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Xia Wei,1,2,* Zhengquan Ma,2,* Nan Yu,3 Jingting Ren,2 Chenwang Jin,1 Jiuyun Mi,2 Meijuan Shi,1 Libin Tian,2 Yanzhong Gao,4 Youmin Guo1 1Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Respiratory Medicine, The Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 3Department of Radiology, The Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Shaanxi, 4Department of Radiology, The Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China *These authors contributed equally to this work Purpose: COPD is a heterogeneous disease, and the available prognostic indexes are therefore limited. This study aimed to identify the factors associated with acute exacerbation leading to hospitalization.Patients and methods: This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria) hospitalized at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016. During follow-up after first hospitalization, the patients who had been rehospitalized within 1 year for acute exacerbation were grouped into the frequent exacerbation (FE) group, while the others were grouped into the infrequent exacerbation (IE) group. The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the two groups.Results: Compared with the IE group, the FE group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25–75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04). According to generations of bronchi, the percentage of the wall area (%WA) of lobes was found to be higher in the FE group. Emphysema index (EI), mean emphysema density (MED)whole and MEDleft lung in the FE group were significantly worse than in the IE group (P10% (OR 2.9, 95% CI 1.2–7.1, P=0.02) were independently associated with frequent acute exacerbation of COPD (AECOPD) hospitalization.Conclusion: Exacerbation hospitalizations in the past year and imaging features of emphysema (EI) were independently associated with FE hospitalization. Keywords: acute exacerbation, COPD, pulmonary function test, frequent hospitalization, respiratory function tests, computed tomography

Background and Objectives: US children experience lead poisoning, which has detrimental health effects and significant individual and societal costs. This study aimed to describe the sociodemographic and hospitalization characteristics of children hospitalized for lead poisoning and assess the proportion of inpatients who received blood lead testing and appropriate follow-up testing before hospitalization., Methods: 2015-2021 hospital discharge data were linked to lead surveillance data for Pennsylvania children aged 0 to 5 years. Demographics, hospitalization characteristics, and lead testing data from children with a primary diagnosis code of lead poisoning were used. The number of hospitalizations, associated hospital length of stay and charges, and the proportion of inpatients who received lead testing and follow-up testing after identification of high blood lead levels before hospitalization were analyzed by selected characteristics., Results: During the study period, there were 93 children hospitalized for lead poisoning, incurring 443 inpatient days and approximately 6 million dollars in inpatient charges. Of these inpatients, 69.9% were males, 36.6% were non-Hispanic Black, 67.7% were aged 0 to 2 years, 14% had repeated admissions, and 88.2% of admissions were paid by Medicaid. In addition, 20.4% did not have lead testing, and 34.4% had appropriate follow-up testing before hospitalization. Non-Hispanic whites and children with developmental, behavioral, and emotional disorders had relatively low proportions of having appropriate follow-up testing., Conclusions: Severe childhood lead poisoning is a significant health and economic burden, especially among children with Medicaid. Further improvements in blood lead testing and follow-up testing can help prevent childhood lead poisoning., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Rationale: Neuroendocrine tumors (NET) refer to a group of uncommon tumors arising in the neuroendocrine system. Most NETs occur in the digestive tract and bronchi but are rare in the central nervous system, especially in the spinal canal. NET in the central nervous system mainly metastasize from other systems, with non-specific clinical symptoms. In this study, we report the diagnosis and treatment of intraspinal NET to provide clinical guidance as well as to avoid misdiagnosis and missed diagnosis., Patient Concerns: A 59-year-old male patient, presented with recurrent right lower limb pain for half a year, accompanied by numbness and weakness for 4 months and aggravation for 2 months. Lumbar spine magnetic resonance imaging (MRI) revealed a space-occupying lesion in the spinal canal. The diagnosis of primary intraspinal NET was confirmed by topathological examination., Diagnosis: Primary intraspinal NET tumor., Interventions: Surgical resection., Outcomes: Significant improvements in right lower limb pain, numbness, and weakness were observed, and lumbar spine MRI was performed again to dynamically observe the changes in intraspinal NET., Conclusions: Surgical resection may be an effective treatment for intraspinal NETs., Lessons: Intraspinal NETs are relatively rare and mostly manifest as limb numbness, weakness, and pain. Due to its nonspecific clinical symptoms, intraspinal NETs are easily misdiagnosed as lumbar disc herniation with radiculopathy and lumbar spondylolisthesis. Therefore, in patients with long-term symptoms, in addition to common lumbar neuromuscular diseases, lumbar MRI should be performed promptly to exclude the possibility of lumbar NETs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Nanoplastics (NPs) are emerging pollutants that pose risks to living organisms. Recent findings have unveiled the reproductive harm caused by polystyrene nanoparticles (PS-NPs) in female animals, yet the intricate mechanism remains incompletely understood. Under this research, we investigated whether sustained exposure to PS-NPs at certain concentrations in vivo can enter oocytes through the zona pellucida or through other routes that affect female reproduction., Results: We show that PS-NPs disrupted ovarian functions and decreased oocyte quality, which may be a contributing factor to lower female fertility in mice. RNA sequencing of mouse ovaries illustrated that the PI3K-AKT signaling pathway emerged as the predominant environmental information processing pathway responding to PS-NPs. Western blotting results of ovaries in vivo and cells in vitro showed that PS-NPs deactivated PI3K-AKT signaling pathway by down-regulating the expression of PI3K and reducing AKT phosphorylation at the protein level, PI3K-AKT signaling pathway which was accompanied by the activation of autophagy and apoptosis and the disruption of steroidogenesis in granulosa cells. Since PS-NPs penetrate granulosa cells but not oocytes, we examined whether PS-NPs indirectly affect oocyte quality through granulosa cells using a granulosa cell-oocyte coculture system. Preincubation of granulosa cells with PS-NPs causes granulosa cell dysfunction, resulting in a decrease in the quality of the cocultured oocytes that can be reversed by the addition of 17β-estradiol., Conclusions: This study provides findings on how PS-NPs impact ovarian function and include transcriptome sequencing analysis of ovarian tissue. The study demonstrates that PS-NPs impair oocyte quality by altering the functioning of ovarian granulosa cells. Therefore, it is necessary to focus on the research on the effects of PS-NPs on female reproduction and the related methods that may mitigate their toxicity., (© 2024. The Author(s).)

Background: Caries is the most common chronic disease among children. In Pennsylvania, a comprehensive oral health Basic Screening Survey and assessment of the association between caries and community water fluoridation (CWF) among children have not been conducted., Methods: From 2021 through 2022, the first Basic Screening Survey was conducted among third-grade students in Pennsylvania. Oral health and demographic data were collected. CWF data were provided by the Pennsylvania Department of Environmental Protection. The relative risk of developing caries in association with CWF was assessed using the GENMOD procedure in SAS, Version 9.4 (SAS Institute) in this cross-sectional study., Results: Caries prevalence was 59.7% among 4,120 screened students. Participation in the free or reduced lunch program and CWF were each significantly associated with risk of developing caries after adjustment for age, sex, and race and ethnicity. The risk of developing caries was 33% higher among students who participated in the free or reduced lunch program than those who did not participate (relative risk, 1.33; 95% CI, 1.24 to 1.42). Students with the highest CWF coverage had a nearly 16% lower risk of developing caries than those without CWF coverage (relative risk, 0.84; 95% CI, 0.75 to 0.94)., Conclusions: CWF was significantly associated with a reduced risk of developing caries. Efforts are needed to increase CWF coverage, along with promotion of oral health education and healthy dietary habits among Pennsylvania children., Practical Implications: Increasing CWF coverage will reduce caries burden among Pennsylvania children. Although Pennsylvania has no state laws to regulate CWF, these findings are persuasive for local municipalities to consider expanding CWF coverage., Competing Interests: Disclosure None of the authors reported any disclosures., (Copyright © 2024 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Rationale: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon., Patient Concerns: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation., Diagnoses: The patient was diagnosed with a central nervous system infection., Interventions: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders., Outcomes: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided., Conclusions: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective., Lession: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirin high /ODC1 high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.

