A manganese-doped layered double hydroxide loaded with lactate oxidase and DNA repair inhibitors for synergistically enhanced tumor immunotherapy.

Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H2O2), which not only alleviates the ISME, but also provides reactants for the Mn2+-mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn2+ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis. STATEMENT OF SIGNIFICANCE: To improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX generates H2O2 for the Mn2+-mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.

Maternal Characteristics and Prevalence of Infants Born Small for Gestational Age.

Importance: Being born small for gestational age (SGA) is a risk factor for neonatal mortality and adverse outcomes in the short and long term. The maternal profile in China has substantially changed over the past decade, which may affect the risk of infants born SGA. Objectives: To analyze the prevalence of infants born SGA from 2012 through 2020 and explore the association of maternal sociodemographic characteristics and other factors with that prevalence. Design, Setting, and Participants: This cross-sectional study examined data from the National Maternal Near Miss Surveillance System on women who delivered singleton live births at gestational ages of 28 to 42 weeks from January 1, 2012, through December 31, 2020, in China. Statistical analysis was performed from December 2022 to September 2023. Exposures: Characteristics of delivery (year, region of country, and hospital level), mother (age, educational level, marital status, prenatal visits, parity, preexisting diseases, or prenatal complications), and newborn (birth weight, sex, and gestational age). Main Outcomes and Measures: Prevalence of infants born SGA stratified by severity and by region of the country, changes in prevalence based on log-linear Poisson regression with robust variance, and association of maternal characteristics with changes in prevalence of infants born SGA between 2012 and 2020 based on the Fairlie nonlinear mean decomposition. Results: Among 12 643 962 births (6 572 548 [52.0%] male; median gestational age, 39 weeks [IQR, 38-40 weeks]), the overall weighted prevalence of infants born SGA was 6.4%, which decreased from 7.3% in 2012 to 5.3% in 2020, translating to a mean annual decrease rate of 3.9% (95% CI, 3.3%-4.5%). The prevalence of infants born SGA decreased from 2.0% to 1.2% for infants with severe SGA birth weight and from 5.3% to 4.1% for those with mild to moderate SGA birth weight. The mean annual rate of decrease was faster for infants with severe SGA birth weight than for those with mild to moderate SGA birth weight (5.9% [95% CI, 4.6%-7.1%] vs 3.2% [95% CI, 2.6%-3.8%]) and was faster for the less developed western (5.3% [95% CI, 4.4%-6.1%]) and central (3.9% [95% CI, 2.9%-4.8%]) regions compared with the eastern region (2.3% [95% CI, 1.1%-3.4%]). Two-thirds of the observed decrease in the prevalence of infants born SGA could be accounted for by changes in maternal characteristics, such as educational level (relative association, 19.7%), age (relative association, 18.8%), prenatal visits (relative association, 20.4%), and parity (relative association, 19.4%). Conversely, maternal preexisting diseases or prenatal complications counteracted the decrease in the prevalence of infants born SGA (-6.7%). Conclusions and Relevance: In this cross-sectional study of births in China from 2012 to 2020, maternal characteristics changed and the prevalence of infants born SGA decreased. Future interventions to reduce the risk of infants born SGA should focus on primary prevention.

Synthesis and Evaluation of Novel meso-Tetraphenyltetrabenzoporphyrins for Photodynamic Therapy.

To discover effective photosensitizers for photodynamic therapy (PDT), a series of new meso-tetraphenyltetrabenzoporphyrin (m-Ph4TBP) derivatives were designed, prepared, and characterized. All m-Ph4TBPs own two characteristic absorption bands in the range of 450-500 and 600-700 nm and have the ability to generate singlet oxygen upon photoexcitation. Most of the m-Ph4TBPs demonstrated high photoactivity, among which compounds I4, I6, I12, and I13 induced apoptosis and also exhibited excellent photodynamic activities in vivo. Nonetheless, the liver organs of the I4 and I6-PDT groups showed clear calcifications, whereas the liver tissues of the other PDT groups showed no calcification. It was indicated that compared to phenolic m-Ph4TBPs, glycol m-Ph4TBPs exhibited superior biological safety in mice. According to comprehensive evaluations, m-Ph4TBP I12 displayed excellent photodynamic antitumor efficacy and biological safety and can be regarded as a promising antitumor drug candidate.

Targeting Ser78 phosphorylation of Hsp27 achieves potent antiviral effects against enterovirus A71 infection.

