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Based on the principle of super-symmetric lens with quadratic phase gradient transformation, combined with the principle of digital coding of metasurface, we propose a wide-angle coded metalens for focusing control in two-dimensional space. This metalens achieves focus shift in the x-direction by changing the oblique incidence angle of the incident wave, and focus control in the y-direction by combining with the convolution principle of the digitally coded metasurface to achieve flexible control of light focusing in the two-dimensional plane. The metasurface unit is mainly composed of three-layer of metal structure and two layers of medium, and the transmission phase is obtained by changing the middle layer of metal structure, which in turn obtains the required phase distribution of the metalens. The design of the metalens realizes the function of the lens with a large viewing angle at the x-polarized incidence, and realizes two-dimensional focus control. Experimentally, we prepared the designed coding metalens and tested the focus control function of the wide-angle coding metalens. The experimental results are in good agreement with the design results.

Abstract Background Rhodococcus equi (R. equi) is a Gram-positive zoonotic pathogen that frequently leads to illness and death in young horses (foals). This study presents the complete genome sequence of R. equi strain BJ13, which was isolated from a thoroughbred racehorse breeding farm in Beijing, China. Results The BJ13 genome has a length of 5.30 Mb and consists of a complete chromosome and a plasmid measuring 5.22 Mb and 0.08 Mb, respectively. We predicted 4,929 coding gene open reading frames, along with 52 tRNAs and 12 rRNAs. Through analysis of mobile genetic elements, we identified 6 gene islands and 1 prophage gene. Pathogenic system analysis predicted the presence of 418 virulence factors and 225 drug resistance genes. Secretion system analysis revealed the prediction of 297 secreted proteins and 1,106 transmembrane proteins. BJ13 exhibits genomic features, virulence-associated genes, potential drug resistance, and a virulence plasmid structure that may contribute to the evolution of its pathogenicity. Lastly, the pathogenicity of the isolated strain was assessed through animal experiments, which resulted in inflammatory reactions or damage in the lungs, liver, and spleen of mice. Moreover, by the 7th day post-infection, the mortality rate of the mice reached 50.0%, indicating complex immune regulatory mechanisms, including overexpression of IL-10 and increased production of pro-inflammatory cytokines like TNF-α. These findings validate the strong pathogenicity of the isolated strain and provide insights for studying the pathogenic mechanisms of Rhodococcus equi infection. Conclusions The complete genome sequence of R. equi strain BJ13 provides valuable insights into its genomic characteristics, virulence potential, drug resistance, and secretion systems. The strong pathogenicity observed in animal experiments underscores the need for further investigation into the pathogenic mechanisms of R. equi infection.

Abstract Objectives The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. Methods Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. Results The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. Conclusions The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

BackgroundPer- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. ObjectiveTo analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. MethodsBased on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable.ResultsPerfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P 300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income

BackgroundPesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. ObjectiveTo evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. MethodsThis study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑2OPs, ∑2PYRs, and ∑2NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. ResultsThe median creatinine-adjusted concentrations of ∑2OPs, ∑2PYRs, and ∑2NEOs in this study were 419.77, 2.95, and 20.36 nmol·g−1, respectively. The multiple linear regression results showed that the urinary concentration of ∑2OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P

A Ti–48Al–2Cr–2Nb alloy was produced by electron beam powder bed fusion. The effect of the volume energy density parameter on the forming quality was investigated, and the tissue characteristics, hardness distribution, and mechanical properties of the alloy were analyzed. The results showed that the quality was better when the volume energy density parameter was 21.5–22.5 J/mm3. The microstructure of the alloy has the phenomenon of changing with the forming height: with an increase in the forming height, the forming part produces the phenomenon of strip microstructure along the construction direction, and the regional microstructure variability occurs under the cross section of the same height. The average hardness of the alloy reached 375.2 HV at the bottom, 381.8 HV in the middle, and 389.6 HV at the top, and the standard errors of the hardness values were 12.40, 10.49, and 7.12 HV, respectively, with the microhardness showing a gradual increase along the molding direction, and the homogeneity was gradually better. The transverse tensile strength at room temperature reached 526 MPa, the yield strength reached 461 MPa, and the elongation at break reached 1.24%, while the longitudinal tensile strength reached 486 MPa, the yield strength reached 414 MPa, and the elongation at break reached 1.02%.

Based on the new era, “curriculum ideology and politics” as the mainstream advanced educational concept is the focus of teaching reform in higher education institutions. The rapid development of the food industry has put forward higher requirements for “three comprehensive education”. Modern food testing technology, as a fundamental course in the food industry, includes rich knowledge of detecting food through modern technological means, while the course contents also contain rich ideological and political factors, and occupies an important position in China's food discipline. With moral education as the core, it comprehensively promotes the construction of ideological and political courses and meets the high-quality training of high-quality talents, which is the top priority of teaching reform. This study adopts descriptive, qualitative research methods and mixed approach, collecting data through practical operations, interview techniques, and literature review. This analysis utilized continuous participatory techniques, including stages of observation, practice, interviews, case studies, focus group discussions and literature research, presentation, and drawing conclusions. In view of the current practice and exploration, this article extracts the commonalities between science and engineering courses and ideological and political education for integration to break the singularity of teaching practice. At the same time, it constructs a “three in one” collaborative education mechanism to enhance the organic integration of ideological and political education and curriculum teaching, in order to achieve the goal of inheriting the past and opening up the future. By introducing the significance and construction strategies of ideological and political education in the course of Modern Food Testing Technology, this article aims to provide suggestions and references for the reform of ideological and political education in relevant courses in universities.

Abstract The Beijing-Tianjin-Hebei integration plan rose to the status of a national-level strategy in 2014. This paper provides a deep analysis of the Beijing-Tianjin-Hebei area’s inter-city commuter big data. This research analyzed the overview of spatial structure, polycentric structure, hierarchical structure and clustering characteristics of the BTH based on network analysis methods. It reveals that the inter-city commuter network exhibits clear polycentric characteristics, with Beijing acting as the central hub. The degree of network correlation between cities in Tianjin and Hebei is notably low, indicating that the flow of people primarily revolves around Beijing, while interactions between other cities remain limited. Therefore, it is necessary to further decentralize Beijing's non-capital core functions. The level of connectedness among the areas surrounding the Bohai Rim is not very high, and it has not developed the coastal advantage. The cooperation could be strengthed among the cities within Bohai Rim. The polycentric structure has initially taken shape, but it exhibits obvious polarization characteristics. It is necessary to strengthen the interaction of talents between cities to form secondary central units in BTH.

