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Summary: Here, we present a protocol for electrotaxis of large epithelial cell sheets without compromising the integrity of cell epithelia in a high-throughput customized directed current electrotaxis chamber. We describe the fabrication and use of polydimethylsiloxane stencils to control the size and shape of human keratinocyte cell sheets. We detail cell tracking, cell sheet contour assay, and particle image velocimetry to reveal the spatial and temporal motility dynamics of cell sheets. This approach is applicable to other collective cell migration studies.For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The eukaryotic ribosome is essential for cancer cell survival. Perturbation of ribosome biogenesis induces nucleolar stress or ribosomal stress, which restrains cancer growth, as rapidly proliferating cancer cells need more active ribosome biogenesis. In this study, we found that UTP11 plays an important role in the biosynthesis of 18S ribosomal RNAs (rRNA) by binding to the pre-rRNA processing factor, MPP10. UTP11 is overexpressed in human cancers and associated with poor prognoses. Interestingly, depletion of UTP11 inhibits cancer cell growth in vitro and in vivo through p53-depedednt and -independent mechanisms, whereas UTP11 overexpression promotes cancer cell growth and progression. On the one hand, the ablation of UTP11 impedes 18S rRNA biosynthesis to trigger nucleolar stress, thereby preventing MDM2-mediated p53 ubiquitination and degradation through ribosomal proteins, RPL5 and RPL11. On the other hand, UTP11 deficiency represses the expression of SLC7A11 by promoting the decay of NRF2 mRNA, resulting in reduced levels of glutathione (GSH) and enhanced ferroptosis. Altogether, our study uncovers a critical role for UTP11 in maintaining cancer cell survival and growth, as depleting UTP11 leads to p53-dependent cancer cell growth arrest and p53-independent ferroptosis.

BackgroundSkip metastasis in papillary thyroid cancer (PTC), defined as lateral lymph node metastasis (LLNM) without the involvement of central lymph node metastasis (CLNM), is generally unpredictable. Our study aimed to develop a model to predict skip metastasis by using clinicopathological and ultrasound factors of PTC.MethodsWe retrospectively reviewed the medical records of patients who underwent total thyroidectomy and central lymph node dissection (CLND) plus lateral lymph node dissection (LLND) between January 2019 and December 2021 at the First Affiliated Hospital of Soochow University. Furthermore, univariate and multivariate analyses assessed the clinical and ultrasound risk factors. Receiver operating characteristic (ROC) curves were used to find the optimal cut-off values for age and dominant nodule diameter. Multivariate logistic regression analysis results were used to construct a nomogram and were validated internally.ResultsIn all patients, the skip metastasis rate was 15.4% (41/267). Skip metastasis was more frequently found in patients with a tumour size ≤10 mm (OR 0.439; P = 0.033), upper tumour location (OR 3.050; P=0.006) and fewer CLNDs (OR 0.870; P = 0.005). After analysing the clinical and ultrasound characteristics of the tumour, five factors were ultimately associated with lateral lymph node skip metastasis and were used to construct the model. These factors were an age >40 years, tumour diameter

BackgroundThe recently published “Life’s Essential 8” (LE8) by the American Heart Association has overcome some limitations in evaluating cardiovascular health (CVH) in the previous “Life’s Simple 7.” ObjectiveWe aimed to examine the secular trends in CVH, as assessed by the LE8, in US adults from 2005 to 2018. MethodsUsing cross-sectional data from the National Health and Nutrition Examination Survey between 2005-2006 and 2017-2018, we calculated the age-standardized mean scores of overall CVH and each of the LE8 components, where a higher score (range 0-100 points) means a better health status. A total of 21,667 adults aged 20-79 years were included in this analysis. ResultsThe overall CVH did not significantly change between 2005-2006 and 2017-2018 (65.5, 95% CI 63.9-67.1 to 65.0, 95% CI 62.8-67.1; P=.82). The individual metrics did not significantly change for diet (41.0, 95% CI 38.0-43.9 to 41.5, 95% CI 36.5-46.6; P=.94), physical activity (57.5, 95% CI 53.0-61.9 to 53.0, 95% CI 48.7-57.3; P=.26), and blood pressure (68.4, 95% CI 65.2-71.5 to 68.6, 95% CI 65.3-71.9, P=.35), improved for nicotine exposure (64.7, 95% CI 61.1-68.4 to 71.9, 95% CI 67.7-76.2; P

Strong alkali alkali-surfactant-polymer (ASP) flooding produced water is a by-product of oil recovery, and it is a stable system composed of petroleum, polyacrylamide, surfactant, and inorganic salts. Efficient, green, and safe ASP produced water treatment technology is essential for oilfield exploitation and environmental protection. In this study, an anaerobic/anoxic/moving bed biofilm reactor with a microfiltration membrane was established and assessed for the real strong alkali ASP flooding produced water (pH 10.1–10.4) treatment. The results show that the average removal rates of COD, petroleum, suspended solids, polymers and surfactants in this process are 57, 99, 66, 40, and 44%, respectively. GC-MS results show that most of the organic compounds such as alkanes and olefins in the strong alkali ASP produced water are degraded. Microfiltration membrane can significantly improve the efficiency and stability of sewage treatment system. Paracoccus (AN), Synergistaceae (ANO) and Trichococcus (MBBR) are the main microorganisms involved in the degradation of pollutants. This study reveals the potential and adaptability of composite biofilm system in treating the produced water of strong alkali ASP produced water.

Objective: This study was aimed at investigating the screening behaviors of the first-degree relatives (FDRs) of Chinese patients with gastric cancer as well as the factors influencing screening behaviors. Methods: In a cross-sectional design, 197 FDRs of patients with gastric cancer were enrolled at the Peking University Cancer Hospital. Four questionnaires were used: a demographic questionnaire, a knowledge questionnaire of risk factors and warning symptoms for gastric cancer, the Gastric Cancer Health Belief Scale, and a questionnaire screening for behavioral motivators and barriers. Logistic regression analysis was performed to determine the factors influencing screening behaviors. Results: Among the 197 FDRs of patients with gastric cancer, 30.96% (61/197) of patients had undergone gastric cancer screening. Among those who participated in gastric cancer screening, the most common screening methods were gastroscopy and the Helicobacter pylori testing, both of which were applied in 63.93% (39/61) of participants, followed by serum tumor marker testing (55.74%, 34/61) and barium meal examination of the upper digestive tract (29.51%, 18/61). The gastric cancer risk factor knowledge score was 9.02 ​± ​3.95, and the gastric cancer warning symptom knowledge score was 4.39 ​± ​1.85. The participants’ knowledge score was moderate, at 13.41 ​± ​5.16. The total health beliefs score was low, at 88.91 ​± ​12.66. Factors independently associated with the screening behaviors of FDRs included educational background, knowledge of gastric cancer risk factors, and health motivation (P ​

Heatwaves have been more common in China in recent years, largely attributed to human-caused global warming. While ocean variability, notably El Niño–Southern Oscillation (ENSO), influences regional heatwave fluctuations in China, the impact of other oceanic variability remains unclear. Here we show that the tropical Indian Ocean (TIO) and the tropical and subtropical North Atlantic Ocean (TSNAO) significantly modulate the decadal heatwave fluctuations in China. Among them, TIO has the most significant impact on northern China, while TSNAO has a greater impact on eastern China. TIO and TSNAO remotely influence heatwaves in China through abnormal sea surface temperatures (SSTs)-induced changes in atmospheric circulations involving westerlies and Rossby wave trains. Moreover, we demonstrated the physical processes responsible for heatwave fluctuations caused by TIO and TSNAO variability. The heatwave changes were determined jointly by vertical motion-related adiabatic and energy input-related diabatic temperature modifications. Our findings show that, in addition to ENSO, variability in the Indian and Atlantic Oceans is critical for understanding and predicting decadal heatwave changes in China.