A positive-sense (+) single-stranded RNA (ssRNA) virus (e.g. enterovirus A71, EV-A71) depends on viral polypeptide translation for initiation of virus replication after entry. We reported that EV-A71 hijacks Hsp27 to induce hnRNP A1 cytosol redistribution to initiate viral protein translation, but the underlying mechanism is still elusive. Here, we show that phosphorylation-deficient Hsp27-3A (Hsp27S15/78/82A) and Hsp27S78A fail to translocate into the nucleus and induce hnRNP A1 cytosol redistribution, while Hsp27S15A and Hsp27S82A display similar effects to the wild type Hsp27. Furthermore, we demonstrate that the viral 2A protease (2Apro) activity is a key factor in regulating Hsp27/hnRNP A1 relocalization. Hsp27S78A dramatically decreases the IRES activity and viral replication, which are partially reduced by Hsp27S82A. However, Hsp27S15A displays the same activity as the wild-type Hsp27. Peptide S78 potently suppresses EV-A71 protein translation and reproduction through blockage of EV-A71-induced Hsp27 phosphorylation and Hsp27/hnRNP A1 relocalization. A point mutation (S78A) on S78 impairs its inhibitory functions on Hsp27/hnRNP A1 relocalization and viral replication. Taken together, we demonstrate the importance of Ser78 phosphorylation of Hsp27 regulated by virus infection in nuclear translocation, hnRNP A1 cytosol relocation, and viral replication, suggesting a new path (such as peptide S78) for target-based antiviral strategy.

Physiological and transcriptome analysis of changes in endogenous hormone and sugar content during the formation of tender asparagus stems.

Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and underlying mechanisms during the elongation and growth process of asparagus stems, we documented the growth pattern of asparagus and selected stem segments from four consecutive elongation stages using physiological and transcriptome analyses. Notably, the growth rate of asparagus accelerated at a length of 25 cm. A significant decrease in the concentration of sucrose, fructose, glucose, and additional sugars was observed in the elongation region of tender stems. Conversely, the levels of auxin and gibberellins(GAs) were elevated along with increased activity of enzymes involved in sucrose degradation. A significant positive correlation existed between auxin, GAs, and enzymes involved in sucrose degradation. The ABA content gradually increased with stem elongation. The tissue section showed that cell elongation is an inherent manifestation of stem elongation. The differential genes screened by transcriptome analysis were enriched in pathways such as starch and sucrose metabolism, phytohormone synthesis metabolism, and signal transduction. The expression levels of genes such as ARF, GA20ox, NCED, PIF4, and otherswere upregulated during stem elongation, while DAO, GA2ox, and other genes were downregulated. The gene expression level was consistent with changes in hormone content and influenced the cell length elongation. Additionally, the expression results of RT-qPCR were consistent with RNA-seq. The observed variations in gene expression levels, endogenous hormones and sugar changes during the elongation and growth of asparagus tender stems offer valuable insights for future investigations into the molecular mechanisms of asparagus stem growth and development and provide a theoretical foundation for cultivation and production practices.

Can 3D Multiparametric Ultrasound Imaging Predict Prostate Biopsy Outcome?

OBJECTIVES: To assess the value of 3D multiparametric ultrasound imaging, combining hemodynamic and tissue stiffness quantifications by machine learning, for the prediction of prostate biopsy outcomes. METHODS: After signing informed consent, 54 biopsy-naïve patients underwent a 3D dynamic contrast-enhanced ultrasound (DCE-US) recording, a multi-plane 2D shear-wave elastography (SWE) scan with manual sweeping from base to apex of the prostate, and received 12-core systematic biopsies (SBx). 3D maps of 18 hemodynamic parameters were extracted from the 3D DCE-US quantification and a 3D SWE elasticity map was reconstructed based on the multi-plane 2D SWE acquisitions. Subsequently, all the 3D maps were segmented and subdivided into 12 regions corresponding to the SBx locations. Per region, the set of 19 computed parameters was further extended by derivation of eight radiomic features per parameter. Based on this feature set, a multiparametric ultrasound approach was implemented using five different classifiers together with a sequential floating forward selection method and hyperparameter tuning. The classification accuracy with respect to the biopsy reference was assessed by a group-k-fold cross-validation procedure, and the performance was evaluated by the Area Under the Receiver Operating Characteristics Curve (AUC). RESULTS: Of the 54 patients, 20 were found with clinically significant prostate cancer (csPCa) based on SBx. The 18 hemodynamic parameters showed mean AUC values varying from 0.63 to 0.75, and SWE elasticity showed an AUC of 0.66. The multiparametric approach using radiomic features derived from hemodynamic parameters only produced an AUC of 0.81, while the combination of hemodynamic and tissue-stiffness quantifications yielded a significantly improved AUC of 0.85 for csPCa detection (p-value < 0.05) using the Gradient Boosting classifier. CONCLUSIONS: Our results suggest 3D multiparametric ultrasound imaging combining hemodynamic and tissue-stiffness features to represent a promising diagnostic tool for biopsy outcome prediction, aiding in csPCa localization.

