Comparative Accuracy of Barrett Integrated Keratometry Toric Calculator With Predicted Versus Measured Posterior Corneal Astigmatism.

PURPOSE: To compare the prediction accuracy of the Barrett toric calculator using standard or integrated keratometry (IK) mode in combination with predicted or measured posterior corneal astigmatism (PCA) in a group of patients with cataract implanted with non-toric IOLs. METHODS: In this retrospective clinical cohort study, the medical records of patients with age-related cataract who underwent phacoemulsification with the implantation of an aspheric monofocal IOL were reviewed. Four methods, including standard keratometry with predicted PCA (PPCA), IK combined with predicted PCA (IK-PPCA), and IK combined with measured PCA derived from IOLMaster 700 (Carl Zeiss Meditec AG) or CASIA2 (Tomey) (IK-MMPCA or IK-CMPCA), were applied to the Barrett toric calculator to calculate the predicted residual astigmatism. The mean absolute prediction error (MAPE), centroid of the prediction error, and proportion of eyes within the prediction error of ±0.50, ±0.75, and ±1.00 diopters (D) were all ciphered out from the four methods, respectively. RESULTS: Data from 129 eyes of 129 patients were included in this study. The MAPE of the IK-PPCA method (0.57 ± 0.36 D) was significantly smaller than that of the PPCA (0.62 ± 0.38 D) and IK-CMPCA (0.63 ± 0.46 D) methods (P = .048 and .014, respectively). There were no significant differences in the centroid vectors of prediction errors and predictability rates among the four methods (all P > .05). CONCLUSIONS: In the current version of the Barrett toric calculator, the predictive accuracy of the IK mode incorporating PPCA was slightly superior to using the standard keratometry mode or incorporating MPCA. [J Refract Surg. 2024;40(7):e453-e459.].

Endoscopic Endonasal Reconstruction of Intraoperative Cerebrospinal Fluid Leak in Different Skull Base Regions: Outcomes, Meningitis, and Risk Factors.

OBJECTIVES: Various nonvascularized or vascularized techniques have been adopted in endoscopic endonasal surgery (EES) for repairing intraoperative cerebrospinal fluid (CSF) leaks after tumor resection. Vascularized nasoseptal flaps, free nasoseptal grafts, free turbinate grafts, and fascia lata and mashed muscle are frequently used. Outcomes of those grafts applied in the defects of different regions need to be clarified. METHODS: The data from a series of 162 patients with skull base tumor who underwent EES that had intraoperative CSF leak between Jan 2012 and Jan 2021 were retrospectively analyzed. The regions included anterior skull base, sellar region, clivus and infratemporal fossa. Repair failure rate (RFR), meningitis rate, and associated risk factors were assessed. RESULTS: In total, 172 reconstructions were performed in 162 patients for the 4 sites of the skull base. There were 7 cases (4.3%) that had postoperative CSF leaks, which required second repair. The RFR for anterior skull base, sellar region, clivus, and infratemporal fossawas 2.6%, 2.2%, 16.7%, and 0%, respectively. The clivus defect was an independent risk factor for repair failure (P < 0.01). The postoperative meningitis rate was 5.6%. Repair failure was an independent risk factor for meningitis (P < 0.01). CONCLUSIONS: Vascularized nasoseptal flap, free nasoseptal graft, free turbinate graft, and fascia lata and mashed muscle are reliable autologous materials for repairing the dural defects in different regions during EES. Clivus reconstruction remains a great challenge, which had a higher RFR and meningitis rate. Repair failure is significantly associated with postoperative meningitis.

In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection.

Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.

The role of the AMPK/ERK1/2 signaling pathway in neuronal oxidative stress damage following cerebral ischemia-reperfusion.

Cerebral ischemia-reperfusion injury involves a series of pathophysiological processes that occur when blood supply is restored after cerebral vascular obstruction, leading to neuronal damage. The AMPK/ERK1/2 signaling pathway has been identified as crucial in this process, although the exact mechanisms underlying the induction of ischemia-reperfusion injury remain unclear. In this study, we investigated the involvement of the AMPK/ERK1/2 signaling pathway in neuronal oxidative stress damage following cerebral ischemia-reperfusion by establishing animal and cell models. Our experimental results demonstrated that cerebral ischemia-reperfusion leads to oxidative stress damage, including cell apoptosis and mitochondrial dysfunction. Moreover, further experiments showed that inhibition of AMPK and ERK1/2 activity, using U0126 and Compound C respectively, could alleviate oxidative stress-induced cellular injury, improve mitochondrial morphology and function, reduce reactive oxygen species levels, increase superoxide dismutase levels, and suppress apoptosis. These findings clearly indicate the critical role of the AMPK/ERK1/2 signaling pathway in regulating oxidative stress damage and cerebral ischemia-reperfusion injury. The discoveries in this study provide a theoretical basis for further research and development of neuroprotective therapeutic strategies targeting the AMPK/ERK1/2 signaling pathway.