BackgroundAnxiety and depression are common perinatal mental health issues that often occur together and can have serious negative effects on both maternal and infant health. ObjectiveTo examine the relationships between lifestyle factors and comorbid anxiety and depression (CAD) among pregnant women in Shanghai. MethodsThe study estimated the prevalence of CAD during the first, second, and third trimesters of pregnancy using the Self-rating Anxiety Scale (SAS) and Center for Epidemiological Studies-Depression (CES-D) based on data from the China National Birth Cohort (CNBC) embryonic-derived diseases with assisted reproductive technology (ART) sub-cohort. Information on demographics, sleep status, nutritional intake, and exercise during each trimester was collected through self-made questionnaires, the Pittsburgh Sleep Quality Index (PSQI), and the Food Frequency Questionnaire (FFQ). Lifestyle factors (such as sleep status, nutritional intake, and exercise during each trimester) were analyzed using logistic regression and generalized linear mixed models (GLMM) to determine their impacts on the prevalence of CAD (yes or no) among pregnant women. ResultsA total of 2876 pregnant women were included in this study. The prevalence of CAD was 10.6% (305), 3.6% (103), and 5.5% (159) in the first, second, and third trimesters of pregnancy, respectively. The logistic regression analysis revealed that poor sleep quality throughout the entire pregnancy were statistically associated with an increased prevalence of CAD, and the odds ratios (OR) with 95% confidence intervals (CI) were 2.817 (1.845, 4.301), 2.840 (1.855, 4.347), and 9.316 (5.835, 14.876) for the first, second, and third trimesters, respectively, when compared to good sleep quality. Additionally, compared to an intake frequency of 7 times per week, the frequency of egg intake ≤3 times per week in the first trimester (OR=2.025, 95%CI: 1.197, 3.425) and the frequency of egg intake of 4–6 times per week (OR=1.896, 95%CI: 1.117, 3.216) or ≤3 times per week (OR=1.906, 95%CI: 1.082, 3.357) in the third trimester were associated with an increased risk of CAD (P3 times per week, never or almost never exercising in the second trimester (OR=2.218, 95%CI: 1.220, 4.035) was associated with an increased risk of CAD (P

Abstract The COVID-19 pandemic has provided valuable lessons that deserve deep thought to prepare for the future. The decay pattern of surface contamination by SARS-CoV-2 RNA in the residences of COVID-19 patients is important but still unknown. We collected 2,233 surface samples from 21 categories of objects in 141 residences of COVID-19 patients in Shanghai when attacked by the omicron variant in spring 2022. Several characteristics of the patients and their residences were investigated to identify relevant associations. The decay of contamination was explored to determine the persistence. Approximately 8.7% of the surface samples were tested positive for SARS-CoV-2 RNA. The basin, water tap, and sewer inlet had the highest positive rates, all exceeding 20%. Only time was significantly associated with the level of surface contamination with SARS-CoV-2, showing a negative association. The decrease fit a first-order decay model with a decay rate of 0.77 ± 0.07 day−1, suggesting a 90% reduction in three days. Positive associations between the cumulative number of newly diagnosed patients in the same building and the positive rate of SARS-CoV-2 RNA in the public corridor were significant during the three days. Our results, in conjunction with the likely lower infectivity or viability, demonstrate that fomite transmission played a limited role in COVID-19 spread. The time determined SARS-CoV-2 RNA contamination, which was reduced by three days. This study is the first to show the decay patterns of SARS-CoV-2 contamination in real residential environments, providing insight into the patterns of transmission, as well as community-based prevention and control of similar threats.

Both genetic and environmental factors affect the morphology of oysters. Molecular identification is currently the primary means of species identification, but it is inconvenient and costly. In this research, we evaluated the effectiveness of geometric morphometric (GM) techniques in distinguishing between two oyster species, Crassostrea gigas and C. ariakensis. We used traditional morphometric and GM methods, including principal component analysis (PCA), thin-plate spline analysis (TPS) and canonical variable analysis (CVA), to identify specific features that distinguish the two species. We found that differences in shape can be visualised using GM methods. The Procrustes analysis revealed significant differences in shell morphology between C. gigas and C. ariakensis. The shells of C. ariakensis are more prominent at the widest point and are more scattered and have a greater variety of shapes. The shells of C. gigas are more oval in shape. PCA results indicated that PC1 explained 45.22%, PC2 explained 22.09% and PC3 explained 10.98% of the variation between the two species, which suggests that the main morphological differences are concentrated in these three principal components. Combining the TPS analysis function plots showed that the shell shape of C. ariakensis is mainly elongated and spindle-shaped, whereas the shell shape of C. gigas is more oval. The CVA results showed that the classification rate for the two species reached 100% which means that C. ariakensis and C. gigas have distinct differences in shell morphology and can be completely separated, based on morphological characteristics. Through these methods, a more comprehensive understanding of the morphological characteristics of different oyster populations can be obtained, providing a reference for oyster classification and identification.

Accumulating oxidative damage is a primary driver of ovarian reserve decline along with aging. However, the mechanism behind the imbalance in reactive oxygen species (ROS) is not yet fully understood. Here we investigated changes in iron metabolism and its relationship with ROS disorder in aging ovaries of mice. We found increased iron content in aging ovaries and oocytes, along with abnormal expression of iron metabolic proteins, including heme oxygenase 1 (HO-1), ferritin heavy chain (FTH), ferritin light chain (FTL), mitochondrial ferritin (FTMT), divalent metal transporter 1 (DMT1), ferroportin1(FPN1), iron regulatory proteins (IRP1 and IRP2) and transferrin receptor 1 (TFR1). Notably, aging oocytes exhibited enhanced ferritinophagy and mitophagy, and consistently, there was an increase in cytosolic Fe2+, elevated lipid peroxidation, mitochondrial dysfunction, and augmented lysosome activity. Additionally, the ovarian expression of p53, p21, p16 and microtubule-associated protein tau (Tau) were also found to be upregulated. These alterations could be phenocopied with in vitro Fe2+ administration in oocytes from 2-month-old mice but were alleviated by deferoxamine (DFO). In vivo application of DFO improved ovarian iron metabolism and redox status in 12-month-old mice, and corrected the alterations in cytosolic Fe2+, ferritinophagy and mitophagy, as well as related degenerative changes in oocytes. Thereby in the whole, DFO delayed the decline in ovarian reserve and significantly increased the number of superovulated oocytes with reduced fragmentation and aneuploidy. Together, our findings suggest that aging-related disturbance in ovarian iron homeostasis contributes to excessive ROS production and that iron chelation may improve ovarian redox status, and efficiently delay the decline in ovarian reserve and oocyte quality in aging mice. These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women.

Chinese children are exposed to broad environmental risks ranging from well-known hazards, such as pesticides and heavy metals, to emerging threats including many new man-made chemicals. Although anecdotal evidence suggests that the exposure levels in Chinese children are substantially higher than those of children in developed countries, a systematic assessment is lacking. Further, while these exposures have been linked to a variety of childhood diseases, such as respiratory, endocrine, neurological, behavioral, and malignant disorders, the magnitude of the associations is often unclear. This review provides a current epidemiologic overview of commonly reported environmental contaminants and their potential impact on children’s health in China. We found that despite a large volume of studies on various topics, there is a need for more high-quality research and better-coordinated regional and national data collection. Moreover, prevention of such diseases will depend not only on training of environmental health professionals and enhanced research programs, but also on public education, legislation, and networking.