Al (Aluminum) poisoning is a significant limitation to crop yield in acid soil. However, the physiological process involved in the peanut root response to Al poisoning has not been clarified yet and requires further research. In order to investigate the influence of Al toxicity stress on peanut roots, this study employed various methods, including root phenotype analysis, scanning of the root, measuring the physical response indices of the root, measurement of the hormone level in the root, and quantitative PCR (qPCR). This research aimed to explore the physiological mechanism underlying the reaction of peanut roots to Al toxicity. The findings revealed that Al poisoning inhibits the development of peanut roots, resulting in reduced biomass, length, surface area, and volume. Al also significantly affects antioxidant oxidase activity and proline and malondialdehyde contents in peanut roots. Furthermore, Al toxicity led to increased accumulations of Al and Fe in peanut roots, while the contents of zinc (Zn), cuprum (Cu), manganese (Mn), kalium (K), magnesium (Mg), and calcium (Ca) decreased. The hormone content and related gene expression in peanut roots also exhibited significant changes. High concentrations of Al trigger cellular defense mechanisms, resulting in differentially expressed antioxidase genes and enhanced activity of antioxidases to eliminate excessive ROS (reactive oxygen species). Additionally, the differential expression of hormone-related genes in a high-Al environment affects plant hormones, ultimately leading to various negative effects, for example, decreased biomass of roots and hindered root development. The purpose of this study was to explore the physiological response mechanism of peanut roots subjected to aluminum toxicity stress, and the findings of this research will provide a basis for cultivating Al-resistant peanut varieties.

Histones and DNA associate to form the nucleosomes of eukaryotic chromatin. Chromatin assembly factor 1 (CAF-1) complex and histone regulatory protein A (HIRA) complex mediate replication-couple (RC) and replication-independent (RI) nucleosome assembly, respectively. CHAF1B and HIRA share a similar domain but play different roles in nucleosome assembly by binding to the different interactors. At present, there is limited understanding for the similarities and differences in their respective functions. Tetrahymena thermophila contains transcriptionally active polyploid macronuclei (MAC) and transcriptionally silent diploid micronuclei (MIC). Here, the distribution patterns of Caf1b and Hir1 exhibited both similarities and distinctions. Both proteins localized to the MAC and MIC during growth, and to the MIC during conjugation. However, Hir1 exhibited additional signaling on parental MAC and new MAC during sexual reproduction and displayed a punctate signal on developing anlagen. Caf1b and Hir1 only co-localized in the MIC with Pcna1 during conjugation. Knockdown of CAF1B impeded cellular growth and arrested sexual reproductive development. Loss of HIR1 led to MIC chromosome defects and aborted sexual development. Co-interference of CAF1B and HIR1 led to a more severe phenotype. Moreover, CAF1B knockdown led to the up-regulation of HIR1 expression, while knockdown of HIR1 also led to an increase in CAF1B expression. Furthermore, Caf1b and Hir1 interacted with different interactors. These results showed that CAF-1 and Hir1 have independent and complementary functions for chromatin assembly in T. thermophila.

This paper introduces a novel method for enhancing underground pipeline inspection, specifically addressing limitations associated with traditional closed-circuit television (CCTV) systems. These systems, commonly used for capturing visual data of sewer system deformations, heavily rely on subjective human expertise, leading to limited accuracy in detection. Furthermore, their inability to perform quantitative analyses of deformation extent hampers overall inspection effectiveness. Our proposed method leverages laser point cloud data and employs a 3D scanner for objective detection of geometric deformations in underground pipe corridors. By utilizing this approach, we enable a quantitative assessment of blockage levels, offering a significant improvement over traditional CCTV-based methods. The key advantages of our method lie in its objectivity and quantification capabilities, ultimately enhancing detection reliability, accuracy, and overall inspection efficiency.

Rhodophytes (red algae) are an important source of natural products and are, therefore, a current research focus in terms of metabolite production. The recent increase in publicly available Rhodophyte whole genome and transcriptome assemblies provides the resources needed for in silico metabolic pathway analysis. Thus, this study aimed to create a Rhodophyte multi-omics resource, utilising both genomes and transcriptome assemblies with functional annotations to explore Rhodophyte metabolism. The genomes and transcriptomes of 72 Rhodophytes were functionally annotated and integrated with metabolic reconstruction and phylogenetic inference, orthology prediction, and gene duplication analysis to analyse their metabolic pathways. This resource was utilised via two main investigations: the identification of bioactive sterol biosynthesis pathways and the evolutionary analysis of gene duplications for known enzymes. We report that sterol pathways, including campesterol, β-sitosterol, ergocalciferol and cholesterol biosynthesis pathways, all showed incomplete annotated pathways across all Rhodophytes despite prior in vivo studies showing otherwise. Gene duplication analysis revealed high rates of duplication of halide-associated haem peroxidases in Florideophyte algae, which are involved in the biosynthesis of drug-related halogenated secondary metabolites. In summary, this research revealed trends in Rhodophyte metabolic pathways that have been under-researched and require further functional analysis. Furthermore, the high duplication of haem peroxidases and other peroxidase enzymes offers insight into the potential drug development of Rhodophyte halogenated secondary metabolites.

Environmental justice is an important component of sustainable tourism, but stakeholder perspectives related to environmental justice may vary. Using Q-methodology, we investigated different stakeholder perceptions related to environmental justice within the context of tourism and ecological restoration. Specifically, in the Erhai Lake basin, China, we explore perspectives around an ecological restoration effort that included the government mandated closure of 1900 establishments (inns and restaurants) in response to environmental degradation. We identify and explore four environmental justice perspectives: the togetherness, protection, operator loss, and local loss perspectives. These four perspectives are contextualized within three dimensions of environmental justice (i.e., distribution, recognition, and participation). Our findings highlight differing views related to who is affected most by the inn closures (e.g., future generations, local residents, inn owners), and general consensus related to the outcomes of the process being more important than the process itself. Finally, we discuss potential reasons for these differing perspectives and recommend ways to improve environmental justice among different stakeholders. This research can facilitate sustainable development of tourism by highlighting the facets of ecological restoration policy implementation most important to stakeholders, including recognition of diverse stakeholder concerns and identities, clear and well supported rationale for policy design, and increased equity in the distribution of costs and benefits of policies.