Metal nanoparticles could be accumulated in soils, which threatens the ecological stability of crops. Investigating the effects of cuprous oxide nanoparticles (Cu 2 O-NPs) on photosystem Ⅱ (PSⅡ) of wheat seedling leaves holds considerable importance in comprehending the implications of Cu 2 O-NPs on crop photosynthesis. Following the hydroponic method, we investigated the effects of 0, 10, 50, 100, and 200 mg·L -1 Cu 2 O-NPs on chlorophyll fluorescence induction kinetics and photosynthetic-related genes in wheat seedlings of "Zhoumai 18". The results showed that, with the increases of Cu 2 O-NPs concentrations, chlorophyll contents in wheat leaves decreased, and the standardization of the OJIP curve showed a clearly K-phase (ΔK＞0). Cu 2 O-NPs stress increased the parameters of active PSⅡ reaction centers, including the absorption flux per active RC (ABS/RC), the trapping flux per active RC (TRo/RC), the electron transport flux per active RC (ETo/RC), and the dissipation flux per active RC (DIo/RC). Cu 2 O-NPs stress decreased the parameters of PSⅡ energy distribution ratio including the maximum quantum yield of PSⅡ ( φ Po ), the quantum yield of electron transport from QA ( φ Eo ), and the probability that a trapped exciton moved an electron further than QA ( Ψ o ), while increased the quantum ratio for heat dissipation ( φ Do ). Moreover, there was a decrease in photosynthetic quantum yield Y(Ⅱ), photochemical quenching coefficient ( q P ), net photosynthetic rate ( P n ), stomatal conductance ( g s ), intercellular CO 2 concentration ( C i ), and transpiration rate ( T r ) of leaves with the increases of Cu 2 O-NPs concentration. Under Cu 2 O-NPs stress, the expression levels of genes which included PSⅡ genes ( PsbD , PsbP , Lhcb1 ), Rubisco large subunit genes ( RbcL ), cytochrome b6/f complex genes ( PetD , Rieske ), and ATP synthase genes ( AtpA , AtpB , AtpE , AtpI ) were downregulated. These results indicated that Cu 2 O-NPs stress altered the activity and structure of PSⅡ in wheat seedlings, affected the activity of PSⅡ reaction centers, performance parameters of PSⅡ donor and acceptor sides. PSⅡ related genes were downregulated and exhibited significant concentration effects.

Objective: To investigate the prevalence of Helicobacter pylori infection among family members, and analyze associated risk factors. Methods: The current investigation was a cross-sectional study. The Qinghai region was stratified into urban areas, agricultural areas, and pastoral areas. The urban areas of Xining City, the agricultural areas of Haidong City, and the pastoral areas of Haibei Tibetan Autonomous Prefecture were selected. A total of 396 resident families (1 131 people) who underwent health checkups from 2021 to 2022 in the above areas were included in the survey study. Questionnaires were administered and H. pylori infection was detected using the 13 C-urea breath test. Numerical data were expressed as cases and percentages, and the Chi-square test was used to compare differences in H. pylori infection rates in the populations and families in each group. Multifactorial logistic regression was used to analyze risk factors for H. pylori infection, and P< 0.05 was considered statistically significant. Results: The prevalence of H. pylori infection in Qinghai province was 52.8% (597/1 131) and the prevalence of H. pylori infection in households was 80.6% (319/396). In H. pylori -positive households with at least 1 infected spouse, 40.4% (36/89) had only 1 infected spouse, and in 59.6% (53/89) both spouses were infected. In analysis of children infected by parents with H. pylori , 20.0% (9/45) of households had fathers and children infected, 48.9% (22/45) had mothers and children infected, and 31.1% (14/45) had both parents and children infected. In univariate analysis there was a statistically significant difference in the overall comparison of H. pylori infection rates among families with different numbers of people living together ( χ 2 =11.12, P =0.004), and between-group comparisons suggested that H. pylori infection rates were higher in families with 4 or 5 people and more than 5 people living together than in families with 2 or 3 people living together. The H. pylori infection rate was higher in families that did not use serving chopsticks and spoons during family meals than in families that did use serving chopsticks and spoons ( χ 2 =6.12, P =0.013). In multifactorial logistic regression analyses the number of people living together in a family and whether or not serving chopsticks and spoons were used at family meals were associated with H. pylori infection ( P <0.05). Conclusion: The H. pylori infection rate in families in Qinghai Province is high, and there is a clear association with family aggregation. It is more common for both members of a couple to be infected, and H. pylori infection of a mother has a greater effect on the children's infection status than H. pylori infection of a father. The infection rate of H. pylori was lower in families that used serving chopsticks and spoons during dinner gatherings, and the fewer the number of people living together in the family, the lower the H. pylori infection rate.

Objectives: To characterize demographics, birth parameters, and social determinants of health among mother-infant dyads affected by neonatal abstinence syndrome (NAS) in Pennsylvania., Methods: We linked 2018-2019 NAS surveillance data to birth record data using probabilistic methods and then geospatially linked to local social determinants of health data based on residential address. We generated descriptive statistics and used multivariable mixed-effects logistic regression to model the association between maternal characteristics, birth parameters, social determinants of health, and NAS., Results: In adjusted models maternal age > 24, non-Hispanic white race/ethnicity, low educational attainment, Medicaid as payor at delivery, inadequate or no prenatal care, smoking during pregnancy, and low median household income were associated with NAS. We found no significant associations between NAS and county-level measures of clinician supply, number of substance use treatment facilities, or urban/rural designation., Conclusions for Practice: This study characterizes mother-infant dyads affected by NAS using linked non-administrative, population data for Pennsylvania. Results demonstrate a social gradient in NAS and inequity in prenatal care receipt among mothers of infants with NAS. Findings may inform implementation of state-based public health interventions., (© 2023. The Author(s).)