Proanthocyanidins delay the senescence of young asparagus stems by regulating antioxidant capacity and synthesis of phytochemicals.

Asparagus, characterized by its high metabolic rate, is susceptible to quality degradation. Proanthocyanidins have antioxidant, antibacterial, antiviral, and other biological functions and can inhibit the production of reactive oxygen species in plants. To enhance the shelf life of asparagus, we investigated the impact of various concentrations of proanthocyanidins on its cold storage and preservation. The findings revealed that proanthocyanidins effectively mitigated water loss, delayed chlorophyll degradation, and prevented firmness decline. Furthermore, they enhanced the activity of antioxidant enzymes (superoxide dismutase, catalase, peroxidase, and polyphenol oxidase), bolstered DPPH free radical scavenging ability, and increased the levels of total phenol, total flavone, rutin, oligomeric procyanidins, proline, and soluble protein. Moreover, proanthocyanidins promoted the accumulation of vitamin C, amino acids, total saponins, and lignin in the later storage stage, contributing to increased mechanical tissue thickness. These results suggest that proanthocyanidins play a crucial role in retarding the deterioration of asparagus quality during storage by affecting the antioxidant capacity and phytochemical (polyphenol,amino acid, total saponin, and lignin) synthesis in asparagus.

Association of interpregnancy interval and risk of adverse pregnancy outcomes in woman by different previous gestational ages.

BACKGROUND: With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages. METHODS: We used individual data from China's National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014-2015, 2016-2017, and 2018-2019) and infant gestational age in previous pregnancy (<28 weeks, 28-36 weeks, and ≥37 weeks). RESULTS: There were 781,731 pregnancies enrolled in this study. A short IPI (≤6 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.63 [1.55, 1.71] for vaginal delivery [VD] and 1.10 [1.03, 1.19] for cesarean section [CS]), low Apgar scores and small for gestational age (SGA), and a decreased risk of diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. A long IPI (≥60 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.18 [1.11, 1.26] for VD and 1.39 [1.32, 1.47] for CS), placenta previa, postpartum hemorrhage, diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes. The estimated risk of preterm birth, low Apgar scores, SGA, diabetes mellitus in pregnancy, and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss. CONCLUSION: For pregnant women with shorter or longer IPIs, more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

Disparities of Heatwave-Related Preterm Birth in Climate Types - China, 2012-2019.

What is already known about this topic?: An association between prenatal heatwave exposure and the risk of preterm birth was found. However, the disparities in heatwave-related preterm birth across different climate types have not been examined. What is added by this report?: This nationwide case-crossover study investigated the association between heatwave exposure and preterm birth across different Köppen-Geiger climate types. Among pregnant women residing in the arid-desert-cold climate type, exposure to compound heatwaves was found to be associated with a significantly higher risk of preterm birth {adjusted odds ratios (AORs) ranged from 1.55 [95% confidence interval ( CI): 1.21-1.97] to 2.11 (95% CI: 1.35-3.31)}. In contrast, among pregnant women residing in the tropical monsoonal climate type, exposure to daytime-only heatwaves was associated with an increased risk of preterm birth [AORs ranged from 1.25 (95% CI: 1.03-1.51) to 1.37 (95% CI: 1.05-1.77)]. What are the implications for public health practice?: Specific interventions should be implemented in China to mitigate the risk of preterm birth related to heatwaves, particularly for pregnant women residing in arid-desert-cold and tropical monsoonal climates.

Association of Daytime-Only, Nighttime-Only, and Compound Heat Waves With Preterm Birth by Urban-Rural Area and Regional Socioeconomic Status in China.