Adults Ischium Age Estimation Based on Deep Learning and 3D CT Reconstruction.

OBJECTIVES: To develop a deep learning model for automated age estimation based on 3D CT reconstructed images of Han population in western China, and evaluate its feasibility and reliability. METHODS: The retrospective pelvic CT imaging data of 1 200 samples (600 males and 600 females) aged 20.0 to 80.0 years in western China were collected and reconstructed into 3D virtual bone models. The images of the ischial tuberosity feature region were extracted to create sex-specific and left/right site-specific sample libraries. Using the ResNet34 model, 500 samples of different sexes were randomly selected as training and verification set, the remaining samples were used as testing set. Initialization and transfer learning were used to train images that distinguish sex and left/right site. Mean absolute error (MAE) and root mean square error (RMSE) were used as primary indicators to evaluate the model. RESULTS: Prediction results varied between sexes, with bilateral models outperformed left/right unilateral ones, and transfer learning models showed superior performance over initial models. In the prediction results of bilateral transfer learning models, the male MAE was 7.74 years and RMSE was 9.73 years, the female MAE was 6.27 years and RMSE was 7.82 years, and the mixed sexes MAE was 6.64 years and RMSE was 8.43 years. CONCLUSIONS: The skeletal age estimation model, utilizing ischial tuberosity images of Han population in western China and employing the ResNet34 combined with transfer learning, can effectively estimate adult ischium age.

Associations of ω-3, ω-6 polyunsaturated fatty acids intake and ω-6: ω-3 ratio with systemic immune and inflammatory biomarkers: NHANES 1999-2020.

Background: In recent years, diseases caused by abnormal immune-inflammatory responses have become increasingly severe. Dietary intervention involving omega-3 polyunsaturated fatty acids (ω-3 PUFAs) has emerged as a potential treatment. However, research investigating the relationship between ω-3, ω-6 PUFAs, and ω-6 to ω-3 ratio with inflammatory biomarkers remains controversial. Methods: To investigate the correlation between the intake of ω-3 and ω-6 PUFAs and the ratio of ω-6: ω-3 with biomarkers of inflammation, the National Health and Nutrition Examination Survey (NHANES) data (1999 to 2020) was utilized. The systemic immune-inflammation index (SII), platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and white blood cell (WBC) were selected as study subjects. Dietary data for ω-3 and ω-6 PUFAs were collected via two 24-h dietary recall interviews. SII index and other indicators were obtained from the blood routine data. The multiple linear regression and restricted cubic spline models were utilized to evaluate the association of ω-3, ω-6 PUFAs intake, and ω-6: ω-3 ratio to SII and secondary measures. Results: This study involved a total of 43,155 American adults. ω-3 and ω-6 PUFAs exhibited negative correlations with SII, PLR, NLR, and WBC. The correlation between ω-6: ω-3 ratio and SII, PLR, NLR, and WBC was not significant. Furthermore, the dose-response relationship showed that the relationship between the intake of ω-3 and ω-6 PUFAs and SII was an "L" pattern. Conclusion: Intake of dietary ω-3 and ω-6 PUFAs reduces the levels of several inflammatory biomarkers in the body and exerts immunomodulatory effects.

The influence of carbon emission trading on the optimization of regional energy structure.

The optimization of the energy structure is a crucial element in the development of green and low-carbon economies and societies. Market-based environmental regulations, such as carbon emissions trading, play a significant role in facilitating this transition. This study analyzes panel data from 30 provinces in China from 2007 to 2020. It empirically examines the impact and mechanism of carbon emissions trading pilot schemes on the transformation of energy consumption structure at the macro level, using the difference-in-differences method. The research findings indicate that provinces with carbon emissions trading pilots have experienced significant reductions in carbon emissions and carbon intensity, demonstrating clear emission reduction effects. Additionally, the transformation process of energy consumption structure has been notably accelerated, highlighting the correlation between initial carbon emissions trading and the regional energy utilization framework. Furthermore, in our extended mechanism analysis, we introduce two new variables - green finance and environmental regulation. Our analysis reveals that the level of green finance in carbon emissions trading pilot provinces significantly influences the degree of carbon emissions in these areas. Additionally, environmental regulation has a significant positive impact on the optimization of energy consumption structure.