Malate dehydrogenase (MDH) is one kind of oxidation–reduction enzyme that catalyzes the reversible conversion of oxaloacetic acid to malic acid. It has vital functions in plant development, photosynthesis, abiotic stress responses, and so on. However, there are no reports on the genome-wide identification and gene expression of the MDH gene family in Arachis hypogaea. In this study, the MDH gene family of A. hypogaea was comprehensively analyzed for the first time, and 15 AhMDH sequences were identified. According to the phylogenetic tree analysis, AhMDHs are mainly separated into three subfamilies with similar gene structures. Based on previously reported transcriptome sequencing results, the AhMDH expression quantity of roots and leaves exposed to manganese (Mn) toxicity were explored in A. hypogaea. Results revealed that many AhMDHs were upregulated when exposed to Mn toxicity, suggesting that those AhMDHs might play an important regulatory role in A. hypogaea’s response to Mn toxicity stress. This study lays foundations for the functional study of AhMDHs and further reveals the mechanism of the A. hypogaea signaling pathway responding to high Mn stress.

After the COVID-19 pandemic has subsided, the catering industry has returned to its previous thriving scene. Many restaurants have launched group buying services and collaborate with third-party online platforms to attract more customers. For the optimal decisions and maximum profits of restaurants and online platforms, a two-layer supply chain model is designed to investigate and study the price strategies and service strategies. Considering the service levels of restaurants and platforms, we construct the mathematical expressions of the offline retail model, online retail model, and online group buying model, respectively, and solve the game equilibrium. The results are shown as follows: (1) With cooperation between the restaurant and platform, both the restaurant and platform can obtain their maximum profits when they apply optimal pricing strategies. (2) The optimal pricing strategies of the restaurant are influenced by the sensitivity coefficients of customers to the restaurant and platform’s service levels, and the cost coefficients of the restaurant and platform’s service levels. (3) The maximum profit of the restaurant is directly proportional to the number of new potential consumers who are attracted. The more potential consumers who are attracted, the higher the profit the restaurant earns. The research results provide a reference for restaurants and platforms to formulate price strategies and service strategies, to help restaurants and platforms achieve more profits.

Abstract Many cell types migrate in response to naturally generated electric fields. Furthermore, it has been suggested that the external application of an electric field may be used to intervene in and optimize natural processes such as wound healing. Precise cell guidance suitable for such optimization may rely on predictive models of cell migration, which do not generalize. Here, we present a machine learning model that can forecast directedness of cell migration given a timeseries of previous directedness and electric field values. This model is trained using time series galvanotaxis data of mammalian cranial neural crest cells obtained through time-lapse microscopy of cells cultured at 37 °C in a galvanotaxis chamber at ambient pressure. Next, we show that our modeling approach can be used for a variety of cell types and experimental conditions with very limited training data using transfer learning methods. We adapt the model to predict cell behavior for keratocytes (room temperature, ~ 18–20 °C) and keratinocytes (37 °C) under similar experimental conditions with a small dataset (~ 2–5 cells). Finally, this model can be used to perform in silico studies by simulating cell migration lines under time-varying and unseen electric fields. We demonstrate this by simulating feedback control on cell migration using a proportional–integral–derivative (PID) controller. This data-driven approach provides predictive models of cell migration that may be suitable for designing electric field based cellular control mechanisms for applications in precision medicine such as wound healing.

Abstract Background Lung cancer, the primary cause of cancer‐related deaths worldwide, is diagnosed at an advanced stage and has a poor prognosis. Non‐small cell lung cancer (NSCLC) is a major histological type of lung malignancy. This study investigated the effect of ACT001, a novel sesquiterpene lactone derivative, on the proliferation of NSCLC cells and explored the underlying mechanism. Methods The effect of ACT001 on cell proliferation was examined by clone formation and MTT assay. Differentially expressed genes and enrichment pathways were analyzed by RNA‐seq. Flow cytometry and cell cycle‐related protein expression analysis were performed to study the cell cycle. Phosphorylated AKT was detected to explore the mechanism in natural killer cell triggering receptor (NKTR) KD cells with AKT activator and/or inhibitor. The therapeutic effect of ACT001 in vivo was studied in the xenograft tumor model. Results ACT001 inhibited the proliferation and G1/S transition in NSCLC cell lines. By RNA‐seq analysis, NKTR may be the target of ACT001. Moreover, knockdown NKTR promoted cell proliferation and reversed the effects of ACT001. In addition, ACT001 inhibited AKT phosphorylation, but NKTR knockdown promoted AKT phosphorylation. Conclusion Our results suggested NKTR may be the target of ACT001 in NSCLC. ACT001 holds promise as a novel method for the treatment of NSCLC.

Abstract Medium frequency transformer (MFT) plays a key role in future power systems and new energy systems. It is very important for the safe operation of MFT to correctly calculate the temperature rise and hot spot position. According to the heat dissipation of transformer, the equivalent thermal network model of the core‐type transformer is established in this paper. The traditional thermal network model ignores the heat dissipation of the magnetic core column and the inner surface of the yoke to the air. In this paper, the magnetic core column is divided into the air surrounding part and winding surrounding part. The heat dissipation on the inner surface of the yoke is further considered. The improved thermal network model is verified by finite element simulation. The results show that compared with the traditional thermal network model, the improved thermal network model proposed in this paper can more comprehensively analyse the temperature field distribution and calculate the node temperature more accurately.

Highlights 1. The adsorption performance of BC/PU-5 for n-hexane reached the maximum of 23.6 g g−1. 2. Based on the kinetic calculation and DFT simulation, the adsorption mechanism of OSs on BC/PU-5 was discussed. 3. The quantitative correlation between the structural parameters of OSs and the adsorption properties of BC/PU-5 was established.

Abstract Schistosomiasis is a medically significant disease caused by helminth parasites of the genus Schistosoma. The schistosome life cycle requires chemically mediated interactions with an intermediate (aquatic snail) and definitive (human) host. Blocking parasite development within the snail stage requires improved understanding of the interactions between the snail host and the Schistosoma water-borne free-living form (miracidium). Innovations in snail genomics and aquatic chemical communication provide an ideal opportunity to explore snail-parasite coevolution at the molecular level. Rhodopsin G protein-coupled receptors (GPCRs) are of particular interest in studying how trematode parasites navigate towards their snail hosts. The potential role of GPCRs in parasites makes them candidate targets for new antihelminthics that disrupt the intermediate host life-cycle stages, thus preventing subsequent human infections. A genomic-bioinformatic approach was used to identify GPCR orthologs between the snail Biomphalaria glabrata and miracidia of its obligate parasite Schistosoma mansoni. We show that 8 S. mansoni rhodopsin GPCRs expressed within the miracidial stage share overall amino acid similarity with 8 different B. glabrata rhodopsin GPCRs, particularly within transmembrane domains, suggesting conserved structural features. These GPCRs include an orphan peptide receptor as well as several with strong sequence homologies with rhabdomeric opsin receptors, a serotonin receptor, a sulfakinin (SK) receptor, an allatostatin-A (buccalin) receptor and an FMRFamide receptor. Buccalin and FMRFa peptides were identified in water conditioned by B. glabrata, and we show synthetic buccalin and FMRFa can stimulate significant rates of change of direction and turn-back responses in S. mansoni miracidia. Ortholog GPCRs were identified in S. mansoni miracidia and B. glabrata. These GPCRs may detect similar ligands, including snail-derived odorants that could facilitate miracidial host finding. These results lay the foundation for future research elucidating the mechanisms by which GPCRs mediate host finding which can lead to the potential development of novel anti-schistosome interventions.

