The Methodological Quality of Observational Studies Examining the Risk of Pregnancy Drug Use on Congenital Malformations Needs Substantial Improvement: A Cross-Sectional Survey.

BACKGROUND AND OBJECTIVE: An increasing number of observational studies have investigated the risk of using drugs during pregnancy on congenital malformations. However, the credibility of the causal relationships drawn from these studies remains uncertain. This study aims to evaluate the potential methodological issues in existing observational studies. METHODS: We used a stepwise approach to investigate this issue. First, we identified observational studies published in 2020 that examined the risk of congenital malformations associated with medication use during pregnancy. We assessed the methodological characteristics for establishing causality, including study design, confounding control, and sensitivity analysis, and compared them between "core clinical journals" and "general journals." For studies reporting an increased risk of congenital malformations in core clinical journals, we searched for subsequent studies addressing the same research question published between January 2021 and May 2023 to assess the consistency of the literature. RESULTS: A total of 40 eligible studies were published in 2020, primarily focused on the safety of vitamin B12 and folic acid (n = 4), antidepressants (n = 4), and others (n = 32). Our findings suggest that only two (5.00%) studies used causal models to guide the identification of confounding, and only eight (20.00%) studies assessed the potential dose-response relationship. In all, 15 (37.50%) studies used propensity score analysis strategy to achieve "mimic-randomization." In addition, 22 studies (55.00%) performed sensitivity analyses, while 10 (45.45%) showed inconsistency with the primary outcome. Furthermore, 5 studies reported positive outcomes, whereas only 1 out of 11 studies demonstrated a positive correlation between drug usage during pregnancy and major malformations in subsequent studies. CONCLUSION: A significant portion of the studies has failed to sufficiently consider the essential methodological characteristics required to improve the credibility of causal inferences. The increased risk of congenital malformations documented in core clinical journal was not adequately replicated in subsequent studies.

Guidance of development, validation, and evaluation of algorithms for populating health status in observational studies of routinely collected data (DEVELOP-RCD).

BACKGROUND: In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked. METHODS: We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it. RESULTS: A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm's suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance. CONCLUSIONS: The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.

Construction of carbon quantum dots/riboflavin fluorescent probe and its application in the detection of ciprofloxacin.

The research outlined a novel approach for creating a sensitive and efficient ratio fluorescent probe for ciprofloxacin (CIP) detection. The method used the biomass materials passionfruit shell and diethylenetriamine as carbon and nitrogen sources, respectively, to prepare blue fluorescent carbon quantum dots (b-CQDs) with an average size of 3.29 nm and a quantum yield of 19.6% by a hydrothermal method. The newly designed b-CQDs/riboflavin ratio fluorescent probe demonstrates a distinct advantage for CIP monitoring, exhibiting a marked increase in fluorescence intensity at 445 nm upon interaction with CIP, while maintaining a stable intensity at 510 nm. In the water system, the I445 nm/I510 nm ratio of the fluorescent probe showed a significant linear relationship with CIP at the concentrations of 0-250 µmol·L-1, and the probe boasts a low detection limit of 0.86 µmol·L-1. The outstanding selectivity, broad detection range, low detection limits, and high quantum yield of the b-CQDs highlight their significant potential in the development of advanced sensing probes for efficient detection of ciprofloxacin, offering promising insights for future sensor technology advancements.

Efficient Solar Steam Generation by Multiscale Photothermal Structures Derived from Cactus Stems.

Solar steam generation (SSG) is a promising technique that may find applications in seawater desalination, sewage treatment, etc. The core component for SSG devices is photothermal materials, among which biomass-derived carbon materials have been extensively attempted due to their low cost, wide availability, and diversified microstructures. However, the practical performance of these materials is not satisfactory because of the multifaceted structural requirements for photothermal materials in SSG scenarios. In this work, cactus stems, which possess abundant and multiscaled pores for simultaneous sunlight gathering and water evaporation, are applied as the photothermal structure for SSG devices after mild heat treatment. Consequently, the SSG device based on the carbonized cactus stems delivers high performance (an absorption rate of 93.7% of the solar spectrum, an evaporation rate of 2.02 kg m-2 h-1, and an efficiency of 91.4% under one solar irradiation). We anticipate that the material can be a potential candidate for efficient SSG devices and may shed light on the sustainable supply of water.