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective To analyze the expression of cyclooxygenase-2 (COX-2) in the patients with snow-white sign of advanced colorectal adenoma (ACA) and explore its clinical significance.Method Western blotting was employed to determine the expression of COX-2 in the adenoma tissue and the normal tissue adjacent to the adenoma tissue (>5 cm away from the distal end of the adenoma tissue) of 40 ACA patients with snow-white sign and 40 ACA patients without snow-white sign.Results The appearance of snow-white sign in ACA patients was associated with patient age ( P =0.001) and not associated with sex,smoking history,drinking history,ethnic groups,family history of colorectal cancer,abdominal pain,diarrhea,constipation,fecal occult blood,or tumor markers (all P >0.05).Snow-white sign mainly appeared in the ACA patients with multiple adenomas ( P =0.004),large adenomas ( P =0.006),adenomas in distal colon ( P =0.015),protruding polyps ( P =0.044),and late-stage pathology ( P =0.010).The occurrence of snow-white sign showed no difference in the ACA patients with different results of Japan NBI Expert Team classification ( P =0.502).The expression of COX-2 in the adenoma tissue was higher than that in the adjacent normal tissue in the patients with and without snow-white sign ( P <0.001, P =0.004).The patients with snow-white sign had higher expression of COX-2 protein in the adenoma tissue than the patients without snow-white sign ( P =0.001).The expression of COX-2 protein in the adjacent healthy tissue had no significant difference between the patients with and without snow-white sign ( P =0.603).Conclusions Snow-white sign is more like to appear in the ACA patients with young age,multiple and large adenomas,adenomas in distal colon,protruding polyps,and late-stage pathology.Moreover,the expression of COX-2 in the ACA patients with snow-white sign is significantly higher than that in the ACA patients without snow-white sign.The adults with snow-white sign are prone to cancerization than those without snow-white sign.

Background: Sexting is common among adolescents and is associated with numerous health risk behaviors and negative psychosocial constructs. This study examined the relationships between high school students' experiences with sexual violence victimization, dating violence victimization, and engagement in risky sexual behaviors with experiences of receiving sexts., Methods: Cross-sectional data from the 2014 to 2016 data from Pennsylvania Youth Risk Behavior. Participants were selected using an independent 2-stage cluster sample design to produce a statewide population-based sample. The pencil and paper surveys were conducted in school. Participants included 6734 Pennsylvania high school students in grades 9-12., Results: Overall, 29.0% of Pennsylvania high school students had received a sext, which varied by sex, race/ethnicity, school grade, and sexual identity. Students who engaged in sexual risk behaviors, experienced dating violence, or experienced lifetime sexual violence outside of the dating context had a significantly higher prevalence of receiving a sext than students who did not engage in those behaviors or have those experiences., Conclusions: Early screening and prevention efforts that include discussions about sexting behaviors may help prevent other negative outcomes, such as risky sexual behaviors and interpersonal violence. Addressing sexting in the education and health sectors may help to prevent other related harmful health and violence experiences during adolescence., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Cherry tomatoes ( Solanum lycopersicum ) are becoming increasingly popular due to their nutrition and delicious flavor. However, cherry tomatoes are highly perishable and susceptible to various pathogenic microorganisms after harvest, such as Botrytis cinerea . In the pretest experiment, we screened out three kinds of plant essential oils (EOs) ( Torreya grandis oil, Eriobotrya japonica oil, and Citrus medica oil) that have strong fungicidal activity on B. cinerea from cherry tomatoes. To further evaluate the postharvest preservation application prospect of these three oils for cherry tomatoes, the oils were extracted from different parts of three plants by hydrodistillation, and their chemical constituents were analyzed by gas chromatography-mass spectrometry. The main representative components of T. grandis oil, E. japonica oil, and C. medica oil were δ-cadinene (11.76%), transnerolidol (9.70%), and 5,7-dimethoxycoumarin (23.22%), respectively. These three EOs effectively inhibited the mycelial growth of B. cinerea in vitro, with EC 50 values of 81.672, 144.046, and 221.500 μl/liter, respectively. Compared with the blank control and other oil treatments, the T. grandis oil (at a concentration of 200 µl/liter) fumigation treatment was more effective at inhibiting the growth rate of the pathogen. In addition, the phenolic content and phenylalanine ammonia lyase, β-1,3-glucanase, chitinase, and peroxidase activities of tomatoes significantly increased on the seventh day due to the T. grandis oil treatment. The present study shows that these three oils with high extraction rates have preservation potential for cherry tomatoes. Among these three EOs, T. grandis oil can be used to further develop preservative products as a fumigant., Competing Interests: The author(s) declare no conflict of interest.

Diabetes has been regarded as an independent risk factor for Alzheimer's disease (AD). Our previous study found that diabetes activated autophagy, but lysosome function was impaired. Autophagy-lysosome dysfunction may be involved in Aβ deposition in diabetic cognitive impairment. In the present study, we used STZ-induced diabetic rats and SH-SY5Y cells to investigate whether diabetes inhibits autophagosome fusion with lysosomes. We found that in the in vivo study, STZ-induced diabetic rats exhibited cognitive dysfunction, and the lysosome function-related factors CTSL, CTSD, and Rab7 were decreased (P < 0.05). In an in vitro study, the mRFP-GFP-LC3 assay showed that the fusion of autophagosomes with lysosomes was partly blocked in SH-SY5Y cells. High glucose treatment downregulated the number of autophagolysosomes, downregulated CTSD, CTSL, and Rab7 expression (P < 0.05), and then influenced the function of ACP2 to partly block the fusion of autophagosomes and lysosomes to inhibit Aβ clearance. These findings indicate that high glucose treatment affected lysosome function, interfered with the fusion of autophagosomes with lysosomes, and partly blocked autophagic flux to influence Aβ clearance., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: The aim of this study was to assess the proportions and likelihood of children who receive confirmatory and follow-up blood lead testing within the recommended time frames after an initial capillary elevated blood lead level (EBLL) and confirmed EBLL, respectively, by individual and neighborhood-level sociodemographic characteristics., Design: We linked and used blood testing and sociodemographic characteristics data from a Pennsylvania birth cohort including children born between 2017 and 2018. Generalized linear mixed models were constructed to examine the associations between sociodemographic factors and having recommended confirmatory and follow-up testing., Setting: A population-based, retrospective cohort study., Participants: In this birth cohort, children who underwent at least 1 BLL test were followed up to 24 months of age. Children with a first unconfirmed (n = 6259) and confirmed BLL (n = 4213) ≥ 5 μg/dL were included in the analysis., Main Outcome Measure: Children had confirmatory and follow-up testing within the recommended time frames., Results: Of the children with unconfirmed and confirmed EBLLs, 3555 (56.8%) and 1298 (30.8%) received confirmatory and follow-up testing, respectively. The proportions of the 2 outcome measures were lower among children experiencing certain sociodemographic disadvantages. In the univariate analyses, lower initial BLLs, older age, non-Hispanic Blacks, lower maternal educational levels, maternal Medicaid, The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) enrollment, maternal smoking, and higher quartiles of neighborhood poverty and old housing were associated with lower odds of having confirmatory and follow-up testing. However, in multivariate models, children with lower initial BLLs, older age, maternal smoking, and non-Hispanic Blacks were significantly less likely to have confirmatory and follow-up testing., Conclusions: There were deficiencies in having recommended confirmatory and follow-up blood lead testing among children, especially those with sociodemographic disadvantages. Public health agencies and stakeholders should finetune policies to improve follow-up testing in conjunction with primary and secondary preventions for early detection and reduction of lead exposure among targeted children at risk of lead poisoning., Competing Interests: The authors declare that they have no conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To develop and validate a deep learning model based on fundus photos for the identification of coronary heart disease (CHD) and associated risk factors. Methods: Subjects aged>18 years with complete clinical examination data from 149 hospitals and medical examination centers in China were included in this retrospective study. Two radiologists, who were not aware of the study design, independently evaluated the coronary angiography images of each subject to make CHD diagnosis. A deep learning model using convolutional neural networks (CNN) was used to label the fundus images according to the presence or absence of CHD, and the model was proportionally divided into training and test sets for model training. The prediction performance of the model was evaluated in the test set using monocular and binocular fundus images respectively. Prediction efficacy of the algorithm for cardiovascular risk factors (e.g., age, systolic blood pressure, gender) and coronary events were evaluated by regression analysis using the area under the receiver operating characteristic curve ( AUC ) and R 2 correlation coefficient. Results: The study retrospectively collected 51 765 fundus images from 25 222 subjects, including 10 255 patients with CHD, and there were 14 419 male subjects in this cohort. Of these, 46 603 fundus images from 22 701 subjects were included in the training set and 5 162 fundus images from 2 521 subjects were included in the test set. In the test set, the deep learning model could accurately predict patients' age with an R 2 value of 0.931 (95% CI 0.929-0.933) for monocular photos and 0.938 (95% CI 0.936-0.940) for binocular photos. The AUC values for sex identification from single eye and binocular retinal fundus images were 0.983 (95% CI 0.982-0.984) and 0.988 (95% CI 0.987-0.989), respectively. The AUC value of the model was 0.876 (95% CI 0.874-0.877) with either monocular fundus photographs and AUC value was 0.885 (95% CI 0.884-0.888) with binocular fundus photographs to predict CHD, the sensitivity of the model was 0.894 and specificity was 0.755 with accuracy of 0.714 using binocular fundus photographs for the prediction of CHD. Conclusion: The deep learning model based on fundus photographs performs well in identifying coronary heart disease and assessing related risk factors such as age and sex.