IntroductionThis article aimed to compare the prevalence of dyslipidemia and determine risk factors associated with lipid levels in a cohort of HIV-infected patients receiving two different antiretroviral therapy (ART) regimens, nucleoside reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and nucleoside reverse transcriptase inhibitor/integrase strand transfer inhibitor (NRTI/INSTI).MethodsThis longitudinal study analyzed 633 HIV-infected patients with complete blood lipid profile records for at least 1 year at the ART clinic of Zhongnan Hospital of Wuhan University, China, from June 2018 to March 2021. Demographic and clinical data, including age, gender, body weight, height, current/former/non-smoker, current drinker, diabetes mellitus, hypertension, were extracted from electronic medical records. Laboratory tests included hematology, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a) and CD4 cell count. The observation duration of this study was a maximum of 33 months. Data comparisons were performed using the Chi-square test, Student’s t-test and Mann–Whitney U test. Generalized linear mixed-effects model (GLMM) and value of p

Abstract This paper introduces the in vitro test method of hypoglycemic components in food‐grade natural products. The specific steps and results of the experimental methods were introduced in detail, including enzyme inhibition test, inhibition kinetics test, multispectral analysis, cell screening model test, molecular docking, and molecular dynamics test. Through the above series of tests, we can judge whether the components in natural products have a lowering effect on blood glucose and analyze the mechanism of action.

BackgroundIt is well documented that birth weight and childhood weight are associated with the blood pressure (BP) levels in childhood. However, the impact of weight status change from birth to childhood on BP among children is less well described. We aimed to assess the association between changes in weight status from birth to childhood and high BP in childhood.Methods and resultsData were obtained from a cross-sectional survey conducted in Jinan, China, and a total of 5,546 children aged 6–17 years were included in this study. Based on the birth weight status [high weight (> 4,000 g) vs. normal weight (2,500–4,000 g)] and childhood weight status during the survey period [high weight (overweight and obesity) vs. normal weight], children were assigned into four groups: persistently normal weight (normal birth weight and normal childhood weight), resolved high weight (high birth weight but normal childhood weight), incident high weight (normal birth weight but high childhood weight), and persistently high weight (high birth weight and high childhood weight). After adjustment for sex and age, BP in childhood was more responsive to current body mass index (BMI) than birth weight. After adjustment for the potential covariates, compared with children who had persistently normal weight from birth to childhood, those with incident high weight (odds ratio [OR] = 3.88, 95% confidence interval [CI] = 3.29–4.57) and persistently high weight (OR = 3.52, 95% CI = 2.71–4.57) were associated with the increased odds of childhood high BP. However, children who had resolved high weight did not have significantly increased odds of high BP in childhood (OR = 0.86, 95% CI = 0.59–1.25).ConclusionThe association of BP with recent BMI was stronger than with birth weight. Children who had incident or persistently high weight from birth to childhood had increased odds of high BP in childhood, whereas the odds was not significantly increased among those with high birth weight but changed to normal weight in childhood. Our findings highlight the importance of maintaining an appropriate weight in the early lifetime for the prevention of high BP and other related diseases, especially for those with high birth weight.

BackgroundVitamin D deficiency is common in critically ill patients with suspected infection and is strongly associated with the predisposition of sepsis and a poor prognosis. The effectiveness of vitamin D supplementation for preventing sepsis remains unclear. This retrospective cohort study investigated the effect of vitamin D supplementation on sepsis prophylaxis in critically ill patients with suspected infection.MethodsThis retrospective cohort study included 19,816 adult patients with suspected infection in intensive care units (ICU) from 2008 to 2019 at the Beth Israel Deaconess Medical Center, Boston, USA. The included patients were divided into the vitamin D cohort or non-vitamin D cohort according to vitamin D administration status. The primary outcomes were the incidence of sepsis in ICU. The secondary outcomes included 28-day all-cause mortality, length of ICU and hospital stay and the requirements of vasopressors or mechanical ventilation. A propensity score matching cohort was used to test the differences in primary and secondary outcomes between groups.ResultsThe results showed that vitamin D supplementation demonstrated a lower risk of sepsis (odd ratio 0.46; 95% CI 0.35–0.60; P < 0.001) and a lower risk of new mechanical ventilation requirement (odd ratio 0.70; 95% CI 0.53-0.92; P = 0.01), but no significant difference in the risk of 28-day mortality was observed (hazard ratio 1.02; 95% CI 0.77–1.35; P = 0.89). In the sensitive analysis, among the patients who suspected infection within 24 h before or after ICU admission, a lower risk of sepsis and a lower percentage of new mechanical ventilation also were detected in the vitamin D cohort.ConclusionVitamin D supplementation may have a positively prophylactic effect on sepsis in critically ill patients with suspected infection.

BackgroundIt is well-known that secondhand smoke exposure in childhood or adolescence is positively associated with morbidity and mortality. However, less is known about the current status of and most recent trends in secondhand smoke exposure among adolescents in China. ObjectiveWe aimed to assess recent changes in the prevalence of secondhand smoke exposure among adolescents in China using nationally representative data. MethodsWe used data from 2 repeated national cross-sectional surveys conducted in 2013-2014 and 2019. A total of 155,117 students (median age 13.5 years) in 2013-2014 and 147,270 students (median age 13.1 years) in 2019 were included in this study. Sociodemographic factors and secondhand smoke exposure information were collected via a standardized questionnaire. Exposure was defined as secondhand smoke exposure ≥1 day during the past 7 days at home or in public places. Other frequencies of secondhand smoke exposure (ie, ≥3 days, ≥5 days, and every day) during the past 7 days were also assessed. The weighted prevalence of secondhand smoke exposure was calculated according to the complex sample design for surveys. ResultsThe prevalence of secondhand smoke exposure in any place (home or public places ≥1 day during the past 7 days) decreased from 2013-2014 (72.9%, 95% CI 71.5%-74.3%) to 2019 (63.2%, 95% CI 62%-64.5%), as did exposure at home (2013-2014: 44.4%, 95% CI 43.1%-45.7%; 2019: 34.1%, 95% CI 33.1%-35.2%) and in public places (2013-2014: 68.3%, 95% CI 66.9%-69.6%; 2019: 57.3%, 95% CI 56%-58.6%). The prevalence of secondhand smoke exposure decreased with increased gross domestic product per capita in each of the 2 survey years irrespective of exposure frequency or location. The prevalence of exposure at other frequencies (ie, ≥3 days, ≥5 days, or every day during the past 7 days) also decreased in any place, at home, and in public places. Secondhand smoke exposure was associated with higher school grade level (ninth vs seventh grade: odds ratio [OR] 1.76, 95% CI 1.68-1.84), gender (boys vs girls: OR 1.18, 95% CI 1.15-1.22), urban status (urban vs rural: OR 1.10, 95% CI 1.01-1.19), and cigarette smoking (yes vs no: OR 6.67, 95% CI 5.83-7.62). ConclusionsAlthough the prevalence of secondhand smoke exposure among Chinese adolescents declined from 2013-2014 to 2019, it remains unacceptably high. More effective strategies and stronger action are needed in China to further, and dramatically, curb secondhand smoke exposure among adolescents.