Importance: Associations between heat waves and preterm birth (PTB) have been reported. However, associations of daytime-only, nighttime-only, and compound heat waves with PTB have yet to be explored at a national level. Furthermore, possible heterogeneity across urban-rural communities with different socioeconomic statuses needs to be explored. Objective: To examine the association between daytime-only, nighttime-only, and compound heat waves and PTB in China and to find variations between urban and rural regions. Design, Setting, and Participants: This case-crossover study used nationwide representative birth data between January 1, 2012, and December 31, 2019, from China's National Maternal Near Miss Surveillance System. This multisite study covered 30 provinces in China and ensured the representation of urban and rural populations across 3 socioeconomic regions. Singleton live births delivered in the warm seasons from April to October during the study period were included. Exclusion criteria consisted of gestational age younger than 20 or older than 45 weeks, maternal ages younger than 13 or older than 50 years, conception dates earlier than 20 weeks before January 1, 2012, and later than 45 weeks before December 31, 2019, and an inconsistent combination of birthweight and gestational age according to growth standard curves of Chinese newborns. Data were analyzed from September 10, 2021, to April 25, 2023. Exposures: Eighteen definitions of heat waves by 3 distinct types, including daytime only (only daily maximum temperature exceeds thresholds), nighttime only (only daily minimum temperature exceeds thresholds), and compound (both daily maximum and minimum temperature exceeds thresholds) heat waves, and 6 indexes, including 75th percentile of daily temperature thresholds for 2 or more (75th-D2), 3 or more (75th-D3), or 4 or more (75th-D4) consecutive days and 90th percentile of daily temperature thresholds for 2 or more (90th-D2), 3 or more (90th-D3), and 4 or more (90th-D4) consecutive days. Main Outcomes and Measures: Preterm births with less than 37 completed weeks of gestation. Results: Among the 5 446 088 singleton births in the final analytic sample (maternal mean [SD] age, 28.8 [4.8] years), 310 384 were PTBs (maternal mean [SD] age, 29.5 [5.5] years). Compared with unexposed women, exposure of pregnant women to compound heat waves in the last week before delivery was associated with higher risk for PTB, with the adjusted odds ratios (AORs) ranging from 1.02 (95% CI, 1.00-1.03) to 1.04 (95% CI, 1.01-1.07) in 6 indexes. For daytime-only heat wave exposures, AORs ranged from 1.03 (95% CI, 1.01-1.05) to 1.04 (95% CI, 1.01-1.08) in the 75th-D4, 90th-D2, 90th-D3, and 90th-D4 indexes. Such associations varied by rural (AOR range, 1.05 [95% CI, 1.01-1.09] to 1.09 [95% CI, 1.04-1.14]) and urban (AOR range, 1.00 [95% CI, 0.98-1.02] to 1.01 [95% CI, 0.99-1.04]) regions during exposure to daytime-only heat waves in the 75th-D3 and 90th-D3 indexes. Conclusions and Relevance: In this case-crossover study, exposure to compound and daytime-only heat waves in the last week before delivery were associated with PTB, particularly for pregnant women in rural regions exposed to daytime-only heat waves. These findings suggest that tailored urban-rural preventive measures may improve maternal health in the context of climate change.

Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection.

The coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden to our society. Most patients infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Although only a small proportion of patients progressed to severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, and cardiovascular disorders, severe COVID-19 is accompanied by high mortality rates with near 7 million deaths. Nowadays, effective therapeutic patterns for severe COVID-19 are still lacking. It has been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate host metabolism to avoid immunity, facilitate their own replication, or to initiate pathological response. Targeting the interaction between SARS-CoV-2 and host metabolism holds promise for developing therapeutic strategies. In this review, we summarize and discuss recent studies dedicated to uncovering the role of host metabolism during the life cycle of SARS-CoV-2 in aspects of entry, replication, assembly, and pathogenesis with an emphasis on glucose metabolism and lipid metabolism. Microbiota and long COVID-19 are also discussed. Ultimately, we recapitulate metabolism-modulating drugs repurposed for COVID-19 including statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, and metformin.

Multimorbidity of Allergic Conditions in Urban Citizens of Southern China: A Real-World Cross-Sectional Study.