Astroglial morphological changes in periaqueductal grey in different pain and itch mice models.

BACKGROUND: The periaqueductal gray (PAG) plays a well-established pivotal role in the descending pain modulatory circuit. The objective of this study was to investigate morphological changes in the astroglia in models that are commonly used in pain and itch studies. METHODS: Five different mouse models of pain, as well as two models of chronic itch, were established using complete Freund's adjuvant (CFA), spared nerve injury (SNI), bone cancer pain (BCP), cisplatin (CIS), and paclitaxel (PTX) for pain, and diphenylcyclopropenone (DCP) and acetone and diethyl ether followed by water (AEW) for chronic itch. von Frey tests and video recordings were employed to assess pain and itching behaviors. The immunofluorescence of S100ß, pSTAT3, and glial fibrillary acidic protein (GFAP) was examined. Two- and three-dimensional studies were used to evaluate changes in astrocyte morphology. RESULTS: Significant scratching was caused by DCP and AEW, whereas the administration of CFA, SNI, BCP, CIS, and PTX produced clear mechanical allodynia. The expression of GFAP in the lPAG/vlPAG was upregulated in CFA, SNI, BCP, CIS, PTX, and DCP mice but decreased in AEW mice. According to Sholl analysis, CFA, SNI, PTX, and BCP mice showed substantially higher astrocyte intersections in the vlPAG, whereas CFA, SNI, BCP, CIS, and DCP mice presented longer peak lengths. In three-dimensional analysis, CFA, SNI, PTX, and DCP mice showed increased astrocyte surface areas, while CIS and AEW mice showed both reduced surface areas and/or volumes of astrocytes. CONCLUSION: The findings showed that different pain and itching conditions have different astrocyte morphologies, and these variations in morphological changes help to explain the pathophysiology of these conditions.

Efficacy and safety of mirror therapy for post-stroke aphasia: A systematic review and meta-analysis protocol.

BACKGROUND: Aphasia is one of the most common complications of stroke. Mirror therapy (MT) is promising rehabilitation measure for the treatment of post-stroke aphasia. Although some studies suggested that MT is effective and safe for aphasia, the effects and safety remain uncertain due to lacking strong evidence, such as the relevant systematic review and meta- analysis. METHODS: This study will search PubMed, Web of Science, Cochrane Library, EMBASE, Medline, China Knowledge Network (CNKI), WANFANG, China Biomedical Literature Database (CBM), from inception to 1th May 2023 to identify any eligible study. No language or date of publication shall be limited. We will only include randomised controlled trials of MT in the Treatment of poststroke aphasia. Two investigators will work separately on the study selection, data extraction, and study quality assessment. The western aphasia battery (WAB) and aphasia quotient (AQ) will be included as the main outcomes. Boston diagnostic aphasia examination method (BDAE), Chinese standard aphasia examination (CRRCAE) will be included as the secondary outcomes. The statistical analysis will be conducted by RevMan V.5.4 software. The risk of bias of included studies will be assessed by the Cochrane 'Risk of bias' tool. The quality of proof of the results will be evaluated by using the Grading of Recommendations Assessment, Development and Evaluation guidelines. RESULTS: The finding will be presented in a journal or related conferences. CONCLUSION: This study will provide a basis for whether mirror therapy (MT) is effective and safe in the treatment of post-stroke aphasia. TRIAL REGISTRATION: Systematic review registration INPLASY registration number: INPLASY 202340054.

Crystalline-Amorphous Heterophase PdMoCrW Tetrametallene: Highly Efficient Oxygen Reduction Electrocatalysts for a Long-Term Zn-Air Battery.