AI-based derivation of atrial fibrillation phenotypes in the general and critical care populations.

BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia worldwide and is linked to a higher risk of mortality and morbidity. To predict AF and AF-related complications, clinical risk scores are commonly employed, but their predictive accuracy is generally limited, given the inherent complexity and heterogeneity of patients with AF. By classifying different presentations of AF into coherent and manageable clinical phenotypes, the development of tailored prevention and treatment strategies can be facilitated. In this study, we propose an artificial intelligence (AI)-based methodology to derive meaningful clinical phenotypes of AF in the general and critical care populations. METHODS: Our approach employs generative topographic mapping, a probabilistic machine learning method, to identify micro-clusters of patients with similar characteristics. It then identifies macro-cluster regions (clinical phenotypes) in the latent space using Ward's minimum variance method. We applied it to two large cohort databases (UK-Biobank and MIMIC-IV) representing general and critical care populations. FINDINGS: The proposed methodology showed its ability to derive meaningful clinical phenotypes of AF. Because of its probabilistic foundations, it can enhance the robustness of patient stratification. It also produced interpretable visualisation of complex high-dimensional data, enhancing understanding of the derived phenotypes and their key characteristics. Using our methodology, we identified and characterised clinical phenotypes of AF across diverse patient populations. INTERPRETATION: Our methodology is robust to noise, can uncover hidden patterns and subgroups, and can elucidate more specific patient profiles, contributing to more robust patient stratification, which could facilitate the tailoring of prevention and treatment programs specific to each phenotype. It can also be applied to other datasets to derive clinically meaningful phenotypes of other conditions. FUNDING: This study was funded by the DECIPHER project (LJMU QR-PSF) and the EU project TARGET (10113624).

Efficacy of corticosteroids in patients with acute respiratory distress syndrome: a meta-analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS), are respiratory diseases with high morbidity and mortality. Clinical trials investigating the efficacy of corticosteroids in the treatment of ARDS often yield contradictory results. We hereby conducted a systematic review and meta-analysis to investigate the efficacy of corticosteroids in ARDS management. MATERIALS AND METHODS: We conducted a search for randomized clinical trials (RCT) and observational studies that utilized corticosteroids for patients with ARDS in Web of Science, PubMed, and Embase. The primary outcome was mortality. Risk of bias was assessed using Cochrane or NOS scales. Statistical effect size was analyzed using the Mantel-Haenszel method. RESULTS: A total of 20 studies, comprising 11 observational studies and 9 RCTs, were eligible for analysis. In RCTs, corticosteroids were associated with a reduction of mortality in ARDS patients (relative risk [RR] = 0.80, 95%CI: 0.71-0.91, p = 0.001). Further subgroup analysis indicated that specific variables, such as low-dose (RR = 0.81; 95%CI: 0.67-0.98; p = 0.034), methylprednisolone (RR = 0.70; 95%CI: 0.49-0.98; p = 0.035), and dexamethasone (RR = 0.82; 95%CI: 0.69-0.98; p = 0.029) were associated with mortality among patients receiving corticosteroids. However, in observational studies, corticosteroids increased the risk of death (RR = 1.16, 95%CI: 1.04-1.29; p = 0.001). Subgroup analysis showed that the use of high-dose corticosteroids was associated with higher patient mortality (RR = 1.20; 95%CI: 1.04-1.38; p = 0.001). CONCLUSIONS: The efficacy of corticosteroids on the mortality of ARDS differed by the type and dosage of corticosteroids used, as well as the etiologies. Current data do not support routine use of corticosteroids in ARDS since protective effects were observed in RCTs but increased mortality was found in observational studies. More well designed and large clinical trials are needed to specify the favorable subgroups for corticosteroid therapy.

Corticosteroid use may reduce the risk of death in patients with acute respiratory distress syndrome (ARDS) according to randomized controlled trials.Observational studies indicate that corticosteroid use may increase the risk of death in non-COVID-19 ARDS patients but not in COVID-19 ARDS patients.Both regular and low-dose corticosteroids show benefits in reducing mortality in RCTs, but observational studies associate these doses with increased mortality.

