Search

Hydro-viscous clutch has become an inevitable choice for special vehicle transmissions. As a nonlinear dynamic system with large lagging link, its timing performance is affected by input rotational speed, lubricating oil temperature and pressure and other factors. However, from the control perspective, the speed regulation law, formation mechanism control characteristics, global model of hydro-viscous speed control system (HSCS) are unclear. To solve these problems, this paper presents a comprehensive analysis of the Hydro-viscous Speed Control System (HSCS), focusing on its steady-state and dynamic speed control characteristics. A data-driven model is established to describe the relationship between input rotational speed, output speed, control oil pressure, and lubricating oil temperature. The findings provide a foundation for optimizing HSCS structure and parameters, enhancing the performance and reliability of such systems in special vehicle transmissions and establishing a temperature-speed control system for special vehicle transmissions., (© 2024. The Author(s).)

Resident microbiota produces small molecules that influence the chemical microenvironments on leaves, but its signalling roles in pathogen defence are not yet well understood. Here we show that Aspergillus cvjetkovicii, enriched in rice leaf microbiota, subverts Rhizoctonia solani infections via small-molecule-mediated interspecies signalling. 2,4-Di-tert-butylphenol (2,4-DTBP), identified as a key signalling molecule within the Aspergillus-enriched microbiota, effectively neutralizes reactive oxygen species-dependent pathogenicity by switching off bZIP-activated AMT1 transcription in R. solani. Exogenous application of A. cvjetkovicii and 2,4-DTBP demonstrated varying degrees of protective effects against R. solani infection in diverse crops, including cucumber, maize, soybean and tomato. In rice field experiments, they reduced the R. solani-caused disease index to 19.7-32.2%, compared with 67.2-82.6% in the control group. Moreover, 2,4-DTBP showed activity against other rice phytopathogens, such as Fusarium fujikuroi. These findings reveal a defensive strategy against phytopathogens in the phyllosphere, highlighting the potential of symbiotic microbiota-driven neutralization of pathogenicity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Nonlinear friction, system uncertainty, and external disturbances have a significant impact on the performance of high-precision servo feed systems. In order to achieve higher tracking accuracy, a sliding mode controller based on a generalized extended state observer with the double critic deep deterministic policy gradient algorithm is designed. Firstly, a flexible two mass drive model (FTMDM) is established for the two-axis differential micro-feed system (TDMS). Next, a generalized extended state observer (GESO) is designed to estimate matched interference and mismatched interference. And it is proved that the observation error of GESO is bounded. A sliding mode controller based on GESO is further proposed. The stability of the controller has been proven through Lyapunov theory, and the error is bounded and converges to zero in finite time. The tuning process of controller parameters is simplified by using quadratic optimal control principle. Furthermore, a double critic deep deterministic policy gradient algorithm (DCDDPG) is proposed to achieve dynamic optimization of parameters about GESO. The simulation results show that GESO with DCDDPG can reduce the observation error of step signal and sinusoidal signal, and improve the observation accuracy of nonlinear friction significantly. Finally, experimental results show that the proposed control method achieves more accurate position tracking performance on TDMS., (© 2024. The Author(s).)

To evaluate the effectiveness and biocompatibility of Wistend, a novel Schlemm's canal (SC) microstent made of Nitinol designed to improve aqueous humor outflow. New Zealand white (NZW) rabbits were divided into blank, sham-operated and Wistend groups. ICare ® Tonovet Plus ® , swept-source optical coherence tomography (SS-OCT), slit lamp biomicroscopy, retinal camera and scanning electron microscopy (SEM) were used for preoperative and postoperative observations. Hematoxylin and Eosin (H&E) tissue staining was adopted for biocompatibility. A significant difference in intraocular pressure (IOP) between the Wistend group and the control groups was observed during the six-month follow-up. SS-OCT identified arc line internal reflections within the SC in the anterior chamber angle. Conjunctival congestion and edema gradually diminished in the early stages. No corneal vascularization, no anterior chamber inflammatory response and no significant tissue reactions were noted in any groups. SEM showed the Wistend's windows and orifices remained clear, encircled by minimal incidental ocular tissue and free from blockage. Histopathological examination revealed no discernible differences between the Wistend-implanted and sham-operated eyes. These in vivo studies demonstrate the effectiveness and biocompatibility of the microstent. Our findings suggest a promising potential for Wistend in significantly reducing IOP and effectively facilitating the outflow of aqueous humor., (© 2024. The Author(s).)

Unmanned Aerial Vehicle (UAV) oblique photogrammetry has been extensively employed in mining, albeit predominantly for reconstructing three-dimensional scenes and detecting changes within mining sites, lacking predictive capabilities. Leveraging 3D real scene model data, this study presents a two-stage prediction model, merging the probabilistic integral method with recurrent neural network (PIMF-RNN), to mitigate the impact of internal and external factors on surface subsidence, thereby enhancing predictive accuracy. Building upon this framework, a methodology was developed to forecast the maximum surface subsidence height and affected area under the block caving method, offering crucial data support for mitigating hazards associated with this mining technique. Analysis of surface data from Pulang copper mine during 2018-2020 demonstrates a prediction accuracy of 91.47% for maximum surface subsidence height and 87.52% for subsidence area. This research expands the potential applications of UAV oblique photogrammetry techniques within mining contexts. Furthermore, it establishes a cost-effective and efficient operational procedure for predicting mine surface subsidence., (© 2024. The Author(s).)

Gaining the molecular understanding for myelination development and regeneration has been a long-standing goal in neurological research. Mutations in the transcription cofactor Mediator Med23 subunit are often associated with intellectual disability and white matter defects, although the precise functions and mechanisms of Mediator in myelination remain unclear. In this study, we generated a mouse model carrying an Med23 Q649R mutation that has been identified in a patient with hypomyelination features. The MED23 Q649R mouse model develops white matter thinning and cognitive decline, mimicking common clinical phenotypes. Further, oligodendrocyte-lineage specific Med23 knockout mice verified the important function of MED23 in regulating central nervous system myelination and postinjury remyelination. Utilizing the in vitro cellular differentiation assay, we found that the oligodendrocyte progenitor cells, either carrying the Q649R mutation or lacking Med23, exhibit significant deficits in their capacity to differentiate into mature oligodendrocytes. Gene profiling combined with reporter assays demonstrated that Mediator Med23 controls Sp1-directed gene programs related to oligodendrocyte differentiation and cholesterol metabolism. Integrative analysis demonstrated that Med23 modulates the P300 binding to Sp1-targeted genes, thus orchestrating the H3K27 acetylation and enhancer activation for the oligodendrocyte lineage progression. Collectively, our findings identified the critical role for the Mediator Med23 in oligodendrocyte fate determination and provide mechanistic insights into the myelination pathogenesis associated with MED23 mutations., (© 2024. The Author(s).)