Due to the superior thermal conductivity and high uranium density, U3Si2 is an excellent candidate for conventional UO2 nuclear fuel and shows great potential application in accident-tolerant fuel (ATF) assembly of light water reactors (LWRs). Currently, the behavior of Xe bubbles with internal or applied stress is rarely investigated, restricting further understanding of swelling in U3Si2. The mesoscopic phase-field method has been developed in this work to study the spatial and temporal Xe bubble evolution in U3Si2. The results show that the bubble density and its average size increase as the fission rate increases. Applied stress accelerates the nucleation and growth of gas bubbles, reshaping the bubbles’ morphology from spherical in a stress-free state into elongated along the applied direction in a stressed state. The gas bubbles in a local dislocation stress field nucleate preferentially at stress-concentrated sites and spread over the whole system in succession, and the bubble coarsening is controlled by the stress overlap of the dislocation pair. The results show a practical phase-field method for Xe bubble evolution study in U3Si2, which can be expanded into swelling behavior investigation in other fuels and lay a solid foundation for the development of ATF assembly.

Background: The metabolic processes involving amino acids are intimately linked to the onset and progression of cancer. Long non-coding RNAs (LncRNAs) perform an indispensable function in the modulation of metabolic processes as well as the advancement of tumors. Non-etheless, research into the role that amino acid metabolism-related LncRNAs (AMMLs) might play in predicting the prognosis of stomach adenocarcinoma (STAD) has not been done. Therefore, This study sought to design a model for AMMLs to predict STAD-related prognosis and elucidate their immune properties and molecular mechanisms.Methods: The STAD RNA-seq data in the TCGA-STAD dataset were randomized into the training and validation groups in a 1:1 ratio, and models were constructed and validated respectively. In the molecular signature database, This study screened for genes involved in amino acid metabolism. AMMLs were obtained by Pearson’s correlation analysis, and predictive risk characteristics were established using least absolute shrinkage and selection operator (LASSO) regression, univariate Cox analysis, and multivariate Cox analysis. Subsequently, the immune and molecular profiles of high- and low-risk patients and the benefit of the drug were examined.Results: Eleven AMMLs (LINC01697, LINC00460, LINC00592, MIR548XHG, LINC02728, RBAKDN, LINCOG, LINC00449, LINC01819, and UBE2R2-AS1) were used to develop a prognostic model. Moreover, high-risk individuals had worse overall survival (OS) than low-risk patients in the validation and comprehensive groups. A high-risk score was associated with cancer metastasis as well as angiogenic pathways and high infiltration of tumor-associated fibroblasts, Treg cells, and M2 macrophages; suppressed immune responses; and a more aggressive phenotype.Conclusion: This study identified a risk signal associated with 11 AMMLs and established predictive nomograms for OS in STAD. These findings will help us personalize treatment for gastric cancer patients.

Summary: Background: Association of timing and intensity of maternal smoking during pregnancy with all-cause and cause-specific infant death remains inconclusive. We aimed to examine the dose–response association of maternal smoking during each of the three trimesters of pregnancy with all-cause and cause-specific infant death. Methods: In this nationwide, population-based, retrospective cohort study, data were extracted from the U.S. National Vital Statistics System, 2015–2019. We included mother–infant pairs after excluding twin or multiple births, newborns with gestation age

Activin receptor-like kinase 7 (ALK7) is a type I receptor in the TGF-β superfamily preferentially expressed in adipose tissue and associated with lipid metabolism. Inactivation of ALK7 signaling in mice results in increased lipolysis and resistance to both genetic and diet-induced obesity. Human genetic studies have recently revealed an association between ALK7 variants and both reduced waist to hip ratios and resistance to development of diabetes. In the present study, treatment with a neutralizing mAb against ALK7 caused a substantial loss of adipose mass and improved glucose intolerance and insulin resistance in both genetic and diet-induced mouse obesity models. The enhanced lipolysis increased fatty acid supply from adipocytes to promote fatty acid oxidation in muscle and oxygen consumption at the whole-body level. The treatment temporarily increased hepatic triglyceride levels, which resolved with long-term Ab treatment. Blocking of ALK7 signals also decreased production of its ligand, growth differentiation factor 3, by downregulating S100A8/A9 release from adipocytes and, subsequently, IL-1β release from adipose tissue macrophages. These findings support the feasibility of potential therapeutics targeting ALK7 as a treatment for obesity and diabetes.

Previous studies on English natives have shown that encountering an English cataphoric pronoun triggers an active search for its antecedent and this searching process is modulated by syntactic constraints. It remains unknown whether the conclusion is universal to EFL (English as a Foreign Language) learners, particularly those with distinct L1 like Chinese in linguistic typology. Therefore, this study used two eye-tracking experiments to investigate how Chinese EFL learners resolve English cataphora. The experiments adopted the gender-mismatch paradigm. Experiment 1 investigated whether Chinese EFL learners with different proficiency would adopt the similar processing pattern to English natives and found that gender congruency elicited longer reading times than gender incongruency between the first potential antecedent and the cataphoric pronoun, the effect early observed in high-proficiency relative to low-proficiency learners. Experiment 2 explored whether the cataphora resolution process was modulated by Binding Principle B and revealed that longer first fixation durations and first pass reading times were observed in gender-mismatch than in gender-match conditions no matter the antecedents are binding-accessible or not while longer regression path durations occurred in gender-mismatch than in gender-match conditions only as the antecedents are binding-accessible. Taken together, these results indicate that Chinese EFL learners also adopt an active search mechanism to resolve cataphoric pronouns, yet along a processing path distinct from English natives’. Specifically, Chinese EFL learners predictively link a cataphoric pronoun to the first potential antecedent in the sentence but only a gender-matching antecedent can prompt them to engage in deep processing of the antecedent. Moreover, the processing time varies with the learners’ English proficiency. Furthermore, unlike native English speakers’ early application of syntactic constraints in their cataphora resolution, Chinese EFL learners try to establish co-reference relations between cataphoric pronouns and antecedents regardless of following or flouting Binding Principle B in early processing stages whereas they exclusively link the cataphoric pronouns to the binding-accessible antecedents in late processing stages. This study adds evidence to the Shallow Structure Hypothesis whereby L2 learners resort to lexical prior to syntactic cues to process sentences in general, which is just opposite to the fashion adopted by the natives.