Epidemiology and etiology of hand, foot, and mouth disease in Zhengzhou, China, from 2009 to 2021.

Background: Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by a variety of enteroviruses (EVs). To explore the epidemiological characteristics and etiology of HFMD in Zhengzhou, China, we conducted a systematic analysis of HFMD surveillance data from Zhengzhou Center for Disease Control and Prevention from January 2009 to December 2021 (https://wjw.zhengzhou.gov.cn/). Methods: Surveillance data were collected from Zhengzhou Center for Disease Control and Prevention from January 2009 to December 2021 (https://wjw.zhengzhou.gov.cn/). Cases were analyzed according to the time of onset, type of diagnosis, characteristics, viral serotype, and epidemiological trends. Results: We found that the primary causative agent responsible for the HFMD outbreaks in Zhengzhou was Enterovirus A71 (EVA-71) (48.56%) before 2014. After 2015, other EVs gradually became the dominant strains (57.68%). The data revealed that the HFMD epidemics in Zhengzhou displayed marked seasonality, with major peaks occurring from April to June, followed by secondary peaks from October to November, except in 2020. Both the severity and case-fatality ratio of HFMD decreased following the COVID-19 pandemic (severity ‰: 13.46 vs. 0.17; case-fatality ‰: 0.21 vs. 0, respectively). Most severe cases were observed in patients aged 1 year and below, accounting for 45.81%. Conclusions: Overall, the incidence rate of HFMD decreased in Zhengzhou following the introduction of the EVA-71 vaccine in 2016. However, it is crucial to acknowledge that HFMD prevalence continues to exhibit a distinct seasonal pattern and periodicity, and the occurrence of other EV infections poses a new challenge for children's health.

Synthesis of InAl-alloyed Ga2O3 nanowires for self-powered ultraviolet detectors by a CVD method.

Ga2O3 is a kind of wide-band gap semiconductor, which has great potential in deep ultraviolet detection because of its high efficiency and fast response. Doping can improve the photoelectric properties of Ga2O3 materials. In this paper, In and Al elements alloyed Ga2O3 nanowires (InAl-Ga2O3 NWs) were successfully grown on p-GaN using a cost-effective chemical vapor deposition method and a vertical structure. The GaN/InAl-Ga2O3 NWs p-n self-powered wide-gap UV photodetector (PD) was constructed based on sputtered gold film as the bottom and top electrodes, and spin coated with polymethyl methacrylate as the insulating layer in the vertical direction. The GaN/InAl-Ga2O3 UV PD exhibits excellent performances, including an extremely low dark current of 0.015 nA, a maximum photocurrent of about 16 nA at zero-bias voltage under 265 nm illumination, and a light-to-dark current ratio greater than 103. The responsivity is 0.94 mA W-1, the specific detectivity is 9.63 × 109 jones, and the good fast response/attenuation time is 31.2/69.6 ms. The self-powered characteristics are derived from the internal electric field formed between p-type GaN and n-type InAl-Ga2O3 NWs, which is conducive to the rapid separation and transfer of photogenerated carriers. This work provides an innovative mechanism of high-performance metal oxide nanowires for the application of p-n junction photodetectors, which can operate without any external bias.

Enrollment of Black, Indigenous and People of Color (BIPOC) and female participants in the US diabetes trials spanning 2000 to 2020: A chronological survey.