Acute respiratory distress syndrome (ARDS) is a heterogeneous disease with extremely high mortality. We hypothesized that the serum β2-microglobulin (β2MG) level would be elevated and be an independent risk factor for 28-day mortality in patients with ARDS caused by bacterial infection. We retrospectively enrolled 257 patients with ARDS caused by bacterial infection from January 1, 2015 to February 28, 2021. Patients were followed for up to 28 days and were divided into a survival group and non-survival group according to their clinical outcomes. The serum β2MG levels and other clinical data were collected. The relationship between β2MG levels and 28-day mortality was explored by performing a Cox regression analysis adjusted for age, updated Charlson comorbidity index, disorders of consciousness, septic shock, albumin level, cardiac troponin I level, procalcitonin level, lactic acid level, prothrombin time, partial pressure of arterial oxygen/fraction of inspired oxygen ratio, estimated glomerular filtration rate and Sequential Organ Failure Assessment. In this cohort, 96 patients died in 28 days, yielding a 28-day mortality of 37.4%. The median level of serum β2MG for all enrolled patients was 4.7 (interquartile range [IQR]: 2.9-8.5) mg/L. Higher β2MG levels were significantly associated with 28-day mortality when the β2MG level was analysed as a continuous variable (hazard ratio [HR]: 1.053; 95% confidence interval [CI] 1.004-1.104; P = 0.032) and when it was categorized into tertiles (HR: 3.241; 95% CI 1.180-8.905; P = 0.023). The β2MG level exhibited a high diagnostic accuracy for predicting 28-day mortality (area under the curve [AUC] = 0.732; 95% CI 0.673-0.785; sensitivity: 74.0%; specificity: 64.0%; P < 0.001). The level of serum β2MG is elevated and is an independent risk factor of 28-day mortality in patients with ARDS caused by bacterial infection., (© 2024. The Author(s).)

This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Racial and ethnic disparities persist in cancer survival rates across the United States, despite overall improvements. This comprehensive analysis examines trends in 5-year relative survival rates from 2002-2006 to 2015-2019 for major cancer types, elucidating differences among racial/ethnic groups to guide equitable healthcare strategies. Data from the SEER Program spanning 2000-2020 were analyzed, focusing on breast, colorectal, prostate, lung, pancreatic cancers, non-Hodgkin lymphoma, acute leukemia, and multiple myeloma. Age-standardized relative survival rates were calculated to assess racial (White, Black, American Indian/Alaska Native, Asian/Pacific Islander) and ethnic (Hispanic, Non-Hispanic) disparities, utilizing period analysis for recent estimates and excluding cases identified solely through autopsy or death certificates. While significant survival improvements were observed for most cancers, notable disparities persisted. Non-Hispanic Blacks exhibited the largest gain in breast cancer survival, with an increase of 5.2% points (from 77.6 to 82.8%); however, the survival rate remained lower than that of Non-Hispanic Whites (92.1%). Colorectal cancer survival declined overall (64.7-64.1%), marked by a 6.2% point drop for Non-Hispanic American Indian/Alaska Natives (66.3-60.1%). Prostate cancer survival declined across all races, with Non-Hispanic American Indian/Alaska Natives showing a decrease of 7.7% points (from 96.9 to 89.2%). Lung cancer, acute leukemia, and multiple myeloma showed notable increases across groups. Substantial racial/ethnic disparities in cancer survival underscore the notable need for tailored strategies ensuring equitable access to advanced treatments, particularly addressing significant trends in colorectal and pancreatic cancers among specific minority groups. Careful interpretation of statistical significance is warranted given the large dataset., (© 2024. The Author(s).)

Bruton tyrosine kinase inhibitor (BTKi) combined with rituximab-based chemotherapy benefits diffuse large B-cell lymphoma (DLBCL) patients. However, drug resistance is the major cause of relapse and death of DLBCL. In this study, we conducted a comprehensive analysis BTKi-resistance related genes (BRRGs) and established a 10-gene (CARD16, TRIP13, PSRC1, CASP1, PLBD1, CARD6, CAPG, CACNA1A, CDH15, and NDUFA4) signature for early identifying high-risk DLBCL patients. The resistance scores based on the BRRGs signature were associated with prognosis. Furthermore, we developed a nomogram incorporating the BRRGs signature, which demonstrated excellent performance in predicting the prognosis of DLBCL patients. Notably, tumor immune microenvironment, biological pathways, and chemotherapy sensitivity were different between high- and low-resistance score groups. Additionally, we identified TRIP13 as a key gene in our model. TRIP13 was found to be overexpressed in DLBCL and BTKi-resistant DLBCL cell lines, knocking down TRIP13 suppresses cell proliferation, promotes cell apoptosis, and enhances the apoptosis effect of BTKi on DLBCL cells by regulating the Wnt/β-catenin pathway. In conclusion, our study presents a novel BRRGs signature that could serve as a promising prognostic marker in DLBCL, and TRIP13 might be a potential therapeutic target for resistant DLBCL., (© 2024. The Author(s).)

Several international epidemiological studies have established a link between obesity and upper gastrointestinal cancer (UGC), but Chinese evidence is limited. This study aimed to determine the prevalence of obesity, especially central obesity, while investigating its association with upper gastrointestinal diseases in the high-risk population of Yangzhong, a typical high-risk area for UGC in southeastern China. We conducted a cross-sectional study from November 2017 to June 2021 involving 6736 residents aged 40-69. Multivariate logistic regression was used to assess independent factors influencing overweight/obesity and central obesity. We also analyzed the relationship between obesity and upper gastrointestinal diseases using multinomial logistic regression. The prevalence of overweight, obesity, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)-central obesity were 40.6%, 12.0%, 49.9%, 79.4%, and 63.7%, respectively. Gender, age, smoking, tea consumption, sufficient vegetable, pickled food, spicy food, eating speed, physical activity, family history of cancer, and family history of common chronic disease were associated with overweight /obesity and central obesity. Besides, education and missing teeth were only associated with central obesity. General and central obesity were positively associated with UGC, while general obesity was negatively associated with UGC precancerous diseases. There were no significant associations between obesity and UGC precancerous lesions. Subgroup analyses showed that general and central obesity was positively associated with gastric cancer but not significantly associated with esophageal cancer. Obesity is negatively and positively associated with gastric and esophageal precancerous diseases, respectively. In conclusion, general and central obesity were at high levels in the target population in this study. Most included factors influenced overweight/obesity and central obesity simultaneously. Policymakers should urgently develop individualized measures to reduce local obesity levels according to obesity characteristics. Besides, obesity increases the risk of UGC but decreases the risk of UGC precancerous diseases, especially in the stomach. The effect of obesity on the precancerous diseases of the gastric and esophagus appears to be the opposite. No significant association between obesity and upper gastrointestinal precancerous lesions was found in the study. This finding still needs to be validated in cohort studies., (© 2024. The Author(s).)