Metallenes have received sustained attention owing to their unique microstructure characteristics and compelling catalytic applications, but the synthesis of multielement crystalline-amorphous metallenes remains a formidable challenge. Herein, we report a one-step wet chemical reduction method to synthesize composition-tunable crystalline-amorphous heterophase PdMoCrW tetrametallene. As-synthesized PdMoCrW tetrametallene is composed of approximately six to seven atomic layers and has flexible crimpiness, a crystalline-amorphous heterophase structure, and high-valence metal species. Time-dependent experiments show that PdMoCrW tetrametallene follows a three-step growth mechanism that includes nucleation, lateral growth, and atom diffusion, respectively. The novel ultrathin structure, optimized Pd electronic structure, and hydrophilic surface together greatly promote the activity and stability of PdMoCrW tetrametallene in the alkaline oxygen reduction reaction. Pd75.9Mo9.4Cr8.9W5.8/C exhibits excellent mass and specific activities of 2.81 A mgPd-1 and 4.05 mA cm-2, which are 20.07/14.46 and 23.42/16.20 times higher than those of commercial Pt/C and Pd/C, respectively. Furthermore, a Zn-air battery assembled using Pd75.9Mo9.4Cr8.9W5.8/C as a cathode catalyst achieves a peak power density of 156 mW cm-2 and an ultralong durability of 329 h. This study reports an effective strategy for constructing crystalline-amorphous quaternary metallenes to advance non-Pt electrocatalysts toward oxygen reduction reaction (ORR) performance and for a Zn-air battery.

The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

Gut bacterium Burkholderia cepacia (BsNLG8) and immune gene Defensin A contribute to the resistance against Nicotine-induced stress in Nilaparvata lugens (Stål).

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin, lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A, a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts.

[Prediction of Ozone Pollution in Sichuan Basin Based on Random Forest Model].

To study the long-term variation in ozone (O3) pollution in Sichuan Basin,the spatiaotemporal distribution of O3 concentrations during 2017 to 2020 was analyzed using ground-level O3 concentration data and meteorological observation data from 18 cities in the basin. The dominant meteorological factors affecting the variation in O3 concentration were screened out,and a prediction model between meteorological factors and O3 concentration was constructed based on a random forest model. Finally,a prediction analysis of O3 pollution in the Sichuan Basin urban agglomeration during 2020 was carried out. The results showed that:① O3 concentrations displayed a fluctuating trend during the period from 2017 to 2020,with a downward trend in 2019 and a rebound in 2020. ② The fluctuating trend of O3 concentration was significantly influenced by relative humidity,daily maximum temperature,and sunshine hours,whereas wind speed,air pressure,and precipitation had less impact. The linear relationships between meteorological factors were different. Air pressure was negatively correlated with other meteorological factors,whereas the remaining meteorological factors had a positive correlation. ③ The goodness of fit statistics (R2) between the predicted and actual values of the O3 prediction model constructed based on random forest demonstrated a strong predictive performance and ability to accurately forecast the long-term daily variations in O3 concentration. The random forest O3 prediction model exhibited excellent stability and generalization capability. ④ The prediction analysis of O3 concentrations in 18 cities in the basin showed that the explanation rate of variables in the prediction model reached over 80% in all cities (except Ya'an),indicating that the random forest model predicted the trend of O3 concentration accurately.

Off-label use of Baricitinib improves moderate and severe atopic dermatitis in China through inhibiting MAPK and PI3K/Akt/mTOR pathway via targeting JAK-STAT signaling of CD4+ cells.

As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD.

Physical drivers of Noctiluca scintillans (Dinophyceae) blooms outbreak in the northern Taiwan Strait: A numerical study.

The red Noctiluca scintillans (RNS) blooms often break out near Pingtan Island, in the northern Taiwan Strait from April to June. It is essential to gain insights into their formation mechanism to predict and provide early warnings for these blooms. Previous studies and observations showed that RNS blooms are the most likely to occur when winds are weak and shifting in direction. To explore this phenomenon further, we employed a high-resolution coastal model to investigate the hydrodynamics influencing RNS blooms around Pingtan Island from April to June 2022. The model results revealed that seawater exhibited weak circulation but strong stratification during RNS blooms. Residence time were examined through numerical experiments by releasing passive neutrally buoyant particles in three bays of Pingtan Island. The results showed a significantly longer residence time during RNS blooms, indicating reduced flushing capabilities within the bays, which could give RNS a stable environment to multiply and aggregate. This hydrodynamic condition provided a favorable basis for RNS blooms breakout near Pingtan Island. The shifts and weakening of the prevailing northeast wind contributed substantially to weakening the flow field around Pingtan Island and played a crucial role in creating the hydrodynamics conducive to RNS blooms. Our study offers fresh insights into the mechanisms underpinning RNS blooms formation near Pingtan Island, providing a vital framework for forecasting RNS blooms in this region.

Mesoporous Mo-doped PtBi intermetallic metallene superstructures to enable the complete electrooxidation of ethylene glycol.

