response in Arabidopsis, thus providing deep functional insights of MREs in plants.

The development of a cSMART-based integrated model for hepatocellular carcinoma diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. METHODS: Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. RESULTS: An integrated diagnostic model called "Combined method" was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

Formaldehyde oxidation on Pd/USY catalysts at room temperature: The effect of acid pretreatment on supports.

The complete catalytic oxidation of formaldehyde (HCHO) to CO2 and H2O at room temperature is a green route for indoor HCHO removal. Zeolite is an excellent carrier material for HCHO oxidation due to its large surface area, intricate pores and high adsorption capacity. However, the zeolite-supported noble metal catalysts have currently shown relatively low activity especially at room temperature. In this work, we present a facile acid treatment strategy for zeolite catalysts to improve the hydroxyl concentration and further enhance their catalytic activity for HCHO oxidation. Activity tests illustrated that HCHO could be completely oxidized to CO2 and H2O at a nearly 100% conversion rate with a weight hourly space velocity (WHSV) of 150,000 mL/(g∙hr) at 25°C, when the support of Pd/USY catalysts was pretreated by hydrochloric acid with a concentration of 0.20 mol/L. The characterization results revealed that the active hydroxyl groups originated from the dealumination in the acid treatment play a key role in the HCHO oxidation reaction. The deduced reaction mechanism suggests that bridging hydroxyl groups may oxidize HCHO to dioxymethylene (DOM) species and terminal hydroxyl groups are responsible for the transformation of DOM groups to formate (HCOO) species.

Degradation mechanism of ammonia nitrogen synergistic with bromate under UV or UV/TiO2.

Bromate (BrO3-) and ammonia nitrogen (NH4+) are both typical environmental pollutants: BrO3- has been categorized as one of the Group 2B carcinogen by IARC; an excess of NH4+ might result in the eutrophication of water. The existence of NH4+ could inhibit the transformation of bromide (Br-) to bromate (BrO3-). However, the interaction of NH4+ and BrO3- during the removal process is not clear. This study intends to disclose the mutual relationships of ammonia nitrogen and bromate ions under UV irradiation or UV/TiO2 conditions. Without UV irradiation, BrO3- and NH4+ were both stable even under the presentation of each other. Under UV irradiation or UV/TiO2 conditions, BrO3- and NH4+ promoted the degradation of each other, showing the synergistic degradation mechanism. In the neutral environment, both of BrO3- and NH4+ could be transformed effectively. Furthermore, NH4+ accelerated the transformation of BrO3- to Br- at the reaction beginning and the existence of BrO3- is beneficial for the transformation of NH4+ to N2.

Effect of Salvia Miltiorrhiza Polyphenolic Acid Injection on Improving Limb Use and Cognitive Impairment in Patients with Acute Stroke.

Aims: To investigate the effect of injectable salvia polyphenolic acid on the improvement of limb movement and cognitive dysfunction in acute stroke patients. Materials and Methods: The clinical data of 90 acute stroke patients were collected for retrospective study and divided into 45 cases each in the comparison group and the observation group according to the different treatment methods; using basic treatment + salvianolic acid, the comparison group implemented conventional alteplase and butalbital treatment, and the observation group used injectable salvianolic acid treatment, to observe and compare the clinical efficacy, changes in neurological deficits, cognitive function, and motor function scores before and after treatment in the two groups. Results: The NIHSS (National Institute of Health stroke scale) score, cerebral infarct volume, NSE (neuron-specific enolase), and S100ß (A neurotrophic factor) levels were reduced after treatment compared with those before treatment in this group, and the NIHSS score, cerebral infarct volume, NSE, and S100ß levels in the observation group were lower than those in the comparison group after treatment, and the difference was statistically significant (P < 0.05). Compared with the clinical efficacy of the comparison group and the observation group, the treatment effect of the observation group was better than that of the comparison group, and the difference was statistically significant (P < 0.05). After treatment, the cognitive function and motor function scores of both groups were significantly improved compared with those before treatment, and the degree of improvement of each score in the observation group was significantly better than that in the comparison group (P < 0.05). During the trial, two patients in the comparison group developed a generalized rash and withdrew from the experiment, and the rash subsided after anti-allergic treatment, and no significant adverse events were observed in the remaining participants. There was no statistically significant difference in liver and kidney function and cardiac enzyme test indexes between the two groups of patients at 14 days of treatment (P > 0.05). Conclusion: Danshen polyphenolic acid for injection has definite clinical efficacy in the treatment of acute ischemic stroke, and it can effectively improve cognitive and motor functions and promote neurological recovery in patients with high safety.