To date, the best obesity-related indicators (ORIs) for predicting hypertension, dyslipidaemia, Type 2 diabetes mellitus (T2DM) and multimorbidity are still controversial. This study assessed the ability of 17 ORIs [body mass index (BMI), body fat percentage (BF%), c-index, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), a body shape index (ABSI), body adiposity index (BAI), waist circumference (WC), waist-hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), abdominal volume index (AVI), triglyceride glucose index (TYG), lipid accumulation product (LAP), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), waist triglyceride index (WTI) and cardiometabolic index (CMI)] to predict hypertension, dyslipidemia, T2DM, and multimorbidity in populations aged 40-69 years. From November 2017 to December 2022, 10,432 compliant residents participated in this study. Receiver operating characteristic curves were used to assess the ability of ORIs to predict target diseases across the whole population and genders. The DeLong test was used to analyse the heterogeneity of area under curves (AUCs). Multivariable logistic regression was used to analyse the association of ORIs with hypertension, dyslipidaemia, T2DM, and multimorbidity. The prevalence of hypertension, dyslipidaemia, T2DM, and multimorbidity was 67.46%, 39.36%, 12.54% and 63.58%, respectively. After excluding ORIs associated with the target disease components, in the whole population, CVAI (AUC = 0.656), BMI (AUC = 0.655, not significantly different from WC and AVI), CVAI (AUC = 0.645, not significantly different from LAP, CMI, WHR, and WTI), and TYG (AUC = 0.740) were the best predictor of hypertension, dyslipidemia, T2DM, and multimorbidity, respectively (all P < 0.05). In the male population, BF% (AUC = 0.677), BMI (AUC = 0.698), CMI (AUC = 0.648, not significantly different from LAP and CVAI), and TYG (AUC = 0.741) were the best predictors (all P < 0.05). In the female population, CVAI (AUC = 0.677), CUN-BAE (AUC = 0.623, not significantly different from BF%, WC, WHR, WHtR, BRI and BMI), CVAI (AUC = 0.657, not significantly different from WHR), TYG (AUC = 0.740) were the best predictors (all P < 0.05). After adjusting for all covariates, all ORIs were significantly associated with hypertension, dyslipidaemia, T2DM, and multimorbidity (all P < 0.05), except for ABSI and hypertension and BAI and T2DM, which were insignificant. Ultimately, after considering the heterogeneity of prediction of ORIs among different populations, for hypertension, BF% was the best indicator for men and CVAI for the rest of the population. The best predictors of dyslipidaemia, T2DM, and multimorbidity were BMI, CVAI and TYG, respectively. Screening for common chronic diseases in combination with these factors may help to improve the effectiveness., (© 2024. The Author(s).)

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O 2 and 92% N 2 . In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 μM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

To investigate the impact of different 5' untranslated regions (UTRs) on mRNA vaccine translation efficiency, five dual-reporter gene expression plasmids with different 5'UTRs were constructed. The corresponding mRNA transcripts were transcribed and capped in vitro. By comparing the expression levels of reporter genes with different 5'UTRs, we identified the 5'UTR associated with the highest expression level. Subsequently, HIVgp145 mRNA vaccines containing various 5'UTRs were constructed and verified. The results demonstrated that mRNA 3 (β-globin 5'UTR) displayed the greatest number of green fluorescence-positive cells and the highest luciferase fluorescence intensity in the reporter gene expression system. Further, among the HIVgp145 mRNA vaccines with different 5'UTRs, mRNA 7 (β-globin 5'UTR) exhibited the highest level of expression. These findings indicate that it is feasible to use the 5'UTR of β-globin in an mRNA vaccine, laying the foundation for animal immunogenicity testing., (© 2024. The Author(s).)

To evaluate whether radiomics models based on unenhanced paranasal sinuses CT images could be a useful tool for differentiating inverted papilloma (IP) from chronic rhinosinusitis with polyps (CRSwNP). This retrospective study recruited 240 patients with CRSwNP and 106 patients with IP from three centers. 253 patients from Qilu Hospital were randomly divided into the training set (n = 151) and the internal validation set (n = 102) with a ratio of 6:4. 93 patients from the other two centers were used as the external validation set. The patients with the unilateral disease (n = 115) from Qilu Hospital were selected to further develop a subgroup analysis. Lesion segmentation was manually delineated in CT images. Least absolute shrinkage and selection operator algorithm was performed for feature reduction and selection. Decision tree, support vector machine, random forest, and adaptive boosting regressor were employed to establish the differential diagnosis models. 43 radiomic features were selected for modeling. Among the models, RF achieved the best results, with an AUC of 0.998, 0.943, and 0.934 in the training set, the internal validation set, and the external validation set, respectively. In the subgroup analysis, RF achieved an AUC of 0.999 in the training set and 0.963 in the internal validation set. The proposed radiomics models offered a non-invasion and accurate differential approach between IP and CRSwNP and has some significance in guiding clinicians determining the best treatment plans, as well as predicting the prognosis., (© 2024. The Author(s).)

Vitamin D deficiency is increasingly common in systemic lupus erythematosus (SLE) patients and is associated with the disease activity and proteinuria. Recently, alterations in metabolism have been recognized as key regulators of SLE pathogenesis. Our objective was to identify differential metabolites in the serum metabolome of SLE with vitamin D deficiency. In this study, serum samples from 31 SLE patients were collected. Levels of 25(OH)D3 were assayed by ELISA. Patients were divided into two groups according to their vitamin D level (20 ng/ml). Untargeted metabolomics were used to study the metabolite profiles in serum by high-performance liquid chromatography-tandem mass spectrometry. Subsequently, we performed metabolomics profiling analysis to identify 52 significantly altered metabolites in vitamin D deficient SLE patients. The area under the curve (AUC) from ROC analyses was calculated to assess the diagnostic potential of each candidate metabolite biomarker. Lipids accounted for 66.67% of the differential metabolites in the serum, highlighted the disruption of lipid metabolism. The 52 differential metabolites were mapped to 27 metabolic pathways, with fat digestion and absorption, as well as lipid metabolism, emerging as the most significant pathways. The AUC of (S)-Oleuropeic acid and 2-Hydroxylinolenic acid during ROC analysis were 0.867 and 0.833, respectively, indicating their promising diagnostic potential. In conclusion, our results revealed vitamin D deficiency alters SLE metabolome, impacting lipid metabolism, and thrown insights into the pathogenesis and diagnosis of SLE., (© 2024. The Author(s).)