Chemotherapy is one of the main ways to treat breast cancer clinically. However, the multidrug resistance to anti-tumor drugs limits their clinical use. To overcome these drawbacks, the development of drug delivery systems (DDSs) has attracted more and more attention in cancer therapy. At present, the preparation and purification process are complicated for many reported DDSs, while the clinic calls for new DDSs that are more convenient for preparation. Here a new pH-responsive supramolecular organic framework drug delivery complex loading doxorubicin (DOX) is fabricated. Anti-tumor activity of the system in vitro was investigated by cell cytotoxicity, uptake assay, and cell apoptosis analysis. The anti-tumor activity in vivo was investigated by inspecting nude mice body weight, tumor volume and weight, also a preliminary mechanism probe was conducted by HE and TUNEL staining. The DOX@SOF displayed high stability, good biocompatibility and pH-regulated drug release. At acid condition, the hydrazone bonds would be broken, which result in the dissociation of SOF, and then the drugs would be released from the system. Furthermore, DOX@SOF enhanced cellular internalization. Both in vitro and in vivo experiments reflected that DOX@SOF could enhance the anti-tumor activity of DOX. for the MCF-7/ADR tumor cells and tumors. This study provides a highly efficient strategy to prepare a stimulus-responsive supramolecular drug delivery complex for the treatment of drug-resistant cancer, the results presented inspiring scientific interests in exploring new drug delivery strategies and reversing multi-drug resistance for clinical chemotherapy.

The protein hydrolysate of purple speckled kidney bean (PSKB) was used as the raw material in this study, and the antioxidant peptide of the PSKB protein hydrolysate was purified using macroporous resin. The XAD-7HP macroporous resin was selected as the best purification material, and the static adsorption-desorption of the purified PSKB antioxidant peptide was optimized. The optimum static adsorption and desorption conditions were as follows: the adsorption capacity reached 11.93 ± 0.11 mg/ml at pH 7 for 24 h, and the desorption capacity was 5.24 ± 0.04 mg/ml with 60% ethanol for 30 min. Under this condition, the amount of antioxidant peptide obtained by adsorption-desorption was the highest. The optimum process conditions were as follows: the appropriate flow rate was 1 ml/min, and the optimal injection volume was 40 ml. The adsorption amount at this time can reach 12.19 ± 0.15 mg/ml. The components with an elution time of 10-30 min were separated using the reversed-phase high-performance liquid chromatography (RP-HPLC) technique to obtain three main components, namely, RP 1 , RP 2 , and RP 3 . The DPPH free radical scavenging ability reached 56.26 ± 0.56, 66.42 ± 0.56, and 78.57 ± 0.56%, respectively, which were 36.65, 46.34 ± 0.56, and 54.39 ± 0.56% higher than those before purification. The amino acid sequences of the three components were identified as Phe-Leu-Val-Asp-Arg-Ile, Phe-Leu-Val-Ala-Pro-Asp-Asp, and Lys-Asp-Arg-Val-Ile-Ser-Glu-Leu., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Xu, Yang, Wu, Ma, Zuo and Zhang.)

Background: Melatonin, a natural hormone secreted by the pineal gland, has been reported to exhibit antitumor properties through diverse mechanisms of action. However, the oncostatic function of melatonin on esophageal squamous cell carcinoma (ESCC) remains elusive. This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells., Methods: ESCC cell lines treated with or without melatonin were used in this study. In vitro colony formation and EdU incorporation assays, and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells. RNA-seq, qPCR, Western blotting, recombinant lentivirus-mediated target gene overexpression or knockdown, plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth. IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes' expression and prognosis of ESCC., Results: Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7 (HDAC7), c-Myc and ubiquitin-specific peptidase 10 (USP10) in ESCC cells (P < 0.05). The expressions of HDAC7, c-Myc and USP10 in tumors were detected significantly higher than the paired normal tissues from 148 ESCC patients (P < 0.001). Then, the Kaplan-Meier survival analyses suggested that ESCC patients with high HDAC7, c-Myc or USP10 levels predicted worse overall survival (Log-rank P < 0.001). Co-IP and Western blotting analyses further revealed that HDAC7 physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription. Notably, our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth, and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells. Additionally, we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells., Conclusions: Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth, and provides the reference for identifying biomarkers and therapeutic targets for ESCC., (© 2022. The Author(s).)

Objectives. To (1) determine the prevalence of elevated blood lead levels (EBLLs; ≥ 5 µg/dL) among newly arrived refugee children, (2) understand the demographic characteristics of refugee children with EBLLs, and (3) assess health care providers' compliance with Centers for Disease Control and Prevention (CDC) recommendations for retesting. Methods. We matched refugee demographic data (2015-2019) from the CDC's Electronic Disease Notification (EDN) system with lead-testing laboratory report data from the Pennsylvania National Electronic Disease Surveillance System using Match*Pro software. Results. Of 3833 refugee children 16 years or younger in the EDN system, matching identified 3142 children with blood lead level data. Among children with blood lead level data, 578 (18.4%) had EBLLs. Among children with EBLLs, 341 (59.0%) were male. Of the 1370 children aged 6 years or younger with blood level test results, 335 (24.5%) had initial EBLLs, and only 78 (5.7%) were retested within 3 to 6 months. Of the 335 children 6 years or younger with an initial EBLL, only 44 (13.1%) were retested within 3 to 6 months. Conclusions. Following up on refugee children with EBLLs is necessary to ensure that they do not have continued lead exposure. ( Am J Public Health . 2022;112(S7):S706-S714. https://doi.org/10.2105/AJPH.2022.306856).