AIMS: Little is known about the enrollment practice of both Black, Indigenous and People of Color (BIPOC) and females in the US diabetes trials. We aimed to perform a chronological survey to evaluate the enrollment of BIPOC and female participants in the US diabetes randomized controlled trials (RCTs) over the past two decades. METHODS: We searched databases to systematically include the US diabetes RCTs from 2000 January 1st to 2020 December 31st. Primary outcome was the adequate enrollment of both BIPOC and females, defined by the participation to prevalence ratio (PPR) > 0.8. We tested the temporal trend in adequate enrollment over time and used logistic regression analysis to explore the relationship between adequate enrollment and trial characteristics. RESULTS: A total of 69 US diabetes trials were included for analyses, with a median BIPOC and female enrollment percentage of 29.0 % and 45.4 % respectively. There were 22 (31.9 %) trials with adequate enrollment of both BIPOC and females. No significant trend of adequate enrollment percentage of BIPOC and females over time was observed (P = 0.16). Of trial types, those with medication interventions were significantly related to decreased odds of adequate enrollment, when compared to trials with non-drug interventions (odds ratio = 0.29, 95 % confidence interval: 0.11-0.84). CONCLUSIONS: Less than one third of the US diabetes trials adequately enrolled both BIPOC and females over the past two decades, and no temporal improvement in BIPOC and female participant enrollment was observed. These results highlight the need for more endeavors to mitigate inadequate representation regarding BIPOC and female enrollment in diabetes trials.

[Authenticity discrimination for Galli Gigerii Endothelium Corneum based on UPLC-MS/MS and peptidomics].

Peptidomics was employed to systematically analyze the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants and establish a method for distinguishing Galli Gigerii Endothelium Corneum from its adulterants, including the gizzard membranes from ducks, geese, and pigeons. UPLC-Q-Exactive Orbitrap-MS was combined with multivariate statistical analysis to analyze the peptides in Galli Gigerii Endothelium Corneum and its adulterants. The structures of peptides were identified by pNovo combined with manual recognition of spectra, and synthetic peptide standards were used for validation. LC-MS/MS was used to optimize the sample pre-processing conditions, including the extraction procedure, extraction time, extraction solvents, and solvent volumes, for the characteristic peptide LESY in Galli Gigerii Endothelium Corneum. Multiple reaction monitoring(MRM) in the ESI~+ mode with m/z 511.24→269.11 and 511.24→243.13 as detection ions was employed for qualitative and quantitative analyses. The established UPLC-MS/MS method demonstrated good specificity, stability, and durability. The content of LESY in 16 batches of Galli Gigerii Endothelium Corneum samples ranged from 55.03 to 113.36 µg·g~(-1). Additionally, a qualitative detection method for the common peptide RDPVLVSR in adulterants was established with m/z 471.28→785.45 and 471.28→670.41 as the detection ions. This study established a convenient, rapid, and accurate detection method for the characteristic peptides in Galli Gigerii Endothelium Corneum and its adulterants. The method possesses good specificity, stability, and durability, providing a valuable reference for the identification and quality control of Galli Gigerii Endothelium Corneum and other traditional Chinese medicines derived from animal sources.

Effect of Acupuncture for Methadone Reduction : A Randomized Clinical Trial.

BACKGROUND: Methadone maintenance treatment (MMT) is effective for managing opioid use disorder, but adverse effects mean that optimal therapy occurs with the lowest dose that controls opioid craving. OBJECTIVE: To assess the efficacy of acupuncture versus sham acupuncture on methadone dose reduction. DESIGN: Multicenter, 2-group, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR2200058123). SETTING: 6 MMT clinics in China. PARTICIPANTS: Adults aged 65 years or younger with opioid use disorder who attended clinic daily and had been using MMT for at least 6 weeks. INTERVENTION: Acupuncture or sham acupuncture 3 times a week for 8 weeks. MEASUREMENTS: The 2 primary outcomes were the proportion of participants who achieved a reduction in methadone dose of 20% or more compared with baseline and opioid craving, which was measured by the change from baseline on a 100-mm visual analogue scale (VAS). RESULTS: Of 118 eligible participants, 60 were randomly assigned to acupuncture and 58 were randomly assigned to sham acupuncture (2 did not receive acupuncture). At week 8, more patients reduced their methadone dose 20% or more with acupuncture than with sham acupuncture (37 [62%] vs. 16 [29%]; risk difference, 32% [97.5% CI, 13% to 52%]; P < 0.001). In addition, acupuncture was more effective in decreasing opioid craving than sham acupuncture with a mean difference of -11.7 mm VAS (CI, -18.7 to -4.8 mm; P < 0.001). No serious adverse events occurred. There were no notable differences between study groups when participants were asked which type of acupuncture they received. LIMITATION: Fixed acupuncture protocol limited personalization and only 12 weeks of follow-up after stopping acupuncture. CONCLUSION: Eight weeks of acupuncture were superior to sham acupuncture in reducing methadone dose and decreasing opioid craving. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.