Northwest China has undergone notable alterations in climate and vegetation growth in recent decades. Nevertheless, uncertainties persist concerning the response of different vegetation types to climate change and the underlying mechanisms. This study utilized the Normalized Difference Vegetation Index (NDVI) and three sets of meteorological data to investigate the interannual variations in the association between vegetation and climate (specifically precipitation and temperature) from 1982 to 2015. Several conclusions were drawn. (1) R NDVI-GP (relationship between Growing Season NDVI and precipitation) decreased significantly across all vegetation, while R NDVI-GT (relationship between Growing Season NDVI and temperature) showed an insignificant increase. (2) Trends of R NDVI-GP and R NDVI-GT exhibited great variations across various types of vegetation, with forests displaying notable downward trends in both indices. The grassland exhibited a declining trend in R NDVI-GP but an insignificant increase in R NDVI-GT , while no significant temporal changes in R NDVI-GP or R NDVI-GT were observed in the barren land. (3) The fluctuations in R NDVI-GP and R NDVI-GT closely aligned with variations in drought conditions. Specifically, in regions characterized by VPD (vapor pressure deficit) trends less than 0.02 hpa/yr, which are predominantly grasslands, a rise in SWV (soil water volume) tended to cause a reduction in R NDVI-GP but an increase in R NDVI-GT. However, a more negative trend in SWV was associated with a more negative trend in both R NDVI-GP and R NDVI-GT when the VPD trend exceeded 0.02 hPa/yr, primarily in forests. Our results underscore the variability in the relationship between climate change and vegetation across different vegetation types, as well as the role of drought in modulating these associations., (© 2024. The Author(s).)

BRCA1, a breast cancer susceptibility gene, has emerged as a central mediator that brings together multiple signaling complexes in response to DNA damage. The A, B, and C complexes of BRCA1, which are formed based on their phosphorylation-dependent interactions with the BRCA1-C-terminal domains, contribute to the roles of BRCA1 in DNA repair and cell cycle checkpoint control. However, their functions in DNA damage response remain to be fully appreciated. Specifically, there has been no systematic investigation of the roles of BRCA1-A, -B, and -C complexes in the regulation of BRCA1 localization and functions, in part because of cellular lethality associated with loss of CtIP protein, which is an essential component in BRCA1-C complex. To systematically investigate the functions of these complexes in DNA damage response, we depleted a key component in each of these complexes. We used the degradation tag system to inducibly deplete endogenous CtIP and obtained a series of RAP80/FANCJ/CtIP single-, double-, and triple-knockout cells. We showed that loss of BRCA1-B/FANCJ and BRCA1-C/CtIP, but not BRCA1-A/RAP80, resulted in reduced cell proliferation and increased sensitivity to DNA damage. BRCA1-C/CtIP and BRCA1-A/RAP80 were involved in BRCA1 recruitment to sites of DNA damage. However, BRCA1-A/RAP80 was not essential for damage-induced BRCA1 localization. Instead, RAP80/H2AX and CtIP have redundant roles in BRCA1 recruitment. Altogether, our systematic analysis uncovers functional differences between BRCA1-A, -B, and -C complexes and provides new insights into the roles of these BRCA1-associated protein complexes in DNA damage response and DNA repair., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Enhancing crop water productivity is crucial for regional water resource management and agricultural sustainability, particularly in arid regions. However, evaluating the spatial heterogeneity and temporal dynamics of crop water productivity in face of data limitations poses a challenge. In this study, we propose a framework that integrates remote sensing data, time series generative adversarial network (TimeGAN), dynamic Bayesian network (DBN), and optimization model to assess crop water productivity and optimize crop planting structure under limited water resources allocation in the Qira oasis. The results demonstrate that the combination of TimeGAN and DBN better improves the accuracy of the model for the dynamic prediction, particularly for short-term predictions with 4 years as the optimal timescale (R 2  > 0.8). Based on the spatial distribution of crop suitability analysis, wheat and corn are most suitable for cultivation in the central and eastern parts of Qira oasis while cotton is unsuitable for planting in the western region. The walnuts and Chinese dates are mainly unsuitable in the southeastern part of the oasis. Maximizing crop water productivity while ensuring food security has led to increased acreage for cotton, Chinese dates and walnuts. Under the combined action of the five optimization objectives, the average increase of crop water productivity is 14.97%, and the average increase of ecological benefit is 3.61%, which is much higher than the growth rate of irrigation water consumption of cultivated land. It will produce a planting structure that relatively reduced irrigation water requirement of cultivated land and improved crop water productivity. This proposed framework can serve as an effective reference tool for decision-makers when determining future cropping plans., (© 2024. The Author(s).)

Breast cancer (BRCA) has become the most common type of cancer in women. Improving the therapeutic response remains a challenge. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a classic tumour suppressor with emerging new functions discovered in recent years, and myeloid PTEN loss has been reported to impair antitumour immunity. In this study, we revealed a novel mechanism by which myeloid PTEN potentially affects antitumour immunity in BRCA. We detected accelerated stress granule (SG) assembly under oxidative stress in PTEN-deficient bone marrow-derived macrophages (BMDMs) through the EGR1-promoted upregulation of TIAL1 transcription. PI3K/AKT/mTOR (PAM) pathway activation also promoted SG formation. ATP consumption during SG assembly in BMDMs impaired the phagocytic ability of 4T1 cells, potentially contributing to the disruption of antitumour immunity. In a BRCA neoadjuvant cohort, we observed a poorer response in myeloid PTEN low patients with G3BP1 aggregating as SGs in CD68+ cells, a finding that was consistent with the observation in our study that PTEN-deficient macrophages tended to more readily assemble SGs with impaired phagocytosis. Our results revealed the unconventional impact of SGs on BMDMs and might provide new perspectives on drug resistance and therapeutic strategies for the treatment of BRCA patients., (© 2024. The Author(s).)