Background: The aberrant regulation of cell cycle is significantly correlated with cancer carcinogenesis and progression, in which cell cycle checkpoints control phase transitions, cell cycle entry, progression, and exit. However, the integrative role of cell cycle checkpoint-related genes (CRGs) in bladder carcinoma (BC) remains unknown., Methods: The transcriptomic data and clinical features of BC patients were downloaded from The Cancer Genome Atlas (TCGA), used to identify CRGs correlated with overall survival (OS) by univariate Cox regression analysis. Then, the multivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses further developed a prognostic CRG signature, which was validated in three external datasets retrieved from Gene Expression Omnibus (GEO). The receiver operating characteristic curve (ROC) analysis was conducted for evaluating the performance of the CRG signature in prognosis prediction. RNA sequencing (RNA-Seq) was performed to explore the expression difference in the identified CRGs between tumor and normal tissue samples from 11 BC patients in the local cohort. Ultimately, genomic profiles and tumor microenvironment (TME), and the Genomics of Drug Sensitivity in Cancer (GDSC) were investigated to guide precision treatment for BC patients with different CRG features., Results: The novel constructed 23-CRG prognostic signature could stratify BC patients into high-risk and low-risk groups with significantly different outcomes (median OS: 13.64 vs. 104.65 months). Notably, 19 CRGs were the first to be identified as being associated with BC progression. In three additional validation datasets (GSE13507, GSE31684, and GSE32548), higher CRG scores all indicated inferior survival, demonstrating the robust ability of the CRG signature in prognosis prediction. Moreover, the CRG signature as an independent prognostic factor had a robust and stable risk stratification for BC patients with different histological or clinical features. Then, a CRG signature-based nomogram with a better performance in prognostic prediction [concordance index (C-index): 0.76] was established. Functional enrichment analysis revealed that collagen-containing extracellular matrix (ECM), and ECM-related and MAPK signaling pathways were significantly associated with the signature. Further analysis showed that low-risk patients were characterized by particularly distinctive prevalence of FGFR3 (17.03% vs. 6.67%, p < 0.01) and POLE alterations (7.97% vs. 2.50%, p < 0.05), and enrichment of immune infiltrated cells (including CD8+ T cells, CD4+ naïve T cells, follicular helper T cells, Tregs, and myeloid dendritic cells). RNA-seq data in our local cohort supported the findings in the differentially expressed genes (DEGs) between tumor and normal tissue samples, and the difference in TME between high-risk and low-risk groups. Additionally, CRG signature score plus FGFR3 status divided BC patients into four molecular subtypes, with distinct prognosis, TME, and transcriptomic profiling of immune checkpoint genes. Of note, CRG signature score plus FGFR3 status could successfully distinguish BC patients who have a higher possibility of response to immunotherapy or chemotherapy drugs., Conclusions: The CRG signature is a potent prognostic model for BC patients, and in combination with FGFR3 alterations, it had more practical capacity in the prediction of chemotherapy and immunotherapy response, helping guide clinical decision-making., (Copyright © 2022 Shi, Guan, Long, Song, Xiong, Qin, Ma, Hu and Yang.)

Mortality due to opioid misuse and overdose has increased substantially in the United States over the past two decades. The study objective was to describe the causes of death among persons with opioid-related hospitalizations and examine survival by Hepatitis C virus (HCV) or HIV. Opioid-related hospitalization records in Pennsylvania from 2000 to 2010 were linked to death registry files to assess cause of death, and survival from first hospital discharge date to death date, or December 31, 2010. Accelerated failure time models were used to compare survival between persons with and without HCV or HIV diagnoses. Among the 136,416 individuals with an opioid-related hospitalization, 13.0% died over a median of 56 months of follow-up; the most common causes of death were circulatory diseases (26.4%) and drug overdose (23.5%). There were 27,122 (19.9%) and 3662 (2.7%) persons who had an HCV and HIV diagnosis, respectively. Among patients aged ≥20 years, those with HCV had shorter survival time compared to those without HCV, with discrepancies more pronounced at older ages. Patients with HIV also had shorter survival time (time ratio: 0.29 [95% CI: 0.26, 0.34]) compared to without HIV. These findings show that in a cohort of patients with opioid-related hospitalizations, those with HCV or HIV diagnoses have shorter survival. This has public health implications, providing further evidence that medical providers should educate patients who use opioids about the risks of HCV and HIV infection and focus prevention and treatment to decrease mortality among patients hospitalized for opioid use., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A series of benzylidene analogs of oleanolic acid 4a∼4s were synthesized and assessed for their α -glucosidase and α -amylase inhibitory activities. The results presented that all synthesized analogs exhibited excellent-to-moderate inhibitory effects on α -glucosidase and α -amylase. Analog 4i showed the highest α -glucosidase inhibition (IC 50 : 0.40 μM), and analog 4o presented the strongest α -amylase inhibition (IC 50 : 9.59 μM). Inhibition kinetics results showed that analogs 4i and 4o were reversible and mixed-type inhibitors against α -glucosidase and α -amylase, respectively. Simulation docking results demonstrated the interaction between analogs and two enzymes. Moreover, analogs 4i and 4o showed a high level of safety against 3T3-L1 and HepG2 cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ke, Lin, Zhang, Wu, Zheng, Hu, Kang, Zhang, Xiong and Ma.)

The Chinese government triggered the immediate implementation of a lockdown policy in China following the outbreak of the COVID-19 pandemic, leading to drastic decreases in air pollutant emissions. However, concentrations of PM 2.5 and other pollutants increased during the COVID-19 lockdown over the Jing-Jin-Ji region compared with those averaged over 2015-2019, and two PM 2.5 pollution events occurred during the lockdown. Using the ERA5 reanalysis data, we found that the Jing-Jin-Ji region during the COVID-19 lockdown was characterized by higher relative humidity, lower planetary boundary layer height, and anomalous updraft. These conditions were favorable for condensation and the secondary formation of aerosols and prevented turbulent diffusion of pollutants. Furthermore, we conducted sensitivity tests using the WRF-Chem model and found that ρ (PM 2.5 ) increased by 20-55 μg·m -3 (60%-170%) over the middle region of Jing-Jin-Ji during the COVID-19 lockdown due to changes in meteorological conditions. Furthermore, the enhanced aerosol chemistry and unfavorable diffusion conditions were identified as the key factors driving increases in PM 2.5 concentrations during the lockdown. Planetary boundary layer height and relative humidity may become the important factors in forecasting PM 2.5 pollution events over the Jing-Jin-Ji region under the background of emission reduction.