Abstract Background The multimorbidity of Atherosclerotic cardiovascular disease (ASCVD) and many other chronic conditions is becoming common. This study aimed to assess multimorbidity distribution in ASCVD among adults in the United States from 1999 to 2018. Methods This cross-sectional survey from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 using stratified multistage probability design. Among the 53,083 survey respondents during the study period, 5,729 US adults aged ≥ 20 years with ASCVD. Joinpoint regression was used to assess the statistical significance of prevalence trends in the prevalence of ASCVD stratified by multimorbidity. The Apriori association rule mining algorithm was used to identify common multimorbidity association patterns in ASCVD patients. Results Overall, 5,729 of 53,083 individuals had ASCVD, and the prevalence showed a slow declining trend (biannual percentage change = -0.81%, p = 0.035, average 7.71%). The prevalence of ASCVD significantly decreased in populations without dyslipidemia, diabetes mellitus (DM), hypertension, asthma, chronic obstructive pulmonary disease (COPD), and arthritis (all groups, p

Abstract Background Patinopecten yessoensis, a large and old molluscan group, has been one of the most important aquaculture shellfish in Asian countries because of its high economic value. However, the aquaculture of the species has recently been seriously affected by the frequent outbreaks of Polydora disease, causing great economic losses. Long non-coding RNAs (lncRNAs) exhibit exhibit crucial effects on diverse biological processes, but still remain poorly studied in scallops, limiting our understanding of the molecular regulatory mechanism of P. yessoensis in response to Polydora infestation. Results In this study, a high-throughput transcriptome analysis was conducted in the mantles of healthy and Polydora-infected P. yessoensis by RNA sequencing. A total of 19,133 lncRNAs with 2,203 known and 16,930 novel were identified. The genomic characterizations of lncRNAs showed shorter sequence and open reading frame (ORF) length, fewer number of exons and lower expression levels in comparison with mRNAs. There were separately 2280 and 1636 differentially expressed mRNAs and lncRNAs (DEGs and DELs) detected in diseased individuals. The target genes of DELs were determined by both co-location and co-expression analyses. Functional enrichment analysis revealed that DEGs involved in melanization and biomineralization were significantly upregulated; further, obviously increased melanin granules were observed in epithelial cells of the edge mantle in diseased scallops by histological and TEM study, indicating the crucial role of melanizaiton and biomineralization in P. yessoensis to resist against Polydora infestation. Moreover, many key genes, such as Tyrs, Frizzled, Wnts, calmodulins, Pifs, perlucin, laccase, shell matrix protein, mucins and chitins, were targeted by DELs. Finally, a core lncRNA-mRNA interactive network involved in melanization and biomineralization was constructed and validated by qRT-PCR. Conclusions This work provides valuable resources for studies of lncRNAs in scallops, and adds a new insight into the molecular regulatory mechanisms of P. yessoensis defending against Polydora infestation, which will contribute to Polydora disease control and breeding of disease-resistant varieties in molluscs.

Two new sulfur glycosides, bursapastoris A–B (3–4), were extracted and isolated from shepherd’s purse seed, along with two new natural products, 11-(methylsulfinyl)undecanoic acid (2) and 10-(methylsulfinyl)decanoic acid (1). Their structures were determined though infrared spectroscopy, one-dimensional nuclear magnetic resonance (1H and 13C), and electrospray ionization mass spectrometry. Additionally, the structures of 3–4 were further identified by two-dimensional nuclear magnetic resonance (HMBC, HSQC, 1H-1H COSY, and NOESY). Compounds 1–4 showed relatively favorable docking to NF-κB. Unfortunately, we only discovered that compound 1–4 had weak anti-radiation activity at present. Therefore, further research regarding the biological activity of these organosulfur compounds is required at a later stage.

Establishing a quantitative relationship between Synthetic Aperture Radar (SAR) data and optical data can facilitate the fusion of these two data sources, enhancing the time-series monitoring capabilities for remote sensing of a land surface. In this study, we analyzed the Normalized Difference Vegetation Index (NDVI) and Shortwave Infrared Transformed Reflectance (STR) with the backscatter coefficients in vertical polarization VV (σ0VV) and cross polarization VH (σ0VH) across different seasons. We used optical and microwave satellite data spanning from the southern Gobi Desert region to the steppe region in northern Mongolia. The results indicate a relatively high correlation between the NDVI derived from Sentinel-2 and σ0VH (RVH = 0.29, RVH = 0.44, p < 0.001) and a low correlation between the NDVI and σ0VV (RVH = 0.06, RVH = 0.14, p < 0.01) in the Gobi Desert region during summer and fall. STR showed a positive correlation with both σ0VH and σ0VV except in spring, with the highest correlation coefficients observed in summer (RVV = 0.45, RVV = 0.44, p < 0.001). In the steppe region, significant seasonal variations in the NDVI and σ0VH were noted, with a strong positive correlation peaking in summer (RVH = 0.71, p < 0.001) and an inverse correlation with σ0VV except in summer (RVV = −0.43, RVV = −0.34, RVV = −0.13, p < 0.001). Additionally, STR showed a positive correlation with σ0VH and σ0VV in summer (RVH = 0.40, RVV = 0.39, p < 0.001) and fall (RVH = 0.38, RVV = 0.09, p < 0.01), as well as an inverse correlation in spring (RVH= −0.17, RVV= −0.38, p < 0.001) and winter (RVH = −0.21, RVV = −0.06, p < 0.001). The correlations between the NDVI, STR, σ0VH, and σ0VV were shown to vary by season and region. In the Gobi Desert region, perennial shrubs are not photosynthetic in spring and winter, and they affect backscatter due to surface roughness. In the steppe region, annual shrubs were found to be the dominant species and were found to photosynthesize in spring, but not enough to affect the backscatter due to surface roughness.

The Ylistrum japonicum is a commercially valuable scallop known for its long-distance swimming abilities. Despite its economic importance, genetic and genomic research on this species is limited. This study presents the first complete mitochondrial genome of Y. japonicum. The mitochondrial genome is 19,475 bp long and encompasses 13 protein-coding genes, three ribosomal RNA genes, and 23 transfer RNA genes. Two distinct phylogenetic analyses were used to explore the phylogenetic position of the Y. japonicum within the family Pectinidae. Based on one mitochondrial phylogenetic analysis by selecting 15 Pectinidae species and additional outgroup taxa and one single gene phylogenetic analysis by 16S rRNA, two phylogenetic trees were constructed to provide clearer insights into the evolutionary placement of Y. japonicum within the family Pectinidae. Our analysis reveals that Ylistrum is a basal lineage to the Pectininae clade, distinct from its previously assigned tribe, Amusiini. This study offers critical insights into the genetic makeup and evolutionary history of Y. japonicum, enhancing our knowledge of this economically vital species.