Addressing the Global Burden of Cardiovascular Disease in Women: JACC State-of-the-Art Review.

Cardiovascular diseases (CVDs) are responsible for approximately 35% of all deaths in women. In 2019, the global age-standardized CVD prevalence and mortality of women were 6,403 per 100,000 and 204 per 100,000, respectively. Although the age- and population-adjusted prevalence has decreased globally, opposite trends are evident in regions of socioeconomic deprivation. Cardiovascular health and outcomes are influenced by regional socioeconomic, environmental, and community factors, in addition to health care system and individual factors. Cardiovascular care in women is commonly plagued by delayed diagnoses, undertreatment, and knowledge gaps, particularly in women-specific or women-predominant conditions. In this paper, we describe the global epidemiology of CVD and highlight multilevel determinants of cardiometabolic health. We review knowledge and health care gaps that serve as barriers to improving CVD outcomes in women. Finally, we present national, community, health care system, and research strategies to comprehensively address cardiometabolic risk and improve outcomes in women.

Journal requirement for data sharing statements in clinical trials: a cross-sectional study.

OBJECTIVES: Data sharing statements are considered routine in clinical trial reporting and represent a step toward data transparency. The International Committee of Medical Journal Editors (ICMJE) required clinical trials to publish data sharing statements. We aimed to assess the requirement for data sharing statements of individual participant data by biomedical journals and explore associations between journal characteristics and journal requirements for data sharing statements. STUDY DESIGN AND SETTING: In this cross-sectional study, we included all biomedical journals that published clinical trials from January 1, 2019, to December 31, 2022, and that were indexed by the Journal Citation Reports. The study outcome was the journal requirement for data sharing statements. Multivariable logistic regression analysis was used to assess the relationship between journal characteristics and requirement for data sharing statements. RESULTS: Of the 3229 biomedical journals included in the analysis, 2345 (72.6%) required authors to include data sharing statements. Journals published in the UK (OR, 3.19 [95% CI, 2.43-4.22]) and endorsing the Consolidated Standards of Reporting Trials (OR, 3.30 [95% CI, 2.78-3.92]) had greater odds of requiring data sharing statements. Journals that were open access, non-English language, in the Journal Citation Reports group of clinical medicine, and on the ICMJE list had lower odds of requiring data sharing statements, with ORs ranging from 0.18 to 0.81. CONCLUSION: Despite ICMJE recommendations, more than 27% of the biomedical journals that published clinical trials did not require clinical trials to include data sharing statements, highlighting room for improved transparency.

Synthesis of Structure-Adjustable R-Au/Pt-CdS Nanohybrids with Strong Plasmon Coupling and Improved Photothermal Conversion Performance.

Noble metal nanomaterials with a localized surface plasmon resonance effect exhibit outstanding advantages in areas such as photothermal therapy and photocatalysis. As a unique plasmonic metal nanostructure, gold nanobipyramids have been attracting much interest due to their strong specific local electric field intensity, large optical cross sections, and high refractive index sensitivity. In this study, we propose a novel three-component hetero-nanostructure composed of rough gold nanobipyramids (R-Au NBPs), Pt, and CdS. Initially, purified gold nanobipyramids are regrown to form R-Au NBPs that have a certain degree of roughness. These R-Au NBP substrates with a rough surface provide more hotspots and strengthen the intensity of localized electric fields. Subsequently, Pt and CdS nanoparticles are selectively deposited onto the surface of R-Au NBPs. Pt nanoparticles can provide more active sites. Each component of this hetero-nanostructure directly contacts others, creating multiple electron transfer channels. This novel design allows for tunable localized plasmon resonance wavelengths ranging from the visible to near-infrared regions. These factors contribute to the final superior photothermal conversion performance of the R-Au/Pt-CdS nanohybrids. Under the irradiation of near-infrared light (1064 nm), the photothermal conversion efficiency of R-Au/Pt-CdS reached 38.88%, which is 4.49, 1.5, and 1.22 times higher than that of Au NBPs, R-Au NBPs, and R-Au NBPs/Pt, respectively.