BACKGROUND: Extensive knowledge of allergic multimorbidities is required to improve the management of allergic diseases with the industrialization of China. However, the demography and allergen distribution patterns of allergic multimorbidities in China remain unclear, despite the increasing prevalence of allergies. METHODS: This was a real-world, cross-sectional study of 1273 outpatients diagnosed with one or more allergic diseases in Guangzhou, the most populated city of southern China, with leading industrial and commercial centers, between April 2021 and March 2022. Seven allergic diseases (allergic rhinitis (AR), asthma (AS)/cough variant asthma (CVA), atopic dermatitis (AD)/eczema, food allergy (FA), allergic conjunctivitis (AC), drug allergy (DA), and anaphylaxis) were assessed. Positive rates of sensitization to different allergens were measured using an allergen detection system of the UniCAP (Pharmacia Diagnostics, Sweden) instrument platform to compare the groups of allergic multimorbidities against a single entity. RESULTS: There were 659 (51.8%) males and 614 (48.2%) females aged from 4 months to 74 years included in the analysis. The study participants who were diagnosed with allergic diseases had an average of 1.6 diagnoses. Overall, 46.5% (592 of 1273) of the patients had more than one allergic condition, and allergic rhinitis was the most common type of multimorbidity. Women were more likely to suffer from an allergic disease alone, whereas allergic multimorbidities were more likely to be diagnosed in men (p = 0.005). In addition, allergic multimorbidities were common in all age groups, with an incidence ranging from 37.1% to 57.4%, in which children and adolescents were more frequently diagnosed with allergic multimorbidities than adults (18-60 years old) (all p < 0.05). Allergic multimorbidity was observed throughout the year. A difference in the positive rate of allergens sensitization and total immunoglobulin E (tIgE) levels between different allergic multimorbidities was observed. CONCLUSIONS: Allergic multimorbidities were very commonly found in nearly half of all patients with allergies. The proportion of allergic multimorbidities varied with the type of disease, sex, age, and allergen distribution pattern. These findings may help clinicians to develop "One health" strategies for the clinical management of allergic diseases.

Exploring the clinical features and risk factors for children tinea capitis complicated with allergic diseases.

BACKGROUND: Tinea capitis, atopic dermatitis and allergic rhinitis are the most common disorders endured by prepubescent children. Dermatophyte infections have been linked to allergic disorders, such as increased sensitivity to dermatophytes in patients with atopic dermatitis. OBJECTIVES: To explore the correlation between tinea capitis and allergic diseases in children and to analyse their risk factors. METHODS: This study monitored epidemiological changes in childhood tinea capitis and risk factors for whom with allergic disease in a single centre in three consecutive five-year intervals by reviewing clinical data and multivariate logistic data analysis. RESULTS: Between 2007 and 2022, there were 127 children patients with tinea capitis, the mean age was 4.83 years, and the male-to-female ratio was 1.76:1. Zoophilic Microsporum canis and Trichophyton mentagrophytes were the most prevalent pathogens, and the proportions remained relatively constant every 5 years. There were 34 (26.8%) children with tinea capitis complicated with allergic disease, among them 14 children with atopic dermatitis/eczema, 13 with allergic rhinitis, 8 urticaria, 6 food allergies and 1 allergic asthma. Male, kerion, zoophilic species infections and animal contact history were prevalent features in allergic disease combined with tinea capitis. Patients with tinea capitis plus allergic disease mostly had a family history with similar complications. CONCLUSION: M. canis and T. mentagrophytes were the most prevalent pathogens of tinea capitis in the last 15 years; atopic dermatitis/eczema and allergic rhinitis were the most frequently associated allergic diseases. Male, kerion, zoophilic pathogen and animal contact history are risk factors.