After surgical or natural menopause, women face a high risk of nonalcoholic fatty liver disease (NAFLD), which can be diminished by hormone replacement therapy (HRT). The gut microbiota is subject to modulation by various physiological changes and the progression of diseases. This microbial ecosystem coexists symbiotically with the host, playing pivotal roles in immune maturation, microbial defense mechanisms, and metabolic functions essential for nutritional and hormone homeostasis. E2 supplementation effectively prevented the development of NAFLD after bilateral oophorectomy (OVX) in female rats. The changes in the gut microbiota such as abnormal biosynthetic metabolism of fatty acids caused by OVX were partially restored by E2 supplementation. The combination of liver transcriptomics and metabolomics analysis revealed that linoleic acid (LA) metabolism, a pivotal pathway in fatty acids metabolism was mainly manipulated during the induction and treatment of NAFLD. Further correlation analysis indicated that the gut microbes were associated with abnormal serum indicators and different LA metabolites. These metabolites are also closely related to serum indicators of NAFLD. An in vitro study verified that LA is an inducer of hepatic steatosis. The changes in transcription in the LA metabolism pathway could be normalized by E2 treatment. The metabolic perturbations of LA may directly and secondhand impact the development of NAFLD in postmenopausal individuals. This research focused on the sex-specific pathophysiology and treatment of NAFLD, providing more evidence for HRT and calling for the multitiered management of NAFLD.

Patients with pre-existing medical conditions are at a heightened risk of contracting severe acute respiratory syndrome (SARS), SARS-CoV-2, and influenza viruses, which can result in more severe disease progression and increased mortality rates. Nevertheless, the molecular mechanism behind this phenomenon remained largely unidentified. Here, we found that microRNA-19a/b (miR-19a/b), which is a constituent of the miR-17-92 cluster, exhibits reduced expression levels in patients with coronary heart disease in comparison to healthy individuals. The downregulation of miR-19a/b has been observed to facilitate the replication of influenza A virus (IAV). miR-19a/b can effectively inhibit IAV replication by targeting and reducing the expression of SOCS1, as observed in cell-based and coronary heart disease mouse models. This mechanism leads to the alleviation of the inhibitory effect of SOCS1 on the interferon (IFN)/JAK/STAT signaling pathway. The results indicate that the IAV employs a unique approach to inhibit the host’s type I IFN-mediated antiviral immune responses by decreasing miR-19a/b. These findings provide additional insights into the underlying mechanisms of susceptibility to flu in patients with coronary heart disease. miR-19a/b can be considered as a preventative/therapy strategy for patients with coronary heart disease against influenza virus infection.

Objective To explore the feasibility of ultrasound measurement of the transverse diameter of the cervical trachea at its narrowest point in patients undergoing severe scoliosis orthopedic surgery. Methods A total of 110 patients, aged 18-65, who scheduled for elective orthopedic surgery for severe scoliosis were included. Prior to surgery, all patients underwent two types of tracheal inner diameter measurements: (1) CT measurement of the anteroposterior diameter (D min,AP ) and transverse diameter (D min,T ) of the cervical trachea at its narrowest point; and (2) ultrasound measurement of D min,T . Based on the measurement results, the patients were randomly divided into two groups, the CT group ( n = 55) and the ultrasound group ( n = 55). We compared the D min,AP and D min,T measured by CT for all patients. Then, we compared CT and ultrasound measurements of D min,T . Furthermore, we conducted an analysis to determine the correlation and consistency between the two methods. Additionally, we examined the success rate of first-attempt tracheal intubation and the occurrence rate of tracheal tube being too wide or too narrow between the two groups, and assessed the occurrence of postoperative 24-h pharyngeal pain and hoarseness. Results When comparing the D min,AP and D min,T measured by CT in all patients, a statistically significant difference was observed ( p < .001). When comparing the measurements of D min,T between CT and ultrasound in all patients, no statistically significant differences were found ( p > .05). The correlation coefficient (r) between CT and ultrasound measurements of D min,T was 0.849 ( p < .001). The mean difference in D min,T was 0.19 mm, and the limits of agreement (LoA) were −2.24 mm to 2.62 mm. Conclusions Ultrasound measurement of D min,T in severe scoliosis patients is feasible and provides valuable guidance for the selection of endotracheal tube sizes. It serves as a non-invasive and bedside auxiliary examination method for perioperative airway assessment.

Aspongopus chinensis Dallas is a traditional Chinese medicinal insect with several anticancer properties can inhibit cancer cell growth, by inhibiting cell division, autophagy and cell cycle. However, the precise therapeutics effects and mechanisms of this insect on liver cancer are still unknown. This study examined the inhibitory influence of A. chinensis on the proliferation of hepatocellular carcinoma (HCC) cells and explore the underlying mechanism using high-throughput sequencing. The results showed that A. chinensis substantially reduced the viability of Hep G2 cells. A total of 33 miRNAs were found to be upregulated, while 43 miRNAs were downregulated. Additionally, 754 mRNAs were upregulated and 863 mRNAs were downregulated. Significant enrichment of differentially expressed genes was observed in signaling pathways related to tumor cell growth, cell cycle regulation, and apoptosis. Differentially expressed miRNAs exhibited a targeting relationship with various target genes, including ARC, HSPA6, C11orf86, and others. Hence, cell cycle and apoptosis were identified by flow cytometry. These findings indicate that A. chinensis impeded cell cycle advancement, halted the cell cycle in the G0/G1 and S stages, and stimulated apoptosis. Finally, mouse experiments confirmed that A. chinensis significantly inhibits tumor growth in vivo. Therefore, our findings indicate that A. chinensis has a notable suppressive impact on the proliferation of HCC cells. The potential mechanism of action could involve the regulation of mRNA expression via miRNA, ultimately leading to cell cycle arrest and apoptosis. The results offer a scientific foundation for the advancement and application of A. chinensis in the management of HCC.