ABSTRACT Clostridioides difficile infection (CDI), recurrently reported as an urgent threat owing to its increased prevalence and mortality, has attracted significant attention. As the use of antibiotics to treat CDI has many limitations, such as high recurrence rate, the need to actively seek and develop other drugs that can effectively treat CDI with fewer side effects has become a key issue in CDI prevention and treatment. This study aimed to evaluate the inhibitory effect of Galla chinensis (GC) and its main component, tannic acid (TA), against C. difficile in vitro and its therapeutic effect on CDI in vivo. When GC and TA concentrations were 250 and 64 mg/L, respectively, the cumulative antibacterial rate against C. difficile reached 100%. The sub-MIC of TA significantly inhibited C. difficile sporulation, toxin production, and biofilm formation in vitro. Compared with the CDI control group, TA-treated mice lost less weight and presented a significantly improved survival rate. TA significantly reduced the number of spores in feces, decreased serum TcdA level, and increased serum interleukin 10 (IL-10). Based on the inhibitory effect of TA on C. difficile in vitro and its therapeutic effect on the CDI mouse model, we consider TA as a potentially effective drug for treating CDI. IMPORTANCE Clostridioides difficile is one of the major pathogens to cause antibiotic-associated diarrhea. Although antibiotic treatment is still the most commonly used and effective treatment for CDI, the destruction of indigenous intestinal microbiota by antibiotics is the main reason for the high CDI recurrence rate of about 20%, which is increasing every year. Moreover, the growing problem of drug resistance has also become a major hidden danger in antibiotic treatment. GC has been used to treat diarrhea in traditional Chinese medicine. In the present study, we evaluated the inhibitory effect of TA, the main component of GC, on dissemination and pathogenic physiological functions of C. difficile in vitro, as well as its therapeutic efficacy in a CDI model. Overall, TA is considered to be a potentially effective drug for CDI treatment.

IntroductionPlant-associated microbes critically shape the dynamics of plant-and insect-associated communities. In previous studies, we reported that the yellow peach moth Conogethes punctiferalis (YPM) preferred to Penicillium digitatum-infected apples (PDA) for oviposition. However, the underlying mechanisms remains unclear.MethodsIn the present study, the behavioral and physiological experiments were conducted to determine how P. digitatum affects the oviposition selection of mated YPM females via altering host plant volatile organic compounds (VOCs).ResultsMated YPM females were attracted to and laid more eggs on PDA than on non-infected apples (NIA), mechanically damaged apples (MDA), and P. digitatum in potato dextrose agar medium (PPD) in the oviposition selection experiments. Four-arm olfactometer assays further confirmed that odors in PDA were responsible for the attractiveness of mated YPM females. Further analyses showed that 38 VOCs were collected and identified from all treatments by GC-MS, with five specific VOCs (methyl 2-methylbutyrate, styrene, methyl caproate, butyl caprylate, and n-tetradecane) emitting from PDA. A principal component analysis (PCA) based on the absolute contents of 38 VOCs revealed a clear separation of PDA from NIA, MDA, and PPD. Moreover, when P. digitatum-induced specific VOCs were added to apples in individual or synthetic blends, there was a significantly higher percentage of mated YPM females to apples with individual or synthetic blends consisting of methyl 2-methylbutyrate, butyl caprylate, or n-tetradecane in Y-tube olfactometer experiments, suggesting that these three specific VOCs acted as predominant olfactory signals for mated YPM females to PDA.DiscussionTaken together, the microbe P. digitatum was an important driver of the interactions between YPMs and host plants by altering plant volatiles. These findings may form the basis for developing attractant baits for field trapping YPMs in the future.

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods: A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians’ mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results: A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p

Abstract Background Wild birds may harbor and transmit viruses that are potentially pathogenic to humans, domestic animals, and other wildlife. Results Using the viral metagenomic approach, we investigated the virome of cloacal swab specimens collected from 3182 birds (the majority of them wild species) consisting of > 87 different species in 10 different orders within the Aves classes. The virus diversity in wild birds was higher than that in breeding birds. We acquired 707 viral genomes from 18 defined families and 4 unclassified virus groups, with 265 virus genomes sharing < 60% protein sequence identities with their best matches in GenBank comprising new virus families, genera, or species. RNA viruses containing the conserved RdRp domain with no phylogenetic affinity to currently defined virus families existed in different bird species. Genomes of the astrovirus, picornavirus, coronavirus, calicivirus, parvovirus, circovirus, retrovirus, and adenovirus families which include known avian pathogens were fully characterized. Putative cross-species transmissions were observed with viruses in wild birds showing > 95% amino acid sequence identity to previously reported viruses in domestic poultry. Genomic recombination was observed for some genomes showing discordant phylogenies based on structural and non-structural regions. Mapping the next-generation sequencing (NGS) data respectively against the 707 genomes revealed that these viruses showed distribution pattern differences among birds with different habitats (breeding or wild), orders, and sampling sites but no significant differences between birds with different behavioral features (migratory and resident). Conclusions The existence of a highly diverse virome highlights the challenges in elucidating the evolution, etiology, and ecology of viruses in wild birds. Video Abstract

Abstract Genomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC.

Abstract Background The mitochondrial (mt) genomes of 15 species of sucking lice from seven families have been studied to date. These louse species have highly dynamic, fragmented mt genomes that differ in the number of minichromosomes, the gene content, and gene order in a minichromosome between families and even between species of the same genus. Results In the present study, we analyzed the publicly available data to understand mt genome fragmentation in seal lice (family Echinophthiriidae) and gorilla louse, Pthirus gorillae (family Pthiridae), in particular the role of minichromosome split and minichromosome merger in the evolution of fragmented mt genomes. We show that 1) at least three ancestral mt minichromosomes of sucking lice have split in the lineage leading to seal lice, 2) one minichromosome ancestral to primate lice has split in the lineage to the gorilla louse, and 3) two ancestral minichromosomes of seal lice have merged in the lineage to the northern fur seal louse. Minichromosome split occurred 15-16 times in total in the lineages leading to species in six families of sucking lice investigated. In contrast, minichromosome merger occurred only four times in the lineages leading to species in three families of sucking lice. Further, three ancestral mt minichromosomes of sucking lice have split multiple times independently in different lineages of sucking lice. Our analyses of mt karyotypes and gene sequences also indicate the possibility of a host switch of crabeater seal louse to Weddell seals. Conclusions We conclude that: 1) minichromosome split contributes more than minichromosome merger in mt genome fragmentation of sucking lice, and 2) mt karyotype comparison helps understand the phylogenetic relationships between sucking louse species.

Abstract In this paper, a cyber‐physical description of mixed traffic that can reflect the interaction between vehicles is first proposed. By treating vehicles as nodes and the cyber‐physical interaction between vehicles as directed edges between nodes, the network of vehicles in traffic is obtained. The small‐world and scale‐free characteristics of mixed traffic are found under this description. Then the CPS‐based pinning approach for achieving indirect control of HVs is proposed. Besides the control algorithm of pinning nodes, the impact of the spatial distribution of automated vehicles on traffic is studied. The approach is compatible with the existing control of automated vehicle in mixed vehicle platoon. Numerical simulation results under three‐lane scenario illustrated the effectiveness of the proposed pinning approach.

Despite effective vaccines against SARS-CoV-2, therapeutic options such as anti-virals and neutralizing antibodies are critical in treating disease, especially given the breakthrough infections of emerging VOCs. Here, Peng et al. generate two potent monoclonal antibodies and a bispecific antibody with two antigenrecognition variable regions targeting SARS-CoV-2 spike, provide CryoEM structures and show in vitro and in vivo efficacy of a humanized antibody against wildtype virus and delta variant.