Long-Term Prognostic Factors in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A 15-Year Multicenter Retrospective Study.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. Materials and Methods: A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. Results: In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Conclusion: Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

MiR-143-3p Increases the Radiosensitivity of Breast Cancer Cells Through FGF1.

Breast cancer is a common malignant tumor in women. At present, the main treatment for breast cancer is radiotherapy. Due to the difference in radiosensitivity between individuals or tumor cells, the effect of radiotherapy is not good. Therefore, in radiotherapy, how to use various auxiliary means to reduce the radiation resistance of tumor, Therefore, it has become an important research topic to improve the radiosensitivity of the tumor. Fibroblast growth factor-1 (FGF1) plays an important role in tumor migration. Therefore, the study of miR-143-3p increasing the radiosensitivity of breast cancer cells through FGF1 is proposed in this paper. In this study, a control group experiment was set up to study. During the experiment, the relative expression of miR-143-3p was detected by fluorescent quantitative PCR of miRNA, and the cell irradiation experiment was created to analyze the radiosensitivity of breast cancer cells by comparing their survival fraction. The results of this study showed that when the radiation dose was 0, the survival scores of the three groups were all 1. The survival fraction of the experimental group decreased from 0.26 ± 0.045 to 0.068 ± 0.008 when the dose was added to 4Gy. The survival fraction of the experimental group was always greater than that of the two control groups. The results of this study show that miR-143-3p can increase the radiosensitivity of breast cancer cells through FGF1.

A Multicancer Malignant Pleural Effusion Diagnostic Test Using Hexokinase 2 and Single-Cell Sequencing.

BACKGROUND: Malignant pleural effusion (MPE) represents advanced malignant disease with poor prognosis. To date, pleural effusion cytology remains the best test to diagnose MPE but suffers from limited diagnostic sensitivity and high variation. We report a hexokinase 2-based method (HK2-seq) as a novel diagnostic method for multicancer MPE diagnosis. METHODS: HK2-seq employed HK2 as a new metabolic function-associated marker to detect disseminated tumor cells engaging increased glycolysis in pleural effusion from many cancer types. Single-cell sequencing was used to confirm the malignancy of HK2-derived high glycolytic tumor cells (hgTCs) at the single-cell level via surveying genome-wide copy number alterations (CNAs), leading to establishment of definitive MPE diagnosis. RESULTS: In a prospective cohort study including 111 patients with pleural effusion, the HK2 test showed diagnostic sensitivity, diagnostic specificity, positive predictive value, and negative predictive value of 91% (95% CI: 80%-97%), 84% (95% CI: 68%-93%), 90% (95% CI: 79%-96%), and 86% (95% CI: 70%-95%), respectively, in MPE diagnosis across 12 different cancer types. In contrast, pleural effusion cytology exhibits an overall diagnostic sensitivity of 45%. In addition to confirming the tumor origin of hgTCs, single-cell sequencing allowed identification of prognostic or targetable CNAs in hgTCs, especially CNAs found in liquid biopsies but absent in solid biopsies. CONCLUSIONS: HK2-seq establishes definitive MPE diagnosis across many cancer types with high diagnostic performance. It has the potential to be used for multicancer detection of circulating tumor cells in blood and other types of body fluids, as well as liquid biopsy-based genomic characterization for informative diagnosis.

PM2.5-bound elements in Hebei Province, China: Pollution levels, source apportionment and health risks.

Particle-bound elements have attracted increasing attentions due to their health effects and atmospheric catalytic reactivity. However, elements in atmospheric fine particulate matter (PM2.5) have not been well investigated even in some highly polluted area. In this study, 22 elements in PM2.5 were measured by a multi-metal monitor in ten prefecture-level and county-level cities in Hebei province, one of the most polluted provinces in China, during the heating and non-heating seasons. Source apportionment of PM2.5-bound elements were conducted, and health risks of individual elements and different sources were assessed. The results showed that, total elements (TEs) measured contributed to 2%-7% of the PM2.5 mass, with potassium (K), calcium (Ca), iron (Fe), and zinc (Zn) as the most abundant elements, accounting for about 71%- 87% of TEs mass. Concentrations of chromium (Cr), arsenic (As), and cadmium (Cd) were more likely to exceed the World Health Organization (WHO) limits. Source apportionment results indicated that PM2.5-bound elements were primarily from coal combustion, dust, traffic, ferrous metal smelting and oil combustion, and other industrial related sources. Therein, ferrous metal smelting and oil combustion, coal combustion and industry were the predominant source of Cr, As and Cd, respectively. Health risk assessment indicated that the carcinogenic and non-carcinogenic risks of As for children could exceed the precautionary criteria, and coal combustion source had the highest carcinogenic and non-carcinogenic risks. This study suggested that attentions should be paid not only on PM2.5 mass but also PM2.5-bound compounds especially heavy metals and metalloids to reduce health risks in the future.