Global expansion in wind energy development is a notable achievement of the international community's effort to reduce carbon emissions during energy production. However, the increasing number of wind turbines have unintended consequences for migratory birds and bats. Wind turbine curtailment and other mitigation strategies can reduce fatalities, but improved spatial and temporal data are needed to identify the most effective way for wind energy development and volant migratory species to coexist. Mexican free-tailed bats (Tadarida brasiliensis mexicana) account for a large proportion of known bat fatalities at wind facilities in the southwestern US. We examined the geographic concordance between existing wind energy generation facilities, areas of high wind potential amenable for future deployment of wind facilities, and seasonally suitable habitat for these bats. We used ecological niche modeling to determine species distribution during each of 4 seasons. We used a multi-criteria GIS-based approach to produce a wind turbine siting suitability map. We identified seasonal locations with highest and lowest potential for the species' probability of occurrence, providing a potential explanation for the higher observed fatalities during fall migration. Thirty percent of 33,606 wind turbines within the southwestern US occurred in highly suitable areas for Mexican free-tailed bats, primarily in west Texas. There is also broad spatial overlap between areas of high wind potential and areas of suitable habitat for Mexican free-tailed bats. Because of this high degree of overlap, our results indicate that post-construction strategies, such as curtailing the timing of operations and deterrents, would be more effective for bat conservation than strategic siting of new wind energy installations., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

While numerous single nucleotide variants and small indels have been identified in Parkinson's disease (PD), the contribution of structural variants (SVs), copy number variants (CNVs), and short tandem repeats (STRs) remains poorly understood. Here we investigated the association using the high-depth whole-genome sequencing data from 466 Chinese PD patients and 513 controls. Totally, we identified 29,561 SVs, 32,153 CNVs, and 174,905 STRs, and found that CNV deletions were significantly enriched in the end-proportion of autosomal chromosomes in PD. After genome-wide association analysis and replication in an external cohort of 352 cases and 547 controls, we validated that the 1.6 kb-deletion neighboring MUC19, 12.4kb-deletion near RXFP1 and GGGAAA repeats in SLC2A13 were significantly associated with PD. Moreover, the MUC19 deletion and the SLC2A13 5-copy repeat reduced the penetrance of the LRRK2 G2385R variant. Moreover, genes with these variants were dosage-sensitive. These data provided novel insights into the genetic architecture of PD., (© 2024. The Author(s).)

The dual activation of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) has emerged as a promising therapeutic strategy for managing type 2 diabetes and obesity. Tirzepatide, a dual agonist peptide, has exhibited superior clinical efficacy in glycemic and weight control compared to selective GLP-1R agonists. Nevertheless, the structural basis of Tirzepatide's extended half-life, attributed to an acylation side chain on the parent peptide, raises questions regarding its partial agonistic activity. Employing molecular dynamics simulations, we explored the dynamic processes of peptide-receptor interactions. We uncovered a crucial salt bridge between parent peptide and GLP-1R/GIPR at K20, a feature not discernible in cryo-electron microscopy structures. Building upon these insights, we developed an optimization strategy based on the parent peptide which involved repositioning the acylation side chain. The results of both in vitro and in vivo experiments demonstrated that the optimized peptide has twofold to threefold increase in agonistic activity compared to Tirzepatide while maintaining its extended half-life in plasma. This led to the design of BGM0504, which proved to be more effective than its predecessor, Tirzepatide, in both laboratory and animal studies., (© 2024. The Author(s).)

Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers., (© 2024. The Author(s).)

T-cell receptor (TCR) detection can examine the extent of T-cell immune responses. Therefore, the article analyzed characteristic data of glioma obtained by DNA-based TCR high-throughput sequencing, to predict the disease with fewer biomarkers and higher accuracy. We downloaded data online and obtained six TCR-related diversity indices to establish a multidimensional classification system. By comparing actual presence of the 602 correlated sequences, we obtained two-dimensional and multidimensional datasets. Multiple classification methods were utilized for both datasets with the classification accuracy of multidimensional data slightly less to two-dimensional datasets. This study reduced the TCR β sequences through feature selection methods like RFECV (Recursive Feature Elimination with Cross-Validation). Consequently, using only the presence of these three sequences, the classification AUC value of 96.67% can be achieved. The combination of the three correlated TCR clones obtained at a source data threshold of 0.1 is: CASSLGGNTEAFF&#95;TRBV12&#95;TRBJ1-1, CASSYSDTGELFF&#95;TRBV6&#95;TRBJ2-2, and CASSLTGNTEAFF&#95;TRBV12&#95;TRBJ1-1. At 0.001, the combination is: CASSLGETQYF&#95;TRBV12&#95;TRBJ2-5, CASSLGGNQPQHF&#95;TRBV12&#95;TRBJ1-5, and CASSLSGNTIYF&#95;TRBV12&#95;TRBJ1-3. This method can serve as a potential diagnostic and therapeutic tool, facilitating diagnosis and treatment of glioma and other cancers., (© 2024. The Author(s).)

The C-reactive protein-triglyceride glucose index (CTI) is emerging as a novel indicator for comprehensively assessing the severity of both inflammation and insulin resistance. However, the association between CTI and erectile dysfunction (ED) remains largely unexplored. Participant data for this study were sourced from NHANES 2001-2004, with exclusion criteria applied to those lacking information on clinical variables. The CTI was defined as 0.412*Ln (CRP) + ln [T.G. (mg/dL) × FPG (mg/dL)/2]. Weighted univariable and multivariable logistic regression models were utilized to examine the correlation between the CTI and ED, assessing the CTI as both a continuous and categorical variable (quartile). Moreover, subgroup analyses were conducted to pinpoint sensitive populations, and interaction analysis was performed to validate the findings. A total of 1502 participants were included in the final analysis, encompassing 302 with ED and 1200 without ED. After adjusting for potential confounders, the CTI was positively associated with ED incidence (OR = 1.56, 95% CI: 1.27-1.90, P = 0.002). The fourth quartile of the CTI significantly increased the incidence of ED (OR = 2.69, 95% CI: 1.07-6.74, P = 0.04), and the lowest quartile of CTI was used as the reference. The dose-response curve revealed a positive linear relationship between the CTI and the incidence of ED. Subgroup analysis confirmed the consistent positive relationship between the CTI and ED. The interaction test indicated no significant impact on this association. Finally, a sensitivity analysis was performed to verify the significant positive correlation between the CTI and severe ED (OR = 1.44, 95% CI: 1.19-1.76, P = 0.004). Our national data indicate that a greater CTI is positively linked to an increased risk of ED in US men, suggesting its potential for use in clinical practice for ED prevention or early intervention. Additional large-scale prospective studies are warranted to substantiate the causative relationship between CTI and ED., (© 2024. The Author(s).)

Genome-wide association study (GWAS) is a powerful tool to identify genomic loci underlying complex traits. However, the application in natural populations comes with challenges, especially power loss due to population stratification. Here, we introduce a bivariate analysis approach to a GWAS dataset of Arabidopsis thaliana. We demonstrate the efficiency of dual-phenotype analysis to uncover hidden genetic loci masked by population structure via a series of simulations. In real data analysis, a common allele, strongly confounded with population structure, is discovered to be associated with late flowering and slow maturation of the plant. The discovered genetic effect on flowering time is further replicated in independent datasets. Using Mendelian randomization analysis based on summary statistics from our GWAS and expression QTL scans, we predicted and replicated a candidate gene AT1G11560 that potentially causes this association. Further analysis indicates that this locus is co-selected with flowering-time-related genes. The discovered pleiotropic genotype-phenotype map provides new insights into understanding the genetic correlation of complex traits., (© 2024. The Author(s), under exclusive licence to The Genetics Society.)