High molecular weight hyaluronic acid-liposome delivery system for efficient transdermal treatment of acute and chronic skin photodamage.

Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression.

Association Between Remnant Cholesterol and Risk of Incident Atrial Fibrillation: Population-Based Evidence From a Large-Scale Prospective Cohort Study.

BACKGROUND: Evidence for the relationship between remnant cholesterol (RC) and incident atrial fibrillation (AF) risk remains sparse and limited. METHODS AND RESULTS: Participants were enrolled between 2006 and 2010 and followed up to 2021. The multivariable Cox proportional hazards model was used to examine the relationship between RC quartiles and risk of incident AF. Subgroup analyses and sensitivity analyses were performed to explore the potential modification of the association and the robustness of the main findings. A total of 422 316 participants (mean age, 56 years; 54% women) were included for analyses. During a median follow-up of 11.9 years (first quartile-third quartile, 11.6-13.2 years), there were 24 774 AF events documented with an incidence of 4.92 events per 1000 person-years (95% CI, 4.86-4.98). Participants in higher RC quartiles had a lower risk of incident AF than those in the lowest quartile (first quartile): hazard ratio (HR)=0.96 (95% CI, 0.91-1.00) for second quartile; HR=0.92 (95% CI, 0.88-0.96) for third quartile; and HR=0.85 (95% CI, 0.81-0.89) for fourth quartile (P for trend <0.001). The association between RC quartiles and risk of incident AF was stronger in participants aged ≥65 years, in men, and in participants without history of diabetes when compared with control groups (P<0.001 for interaction). CONCLUSIONS: On the basis of data from this large-scale prospective cohort study, elevated RC was associated with a lower risk of incident AF.

Stevioside Ameliorates Palmitic Acid-Induced Abnormal Glucose Uptake via the PDK4/AMPK/TBC1D1 Pathway in C2C12 Myotubes.

BACKGROUND: Stevioside (SV) with minimal calories is widely used as a natural sweetener in beverages due to its high sweetness and safety. However, the effects of SV on glucose uptake and the pyruvate dehydrogenase kinase isoenzyme (PDK4) as an important protein in the regulation of glucose metabolism, remain largely unexplored. In this study, we used C2C12 skeletal muscle cells that was induced by palmitic acid (PA) to assess the effects and mechanisms of SV on glucose uptake and PDK4. METHODS: The glucose uptake of C2C12 cells was determined by 2-NBDG; expression of the Pdk4 gene was measured by quantitative real-time PCR; and expression of the proteins PDK4, p-AMPK, TBC1D1 and GLUT4 was assessed by Western blotting. RESULTS: In PA-induced C2C12 myotubes, SV could significantly promote cellular glucose uptake by decreasing PDK4 levels and increasing p-AMPK and TBC1D1 levels. SV could promote the translocation of GLUT4 from the cytoplasm to the cell membrane in cells. Moreover, in Pdk4-overexpressing C2C12 myotubes, SV decreased the level of PDK4 and increased the levels of p-AMPK and TBC1D1. CONCLUSION: SV was found to ameliorate PA-induced abnormal glucose uptake via the PDK4/AMPK/TBC1D1 pathway in C2C12 myotubes. Although these results warranted further investigation for validation, they may provide some evidence of SV as a safe natural sweetener for its use in sugar-free beverages to prevent and control T2DM.

Standardized ileal digestibility of amino acids in Chinese fermented soybean meal from different sources fed to mid and late-gestating sows.