The extraction and identification of microleakage signal caused by the corrosion of gathering pipelines in the oil and gas fields is a great technical challenge for leakage monitoring. Therefore, a microleakage locating algorithm of gas gathering pipeline based on whitening filter was proposed for the microleakage signal submerged in the pipeline.noise As the acquired signal of gathering pipeline contains an abundance of low-frequency components, tracking with the adaptive whitening filter can eliminate the low-frequency components, so that the power spectrum of the acquired signal becomes flat and close to the white noise. The microleakage signal processed by whitening filter is enhanced, and the signal-to-noise ratio (SNR) is increased by nearly 4 dB. At the same time, the cross-correlation operation with the signals processed by whitening filter can calculate the time delay of signals at both ends of pipline, futher locate the microleakage point of gathering pipeline by leakage positioning formula. According to the calculation results, the algorithm can accurately locate the microleakage signal of the oil and gas field gathering pipeline, with error of 2 m. Thus, demonstration application should be provided for various media at different pressure levels under different topographic conditions, so as to improve the locating accuracy of the algorithm, further providing technical support for the construction of no-leakage demonstration area.

In the paper, under the stress of aggregation and reproduction mechanism of algae, we proposed a modified algae and fish model with aggregation and Allee effect, its main purpose was to further ascertain the dynamic relationship between algae and fish. Several critical conditions were investigated to guarantee the existence and stabilization of all possible equilibrium points, and ensure that the model could undergo transcritical bifurcation, saddle-node bifurcation, Hopf bifurcation and B-T bifurcation. Numerical simulation results of related bifurcation dynamics were provided to verify the feasibility of theoretical derivation, and visually demonstrate the changing trend of the dynamic relationship. Our results generalized and improved some known results, and showed that the aggregation and Allee effect played a vital role in the dynamic relationship between algae and fish.

Raw camel milk is generally contaminated with varied microbiota, including antibiotic–resistant bacteria (ARB), that can act as a potential pathway for the spread of antibiotic resistance genes (ARGs). In this study, high–throughput quantitative PCR and 16S rRNA gene–based Illumine sequencing data were used to establish a comprehensive understanding of the antibiotic resistome and its relationship with the bacterial community in Bactrian camel milk from Xinjiang. A total of 136 ARGs and up to 1.33 × 108 total ARG copies per gram were identified, which predominantly encode resistance to β–lactamas and multidrugs. The ARGs’ profiles were mainly explained by interactions between the bacteria community and physicochemical indicators (77.9%). Network analysis suggested that most ARGs exhibited co–occurrence with Corynebacterium, Leuconostoc and MGEs. Overall, raw camel milk serves as a reservoir for ARGs, which may aggravate the spread of ARGs through vertical and horizontal gene transfer in the food chain.

Background:The atherogenic index of plasma (AIP), determined by the logarithmic transformation of the ratio of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), was found to be a marker of cardiovascular disease. We sought to investigate the correlation between the atherogenic AIP and coronary collateral circulation (CCC) formation in chronic total occlusive (CTOs) patients. Methods: This retrospective cohort study included 665 non-CTOs and 345 CTOs patients. CTOs were divided into 206 CCC poor formation patients and 139 CCC good formation patients according to the Cohen-Rentrop grade. Spearman correlation analysis was carried out to obtain the relationship between AIP and the Rentrop grade. We used multivariate logistic regression analysis to assess CTOs and CCC poor formation risk factors. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold for AIP to predict CTOs and CCC poor formation. The predicted increment of AIP on CTOs and CCC poor formation was evaluated by calculating the Net Reclassification Index (NRI) and the Integrated Discriminant Index (IDI). Results: AIP in CTOs was significantly elevated compared to non-CTOs patients [(1.55 (1.02, 2.59)) vs (1.26 (0.82, 1.90)), p < 0.001] AIP in the CCC poor formation group was significantly higher than that in the CCC good formation group [(1.73 (1.12, 2.90)) vs (1.37 (0.84, 2.13)), p = 0.002]. There was a negative correlation between AIP and the Rentrop grade (r = –0.145, p = 0.007). The results of multivariate logistic regression revealed that AIP was an independent predictor of CTOs (OR = 4.371, 95% CI: 2.436–7.844, p < 0.001) and CCC poor formation (OR = 3.749, 95% CI: 1.628–8.635, p = 0.002). In the ROC analysis, the area under the curve of AIP for identifying CTOs and CCC poor formation was 0.596 (OR = 3.680, 95% CI: 1.490–9.090, p = 0.005) and 0.597 (95% CI: 0.535–0.658, p = 0.002), respectively. Conclusions: Contrary to previous research, we found that AIP is a moderate but not powerful indicator for detecting both CTO patients and poor CCC formation.

Abnormal corneal wound healing can compromise corneal transparency and lead to visual impairment. Mineralocorticoid receptor antagonists (MRA) are promising candidates to promote corneal remodeling with anti-inflammatory properties and lack gluococorticoids-associated side effects. In this preclinical study, a new polymer-free hydroxypropyl-gamma-cyclodextrin-based eyedrop containing 0.1% spironolactone (SPL), a potent but non-water-soluble MRA, was investigated for its ocular surface tolerance and efficacy in a rat model of corneal wound healing. SPL eyedrops were stable for up to 9 months at 4 °C. The formulation was well-tolerated since no morphological changes or inflammatory reactions were observed in the rat cornea after multiple daily instillations over 7 days. SPL eyedrops accelerated rat corneal wound healing, reduced corneal edema and inflammation, enhanced epithelial integrity, and improved nerve regeneration, suggesting restoration of corneal homeostasis, while potassium canrenoate, an active and soluble metabolite of SPL, had no effect. SPL eyedrops could benefit patients with impaired corneal wound healing, including that secondary to glucocorticoid therapy. Repurposing known drugs with known excipients will expedite translation to the clinic.

Corneal wound healing is a complex biological process that integrates a host of different signals to coordinate cell behavior. Upon wounding, there is the generation of an endogenous wound electric field that serves as a powerful cue to guide cell migration. Concurrently, the corneal epithelium reduces sialylated glycoforms, suggesting that sialylation plays an important role during electrotaxis. Here, we show that pretreating human telomerase-immortalized corneal epithelial (hTCEpi) cells with a sialyltransferase inhibitor, P-3FAX-Neu5Ac (3F-Neu5Ac), improves electrotaxis by enhancing directionality, but not speed. This was recapitulated using Kifunensine, which inhibits cleavage of mannoses and therefore precludes sialylation on N-glycans. We also identified that 3F-Neu5Ac enhanced the responsiveness of the hTCEpi cell population to the electric field and that pretreated hTCEpi cells showed increased directionality even at low voltages. Furthermore, when we increased sialylation using N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz), hTCEpi cells showed a decrease in both speed and directionality. Importantly, pretreating enucleated eyes with 3F-Neu5Ac significantly improved re-epithelialization in an ex vivo model of a corneal injury. Finally, we show that in hTCEpi cells, sialylation is increased by growth factor deprivation and reduced by PDGF-BB. Taken together, our results suggest that during corneal wound healing, reduced sialylated glycoforms enhance electrotaxis and re-epithelialization, potentially opening new avenues to promote corneal wound healing.