Oral squamous cell carcinoma (OSCC) associated pain commonly predicts adverse events among patients. This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy. However, it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression. In this study, we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo, as evidenced by clinical tissue microarray analysis and murine lingual denervation. We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort. Notably, such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A 2A receptor (A 2A R) on trigeminal ganglia. Antagonism of trigeminal A 2A R with a selective A 2A R inhibitor SCH58261 resulted in impeded OSCC growth in vivo. We showed that trigeminal A 2A R overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP, an effect counteracted by SCH58261. We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP. Finally, we diminished the impact of CGRP on OSCC with istradefylline, a clinically available drug that targets neuronal A 2A R. Therefore, we established trigeminal A 2A R-mediated CGRP release as a promising druggable circuit in OSCC treatment., (© 2024. The Author(s).)

Nuclear lamin B1 (LMNB1) is a member of the nuclear lamin protein family. LMNB1 can maintain and ensure the stability of nuclear structure and influence the process of cell senescence by regulating chromatin distribution, DNA replication and transcription, gene expression, cell cycle, etc. In recent years, several studies have shown that the abnormal expression of LMNB1, a classical biomarker of cell senescence, is highly correlated with the progression of various malignant tumors; LMNB1 is therefore considered a new potential tumor marker and therapeutic target. However, the mechanism of action of LMNB1 is influenced by many factors, which are difficult to clarify at present. This article focuses on the recent progress in understanding the role of LMNB1 in cell senescence and malignant tumors and offers insights that could contribute to elucidating the mechanism of action of LMNB1 to provide a new direction for further research., (© 2024. The Author(s).)

The aim of this study was to assess the association between a new metabolic index, the cardiometabolic index (CMI) and erectile dysfunction (ED). The data for this study relied on the National Health and Nutrition Examination Survey (NHANES), a cross-sectional database, between 2001 and 2004. The CMI was calculated as the following formula: Triglyceride (TG) (mmol/L)/ High density lipid-cholesterol (HDL-C) (mmol/L) ×waist-height ratio (WHtR). The multivariate logistic regression analyses were conducted to assess the association between CMI and ED, supplemented by subgroup analysis and dose-response curves. Finally, a total of 1367 adult male participants were identified, and the mean CMI was 0.83 ± 0.02. Multivariate logistic regression analysis showed that in model 2 controlling for all potential confounders, CMI was significantly associated with ED (OR = 1.49, 95% CI: 1.09, 2.04) (p = 0.017). Subsequently, we convert the CMI from a continuous variable to a categorical variable (Tertiles). The results showed that male participants in CMI Tertile 3 group had a higher risk of ED than those in Tertile 1 group in model 2 (OR = 2.07, 95% CI: 1.12, 3.83, P = 0.024). The subgroup analysis of model 2 demonstrated that CMI was significantly associate with ED in participants aged ≥50 y (OR = 2.31, 95% CI: 1.35, 3.95, P = 0.005), body mass index (BMI) > 30 kg/m 2 (OR = 1.78, 95% CI: 1.10, 2.90, P = 0.023), with hypertension (OR = 1.89, 95% CI: 1.63, 3.45, P = 0.020), with diabetes mellitus (OR = 1.67, 95% CI: 1.13, 2.47, P = 0.015), with cardiovascular disease (CVD) (OR = 1.54, 95% CI: 1.12, 2.10, P = 0.011) and smoking (OR = 2.07, 95% CI: 1.26, 3.39, P = 0.007). This study demonstrates a strong association between CMI and ED and an increased risk of ED with higher CMI levels. More prospective studies with large samples and good designs are needed to validate our results in the future., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Understanding water saturation levels in tight gas carbonate reservoirs is vital for optimizing hydrocarbon production and mitigating challenges such as reduced permeability due to water saturation (Sw) and pore throat blockages, given its critical role in managing capillary pressure in water drive mechanisms reservoirs. Traditional sediment characterization methods such as core analysis, are often costly, invasive, and lack comprehensive spatial information. In recent years, several classical machine learning models have been developed to address these shortcomings. Traditional machine learning methods utilized in reservoir characterization encounter various challenges, including the ability to capture intricate relationships, potential overfitting, and handling extensive, multi-dimensional datasets. Moreover, these methods often face difficulties in dealing with temporal dependencies and subtle patterns within geological formations, particularly evident in heterogeneous carbonate reservoirs. Consequently, despite technological advancements, enhancing the reliability, interpretability, and applicability of predictive models remains imperative for effectively characterizing tight gas carbonate reservoirs. This study employs a novel data-driven strategy to prediction of water saturation in tight gas reservoir powered by three recurrent neural network type deep/shallow learning algorithms-Gated Recurrent Unit (GRU), Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), Support Vector Machine (SVM), K-nearest neighbor (KNN) and Decision tree (DT)-customized to accurately forecast sequential sedimentary structure data. These models, optimized using Adam's optimizer algorithm, demonstrated impressive performance in predicting water saturation levels using conventional petrophysical data. Particularly, the GRU model stood out, achieving remarkable accuracy (an R-squared value of 0.9973) with minimal errors (RMSE of 0.0198) compared to LSTM, RNN, SVM, KNN and, DT algorithms, thus showcasing its proficiency in processing extensive datasets and effectively identifying patterns. By achieving unprecedented accuracy levels, this study not only enhances the understanding of sediment properties and fluid saturation dynamics but also offers practical implications for reservoir management and hydrocarbon exploration in complex geological settings. These insights pave the way for more reliable and efficient decision-making processes, thereby advancing the forefront of reservoir engineering and petroleum geoscience., (© 2024. The Author(s).)