Background: Pregnant women in the Shanghai Birth Cohort (SBC) of China faced dual threats of per- and polyfluoroalkyl substances (PFAS) exposure and vitamin D (VD) insufficiency, potentially impacting offspring neurodevelopment. However, little is known about whether maternal VD status modifies PFAS-related neurodevelopment effect. Objectives: To explore the modifying role of maternal VD status in the effect of prenatal PFAS exposure on childhood neurodevelopment. Methods: We included 746 mother–child pairs from the SBC. Ten PFAS congeners and VD levels were measured in maternal blood samples collected during the first and second trimester respectively. At 2 years of age, toddlers underwent neurodevelopment assessments using Bayley-III Scales. Multivariate linear, logistic regression, and weighted quantile sum approach were used to estimate associations of Bayley-III scores with individual and mixture PFAS. We stratified participants into VD sufficient and insufficient groups and further balanced PFAS differences between these groups by matching all PFAS levels. We fitted the same statistical models in each VD group before and after matching. Results: Nearly half (46.5 %) of pregnant women were VD insufficient (

IntroductionThe notion of physical literacy is gaining interest from several countries as a potential mechanism for understanding the development of the physical self. This research endeavor represents an inaugural attempt to translate the Australian Physical Literacy Questionnaire for Children (PL-C Quest) into Chinese to evaluate the reliability and validity of the Chinese version of the PL-C Quest to assess physical literacy among children in mainland China.MethodsThe Beaton translation paradigm was used to carry out language translation, back-translation, cultural adaptation, and presurveys. Data were collected from 642 children aged 6–12 years, with a mean age of 9.71 years (SD 1.816), to test the reliability of the Chinese version of the PL-C Quest.ResultsThe PL-C Quest items translated well (6.187 ~ 15.499) and correlated well (0.441 ~ 0.622). The Chinese version of the PL-C Quest had good reliability, with retest reliability values ranging from 0.91 to 0.74, Cronbach’s alpha from 0.65 to 0.894, and McDonald’s ω from the Spearman-Brown Coefficient was 0.84. The validity results are acceptable because the CFI, IFI, and TLI values are above 0.8 and close to 0.9, but the model fit’s chi-square degrees-of-freedom ratio of 2.299, the RMSEA of 0.05, which was less than 0.08.DiscussionAfter translation and cultural adaptation, the Chinese version of the PL-C Quest is a reliable measurement tool and can be used in the Chinese region.

Abstract Increasing evidence shows the African lineage Zika virus (ZIKV) displays a more severe neurovirulence compared to the Asian ZIKV. However, viral determinants and the underlying mechanisms of enhanced virulence phenotype remain largely unknown. Herein, we identify a panel of amino acid substitutions that are unique to the African lineage of ZIKVs compared to the Asian lineage by phylogenetic analysis and sequence alignment. We then utilize reverse genetic technology to generate recombinant ZIKVs incorporating these lineage-specific substitutions based on an infectious cDNA clone of Asian ZIKV. Through in vitro characterization, we discover a mutant virus with a lysine to arginine substitution at position 101 of capsid (C) protein (termed K101R) displays a larger plaque phenotype, and replicates more efficiently in various cell lines. Moreover, K101R replicates more efficiently in mouse brains and induces stronger inflammatory responses than the wild type (WT) virus in neonatal mice. Finally, a combined analysis reveals the K101R substitution promotes the production of mature C protein without affecting its binding to viral RNA. Our study identifies the role of K101R substitution in the C protein in contributing to the enhanced virulent phenotype of the African lineage ZIKV, which expands our understanding of the complexity of ZIKV proteins.

Abstract Zika virus (ZIKV) infection during pregnancy threatens pregnancy and fetal health. However, the infectivity and pathological effects of ZIKV on placental trophoblast progenitor cells in early human embryos remain largely unknown. Here, using human trophoblast stem cells (hTSCs), we demonstrated that hTSCs were permissive to ZIKV infection, and resistance to ZIKV increased with hTSC differentiation. Combining gene knockout and transcriptome analysis, we demonstrated that the intrinsic expression of AXL and TIM-1, and the absence of potent interferon (IFN)-stimulated genes (ISGs) and IFNs contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived trophoblast organoid (hTSC-organoid), we demonstrated that ZIKV infection disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Single-cell RNA sequencing (scRNA-seq) further demonstrated that ZIKV infection of hTSC-organoids disrupted the stemness of hTSCs and the proliferation of cytotrophoblast cells (CTBs) and probably led to a preeclampsia (PE) phenotype. Overall, our results clearly demonstrate that hTSCs represent the major target cells of ZIKV, and a reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepen our understanding of the characteristics and consequences of ZIKV infection of hTSCs in early human embryos.

The current study aimed to explore the combined and individual effects of vitamin D (VitD) status in three trimesters during pregnancy and cord blood (CB) on child growth trajectories from birth to 4 years of age. Pregnant women (n = 1100) were recruited between 2013 and 2016 in the Shanghai Birth Cohort (SBC) Study. A total of 959 mother–child dyads were included. VitD status was measured by LC-MS/MS at three trimesters (T1, T2, T3) and CB. Children’s weight, length/height, and head circumference were assessed at birth, 42 days, 6, 12, 24 months, and 4 years of age, and standardized into z-scores [weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HCZ) and weight-for-length z-score (WLZ)]. Using the group-based trajectory model (GBTM), the trajectories of the four growth parameters were categorized into discrete groups. The generalized estimating equation (GEE) was employed to analyze the mixed effect of 25(OH)D throughout pregnancy on growth trajectories. The association between 25(OH)D status and each growth trajectory group was examined by multivariable logistic regression. Each 10 ng/mL increase in 25(OH) throughout three trimesters was not associated with four anthropometric parameters. Each 10 ng/mL increase in VitD in T3 was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.75; 95% CI: 0.62, 0.91; p < 0.01). Each 10 ng/mL increase in VitD in CB was associated with a lower risk in the WAZ high-increasing trajectory (aOR: 0.57; 95% CI: 0.43, 0.76; p < 0.01). No significant association was found between maternal or CB VitD and LAZ or HCZ. Three trimesters’ VitD throughout pregnancy had no persistent effect on the offspring’s growth trajectory. However, higher VitD status in the third trimester and CB related to a lower risk of high-increasing WAZ from birth to 4 years of age. Elevated VitD levels in late pregnancy and cord blood may protect against continuous early-life weight growth at high levels.

Background: Recent advancements in artificial intelligence (AI) have significantly improved atrial fibrillation (AF) detection using electrocardiography (ECG) data obtained during sinus rhythm (SR). However, the utility of printed ECG (pECG) records for AF detection, particularly in developing countries, remains unexplored. This study aims to assess the efficacy of an AI-based screening tool for paroxysmal AF (PAF) using pECGs during SR. Methods: We analyzed 5688 printed 12-lead SR-ECG records from 2192 patients admitted to Beijing Chaoyang Hospital between May 2011 to August 2022. All patients underwent catheter ablation for PAF (AF group) or other electrophysiological procedures (non-AF group). We developed a deep learning model to detect PAF from these printed SR-ECGs. The 2192 patients were randomly assigned to training (1972, 57.3% with PAF), validation (108, 57.4% with PAF), and test datasets (112, 57.1% with PAF). We developed an applet to digitize the printed ECG data and display the results within a few seconds. Our evaluation focused on sensitivity, specificity, accuracy, F1 score, the area under the receiver-operating characteristic curve (AUROC), and precision-recall curves (PRAUC). Results: The PAF detection algorithm demonstrated strong performance: sensitivity 87.5%, specificity 66.7%, accuracy 78.6%, F1 score 0.824, AUROC 0.871 and PRAUC 0.914. A gradient-weighted class activation map (Grad-CAM) revealed the model’s tailored focus on different ECG areas for personalized PAF detection. Conclusions: The deep-learning analysis of printed SR-ECG records shows high accuracy in PAF detection, suggesting its potential as a reliable screening tool in real-world clinical practice.