In this paper, we developed a facile route for the preparation of a novel bimetal oxide affinity chromatography (MOAC) material. The TiO 2 /ZrO 2 @MoS 2 was constructed by the electrostatic interaction between titanium oxide/zirconia (w:w, 10:1) and molybdenum disulfide nanosheet. The nanocomposite has the large specific surface area (186.30 m 2 ⋅g -1 ) and pore volume (0.37 cm 3 ⋅g -1 ). Compared with single-metal probes, the combination of bimetallic oxides probe (TiO 2 /ZrO 2 ) and hydrophilicity MoS 2 support offered multitudinous affinity sites for phosphopeptides capturing from tryptic digests of protein samples under 50% acetonitrile-1% trifluoroacetate conditions. Singnificant feasibility of the TiO 2 /ZrO 2 @MoS 2 nanomaterial for the enrichment of phosphopeptides under optimal conditions was proved via the bovine serum albumin (BSA) and the mixtures of β-casein. The phosphopeptide expression was identified using ultra-performance liquid chromatography (uHPLC) separation and-linear ion trap mass spectrometry (MS n ). With these affinity characters of TiO 2 /ZrO 2 @MoS 2 , it exhibited higher binding capacity (25 mg⋅g -1 ), better selectivity for phosphopeptides from β-casein/BSA (1:2000) tryptic digests, high sensitivity (1 fmol⋅µL -1 ) towards phosphopeptides from β-casein tryptic digests, and great reusability of 8 cycles test for capturing phosphopeptides. In addition, the TiO 2 /ZrO 2 @MoS 2 with high sensitivity and selectivity was successfully applied to enriching phosphopeptides from nonfat milk and human serum samples. More importantly, the TiO 2 /ZrO 2 @MoS 2 was further successfully applied to multi-phosphopeptides enrichment, 1779 serine, threonine and tyrosine phosphosites can be identified in A549 cell protein tryptic digest. Compared with commercial TiO 2 from enrichening 416 phosphopeptide from A549 cell lysates, the successful locating of 44 phosphosites were overlapped., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Yiqi Huoxue Decoction (YQHXD) is a traditional Chinese medicine that promotes blood circulation, removes blood stasis, facilitates diuresis, and alleviates edema. It is composed of 10 herbal medicines and has extensive application in treating nephrotic syndrome (NS). However, the active components and the potential mechanism of YQHXD for treating NS remain unclear. Methods: We set up a sensitive and rapid method based on Ultra-High Performance Liquid Chromatograph-Mass (UPLC-MS) to identify the compounds in YQHXD and constituents absorbed into the blood. Disease genes were collected through GeneCards, DisGeNET, and OMIM database. Genes of compounds absorbed into blood were predicted by the TCMSP database. We constructed Disease-Drug-Ingredient-Gene (DDIG) network using Cytoscape, established a Protein-protein interaction (PPI) network using String, Gene biological process (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using DAVID. Cellular experiments were performed to validate the results of network pharmacology. Result: A total of 233 compounds in YQHXD and 50 constituents absorbed into the blood of rats were identified. The 36 core targets in the PPI network were clustered in the phosphatidylinositol 3 kinase-RAC serine/threonine-protein kinase (PI3K-AKT) and nuclear factor kappa-B (NF-κB) signaling pathways. Luteolin, Wogonin, Formononetin, and Calycosin were top-ranking components as potentially active compounds. Conclusion: The results of our studies show that YQHXD is able to enhance renal function, alleviate podocyte injury, and improve adriamycin nephrotic syndrome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YS declared a shared affiliation, with no collaboration, with the authors, to the handling editor at the time of the review., (Copyright © 2022 Feng, Li, Wang, Gu, Zhang, Li, Chen, Ma, Lin, Zhang and Zhao.)

Competing Interests: Conflicts of interests: All authors declared no conflicts of interests.

Wilforine, a compound of sesquiterpene alkaloids isolated from Tripterygium wilfordii, exhibits excellent insecticidal activity against Mythimna separata. In order to clarify the action mechanism of wilforine, the plasma membrane calcium transporting ATPase (PMCA) and inositol 1,4,5-trisphosphate receptor (IP 3 R) from M. separata were studied. Results showed that the open reading frame of MsIP 3 R and MsPMCA were 8118 bp and 3438 bp in length, as well as encoded 2706 and 1146 amino acids, respectively. Multiple sequence alignment and phylogenetic analysis revealed that the MsIP 3 R and MsPMCA had high homology with the IP 3 R and PMCA of other insects, but had low similarity with those of mammals, which means the IP 3 R and PMCA have potential to be the novel targets of insecticides with high selectivity between mammals and insects. Both MsIP 3 R and MsPMCA genes existed throughout the life cycle of M. separata, and were all predominantly expressed in somatic muscle of fifth-instar larvae and the adults. The susceptibilities of PMCA-silenced M. separata to wilforine were significantly lower than that of the normal M. separata, which illustrates that PMCA could be one of the targets of wilforine. However, the susceptibilities of IP 3 R-silenced M. separata to wilforine did not change significantly compared with the susceptibilities of normal M. separata, which shows that wilforine may not interact with the IP 3 R protein. These findings provide clues for elucidating the insecticidal mechanism of wilforine., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The intestinal microecological environment is critical to an infant's growth. For those infants consuming milk power, it is very important to improve the intestinal microecological environment to promote the healthy growth of infants. In this paper, Milk protein hydrolysate (MPH), consisting of different proportions of proteins and small molecule peptides (5:5, 4:6, 3:7, 2:8, 1:9) were added to infant formula powder (IFP). The effects of MFP-enriched IFP addition on proliferation and metabolism of Bifidobacterium L80 were studied. Compared with MPH-free IFP, MFP-enriched IFP with 1:9 of proteins to small molecule peptides significantly enhanced the proliferation of Bifidobacterium L80, resulting in higher cell density, greater viable counts and higher titratable acidity. MFP-enriched IFP increased the content of seven organic acids and H 2 O 2 in the system, and improved the antibacterial activity to E. coli BL21. This study suggested that MPH could be an effective addition to infant formula powder to promote the growth of Bifidobacterium, so to improve the intestinal health of infants., (© 2021. The Author(s).)

Real-time BTEX(including benzene, toluene, ethylbenzene, m -, p -, and o -xylenes) were measured continuously in Tianjin urban site in July 2019 and January 2020 using a Syntech Spectras GC955 analyzer. The BTEX concentration levels, composition, and evolutionary mechanisms during typical pollution episodes were investigated. The potential sources of BTEX were analyzed qualitatively using the diagnostic ratios method. Finally, the BTEX health risk was evaluated by using the human exposure analysis and evaluation method according to US EPA. The averaged total mixing ratio of BTEX were 1.32×10 -9 and 4.83×10 -9 during ozone pollution and haze episodes, respectively. Benzene was the most abundant species, followed by toluene. The mixing ratio of BTEX was largely affected by short southwestern distance transportation in January, while local emissions in July. In addition, the BTEX mixing ratio depended on the influence of temperature and relative humidity(RH) in July, while the concentration was more sensitive to changes in RH when the temperature was low in January. Diagnostic ratios and source implications suggested that the BTEX was affected mainly by biomass/biofuel/coal burning during haze episodes. The traffic related emissions also had an impact except for the influence of biomass/biofuel/coal burning in July. The averaged hazard quotient(HQ) values were 0.072 and 0.29 during ozone pollution and haze episodes, respectively, which were in the upper safety range limit recommended by the US EPA. The carcinogenic risk posed by benzene in both cleaning and pollution processes was higher than the safety threshold set by the US EPA, which should be monitored carefully.