[Robot-assisted laparoscopic radical prostatectomy helps improve postoperative urinary continence recovery in patients with prostate cancer].

OBJECTIVE: To observe the recovery of urinary continence through postoperative rehabilitation training after robot-assisted laparoscopic radical prostatectomy (RARP) versus that after traditional laparoscopic radical prostatectomy (LRP). METHODS: This study included 64 cases of urinary incontinence after surgically treated for PCa from May 2017 to February 2021, 32 by RARP and the other 32 by LRP as the controls. All the patients received standard urinary continence rehabilitation training and routine nursing care postoperatively, followed by comparison of the rate and time of urinary incontinence recovery and the patients' scores on the quality of life (QOL) and satisfaction with treatment between the two groups. RESULTS: There were no statistically significant differences in age, PSA level or pathological stage between the two groups of patients (P > 0.05). After standard urinary continence rehabilitation training, the patients in the RARP group, compared with those in the LRP control, showed a lower grade of urinary incontinence (χ2 = 6.483, P = 0.039), a shorter mean duration of urinary incontinence per day, an earlier recovery of urinary continence (χ2 = 4.73, P = 0.030 at 1－3 months; χ2 = 12.696, P < 0.001 at 4－6 months), a higher rate of overall recovery (χ2 = 13.396, P = 0.004), and higher scores on QOL and satisfaction with treatment. CONCLUSION: RARP can effectively improve the recovery from postoperative urinary incontinence in PCa patients.

Real-time determination of flowering period for field wheat based on improved YOLOv5s model.

The flowering period is one of the important indexes of wheat breeding. The early or late flowering affects the final yield and character stability of wheat. In order to solve the problem that it is difficult to accurately and quickly detect the flowering period of a large number of wheat breeding materials, a determination method of flowering period for field wheat based on the improved You Only Look Once (YOLO) v5s model was proposed. Firstly, a feature fusion (FF) method combing RGB images and corresponding comprehensive color features was proposed to highlight more texture features and reduce the distortion caused by light on the extracted feature images. Second, the YOLOv5s model was selected as a base version of the improved model and the convolutional block attention model (CBAM) was adopted into the feature fusion layer of YOLOV5s model. Florets and spikelets were given greater weight along the channel and spatial dimensions to further refine their effective feature information. At the same time, an integrated Transformer small-target detection head (TSDH) was added to solve the high miss rate of small targets in wheat population images. The accurate and rapid detection of florets and spikelets was realized, and the flowering period was determined according to the proportion of florets and spikelets. The experimental results showed that the average computing time of the proposed method was 11.5ms, and the average recognition accuracy of florets and spikelets was 88.9% and 96.8%, respectively. The average difference between the estimated flowering rate and the actual flowering rate was within 5%, and the determination accuracy of the flowering period reached 100%, which met the basic requirements of the flowering period determination of wheat population in the field.

LncRNA CASC15 Promotes Cerebral Ischemia/Reperfusion Injury via miR-338-3p/ETS1 Axis in Acute Ischemic Stroke.

PURPOSE: Acute ischemic stroke (AIS) is a leading health problem caused by cerebral ischemia/reperfusion (CI/R). This study aimed to unveil the potential clinical value and mechanism of lncRNA CASC15. PATIENTS AND METHODS: The expression of CASC15, miR-338-3p was detected by quantitative real-time PCR (qRT-PCR). The correlations between CASC15 and national institutes of health stroke scale (NIHSS) scores or miR-338-3p were evaluated by Pearson correlation. A receiver operating characteristic (ROC) curve was performed to provide the diagnostic value of CASC15. Cell Counting Kit-8 (CCK-8) and flow cytometer were used to detect the condition of cell viability and apoptosis. The levels of interleukin-1beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA) assay. RESULTS: The expression of CASC15 was increased and the levels of miR-338-3p were decreased in AIS patients. A positive association between CASC15 and NIHSS score and an inverse association between CASC15 and miR-338-3p were revealed by Pearson correlation. CASC15 might discriminate AIS patients from healthy people. Silenced CASC15 exerted neuroprotective roles on cell viability, apoptosis, and inflammation via the miR-338-3p/ETS1 axis. CONCLUSION: CASC15 might act as a potential diagnostic biomarker for AIS patients. CASC15/miR-338-3p/ETS1 axis played an essential role in cell viability, apoptosis, and neuroinflammation.