Characteristics and fetal outcomes of pregnant women with hypertensive disorders in China: a 9-year national hospital-based cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a growing concern and a challenge for maternity care providers as the prevalence of hypertension continues to increase. However, optimal management of HDP is unclear. Therefore, we aimed to explore the differences in adverse fetal outcomes among women with different subtypes of HDP and different blood pressure (BP) levels, to provide evidence-based management of HDP. METHODS: We obtained data from China's National Maternal Near-Miss Surveillance System from 2012 to 2020. Associations between BP management and adverse fetal outcomes, stratified by the four subtypes of HDP, were assessed using logistic regression analysis with a robust variance estimator. RESULTS: For the period, a total of 393,353 pregnant women with HDP were included in the study; 8.51% had chronic hypertension, 2.27% had superimposed preeclampsia, 50.17% had preeclampsia or eclampsia, and 39.04% had gestational hypertension. The BP levels at delivery admission were mostly (61.14%) of non-severe stage 2 (systolic BP 140-159 mm Hg and/or diastolic BP 90-109 mm Hg) hypertension by American Heart Association classification. A high rate of adverse fetal outcomes was observed among women with HDP, especially among those aged < 20 or > 35 y or those diagnosed with superimposed preeclampsia. Compared with those with normal BP levels at delivery admission, we found an upward curve with increased risk among pregnant women with more severe BP levels, including the risk of preterm birth and small for gestational age (SGA) fetus. The odds ratios (ORs) of stillbirth, neonatal death, and low Apgar scores associated with severe stage 2 hypertension increased significantly. In addition, the association between BP at admission and fetal outcomes differed among women with varying HDP subtypes. Pregnant women with preeclampsia or eclampsia had an increased risk for preterm birth (adjusted OR [aOR], 1.33 [95% confidence interval {CI}, 1.07 ~ 1.65]) and SGA (aOR, 1.37 [95% CI, 1.10 ~ 1.71]) even when the admission BP was at stage 1 level. CONCLUSION: Greater attention should be paid to cases involving preeclampsia superimposed on chronic hypertension and pregnant women aged < 20 or > 35 y to mitigate the burden of adverse fetal outcomes caused by HDP.

Fabrication of Ga2O3 Schottky Barrier Diode and Heterojunction Diode by MOCVD.

In this article, we reported on a Ga2O3-based Schottky barrier diode and heterojunction diode from MOCVD. The Si-doped n-type Ga2O3 drift layer, grown by MOCVD, exhibited high crystal quality, flat surfaces, and uniform doping. The distribution of unintentional impurities in the films was studied. Then nickel Schottky barrier diode and p-NiO/n-Ga2O3 heterojunction diode were fabricated and measured. Without any electric field management structure, the Schottky barrier diode and heterojunction diode have specific resistances of 3.0 mΩ·cm2 and 6.2 mΩ·cm2, breakdown voltages of 380 V and 740 V, thus yielding power figures of merit of 48 MW·cm-2 and 88 MW·cm-2, respectively. Besides, both devices exhibit a current on/off ratio of more than 1010. This shows the prospect of MOCVD in power device manufacture.

Spatial Econometric Analysis of the Level and Influencing Factors of Coupling and Coordination between Regional Logistics and the Ecological Environment in China.

With the logistics industry becoming an important part of economic development, logistics activities have given rise to various environmental problems, which that affect the sustainable development of the ecological environment. In order to understand the status of regional sustainable development, it is of great significance to study the level of coordinated development of regional logistics and the ecological environment, and determine which variables will affect their coordinated development. To accomplish this objective, the entropy method is used to give the corresponding weight to each index and calculate the coupling degree and coordination degree of regional logistics and the ecological environment; next, the coupling coordination level of regional logistics and ecological environment in different provinces from 2010 to 2019 is measured by the coupling coordination degree model; then, we study the spatial effect of the influencing factors on the coordinated development level of regional logistics and ecological environment in 30 provinces of China from 2010 to 2019. At the same time, we investigate the spatial effect of each influencing factor on the coordination level. On the basis of the findings, relevant suggestions and measures are proposed. The main conclusions are as follows: (i) As China's economy is in the process of transformation to high-quality development, the coordinated development of regional logistics and the ecological environment is still at a relatively low level; (ii) due to the differences in the development basis of each region, the coordinated development level of regional logistics and the ecological environment is characterized by a regional imbalance; (iii) because of the significant spatial spillover effect, the coordinated development level of regional logistics and ecological environment shows obvious correlation in space.

The Impact of Information Infrastructure on Air Pollution: Empirical Evidence from China.

Information infrastructure construction has become an essential support for the new global technological revolution and industrial change. To examine whether information infrastructure can mitigate the level of air pollution, this paper measures the development level of information infrastructure in each region using the entropy-TOPSIS method based on the data of 31 Chinese provinces from 2013 to 2020. On this basis, it explores the impact of information infrastructure on atmospheric pollution and its mechanism using spatial measures and mediating effects. The results show that: (1) Information infrastructure can effectively improve air quality, though its spatial spillover effect is not obvious. (2) In addition to directly reducing air pollution, information infrastructure can also improve air quality by influencing industrial structure upgrading, or by influencing technological innovation first and then industrial structure upgrading. By exploring the impact of information infrastructure on air pollution and its action path, this paper expects to provide some scientific reference value for the construction of information infrastructure under the background of the new global technological revolution.