To elucidate the neurological features of Hansen disease. The medical records of patients with confirmed Hansen disease transferred from the neurology department were reviewed, and all medical and neurological manifestations of Hansen disease were assessed. Eleven patients with confirmed Hansen disease, 10 with newly detected Hansen disease and 1 with relapsed Hansen disease, who visited neurology departments were enrolled. The newly detected patients with Hansen disease were classified as having lepromatous leprosy (LL, n = 1), borderline lepromatous leprosy (BL, n = 2), borderline leprosy (BB, n = 2), borderline tuberculoid leprosy (BT, n = 1), tuberculoid leprosy (TT, n = 2), or pure neural leprosy (PNL, n = 2). All of the patients with confirmed Hansen were diagnosed with peripheral neuropathy (100.00%, 11/11). The symptoms and signs presented were mainly limb numbness (100.00%, 11/11), sensory and motor dysfunction (100.00%, 11/11), decreased muscle strength (90.90%, 10/11), and skin lesions (81.81%, 9/11). Nerve morphological features in nerve ultrasonography (US) included peripheral nerve asymmetry and segmental thickening (100.00%, 9/9). For neuro-electrophysiology feature, the frequency of no response of sensory nerves was significantly higher than those of motor nerves [(51.21% 42/82) vs (24.70%, 21/85)(P = 0.0183*)] by electrodiagnostic (EDX) studies. Nerve histological features in nerve biopsy analysis included demyelination (100.00%, 5/5) and axonal damage (60.00%, 3/5). In addition to confirmed diagnoses by acid-fast bacteria (AFB) staining (54.54%, 6/11) and skin pathology analysis (100.00%, 8/8), serology and molecular technology were positive in 36.36% (4/11) and 100.00% (11/11) of confirmed patients of Hansen disease, respectively. It is not uncommon for patients of Hansen disease to visit neurology departments due to peripheral neuropathy. The main pathological features of affected nerves are demyelination and axonal damage. The combination of nerve US, EDX studies, nerve biopsy, and serological and molecular tests can improve the diagnosis of Hansen disease., (© 2024. The Author(s).)

Current low-light enhancement algorithms fail to suppress noise when enhancing brightness, and may introduces structural distortion and color distortion caused by halos or artifacts. This paper proposes a content-illumination coupling guided low-light image enhancement network (CICGNet), it develops a truss topology based on Retinex as backbone to decompose low-light image component in an end-to-end way. The preservation of content features and the enhancement of illumination features are carried out along with depth and width direction of the truss topology. Each submodule uses the same resolution input and output to avoid the introduction of noise. Illumination component prevents misestimation of global and local illumination by using pre- and post-activation features at different depth levels, this way could avoid possible halos and artifacts. The network progressively enhances the illumination component and maintains the content component stage-by-stage. The proposed algorithm demonstrates better performance compared with advanced attention-based low-light enhancement algorithms and state-of-the-art image restoration algorithms. We also perform extensive ablation studies and demonstrate the impact of low-light enhancement algorithm on the downstream task of computer vision. Code is available at: https://github.com/Ruini94/CICGNet ., (© 2024. The Author(s).)

Increasing evidence demonstrates the psychological benefits of nature contact. However, the evidence is often established at the population level, and the individual differences in the psychological benefits gained from nature are considered negligible variations. In this study, we performed a cross-sectional online survey in Brisbane and Sydney, Australia, from April 15th and May 15th, 2021 around one year after the first covid-19 pandemic lockdowns. The results show that individuals with a stronger connection to nature are linked with a lower level of stress and anxiety with increased frequency in public greenspace visits, while such an association is less clear for individuals with a weaker connection to nature. We also find that, through the answer to an open-ended question, individuals with a lower connection to nature tend to mention nature-related words less as the reason for visiting greenspace. This indicates that a person's connection to nature is linked with how they interact with nature and thus might determine whether and how much psychological benefit a person gains from experiencing nature., (© 2024. The Author(s).)

Fear-related disorders (for example, phobias and anxiety) cause a substantial public health problem. To date, studies of the neural basis of fear have mostly focused on the amygdala. Here we identify a molecularly defined amygdala-independent tetra-synaptic pathway for olfaction-evoked innate fear and anxiety in male mice. This pathway starts with inputs from the olfactory bulb mitral and tufted cells to pyramidal neurons in the dorsal peduncular cortex that in turn connect to cholecystokinin-expressing (Cck + ) neurons in the superior part of lateral parabrachial nucleus, which project to tachykinin 1-expressing (Tac1 + ) neurons in the parasubthalamic nucleus. Notably, the identified pathway is specifically involved in odor-driven innate fear. Selective activation of this pathway induces innate fear, while its inhibition suppresses odor-driven innate fear. In addition, the pathway is both necessary and sufficient for stress-induced anxiety-like behaviors. These findings reveal a forebrain-to-hindbrain neural substrate for sensory-triggered fear and anxiety that bypasses the amygdala., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health 1 . Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study 2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Understanding drivers of disease vectors' population dynamics is a pressing challenge. For short-lived organisms like mosquitoes, landscape-scale models must account for their highly local and rapid life cycles. Aedes aegypti, a vector of multiple emerging diseases, has become abundant in desert population centers where water from precipitation could be a limiting factor. To explain this apparent paradox, we examined Ae. aegypti abundances at > 660 trapping locations per year for 3 years in the urbanized Maricopa County (metropolitan Phoenix), Arizona, USA. We created daily precipitation layers from weather station data using a kriging algorithm, and connected localized daily precipitation to numbers of mosquitoes trapped at each location on subsequent days. Precipitation events occurring in either of two critical developmental periods for mosquitoes were correlated to suppressed subsequent adult female presence and abundance. LASSO models supported these analyses for female presence but not abundance. Precipitation may explain 72% of Ae. aegypti presence and 90% of abundance, with anthropogenic water sources supporting mosquitoes during long, precipitation-free periods. The method of using kriging and weather station data may be generally applicable to the study of various ecological processes and patterns, and lead to insights into microclimates associated with a variety of organisms' life cycles., (© 2024. The Author(s).)

Alagille Syndrome (ALGS) is a complex genetic disorder characterized by cholestasis, congenital cardiac anomalies, and butterfly vertebrae. The variable phenotypic expression of ALGS can lead to challenges in accurately diagnosing affected infants, potentially resulting in misdiagnoses or underdiagnoses. This study highlights novel JAG1 gene mutations in two cases of ALGS. The first case with a novel p.Pro325Leufs*87 variant was diagnosed at 2 months of age and exhibited a favorable prognosis and an unexpected manifestation of congenital hypothyroidism. Before the age of 2, the second patient was incorrectly diagnosed with liver structural abnormalities, necessitating extensive treatment. In addition, he exhibited delays in language acquisition that may have been a result of SNAP25 haploinsufficiency. The identification of ALGS remains challenging, highlighting the importance of early detection and genetic testing for effective patient management. The variant p.Pro325Leufs*87 is distinct from reported variants linked to congenital hypothyroidism in ALGS patients, thereby further confirming the clinical and genetic complexity of ALGS. This emphasizes the critical need for individualized and innovative approaches to diagnosis and medical interventions, uniquely intended to address the complexity of this syndrome., (© 2024. The Author(s).)