Carboxylesterases (CarEs) usually play critical roles in the detoxification of toxic chemicals and therefore may be involved in insecticide resistance in agricultural pests. Previous work has shown that CarE 001C from Helicoverpa armigera was able to metabolize the isomers of cypermethrin and fenvalerate. In this study, seven mutants of CarE 001C with single amino acid substitution were produced and expressed in the Escherichia coli. Enzyme kinetic analysis indicated that all seven mutations dramatically reduced enzymatic activities toward the generic substrate α-naphthyl acetate, but in vitro metabolism assay showed that two of the mutations, H423I and R322L, significantly improved hydrolase activities toward fenvalerate, with their recorded specific activities being 3.5 and 5.1 nM·s -1 ·mg -1 proteins, respectively. Further, thermostability assay showed that the stability of one mutant enzyme was enhanced. This study will help us better understand the potential of CarEs in insecticide detoxification and resistance in H. armigera., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Under certain terrain and weather conditions, mountain-valley circulation is one of the main meteorological factors affecting aerosol pollution in plain-mountain area. Based on environmental monitoring data and multi-source meteorological data for the Beijing-Tianjin-Hebei region between 2015 and 2019, the characteristics, similarities, and differences of mountain-valley winds in the Beijing Plain and Yanhuai Basin regions were compared. The results show that the mountain-valley winds recorded at the Beijing Observatory are from southwest to northeast compared to from the southeast to northeast at Yanqing station. With the aggravation of pollution levels, the mountain-valley wind intensity decreased by 17.7%-32.4%. When the wind speed at Beijing Observatory was 2-6 m·s -1 , the maximum PM 2.5 concentration in southeast was 83 μg·m -3 , which was higher than in the southwest. When the wind speed at the Yanqing station was 2-6 m·s -1 , the PM 2.5 concentrations in SE-SSE area was 20-40 μg·m -3 higher than in other directions, and the concentrations in the valley winds were 10-12 μg·m -3 higher than the average value for the last five years. Taking the typical heavy pollution event on March 5-8, 2015, as an example, the influence of mountain-valley winds is mainly reflected in the high humidity and regional transmission of southeast winds during the valley wind stage. The PM 2.5 concentrations at the Yanqing station increased by 100-130 μg·m -3 during the valley wind stage on March 6 and 7, 2015. The inversion temperature developed to 1000 m during the mountain wind stage, the local dew point at the Beijing Observatory and the Yanqing station rose by approximately 18℃. The peak dew point at the Yanqing station occurring 2 hours after the Beijing Observatory, and the concentrations of PM 2.5 rose slightly under high humidity conditions. Meanwhile, the thermal gradient between the 400-m-high Yanqing Station and Yudu Mountain gradually decreased, and the mountain-valley wind decreased by 8% and 6%, respectively. The weakening of local circulation may be related to the bidirectional feedback mechanism of the boundary layer and high concentrations of aerosols.

Human hepatocellular carcinoma (HCC) is the most frequent cancer worldwide with a poor prognosis. Tumor-specific pyruvate kinase M2 (PKM2) is essential for cancer metabolism and tumorigenesis. Shikonin, a specific inhibitor of PKM2, but not PKM1, exhibits significant anticancer effect in HCC, and was deemed as a promising drug for cancer therapy. However, shikonin-mediated bypass signaling in HCC remained unclear. Here, we performed forward/reverse stable isotope labeling with amino acids in cell culture (SILAC)-based proteomics to identify the early molecular events controlled by shikonin. We demonstrated for the first time that shikonin could induce the nuclear translocation of PKM2 for recruiting Nrf2, and transcriptionally activated Nrf2 downstream target gene BAG3, therefore increasing protective effect to sustain cell survival. Knockdown of BAG3 by si-RNA significantly potentiated the anticancer effect of shikonin. These findings provided the first evidence of a new noncanonical function of inhibited PKM2 could act as a transcriptional coactivator of Nrf2 in cancer survival, highlight that shikonin in combined with BAG3 inhibitor could be a promising therapeutic strategy for HCC therapy., Competing Interests: None., (AJCR Copyright © 2021.)

Ozone pollution has recently become a severe air quality issue in the Beijing-Tianjin-Hebei region. Due to the lack of a precursor emission inventory and complexity of physical and chemical mechanism of ozone generation, numerical modeling still exhibits significant deviations in ozone forecasting. Owing to its simplicity and low calculation costs, the time series analysis model can be effectively applied for ozone pollution forecasting. We conducted a time series analysis of ozone concentration at Shangdianzi, Baoding, and Tianjin sites. Both seasonal and dynamic ARIMA models were established to perform mid- and long-term ozone forecasting. The correlation coefficient R between the predicted and observed value can reach 0.951, and the RMSE is only 10.2 μg·m -3 for the monthly average ozone prediction by the seasonal ARIMA model. The correlation coefficient R between the predicted and observed value increased from 0.296-0.455 to 0.670-0.748, and RMSE was effectively reduced for the 8-hour ozone average predicted by the dynamic ARIMA model.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P >0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P <0.001), smaller maximum tumor diameter ( t =3.969, P <0.001), less number of metastatic lymph nodes ( t =1.343, P <0.001), lower ratio of vessel invasion (χ(2)=11.897, P =0.001) and nerve invasion (χ(2)=12.338, P <0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P =0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P =0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P <0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P <0.05); patients over 45 years of age ( P <0.05) and with normal body mass ( P <0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly ( P <0.05); patients with signet ring cell carcinoma benefited little ( P >0.05); tumors in the gastric body and gastric antrum benefited more significantly ( P <0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Ethnopharmacological Relevance: Ranunculus japonicus Thunb. (short for R. japonicus) is a topically applied herb with the activities of removing jaundice, nebula and edema, preventing malaria, stopping asthma, promoting diuresis and relieving pain. It was firstly recorded in Zhouhou Beiji Fang and has been used for the treatment of malaria, ulcers, carbuncle, jaundice, migraine, stomachache, toothache and arthritis for over 1800 years., Aim of the Study: This study aimed to uncover the potentially effective components of R. japonicus and the pharmacological mechanisms against rheumatoid arthritis (RA) by combing LC-MS and network pharmacology., Materials and Methods: Firstly, the chemical constituents of R. japonicus were qualitatively identified by UPLC-ESI-LTQ-Orbitrap MS. Then we performed target prediction by PharmMapper, protein-protein interaction (PPI) analysis via String, GO and KEGG pathway enrichment analysis by DAVID and constructed the compound-target-pathway network using Cytoscape. Thirdly, crucial compounds in the network were quantitatively analyzed to achieve quality control of R. japonicus. Finally, the pharmacological activities of R. japonicus and two potentially bioactive ingredients were validated in RA-FLSs (Rheumatoid Arthritis Fibroblast-like Synoviocytes) in vitro., Results: Overall fifty-four ingredients of R. japonicus were identified and forty-five components were firstly discovered in R. japonicus. Among them, twenty-seven validated compounds were predicted to act on twenty-five RA-related targets and they might exhibit therapeutic effects against RA via positive regulation of cell migration, etc. Nine potentially bioactive components of R. japonicus which played important roles in the compound-target-pathway network were simultaneously quantified by an optimized UPLC-ESI-Triple Quad method. In vitro, compared to control group, R. japonicus extract, berberine and yangonin significantly inhibited the migration capacity of RA-FLSs after 24 h treatment., Conclusion: This study clarified that R. japonicus and the bioactive ingredients berberine and yangonin might exert therapeutic actions for RA via suppressing the aggressive phenotypes of RA-FLSs through combined LC-MS technology and network pharmacology tools for the first time. The present research provided deeper understanding into the chemical profiling, pharmacological activities and quality control of R. japonicus and offered reference for further scientific research and clinical use of R. japonicus in treating RA., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The combination of photodynamic therapy (PDT) and chemotherapy is a prospective strategy to improve antitumor efficacy. Herein, a series of novel cytotoxic chlorin-based derivatives as dual photosensitizers (PSs) and histone deacetylase inhibitors (HDACIs) were synthesized and investigated for biological activity. Among them, compound 15e showed definite HDAC2 and 10 inhibitory activities by up-regulating expression of acetyl-H4 and highest phototoxicity and dark-toxicity, which was more phototoxic than Talaporfin as a PS while with stronger dark-toxicity compared to vorinostat (SAHA) as a HDACI. The biological assays demonstrated that 15e was liable to enter A549 cells and localized in mitochondria, lysosomes, golgi and endoplasmic reticulum (ER) etc. multiple organelles, resulting in higher cell apoptosis rate and ROS production compared to Talaporfin. Moreover, it could induce tumor cell autophagy as a dual PS and HDACI. All results suggested that compound 15e could be applied as a potential dual cytotoxic drug for PDT and chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Paragonimus proliferus, a lung fluke of the genus Paragonimus, was first reported in Yunnan province, China. P. proliferus can infect Sprague-Dawley (SD) rats and cause lung damage, but there is still no direct evidence of human infection. Until now, there has been a lack of studies on P. proliferus parasitism and development in mammalian lung tissue. The aim of this study was to perform transcriptomic profiling of P. proliferus at different developmental stages. SD rats were infected with P. proliferus metacercariae obtained from crabs; worms isolated from the lungs at different time points as well as metacercariae were subjected to whole transcriptome sequencing. Overall, 34,403 transcripts with the total length of 33,223,828 bp, average length of 965 bp, and N50 of 1833 bp were assembled. Comparative analysis indicated that P. proliferus, similar to other Paragonimus spp., expressed genes related to catabolism, whereas P. proliferus-specific transcripts were related to the maintenance of cellular redox homeostasis, sensitivity to bacteria, and immune response. Transcriptional dynamics analysis revealed that genes involved in the regulation of catabolism and apoptosis had stable expression over the P. proliferus life cycle, whereas those involved in development and immune response showed time-dependent changes. High expression of genes associated with immune response corresponded to that of genes regulating the sensitivity to bacteria and immune protection. We constructed a P. proliferus developmental model, including the development of the body, suckers, blood cells, reproductive and tracheal systems, lymph, skin, cartilage, and other tissues and organs, and an immune response model, which mainly involved T cells and macrophages. Our study provides a foundation for further research into the molecular biology and infection mechanism of P. proliferus.