In this study, we employed geometric morphometrics (GMs) to analyze the shell shape differences among two mass-selected strains of bay scallops (red shell strain (RS) and black shell strain (BS)) and a control group (CG). The results revealed distinct shell shape differences corresponding to shell coloration, with the black shell strain displaying a more elliptical shell compared to the red shell strain. Additionally, the umbonal angle of the red shell strain was smaller than that of the black shell strain, indicating that the black shell strain had a more favorable jet direction that could enhance swimming capabilities. To evaluate the model’s performance in practical applications, leave-one-out cross-validation was carried out on the two shell strains and one control group. The results demonstrated discrimination accuracy rates of 67.44%, 47.62%, and 68.18% for the BS strain, RS strain, and CG, respectively. Similarly, for the right valves, the discrimination accuracy rates were 62.79%, 50.00%, and 75.00% for the BS strain, RS strain, and CG, respectively.

Spiral bevel gear drives are widely used in mechanical transmission devices due to their compact structure, smooth transmission, and cost-effectiveness. With the continuous improvement in mechanical product quality, higher and higher requirements are set for the precision, smoothness, and power density of gear transmission devices. Chatter can lead to poor workpiece surface finish on spiral bevel gears, excessive tool wear, and even damage to machine tools. Therefore, the effective prediction of milling chatter during the processing of spiral bevel gears is essential. Regenerative chatter is one of the most fundamental types of vibration in machining processes. This paper presents an improved fully discrete algorithm for predicting the stability of time-delayed cutting in the milling process of spiral bevel gears. The method is validated using single- and double-degree-of-freedom models, demonstrating its accuracy and computational efficiency. The results show that the proposed method improves computational efficiency while ensuring accuracy.

Cathode materials with conversion mechanisms for aqueous zinc-ion batteries (AZIBs) have shown a great potential as next-generation energy storage materials due to their high discharge capacity and high energy density. However, improving their cycling stability has been the biggest challenge plaguing researchers. In this study, CuO microspheres were prepared using a simple hydrothermal reaction, and the morphology and crystallinity of the samples were modulated by controlling the hydrothermal reaction time. The as-synthesized materials were used as cathode materials for AZIBs. The electrochemical experiments showed that the CuO-4h sample, undergoing a hydrothermal reaction for 4 h, had the longest lifecycle and the best rate of capability. A discharge capacity of 131.7 mAh g−1 was still available after 700 cycles at a current density of 500 mA g−1. At a high current density of 1.5 A g−1, the maintained capacity of the cell is 85.4 mA h g−1. The structural evolutions and valence changes in the CuO-4h cathode material were carefully explored by using ex situ XRD and ex situ XPS. CuO was reduced to Cu2O and Cu after the initial discharge, and Cu was oxidized to Cu2O instead of CuO during subsequent charging processes. We believe that these findings could introduce a novel approach to exploring high-performance cathode materials for AZIBs.

To address the difficulty of accurately characterizing the fluctuations in equipment energy consumption and the dynamic evolution of whole energy consumption in low-carbon workshops, a low-carbon-operation-oriented construction method of the energy footprint model (EFM) for a digital twin workshop (DTW) is proposed. With a focus on considering the fluctuations in equipment energy consumption and the correlation between multiple pieces of equipment at the workshop production process level (CBMEatWPPL), the EFM of a DTW is obtained to characterize the dynamic evolution of whole energy consumption in the workshop. Taking a production unit as a case, on the one hand, an EFM of the production unit is constructed, which achieved the characterization and visualization of the fluctuations in equipment energy consumption and the dynamic evolution of whole energy consumption in the production unit; on the other hand, based on the EFM, an objective function of workshop energy consumption is established, which is combined with the tool life, robot motion stability, and production time to formulate a multi-objective optimization function. The bee colony algorithm is adopted to solve the multi-objective optimization function, achieving collaborative optimization of cross-equipment process parameters and effectively reducing energy consumption in the production unit. The effectiveness of the proposed method and constructed EFM is demonstrated from the above two aspects.

BackgroundNeonicotinoid insecticides (NEOs) are emerging synthetic insecticides that have been used in various pest management regimens worldwide as alternatives to conventional insecticides. Recently, several studies have indicated that humans are widely exposed to NEOs, but limited is known about the levels and associated health risks of NEOs exposure among children.ObjectiveTo estimate exposure levels of four kinds of NEOs in urine samples among 5-year-old children from Laizhou Wan, Shandong Province, and to evaluate health risks of single and cumulative exposure to NEOs among children in this area.MethodsA total of 205 children who participated in the 5-year-old follow-up in Laizhou Wan Birth Cohort (LWBC) were included. Urinary concentrations of four NEOs [imidacloprid (IMI), acetamiprid (ACE), clothianidin (CLO), and thiamethoxam (THM)] were measured by high-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Based on the detected NEOs concentrations, estimated daily intake (EDI) was calculated, and the health risk of exposure to single NEO was assessed using hazard quotient (HQ, risk threshold=1). A relative potency factor (RPF) approach was used to standardize the concentrations of the four NEOs by IMI to calculate their cumulative concentrations. Then, the health risk of cumulative exposure to the four NEOs was further evaluated based on the HQ method.ResultsThe detection rates of the four NEOs in the 5-year-old children were all above 90%, and their median creatinine-adjusted urinary concentrations were in the order from high to low as follows: CLO (1.373 μg·g−1) > THM (0.628 μg·g−1) > IMI (0.310 μg·g−1) > ACE (0.073 μg·g−1). Of the four NEOs, the median EDI of IMI was 0.035 µg·kg−1·d−1, higher than those of CLO (0.032 µg·kg−1·d−1), THM (0.012 µg·kg−1·d−1), and ACE (0.002 µg·kg−1·d−1). The maximum HQ values of IMI, CLO, THM, and ACE were 0.168, 0.152, 0.055, and 0.022, respectively, which were all far lower than the risk threshold of 1. The median concentration of cumulative exposure to the four NEOs standardized by IMI was 21.241 μg·g−1, and its median EDI was 2.370 µg·kg−1·d−1. The maximum HQ of cumulative exposure to the four NEOs was only 0.694, which also did not exceed the risk threshold of 1.ConclusionNEOs exposure is common among the 5-year-old children in Laizhou Wan, Shandong. Although there is no obvious health risk associated with single and cumulative exposure to NEOs in the children in this area, their exposure levels of NEOs are higher than those in some foreign areas. The adverse health effects of long-term exposure to low dose of NEOs deserve our extensive attention.

Abstract Virus spillover remains a major challenge to public health. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) in humans remain largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of a recent pCoV isolate (pCoV-GD01) in human cells and human tracheal epithelium organoids and established animal models in comparison with SARS-CoV-2. pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice and could transmit among cocaged hamsters. Interestingly, in vitro neutralization assays and animal heterologous challenge experiments demonstrated that preexisting immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide at least partial cross-protection against pCoV-GD01 challenge. Our results provide direct evidence supporting pCoV-GD01 as a potential human pathogen and highlight the potential spillover risk.