Metallenes, intermetallic compounds, and porous nanocrystals are the three types of most promising advanced nanomaterials for practical fuel cell devices, but how to integrate the three structural features into a single nanocrystal remains a huge challenge. Herein, we report an efficient one-step method to construct freestanding mesoporous Mo-doped PtBi intermetallic metallene superstructures (denoted M-PtBiMo IMSs) as highly active and stable ethylene glycol oxidation reaction (EGOR) catalysts. The materials retained their catalytic performance, even in complex direct ethylene glycol fuel cells (DEGFCs). The M-PtBiMo IMSs showed EGOR mass and specific activities of 24.0 A mgPt-1 and 61.1 mA cm-2, respectively, which were both dramatically higher than those of benchmark Pt black and Pt/C. In situ infrared spectra showed that ethylene glycol underwent complete oxidation via a 10-electron CO-free pathway over the M-PtBiMo IMSs. Impressively, M-PtBiMo IMSs demonstrated a much higher power density (173.6 mW cm-2) and stability than Pt/C in DEGFCs. Density functional theory calculations revealed that oxophilic Mo species promoted the EGOR kinetics. This work provides new possibilities for designing advanced Pt-based nanomaterials to improve DEGFC performance.

Discover overlooked complications after preeclampsia using electronic health records.

Background: Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and end-organ damage such as proteinuria. PE poses a significant threat to women's long-term health, including an increased risk of cardiovascular and renal diseases. Most previous studies have been hypothesis-based, potentially overlooking certain significant complications. This study conducts a comprehensive, non-hypothesis-based analysis of PE-complicated diagnoses after pregnancies using multiple large-scale electronic health records (EHR) datasets. Method: From the University of Michigan (UM) Healthcare System, we collected 4,348 PE patients for the cases and 27,377 patients with pregnancies not complicated by PE or related conditions for the controls. We first conducted a non-hypothesis-based analysis to identify any long-term adverse health conditions associated with PE using logistic regression with adjustments to demographics, social history, and medical history. We confirmed the identified complications with UK Biobank data which contain 443 PE cases and 14,870 non-PE controls. We then conducted a survival analysis on complications that exhibited significance in more than 5 consecutive years post-PE. We further examined the potential racial disparities of identified complications between Caucasian and African American patients. Findings: Uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity exhibited significantly increased risks whereas hypothyroidism showed decreased risks, in 5 consecutive years after PE in the UM discovery data. UK Biobank data confirmed the increased risks of uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity. Further survival analysis using UM data indicated significantly increased risks in uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity, and significantly decreased risks in hypothyroidism. There exist racial differences in the risks of developing hypertension and hypothyroidism after PE. PE protects against hypothyroidism in African American postpartum women but not Cacausians; it also increases the risks of uncomplicated hypertension but less severely in African American postpartum women as compared to Cacausians. Interpretation: This study addresses the lack of a comprehensive examination of PE's long-term effects utilizing large-scale EHR and advanced statistical methods. Our findings underscore the need for long-term monitoring and interventions for women with a history of PE, emphasizing the importance of personalized postpartum care. Notably, the racial disparities observed in the impact of PE on hypertension and hypothyroidism highlight the necessity of tailored aftercare based on race.

The Discovery of Gut Microbial Metabolites as Modulators of Host Susceptibility to Acetaminophen-Induced Hepatotoxicity.

The mammalian gut microbiota plays diverse and essential roles in modulating host physiology. Key mediators determining the outcome of the microbiota-host interactions are the small molecule metabolites produced by the gut microbiota. The liver is a major organ exposed to gut microbial metabolites, and it serves as the nexus for maintaining healthy interactions between the gut microbiota and the host. At the same time, the liver is the primary target of potentially harmful gut microbial metabolites. In this review, we provide an up-to-date list of gut microbial metabolites that have been identified to either increase or decrease host susceptibility to acetaminophen (APAP)-induced liver injury. The signaling pathways and molecular factors involved in the progression of APAP-induced hepatotoxicity are well-established, and we propose that the mouse model of APAP-induced hepatotoxicity serves as a model system for uncovering gut microbial metabolites with previously unknown functions. Furthermore, we envision that gut microbial metabolites identified to alter APAP-induced hepatotoxicity likely have broader implications in other liver diseases. SIGNIFICANCE STATEMENT: This review provides an overview of the role of the gut microbiota in modulating the host susceptibility to acetaminophen (APAP)-induced liver injury. It focuses on the roles of gut bacterial small molecule metabolites as mediators of the interaction between the gut microbiota and the liver. It also illustrates the utility of APAP-induced liver injury as a model to identify gut microbial metabolites with biological function.

Structural basis for sugar perception by Drosophila gustatory receptors.

Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.