Background: Carboxylesterase (CarE) is a major class of enzyme involved in the detoxification of toxic xenobiotics in various insect species. Previous work has shown that the carboxylesterase gene CarE001G found in Helicoverpa armigera is more active and can metabolize synthesized pyrethroids, such as β-cypermethrin, one of the commonly used commercial insecticides for lepidopteran pest control. In addition, CarE001G is very special as it has a very specific glycine-rich region located adjacent to its C-terminal. But whether mutations in this unique sequence can change the biochemistry and function of CarE001G are unknown., Results: In this study, four variants of CarE001G with different deletions in the glycine-rich region were obtained and functionally expressed in Escherichia coli. The recombinant proteins were purified and confirmed by Western blot and mass spectrometry analyses. These mutant enzymes showed high catalytic efficiency toward the model substrate α-naphthyl acetate. Inhibition study showed that β-cypermethrin had relatively strong inhibition on CarE activities. In vitro metabolism assay showed that the mutant enzymes significantly enhanced their metabolic activities toward β-cypermethrin with specific activities between 4.0 and 5.6 nmol L -1 min -1 mg -1 protein. Molecular docking analyses consistently demonstrated that deletion mutations in the glycine-rich region may facilitate the anchoring of the β-cypermethrin molecule in the active binding pocket of the mutant enzymes., Conclusion: The data show that deletion mutations can cause qualitative change in the capacity of CarEs in the detoxification of β-cypermethrin. This indicates that deletion mutations in the glycine-rich region may have the potential to cause synthesized pyrethroid (SP) resistance in H. armigera in the future. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

Objective: To summarize the clinical characteristics of adult cases of paragonimiasis with lung masses as the main manifestation in Xishuangbanna, Yunnan Province, analyze the causes of misdiagnosis, and improve the levels of clinical diagnosis and treatment., Method: We conducted a retrospective analysis of the clinical data and diagnosis and treatment of 8 adult cases of paragonimiasis with lung masses as the main manifestation that were diagnosed in the Oncology Department of People's hospital of Xishuangbanna Dai Autonomous Prefecture from July 2014 to July 2019., Result: All 8 patients were from epidemic paragonimiasis areas and had a confirmed history of consuming uncooked freshwater crabs. The clinical manifestations were mainly fever, dry cough, and chest pain. The disease durations were long, and peripheral blood eosinophil counts were elevated. The cases had been misdiagnosed as pneumonia or pulmonary tuberculosis. After years of anti-inflammatory or anti-tuberculosis treatment, the symptoms had not improved significantly. Patients eventually sought treatment from the oncology department for hemoptysis. Chest computed tomography showed patchy consolidation in the lungs, with nodules, lung masses, and enlarged mediastinal lymph nodes., Conclusion: Paragonimiasis is a food-borne parasitic disease. Early clinical manifestations and auxiliary examination results are nonspecific. The parasite most often invades the lungs, and the resulting disease is often misdiagnosed as pneumonia, pulmonary tuberculosis, or lung cancer (Acta Trop 199: 05074, 2019). To avoid misdiagnosis, clinicians should inquire, in detail, about residence history and history of unclean food and exposure to infected water and make an early diagnosis based on the inquired information and imaging examination results. For patients who have been diagnosed with pneumonia or pulmonary tuberculosis and whose symptoms do not improve significantly after anti-inflammatory or anti-tuberculosis treatments, their epidemiological history should be traced to further conduct differential diagnosis and avoid misdiagnosis.

To explore the ecotoxicity of Cu 2 O nanoparticles (NPs) on plant roots, the effects of Cu 2 O-NPs with different concentrations of 10, 50, 100 and 200 mg·L -1 on the seedling growth, root morphology, and cytogenetic toxicity of wheat 'Zhoumai 18' ( Triticum aestivum Zhoumai 18) were examined in a hydroponic experiment. The results showed that Cu 2 O-NPs inhibited the growth of wheat seedlings. Cu 2 O-NPs reduced root and shoot lengths, fresh weights of shoot and root, root relative activity and ratio of root to shoot of wheat seedlings, but increased primary root number. Furthermore, with the increases of Cu 2 O-NPs concentrations, the root elongation zone shortened and the root became hard and brittle, while the average diameter of roots increased. Under the concentration of 100 mg·L -1 Cu 2 O-NPs, the mitotic index significantly decreased, and vacuolization, plasma membrane detachment, chromosomal abnormality occurred in the root tip cell. In conclusion, Cu 2 O-NPs are genotoxic to wheat seedlings, with consequences on the growth and development of wheat seedlings and root morphology.