Early and effective surface defect detection in industrial components can avoid the occurrence of serious safety hazards. Since most industrial component surfaces have tiny defects with high similarity to the detection background, there are often issues of missed or false detections when defects are detected, leading to low detection accuracy. To deal with the aforementioned issue, this essay suggests a high-precision detection model for surface defects in industrial components based on the YOLOv5 algorithm. First, the original spatial pyramid pooling (SPPF) is innovated by proposing the SPPFKCSPC module, which improves the network's capacity for feature extraction from targets at different scales and fuses multiscale features better. Then, C3 is combined with SPPFKCSPC and replaces the C3 module of the backbone network, which improves feature expression and enhances the receptive field of the network. Finally, the coordinate attention mechanism (CA) has been embedded into the YOLOv5 neck network, and the bounding box regression loss function of the algorithm is improved to EIOU, not only improving the precision of the target localization and recognition model but also enhancing the overall network performance. Based on the public datasets NEU-DET and PV-Multi-Defect, multiple sets of experiments were conducted using innovative algorithms. On the NEU-DET dataset, we got a mean average accuracy (mAP) of 88.3%, which is 7.2% greater than the original approach. On the PV-Multi-Defect dataset, the mAP value reached 97.5%, an improvement of 1.5%. As shown by the experimental data, the detection results significantly improved., (© 2023. The Author(s).)

The present study investigated the composition, abundance, and diversity of gut microbes in full-term and late-preterm infants from a medical center in eastern China. A total of 144 genomes of stool samples were captured for 16S rRNA metagenomic analyses. A high abundance of commensal intestinal bacteria was detected in these samples such as Phocaeicola vulgatus, Escherichia coli, and Faecalibacterium prausnitzii, indicating a relatively consistent diversity of gut microbes in the present full-term infants aged 38-40 weeks. However, late preterm infants (n = 50) with mandatory antimicrobials feeding exhibited lower diversity but a higher composition of opportunistic pathogens such as Enterococcus species. Centralized on the situation, we explored the regulatory effect of Clostridium butyricum as probiotics on these late preterm infants. The consumption of C. butyricum did not restore the composition of gut microbes altered by antimicrobials to normal levels, although several opportunistic pathogens decreased significantly after probiotic therapy including Staphylococcus aureus, Sphingomonas echinoides, and Pseudomonas putida. We also compared the effects of day-fed versus night-fed probiotics. Intriguingly, the nighttime feeding showed a higher proportion of C. butyricum compared with probiotic day-feeding. Finally, fecal metabolome and metabolites were analyzed in late preterm infants with (n = 20) or without probiotic therapy (n = 20). The KEGG enrichment analysis demonstrated that vitamin digestion and absorption, synaptic vesicle cycle, and biotin metabolism were significantly increased in the probiotic-treated group, while MSEA indicated that a series of metabolism were significantly enriched in probiotic-treated infants including glycerolipid, biotin, and lysine, indicating the complex effects of probiotic therapy on glutathione metabolism and nutrients digestion and absorption in late preterm infants. Overall, this study provided metagenomic and metabolomic profile of the gut microbes in full-term newborns and late preterm infants in eastern China. Further studies are needed to support and elucidate the role of probiotic feeding in late preterm infants with mandatory antimicrobial treatment., (© 2023. The Author(s).)

The occurrence of heart failure following acute myocardial infarction (AMI) significantly increases the risk of post-infarction mortality. Alkaline phosphatase (AP) is considered to be an independent predictor of cardiovascular disease (CVD) and adverse outcomes. Furthermore, in recent years, alkaline phosphatase has been associated with insulin resistance (IR). Our aim was to investigate the correlation between IR substitutes (triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio), AP, and LV dysfunction in patients admitted after AMI. The retrospective study included 810 patients who underwent coronary angiography for myocardial infarction at the First Hospital of Hebei Medical University from August 2018 to December 2021. Patients were categorized into three groups based on their serum AP levels. Clinical characteristics at admission, cardiac echocardiography findings, coronary angiography results, and biochemical markers such as serum AP levels and triglycerides (TG) were recorded during hospitalization. Left ventricular ejection fraction (LVEF) was assessed using cardiac echocardiography conducted from the time of admission until the coronary angiography procedure. A total of 774 patients with AMI were included in this study. The TyG index is significantly correlated with the TG/HDL-C ratio. (R = 0.739, P < 0.001). Binary logistic regression analysis revealed that elevated serum AP (OR 2.598, 95% CI 1.331-5.071, P = 0.005), presence of the left anterior descending (LAD) artery as the infarct-related artery (IRA) (OR 2.452, 95% CI 1.352-4.449, P = 0.003), and triglyceride (TG) levels (OR 0.652, 95% CI 0.429-0.992, P = 0.046) were protective risk factor for an admission LVEF < 40% following AMI. The serum alkaline phosphatase and LAD as IRA are independent risk factors for severe reduction in LVEF during hospitalization for AMI. Conversely, triglyceride are independent protective factor for severe reduction in LVEF during AMI hospitalization., (© 2023. Springer Nature Limited.)

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10 +/- mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26 rtTA ; tet(O)sFgfr2b) were used to determine the effect of Fgf10 hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10 +/- mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10 +/+ control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment., (© 2023. The Author(s).)

Mass spectrometry technology can realize dynamic detection of many complex matrix samples in a simple, rapid, compassionate, precise, and high-throughput manner and has become an indispensable tool in accurate diagnosis. The mass spectrometry data analysis is mainly to analyze all metabolites in the organism quantitatively and to find the relative relationship between metabolites and physiological and pathological changes. A feature construction of mass spectrometry data (MSFS) method is proposed to construct the features of the original mass spectrometry data, so as to reduce the noise in the mass spectrometry data, reduce the redundancy of the original data and improve the information content of the data. Chi-square test is used to select the optimal non-redundant feature subset from high-dimensional features. And the optimal feature subset is visually analyzed and corresponds to the original mass spectrum interval. Training in 10 kinds of supervised learning models, and evaluating the classification effect of the models through various evaluation indexes. Taking two public mass spectrometry datasets as examples, the feasibility of the method proposed in this paper is verified. In the coronary heart disease dataset, during the identification process of mixed batch samples, the classification accuracy on the test set reached 1.000; During the recognition process, the classification accuracy on the test set advanced to 0.979. On the colorectal liver metastases data set, the classification accuracy on the test set reached 1.000. This paper attempts to use a new raw mass spectrometry data preprocessing method to realize the alignment operation of the raw mass spectrometry data, which significantly improves the classification accuracy and provides another new idea for mass spectrometry data analysis. Compared with MetaboAnalyst software and existing experimental results, the method proposed in this paper has obtained better classification results., (© 2023. Springer Nature Limited.)