The accuracy of gridded precipitation products is uncertain in different temporal and spatial dimensions. Analyzing the applicability of precipitation products is a prerequisite before applying them to hydrometeorological and other related research. In this study, we selected three gridded precipitation products, Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG), Global Satellite Mapping of Precipitation (GSMaP), and the fifth generation of atmospheric reanalysis of the European Centre for Medium-Range Weather Forecasts (ERA5), including their data from 2001 to 2020. Using the data from 699 ground observation stations, we evaluated the applicability of these three precipitation products in China. Based on five statistical and five classification indicators, we first assessed the applicability of the three precipitation products on daily, monthly, and annual time scales, respectively, and then evaluated their applicability in different spatial dimensions, including basins, agriculture, and geomorphology. The results showed that: (1) IMERG data had the best accuracy on annual and monthly time scales, with both correlation coefficient (CC) values greater than 0.95 and Kling–Gupta efficiency (KGE) values greater than 0.90. On a daily time scale, the accuracy of all three precipitation products differed when statistical or categorical indicators were considered alone. However, the applicability of IMERG data was best among the three precipitation products when both types of indicators were considered. (2) The accuracy of the three precipitation products gradually decreased along the southeast–northwest direction. The applicability of ERA5 data was better in northern regions than in other regions in China, especially in arid and semi-arid regions in northern China. The applicability of IMERG data was better in southern regions with more precipitation and in high-altitude regions than in other regions in China. (3) The applicability of the three precipitation products in plain areas was generally better than in mountain areas. Among them, ERA5 data were more accurate in plain areas, while IMERG data were more accurate in mountain areas. This study can provide a reference for the selection of data sources of gridded precipitation products in different time scales and spatial dimensions in China.

Background: Cervical cancer is the fourth most common cancer in women, with an estimated 600,000 new cases and 340,000 deaths worldwide in 2020. However, there remains limited understanding of the association between individual socioeconomic status, clinical characteristics, and health-related quality of life (HRQoL) of women with cervical precancerous lesions. This study investigates socioeconomic and clinical variations in HRQoL of women with cervical precancerous lesions and cervical cancer in Yunnan Province, China. Methods: The present study employed a cross-sectional survey design. An EuroQol Five Dimensions Five Level (EQ-5D-5L) questionnaire was used to assess HRQoL of 400 patients with cervical precancerous lesions and cervical cancer in Yunnan Province, China, from 2019 to 2020. Analysis of variance (ANOVA) and independent samples t-tests were performed to identify the independent variables associated with EQ-5D-5L utility scores and visual analogue scale (VAS) scores. Predictors of utility scores were confirmed using a Tobit regression model. Results: The mean EQ-5D-5L utility scores of cervical precancerous lesions and cervical cancer patients was 0.939 (standard deviation (SD), 0.104), and the mean VAS score was 80.84 (SD, 16.551). Patients aged 40–59 years (β = –0.037, p = 0.005), patients who were not aware of the human papillomavirus (HPV) vaccine (β = –0.032, p = 0.004), and patients who underwent radical hysterectomy (β = –0.036, p = 0.006) had significantly lower utility scores, whereas having high monthly household income (β = 0.023, p = 0.033) was significantly associated with higher EQ-5D-5L utility scores. Age (p = 0.023) was statistically significant in differences in patients’ VAS scores. Anxiety/depression was the most frequently reported issue (35.75%) among participants. Conclusions: Future cervical cancer prevention and treatment guidelines should focus on low-income women, women aged 40–59 years, and those lacking knowledge about cervical cancer prevention.

Manganese (Mn) is among one of the essential trace elements for normal plant development; however, excessive Mn can cause plant growth and development to be hindered. Nevertheless, the regulatory mechanisms of plant root response to Mn poisoning remain unclear. In the present study, results revealed that the root growth was inhibited when exposed to Mn poisoning. Physiological results showed that the antioxidase enzyme activities (peroxidase, superoxide dismutase, ascorbate peroxidase, and catalase) and the proline, malondialdehyde, and soluble sugar contents increased significantly under Mn toxicity stress (100 μM Mn), whereas the soluble protein and four hormones’ (indolebutyric acid, abscisic acid, indoleacetic acid, and gibberellic acid 3) contents decreased significantly. In addition, the Mn, Fe, Na, Al, and Se contents in the roots increased significantly, whereas those of Mg, Zn, and K decreased significantly. Furthermore, RNA sequencing (RNA-seq) analysis was used to test the differentially expressed genes (DEGs) of soybean root under Mn poisoning. The results found 45,274 genes in soybean root and 1430 DEGs under Mn concentrations of 5 (normal) and 100 (toxicity) μM. Among these DEGs, 572 were upregulated and 858 were downregulated, indicating that soybean roots may initiate complex molecular regulatory mechanisms on Mn poisoning stress. The results of quantitative RT-PCR indicated that many DEGs were upregulated or downregulated markedly in the roots, suggesting that the regulation of DEGs may be complex. Therefore, the regulatory mechanism of soybean root on Mn toxicity stress is complicated. Present results lay the foundation for further study on the molecular regulation mechanism of function genes involved in regulating Mn tolerance traits in soybean roots.

The automobile is an important part of transportation systems. Accurate prediction of sales prospects of different power vehicles can provide an important reference for national scientific decision making, flexible operation of enterprises and rational purchases of consumers. Considering that China has achieved the goal of 20% sales of new energy vehicles ahead of schedule in 2025, in order to accurately judge the competition pattern of new and old kinetic energy vehicles in the future, the automobile market is divided into three types according to power types: traditional fuel vehicles, new energy vehicles and plug-in hybrid vehicles. Based on the monthly sales data of automobiles from March 2016 to March 2023, the prediction effects of multiple models are compared from the perspective of univariate prediction. Secondly, based on the perspective of multivariate prediction, combined with the data of economic, social and technical factors, a multivariate prediction model with high prediction accuracy is selected. On this basis, the sales volume of various power vehicles from April 2023 to December 2025 is predicted. Univariate prediction results show that in 2025, the penetration rates of three types of vehicles will reach 43.8%, 44.4% and 11.8%, respectively, and multivariate prediction results show that the penetration rates will reach 51.0%, 37.9% and 11.1%, respectively.

The photovoltaic performance of organic solar cells (OSCs) are strongly influenced by the functionality of hole extraction layers. In this work, a bilayer structure hole extraction layer (HEL) of S-MoO3/GO was formed by solution processed MoO3 (S-MoO3) and graphene oxide (GO). The application of hybrid HEL helped polish the interfacial contact between HEL and active layers, resulting in an increased exciton dissociation, diminished charge recombination losses, and more efficient charge extraction probability, and thereby achieving improved photovoltaic performance. The excellent charge extraction capability was proved in nonfullerene PM6:Y6 and fullerene PTB7-Th:PC71BM blend system based cells. A champion efficiency of 13.56% was observed in PM6:Y6 based cell with S-MoO3/GO HEL, which was >34% higher than the efficiency of 10.08% in the control cell with pristine S-MoO3 HEL.