Effectiveness and safety of Jiuwei Zhenxin granules for treating generalized anxiety disorder: A randomized controlled trial.

Background: Generalized anxiety disorder (GAD) is a chronic disorder characterized by excessive, pervasive, persistent worrying that is difficult to control. Jiuwei Zhenxin granules may be safer and more effective than non-benzodiazepine anti-anxiety drugs for treating GAD. This study aimed to assess the efficacy and safety of Jiuwei Zhenxin granules alone or in combination with the benzodiazepine alprazolam. Materials and methods: A total of 710 patients were recruited from outpatient clinics and were randomly divided into two groups to receive Jiuwei Zhenxin granules (single drug group) or Jiuwei Zhenxin granules and alprazolam (combination group). The primary outcome was the response rate, which was defined as a ≥ 50% reduction from the baseline total score on the Hamilton Anxiety Scale (HAMA). Secondary outcome measures included mean changes in HAMA total score, psychological and somatic factors, Hamilton Depression Rating Scale total score, and SF-36 health survey score. Results: At 4 weeks after treatment, the single and combination treatment groups showed significant improvement in the HAMA total score and they did not differ significantly in response rate (77.58 vs. 79.17%) or rate of adverse drug reactions (16.22 vs. 16.07%). Conclusion: Jiuwei Zhenxin granules are an effective, safe, and well-tolerated treatment against GAD. Combining them with alprazolam may not significantly improve efficacy. Clinical trial registration: [www.ClinicalTrials.gov], identifier [CHICTR1800020095].

Rhein ameliorates septic lung injury and intervenes in macrophage metabolic reprogramming in the inflammatory state by Sirtuin 1.

AIMS: Sepsis is an organ dysfunction syndrome caused by the maladjustment of response to infection. Acute lung injury (ALI) appears the earliest, with urgent onset and limited treatments. Previous pharmacological studies have found that rhein (RH), an active ingredient rich in rhubarb, has multiple pharmacological activities such as anti-inflammatory, anti-infection and metabolic regulation. This research aimed to explore whether RH alleviates septic acute lung injury and probe possible mechanisms. MAIN METHODS: In this study, the septic ALI mouse model was established by cecal ligation and perforation (CLP). LPS-induced RAW264.7 model was selected to further explore the protective mechanism of RH. H&E staining, Western blot, qRT-PCR, and 1H NMR analysis were used to verify the protective effect of RH on ALI in vivo and vitro. KEY FINDINGS: RH could relieve pathological lung injury and pulmonary edema, reduce the serum LPS and inhibit inflammatory response in CLP mice. Further studies displayed that RH affected the metabolism in vivo, with significant changes in serum and lung metabolomics. In vitro results demonstrated that RH inhibited the expression of inflammatory mediators and factors in macrophages by affecting metabolic reprogramming and upregulating the expression of Sirtuin 1. SIGNIFICANCE: RH improved the overall metabolic condition of sepsis mice by up-regulating and activating SIRT1, and inhibited the over activation of macrophages by regulating metabolism. These findings reveal the therapeutic mechanism of RH on sepsis ALI from the perspective of metabolism.

Interrupted-time-series analysis of the immediate impact of COVID-19 mitigation measures on preterm birth in China.

Preliminary evidence from China and other countries has suggested that coronavirus disease 2019 (COVID-19) mitigation measures have caused a decline in preterm births, but evidence is conflicting. Utilising a national representative data of 11,714,947 pregnant women in China, we explored the immediate changes in preterm birth rates during the COVID-19 mitigation period using an interrupted-time-series analysis. We defined the period prior to February 1, 2020 as the baseline, followed by the COVID-19 mitigation stage. In the first month of the COVID-19 mitigation, a significant absolute decrease in preterm birth rates of 0.68% (95%CI:-1.10% to -0.26%) in singleton, and of 2.80% (95%CI:-4.51% to -1.09%) in multiple births was noted. This immediate decline in Wuhan was greater than that at the national level among singleton births [-2.21% (95%CI:-4.09% to -0.34% vs. -0.68%)]. Here we report an immediate impact of COVID-19 mitigation measures on preterm birth in China.