Abstract Background A few studies have shown that snoring, in certain populations, is associated with dyslipidemia. However, there are currently no large-scale national studies available that explore this association. Thus, for further clarification, studies using a large sample of the general population need to be conducted. This study aimed to explore this association using the National Health and Nutrition Examination Survey (NHANES) database. Methods A cross-sectional survey was conducted using data from the NHANES database; 2005 to 2008 and 2015 to 2018 datasets were used (weighted to be representative of United States adults aged ≥ 20 years). Information on snoring status, lipid levels, and confounding factors were included. Logistic regression of the generalized linear model was used to analyze the relationship between snoring and dyslipidemia, and hierarchical analysis, interaction analysis, and sensitivity analysis were used to explore the stability of the results. Results Data from 28,687 participants were analyzed, and 67% of the participants had some degree of snoring. The fully adjusted multivariate logistic regression results demonstrated that snoring frequency was significantly positively associated with dyslipidemia (P

Urban system theory seeks to comprehensively capture the complexity of cities. Digital twin cities are “digital mirror images” or symbionts of physical cities, and thus, they form a complex adaptive system. Unlike the reductionist practice of urban informatization and digitalization, digital twins are expected to enable human beings to enjoy the complex beauty of the city for the first time, capable to perceive more information of city and deal with more complex urban problems. Some practical misunderstandings have emerged, however, as a result of simple technical stacking, which is not able to solve urban problems from the root of the problem; has biased thinking about digital twin cities, which treats them as technical tools; and has slowed development of digital twin innovative applications. To solve these problems, we need to draw on basic urban theory. On the basis of complex system theory, in this study, we comprehensively analyzed the characteristics and mechanisms of digital twin cities and constructed a system framework for digital twin cities. We further elucidated the digital twin city and deconstructed it from the perspective of system theory into four subsystems: the planning system, infrastructure system, industrial system, and public service facility system. We then analyzed the subsystem rules and changes in the digital twin city, as well as the principles and development trends that conform to the self-organization and self-adaptive laws of the city.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28–75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30–9.11) and 3.72 (95% CI, 1.91–5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58–0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

IntroductionVascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aorta, which plays a critical role in aortic diseases. Innate immunity is the main driving force for cardiovascular diseases. MethodsTo determine the roles of innate immunity in VSMC and aortic pathologies, we performed transcriptome analyses on aortas from ApoE–/– angiotensin II (Ang II)-induced aortic aneurysm (AAA) time course, and ApoE–/– atherosclerosis time course, as well as VSMCs stimulated with danger-associated molecular patterns (DAMPs).ResultsWe made significant findings: 1) 95% and 45% of the upregulated innate immune pathways (UIIPs, based on data of 1226 innate immune genes) in ApoE–/– Ang II-induced AAA at 7 days were different from that of 14 and 28 days, respectively; and AAA showed twin peaks of UIIPs with a major peak at 7 days and a minor peak at 28 days; 2) all the UIIPs in ApoE–/– atherosclerosis at 6 weeks were different from that of 32 and 78 weeks (two waves); 3) analyses of additional 12 lists of innate immune-related genes with 1325 cytokine and chemokine genes, 2022 plasma membrane protein genes, 373 clusters of differentiation (CD) marker genes, 280 nuclear membrane protein genes, 1425 nucleoli protein genes, 6750 nucleoplasm protein genes, 1496 transcription factors (TFs) including 15 pioneer TFs, 164 histone modification enzymes, 102 oxidative cell death genes, 68 necrotic cell death genes, and 47 efferocytosis genes confirmed two-wave inflammation in atherosclerosis and twin-peak inflammation in AAA; 4) DAMPs-stimulated VSMCs were innate immune cells as judged by the upregulation of innate immune genes and genes from 12 additional lists; 5) DAMPs-stimulated VSMCs increased trans-differentiation potential by upregulating not only some of 82 markers of 7 VSMC-plastic cell types, including fibroblast, osteogenic, myofibroblast, macrophage, adipocyte, foam cell, and mesenchymal cell, but also 18 new cell types (out of 79 human cell types with 8065 cell markers); 6) analysis of gene deficient transcriptomes indicated that the antioxidant transcription factor NRF2 suppresses, however, the other five inflammatory transcription factors and master regulators, including AHR, NF-KB, NOX (ROS enzyme), PERK, and SET7 promote the upregulation of twelve lists of innate immune genes in atherosclerosis, AAA, and DAMP-stimulated VSMCs; and 7) both SET7 and trained tolerance-promoting metabolite itaconate contributed to twin-peak upregulation of cytokines in AAA. DiscussionOur findings have provided novel insights on the roles of innate immune responses and nuclear stresses in the development of AAA, atherosclerosis, and VSMC immunology and provided novel therapeutic targets for treating those significant cardiovascular and cerebrovascular diseases.

IntroductionThe Pacific oyster (Crassostrea gigas), one of the major aquaculture shellfish worldwide, has strong environmental adaptability. However, genetic diversity and population structure of the Pacific oysters in Dalian Sea, the major natural and farming area of the species in China, has not been systematically investigated, especially at genome-wide level, limiting the conservation and management of the species. MethodsIn this study, whole-genome resequencing of 105 individuals from seven Pacific oyster populations, including five wild and one cultured populations in Dalian and one wild population in Qingdao relatively distant from others, were first performed.ResultsA total of 2,363,318 single nucleotide polymorphisms (SNPs) were identified. Based on all these SNPs, similar but relatively low genetic diversity (0.2352~0.2527) was found in the seven populations. The principal component analysis (PCA), phylogenetic and population structure analysis consistently revealed weak differentiation among the seven populations. Frequent migration events were detected among the studied populations by TreeMix, which probably led to a high genetic similarity of these populations. Rapid linkage disequilibrium (LD) decay was observed in the genome of the Pacific oyster. Investigation of genome-wide selection signatures of these populations identified many selected genes involved in the biological processes related to DNA metabolism and stability, shell formation, and environmental stress response, which may be critical for oysters to adapt to the stressful environments.DiscussionThis study laid theoretical basis for the subsequent germplasm conservation, management and genetic breeding of the indigenous Pacific oysters, and provided novel insights for the adaptive evolutionary mechanism of oysters.