We determined apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values of crude protein (CP) and amino acids (AA) in fermented soybean meal from five different sources (FSBM 1 to 5) in China when fed to mid and late-gestating sows. Twenty-four parity four sows (12 at 30 d in gestation and 12 at 80 d in gestation) were fitted with a T-cannula in the distal ileum and used in this experiment. Sows were randomly assigned to a replicated 6 × 3 Youden square design including six diets and three periods. Six diets were provided for sows in mid and late gestation, including a nitrogen-free diet and five test diets containing 26% FSBM from different sources. Results showed that there were differences in AID and SID of CP among the different FSBM samples, but no differences between sow physiological stages were observed. Specifically, when mid-gestating sows were fed FSBM 2, the AID of CP was the lowest, whereas FSBM 3 exhibited a greater AID of CP when compared to the other FSBM samples (P < 0.01). Furthermore, during late gestation, FSBM 3 consistently had greater SID of CP when compared to other FSBM samples (P < 0.01). The ileal digestibility of most AA varied with different FSBM samples. In both mid and late gestation, differences (P < 0.05) were observed for AID of lysine, tryptophan, histidine, and arginine across different FSBM samples. Similarly, the AID of dispensable AA (cysteine, glutamine, and serine) also exhibited differences (P < 0.05) across different FSBM samples in both mid and late-gestating sows. For mid-gestating sows, SID differences relating to lysine, phenylalanine, tryptophan, threonine, and arginine were observed among different diets (P < 0.05). In late-gestating sows, SID values for lysine, tryptophan, leucine, and arginine differed across diets (P < 0.05). Furthermore, the ileal digestibility of some dispensable AA was influenced by physiological stage, as evidenced by greater AID and SID values for glycine, glutamine, cysteine, and serine in late-gestating sows when compared to mid-gestating sows (P < 0.01). In summary, our study determined AA ileal digestibility of different FSBM fed to mid and late-gestating sows. We observed that the AA ileal digestibility differed among five FSBM samples, but the physiological stage of sows did not affect the ileal digestibility of CP and most AA. Additionally, when formulating diets for sows, it is crucial to consider the nutritional value differences of FSBM.

Fermented soybean meal (FSBM) is obtained from the microbial fermentation of soybean meal, which reduces anti-nutritional factor levels and enhances other nutrient content. Substituting soybean meal with FSBM in piglet and growing pig diets improves nutrient digestibility. However, its nutritional value for sows remains unclear. Therefore, five sources of FSBM were fed to sows in mid and late gestation to evaluate apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values of amino acids (AA). We found that different FSBM samples impacted the SID value of AA when fed to gestating sows. Additionally, sow physiological stage influenced the SID of some dispensable AA. These findings provide valuable insights into the incorporation of FSBM into sow diets.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

Peanut LEAFY COTYLEDON1-type genes participate in regulating the embryo development and the accumulation of storage lipids.

KEY MESSAGE: Two peanut LEC1-type genes exhibit partial functional redundancy. AhNFYB10 could complement almost all the defective phenotypes of lec1-2 in terms of embryonic morphology, while AhNF-YB1 could partially affect these phenotypes. LEAFY COTYLEDON1 (LEC1) is a member of the nuclear factor Y (NF-Y) family of transcription factors and has been identified as a key regulator of embryonic development. In the present study, two LEC1-type genes from Arachis hypogeae were identified and designated as AhNF-YB1 and AhNF-YB10; these genes belong to subgenome A and subgenome B, respectively. The functions of AhNF-YB1 and AhNF-YB10 were investigated by complementation analysis of their defective phenotypes of the Arabidopsis lec1-2 mutant and by ectopic expression in wild-type Arabidopsis. The results indicated that both AhNF-YB1 and AhNF-YB10 participate in regulating embryogenesis, embryo development, and reserve deposition in cotyledons and that they have partial functional redundancy. In contrast, AhNF-YB10 complemented almost all the defective phenotypes of lec1-2 in terms of embryonic morphology and hypocotyl length, while AhNF-YB1 had only a partial effect. In addition, 30-40% of the seeds of the AhNF-YB1 transformants exhibited a decreasing germination ratio and longevity. Therefore, appropriate spatiotemporal expression of these genes is necessary for embryo morphogenesis at the early development stage and is responsible for seed maturation at the mid-late development stage. On the other hand, overexpression of AhNF-YB1 or AhNF-YB10 at the middle to late stages of Arabidopsis seed development improved the weight, oil content, and fatty acid composition of the transgenic seeds. Moreover, the expression levels of several genes associated with fatty acid synthesis and embryogenesis were significantly greater in developing AhNF-YB10-overexpressing seeds than in control seeds. This study provides a theoretical basis for breeding oilseed crops with high yields and high oil content.