ABSTRACT Central nervous system infections (CNSIs) are common complications after neurosurgery with a poor prognosis. The traditional microbiological culture methodology has a low detection rate and time consuming. Metagenomic next-generation sequencing (mNGS) has demonstrated the advantages of being faster, more accurate, and more comprehensive in clinical microbiology. Previous studies had suggested that mNGS had a high sensitivity in the diagnosis of CNSIs. Whether the application of mNGS has health economic value in clinical applications remains to be studied. We designed a prospective, single-center, superiority randomized controlled trial to compare the cost-effectiveness of mNGS with traditional methods for diagnosing CNSIs using a decision tree model. A total of 204 patients will be enrolled and randomly assigned to either the mNGS group or the traditional method group. The two groups of patients entered different decision points according to different clinical manifestations and examination results. They will be then given treatment decisions by a panel of specialists at the corresponding decision point. The primary outcome is the incremental cost-effectiveness ratio, which is the increased cost for every 1% increase in recovery rate. The secondary outcomes are a comparison of time cost, detection cost, and costs associated with antibiotics treatment between the two groups.IMPORTANCEDiagnosing and treating postoperative central nervous system infections (PCNSIs) remains challenging due to the low detection rate and time-consuming nature of traditional methods for identifying microorganisms in cerebrospinal fluid. Metagenomic next-generation sequencing (mNGS) technology provides a rapid and comprehensive understanding of microbial composition in PCNSIs by swiftly sequencing and analyzing the microbial genome. The current study aimed to assess the economic impact of using mNGS versus traditional bacterial culture-directed PCNSIs diagnosis and therapy in post-neurosurgical patients from Beijing Tiantan Hospital. mNGS is a relatively expensive test item, and whether it has the corresponding health-economic significance in the clinical application of diagnosing intracranial infection has not been studied clearly. Therefore, the investigators hope to explore the clinical application value of mNGS detection in PCNSIs after neurosurgery.

AbstractObjective Coronary artery calcification (CAC) is positively and independently associated with cardiovascular disease (CVD) in patients undergoing maintenance hemodialysis (MHD). Insulin resistance is independently associated with CAC and is an important risk factor for CVD. The triglyceride–glucose (TyG) index is a reliable biomarker of insulin resistance. This cross-sectional, observational study aimed to investigate the relationship between the TyG index and CAC in asymptomatic non-diabetic patients undergoing MHD.Methods The quantitative coronary artery calcification score (CACS) was calculated and expressed using the Agatston score. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multiple Poisson regression analysis, Spearman correlation analysis, and receiver operating characteristic (ROC) curves were used to investigate the relationship between the TyG index and CAC.Results The 151 patients were divided into three groups according to the tertiles of the TyG index. With an increase in the TyG index, the CACS significantly increased (Spearman’s rho = 0.414, p

BackgroundThere is an increasing tendency toward early pubertal development, and sleep might be related to pubertal onset. We aimed to investigate the association of sleep duration and bedtime with early pubertal development.MethodsThis was a cross-sectional study of 8,007 children (53.6% boys) from Qufu city, Shandong province and Zhongshan city, Guangdong province, China. Data on sleep duration and bedtime were obtained by questionnaire. Early pubertal development was the primary outcome and it was evaluated by the pediatrician according to Tanner staging. Logistic regression models were used to separately examine the association between sleep duration or bedtime and early pubertal development, controlling body mass index (BMI), dietary pattern, soft drink, feeding pattern and mother’s BMI.ResultsIn boys, short sleep duration was strongly related to early pubertal development [OR (95%CI): 4.26 (1.30, 13.94)], and this association was intensified after adjusted BMI, dietary pattern, soft drink, feeding pattern and mother’s BMI. In girls, OR (95%CI) was 1.62 (1.04, 2.51), and increased after controlling BMI. Bedtime was associated with early pubertal development on weekdays [OR (95%CI): 6.39 (1.54, 26.45) in boys and 1.93 (1.23, 3.05) in girls], but not on weekends [OR (95%CI): 2.49 (0.61, 10.21) in boys; 1.31 (0.76, 2.25) in girls].ConclusionThis study underscores the positive association between the risk of early pubertal development and insufficient sleep duration and late bedtime.

Abstract Background The present study intended to establish a predictive nomogram for early relapse (ER) ( UNL, and response less than very good partial response (VGPR) after ASCT. The calibration curve showed good fitness between the nomogram predictions and the actual observations and the nomogram was further validated by a clinical decision curve. The nomogram's C‐index achieved 0.75 (95% CI, 0.70–0.80), which was higher than that of the Revised International Staging System (R‐ISS) (0.62), ISS (0.59), and Durie–Salmon (DS) staging system (0.52). The discrimination ability of the nomogram in the validation cohort was superior to that of the other staging systems (C‐index: 0.73 vs. R‐ISS (0.54), ISS (0.55), and DS staging system (0.53)). DCA showed the prediction nomogram adds much more clinical utility. Different scores of the nomogram draw a distinction of OS. Conclusion The present nomogram could serve as a feasible and accurate prediction of ER in novel drug induction transplantation‐eligible MM patients, which could help modify the post‐ASCT strategy for patients at high risk of ER.

Abstract The present work reports developing the first process analytical technology (PAT)-based real-time feedback control system for maintaining the Ginkgo biloba leaf dripping pills weight during manufacturing. The opening degree of the drop valve and the weight of dripping pills were chosen as the manipulated variable and as the controlled variable, respectively. A proportional-integral controller was programmed to automatically reach the desired dripping pills weight by adjusting the opening degree of the drop valve. The closed-loop feedback control system could automatically compensate for the disturbances and ensure a predefined weight of the dripping pills with excellent robustness, high accuracy, and high efficiency during manufacturing. Furthermore, the closed-loop feedback control system improved the process capability of the dripping process, and the process capability index was > 1.67. This study provides a new approach to real-time control of the weight of dripping pills and improves the process capability during Ginkgo biloba leaf dripping pills manufacturing.

Abstract Background Clinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study. Methods A retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes. Results There were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups. Conclusion Collectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

Idiopathic pulmonary haemosiderosis is a rare disease primarily affecting children. The condition is characterized by widespread bleeding from alveolar capillaries, resulting in symptoms such as haemoptysis, shortness of breath and iron deficiency anaemia. However, it is not a specific disease and sometimes can manifest solely as anaemia, which may be easily overlooked and misdiagnosed. The purpose of this case report was to describe a 1-year-old boy who exhibited haemolytic anaemia as the only symptom of idiopathic pulmonary haemosiderosis, with the intention of offering clinical insights into the precise diagnosis and subsequent management of this rare and easily misdiagnosed disease. Clinicians should keep idiopathic pulmonary haemosiderosis in mind when evaluating children with haemolytic anaemia and promptly initiate testing and treatment to prevent misdiagnosis and improve outcomes.

IntroductionAlveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-γ, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown.MethodsWe used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by Streptococcus pneumoniae. To determine whether CD8 T cells and their released cytokine IFN-γ are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-γ monoclonal antibody (mAb) treatment in vivo. We assessed the effects of CD8 T cells and cytokine IFN-γ on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system in vitro.ResultsWe detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by Streptococcus pneumoniae. Depletion of CD8 T cells or neutralization of cytokine IFN-γ using anti-CD8 or anti-IFN-γ monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-γ with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-γ signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system.DiscussionOur data demonstrate that CD8 T-cell response and cytokine IFN-γ are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia.