G-Quadruplex-Mediated Transcriptional Regulation of SYT7: Implications for Tumor Progression and Therapeutic Strategies.

Synaptotagmin 7 (SYT7), a member of the synaptotagmin family, exhibits high expression in various tumors and is closely associated with patient prognosis. The tight regulation of SYT7 expression assumes paramount significance in the progression of tumorigenesis. In this study, we detected a high GC content in the first 1000 bp of the promoter region of SYT7, suggesting a potential role of the G-quadruplex in its transcriptional regulation. Circular dichroism spectroscopy results showed that -187 to -172 bp sequence can form a typical parallel G-quadruplex structure, and site mutation revealed the critical role of the ninth guanine in its formation. Then, treatment of two ligands of G-quadruplex (TMPyP4 and Pyridostatin) reduced both the expression of SYT7 and subsequent tumor proliferation, demonstrating the potential of the G-quadruplex as a targeted therapy for tumors. By shedding light on the pivotal role of the G-quadruplex in regulating SYT7 transcription, our study not only advances our comprehension of this intricate regulatory mechanism but also emphasizes the significance of SYT7 in tumor proliferation. These findings collectively contribute to a more comprehensive understanding of the interplay between G-quadruplex regulation and SYT7 function in tumor development.

Shifts in Structure and Assembly Processes of Root Endophytic Community Caused by Climate Warming and Precipitation Increase in Alpine Grassland.

Climate change poses great challenges to the survival of plants. Plant endophytes play important roles in improving plant adaptability. However, our knowledge of the effects of climate change on endophytic community structures is limited. Relying on a field experimental platform simulating climate warming, precipitation increases, and their combination in an alpine grassland, the root endophytic bacterial community structures and assembly processes of three coexisting plant species (Elymus nutans, Kobresia humilis, and Melissilus ruthenicus) were measured. The results indicated that Proteobacteria was the dominant phylum, with a relative abundance ranging from 50% to 80%, followed by Actinobacteria and Bacteroidetes. Bacterial diversity decreased significantly under the combined treatment for all three plant species, with the largest reduction observed in E. nutans. The climate manipulation treatments had a minimal effect on the endophytic bacterial community structures. The relative abundance of Burkholderiaceae increased significantly under the combined treatment for the three plant species. Moreover, the endophytic community assembly processes changed from stochastic dominated under control plots to deterministic dominated under the combined plots for E. nutans, while this shift was reversed for M. ruthenicus. The root endophytic bacterial community was affected by the soil's available nitrogen and stoichiometric ratio. These results revealed that the sensitivity of endophyte community structures to climate change varies with host plant species, which has implications for plant fitness differences.

An Acoustofluidic Picoinjector.

Droplet microfluidics has emerged as a valuable technology for a multitude of chemical and biomedical applications, offering the capability to create independent microenvironments for high-throughput assays. Central to numerous droplet microfluidic applications is the picoinjection of materials into individual droplets, yet existing picoinjection methods often exhibit high power requirements, lack biocompatibility, and/or suffer from limited controllability. Here, we present an acoustofluidic picoinjector that generates acoustic pressure at the droplet interface to enable on-demand, energy-efficient, and biocompatible injection at high precision. We validate our platform by performing acid-base titrations by iteratively injecting picoliter volume reagents into droplets to induce pH transitions detectable by color change in solution. Additionally, we demonstrate the versatility of the acoustofluidic picoinjector in the synthesis of metallic nanoparticles, yielding highly monodisperse and reproducible particle morphologies compared to conventional bulk-phase techniques. By facilitating controlled delivery of reagents or biological samples with unparalleled accuracy, acoustofluidic picoinjection broadens the utility of droplet microfluidics for a myriad of applications in chemical and biological research.

Acousto-dielectric tweezers enable independent manipulation of multiple particles.

Acoustic tweezers have gained substantial interest in biology, engineering, and materials science for their label-free, precise, contactless, and programmable manipulation of small objects. However, acoustic tweezers cannot independently manipulate multiple microparticles simultaneously. This study introduces acousto-dielectric tweezers capable of independently manipulating multiple microparticles and precise control over intercellular distances and cyclical cell pairing and separation for detailed cell-cell interaction analysis. Our acousto-dielectric tweezers leverage the competition between acoustic radiation forces, generated by standing surface acoustic waves (SAWs), and dielectrophoretic (DEP) forces, induced by gradient electric fields. Modulating these fields allows for the precise positioning of individual microparticles at points where acoustic radiation and DEP forces are in equilibrium. This mechanism enables the simultaneous movement of multiple microparticles along specified paths as well as cyclical cell pairing and separation. We anticipate our acousto-dielectric tweezers to have enormous potential in colloidal assembly, cell-cell interaction studies, disease diagnostics, and tissue engineering.

Unrefined and Milled Ilmenite as a Cost-Effective Photocatalyst for UV-Assisted Destruction and Mineralization of PFAS.

Per- and polyfluoroalkyl substances (PFAS) are fluorinated and refractory pollutants that are ubiquitous in industrial wastewater. Photocatalytic destruction of such pollutants with catalysts such as TiO2 and ZnO is an attractive avenue for removal of PFAS, but refined forms of such photocatalysts are expensive. This study, for the first time, utilized milled unrefined raw mineral ilmenite, coupled to UV-C irradiation to achieve mineralization of the two model PFAS compounds perfluorooctanoic acid (PFOA) and perfluoro octane sulfonic acid (PFOS). Results obtained using a bench-scale photocatalytic reactor system demonstrated rapid removal kinetics of PFAS compounds (>90% removal in less than 10 h) in environmentally-relevant concentrations (200-1000 ppb). Raw ilmenite was reused over three consecutive degradation cycles of PFAS, retaining >80% removal efficiency. Analysis of degradation products indicated defluorination and the presence of shorter-chain PFAS intermediates in the initial samples. End samples indicated the disappearance of short-chain PFAS intermediates and further accumulation of fluoride ions, suggesting that original PFAS compounds underwent mineralization due to an oxygen-radical-based photocatalytic destruction mechanism induced by TiO2 present in ilmenite and UV irradiation. The outcome of this study implies that raw ilmenite coupled to UV-C is suitable for cost-effective reactor operation and efficient photocatalytic destruction of PFAS compounds.

Differentiation of regioisomers of sulfobenzoic acid by traveling-wave ion mobility mass spectrometry.

An ion mobility mass spectrometry (IM-MS) investigation using a Synapt G2 mass spectrometer was conducted to separate anions generated from the three regioisomers of sulfobenzoic acid. The results revealed that the differences in arrival time distributions (ATDs) were inadequate to differentiate the isomers unambiguously. However, the ATD profiles of the product ions, generated by fragmenting the respective mass-selected m/z 201 precursor ions in the Trap region of the three-compartment traveling-wave ion guide of the Synapt G2 mass spectrometer, were distinctly different, enabling definitive differentiation of the isomers. An arrival-time peak for an ion of m/z 157 resulting from the loss of CO2 from the respective precursors was common to all three mobilograms. However, only the profile recorded from the para-isomer exhibited a unique arrival-time peak for an ion of m/z 137, originating from an SO2 loss. Such a peak corresponding to an SO2 loss was absent in the ATD profiles of the ortho- and meta-isomers. Additionally, the mobilogram of the meta-isomer displayed a unique peak at 3.42 ms. Based on its product ion spectrum, this peak was attributed to the bisulfite anion (m/z 81; HSO3-). Previously, this meta-isomer specific m/z 81 ion had been proposed to originate from a two-step process involving the intermediacy of an m/z 157 ion formed by CO2 loss. However, our detailed tandem mass spectrometric experiments suggest that the m/z 81 is not a secondary product but rather an ion that originated from a direct elimination of a benzyne derivative from the m/z 201 precursor ion.

New Cytotoxic γ-Lactam Alkaloids from the Mangrove-Derived Fungus Talaromyces hainanensis sp. nov. Guided by Molecular Networking Strategy.

The fungus Talaromyces hainanensis, isolated from the mangrove soil, was characterized as a novel species by morphology observation and phylogenetic analyses. Four new γ-lactam alkaloids talaroilactams A-D (1-4) and two reported compounds harzianic acid (5) and isoharzianic acid (6) were identified from the fungus T. hainanensis WHUF0341, assisted by OSMAC along with molecular networking approaches. Their structures were determined through ECD calculations and spectroscopic analyses. Moreover, the biosynthetic route of 1-4 was also proposed. Compound 1 displayed potent cytotoxicity against HepG2 cell lines, with an IC50 value of 10.75 ± 1.11 µM. In addition, network pharmacology was employed to dissect the probable mechanisms contributing to the antihepatocellular carcinoma effects of compound 1, revealing that cytotoxicity was mainly associated with proteolysis, negative regulation of autophagy, inflammatory response, and the renin-angiotensin system. These results not only expanded the chemical space of natural products from the mangrove associated fungi but also afforded promising lead compounds for developing the antihepatocellular carcinoma agents.

Formation of Micelles by Nonionic Detergent Molecules Leads to the Breakthrough Peak in Reversed-Phase Ultraperformance Liquid Chromatography (UPLC).

A peculiar phenomenon known as "breakthrough" occurs under reversed-phase ultraperformance liquid chromatography (UPLC) conditions and has been under scrutiny for decades. This effect takes place when a large volume of analyte solution, prepared in a solvent with an eluotropic strength significantly higher than that of the initial mobile phase solvent, is injected. According to the literature, under specific experimental conditions, a substantial portion of solutes is carried by the mobile phase and detected near the dead time of the chromatographic system. This phenomenon is typically observed when the injected volume of a particular analyte is sufficiently large. However, the underlying physicochemical principles governing this phenomenon have remained elusive. We present evidence demonstrating that breakthroughs can occur even when injecting a sample of a neat solvent devoid of any solute. By mass spectrometric analysis, we identified the breakthrough peak to represent the nonionic detergent Triton. When columns are equilibrated with water, Triton molecules, present as impurities in filtered water, accumulate on the nonpolar stationary phase. Upon the introduction of a solvent with a stronger elution strength, Triton molecules retained on the stationary phase are removed. As detergents, these Triton molecules aggregate into micelles featuring a hydrophobic inner core and a hydrophilic outer shell. These hydrophilic micelles are carried by the polar mobile phase and detected as the breakthrough peak at the dead time of the chromatographic system. When analytes are present, a portion of the injected solutes is captured by the micelles and transported with the breakthrough plug. This assertion was verified and confirmed by liquid chromatography-mass spectrometry (LC-MS) analysis of a methanolic solution of perfluorooctanoic acid (PFOA). The mass spectra corresponding to the breakthrough plug featured a peak for the PFOA anion (m/z 413) in addition to those for Triton.

Automatic detection of epilepsy from EEGs using a temporal convolutional network with a self-attention layer.

BACKGROUND: Over 60% of epilepsy patients globally are children, whose early diagnosis and treatment are critical for their development and can substantially reduce the disease's burden on both families and society. Numerous algorithms for automated epilepsy detection from EEGs have been proposed. Yet, the occurrence of epileptic seizures during an EEG exam cannot always be guaranteed in clinical practice. Models that exclusively use seizure EEGs for detection risk artificially enhanced performance metrics. Therefore, there is a pressing need for a universally applicable model that can perform automatic epilepsy detection in a variety of complex real-world scenarios. METHOD: To address this problem, we have devised a novel technique employing a temporal convolutional neural network with self-attention (TCN-SA). Our model comprises two primary components: a TCN for extracting time-variant features from EEG signals, followed by a self-attention (SA) layer that assigns importance to these features. By focusing on key features, our model achieves heightened classification accuracy for epilepsy detection. RESULTS: The efficacy of our model was validated on a pediatric epilepsy dataset we collected and on the Bonn dataset, attaining accuracies of 95.50% on our dataset, and 97.37% (A v. E), and 93.50% (B vs E), respectively. When compared with other deep learning architectures (temporal convolutional neural network, self-attention network, and standardized convolutional neural network) using the same datasets, our TCN-SA model demonstrated superior performance in the automated detection of epilepsy. CONCLUSION: The proven effectiveness of the TCN-SA approach substantiates its potential as a valuable tool for the automated detection of epilepsy, offering significant benefits in diverse and complex real-world clinical settings.

A new intestinal supplement 'Synbiotics' therapeutically regulates gut microbiota and activates PPARs pathway to inhibit Alzheimer's disease progression in mouse models.

We aimed to investigate the role of Synbiotic preparations on the interaction of gut microbiota with AD development. APP/PS1 mice were randomized into APP/PS1 and Synbiotics groups, and C57BL/6J mice were used as wild type (WT) control group. The mice in the Synbiotics group and the APP/PS1 group were given Synbiotics and xylo-oligosaccharides for 3 months, respectively. The mice in the WT group were given the same amount of normal saline. Cognitive function was measured. Positron emission computed tomography/magnetic resonance imaging (PET/MRI) was used to detect fasting blood glucose level. Immunohistochemical assay, ELISA, western blot and qRT-PCR were carried out to detect inflammatory factors. DNA extraction of fecal sample was performed to carry out sequencing. Bioinformatics analysis, metabolites sample preparation and Liquid Chromatograph Mass Spectrometer (LC/MS) analysis were also performed. Synbiotics treatment can significantly ameliorate learning and memory competence by inhibiting Aß protein deposition. Different bacteria in the intestine were significantly improved and changes in gut microbiota can affect the intestinal metabolism to affect multiple potential pathways after Synbiotics treatment. Synbiotics treatment can activate peroxisome proliferator activated receptor (PPARs) signaling pathway and significantly reduce neuroinflammation in APP/PS1 mice brains. Synbiotics treatment can effectively reduce neuro-inflammatory response through the regulation of intestinal microflora to delay AD development.

Locality Cross-domain Discriminant Analysis for Membranous Nephropathy Recognition using Microscopic Hyperspectral Imaging.

Cross-domain methods have been proposed to learn the domain invariant knowledge that can be transferred from the source domain to the target domain. Existing cross-domain methods attempt to minimize the distribution discrepancy of the domains. However, these methods fail to explore the domain invariant subspace due to the samples of different classes between two domains may overlap in the new subspace. They consider the features in the original space data that may be unnecessary or irrelevant to the final classification, and neglect to preserve the local manifold structure between two domains. To solve these problems, a novel feature extraction method called Locality Cross-domain Discriminant Analysis (LCDA) is proposed. LCDA first aligns the distributions and avoids overlap between two domains. Then, LCDA exploits the local manifold structure to maintain the discriminative capability of the low-dimensional projection matrices. Finally, a robust constraint is utilized to preserve the robustness of the projection matrices. The proposed LCDA not only avoids overlap between different classes but also explores the local manifold information. Experiment results on the medical membranous nephropathy hyperspectral dataset demonstrate that the proposed LCDA has better performance than other relevant feature extraction methods.

Availability of family care resources, bathing assistance and toileting assistance among older adults with functional limitations: an evidence-based study from China.

BACKGROUND: An aging population has contributed to an increasing prevalence of functional limitations among older adults. Family support plays a crucial role in toileting and bathing assistance. Yet, the relationship between availability of family care resources and such actual assistance remains insufficiently explored. Our study aims to describe availability of family care resources and identify the association between availability of family care resources and toileting assistance or bathing assistance. METHODS: This study employed a cross-sectional analysis of data from the 2018 National Survey of the China Health and Retirement Longitudinal Study (CHARLS). The availability of family care resources was assessed using measurements of spouse availability, adult child availability, and living arrangement. Bathing assistance and toileting assistance were measured based on self-reported receipt of such assistance. Descriptive statistics were used to depict the overall and subgroup situation of availability of family care resources. Multivariable logistic models were employed to investigate the relationship between availability of family care resources and the receipt of toileting assistance or bathing assistance. RESULTS: Among the sample of older adults with functional limitations, 69% had a spouse, 63% had at least one adult child, and 80% resided with family members. Among those with bathing disability, 13% reported lacking bathing assistance, and among those with toileting disability, 54% reported lacking toileting assistance. Participants with 1-2 adult children had lower odds of receiving toileting assistance (OR: 0.28, 95% CI: 0.09, 0.91, p= 0.034) compared to those with three or more adult children. Spouse availability and living arrangement did not exhibit statistically significant associations with toileting assistance. Participants without a spouse had lower odds of receiving bathing assistance (OR: 0.27, 95% CI: 0.09-0.78, p= 0.016) in comparison to those with a spouse; however, adult child availability and living arrangement did not display statistically significant associations with bathing assistance. CONCLUSION: The present findings suggest a gap in family commitment when it comes to assisting older adults with functional limitations in bathing/toileting. To address this, policymakers are encouraged to prioritize the implementation of proactive mechanisms for identifying family caregivers, alongside incentives to enhance their engagement in practical caregiving activities. Furthermore, it is crucial to emphasize the prioritization of affordable and easily accessible formal toileting/bathing assistance options for older adults who lack sufficient family care resources.

Diagnosis of Autism Spectrum Disorder by Dynamic Local Graph-Theory Indicators Based on Electroencephalogram.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopment disease characterized by impaired social and cognitive abilities. Despite its prevalence, reliable biomarkers for identifying individuals with ASD are lacking. Recent studies have suggested that alterations in the functional connectivity of the brain in ASD patients could serve as potential indicators. However, previous research focused on static functional-connectivity analysis, neglecting temporal dynamics and spatial interactions. To address this gap, our study integrated dynamic functional connectivity, local graph-theory indicators, and a feature-selection and ranking approach to identify biomarkers for ASD diagnosis. METHODS: The demographic information, as well as resting and sleeping electroencephalography (EEG) data, were collected from 20 ASD patients and 25 controls. EEG data were pre-processed and segmented into five sub-bands (Delta, Theta, Alpha-1, Alpha-2, and Beta). Functional-connection matrices were created by calculating coherence, and static-node-strength indicators were determined for each channel. A sliding-window approach, with varying widths and moving steps, was used to scan the EEG series; dynamic local graph-theory indicators were computed, including mean, standard deviation, median, inter-quartile range, kurtosis, and skewness of the node strength. This resulted in 95 features (5 sub-bands × 19 channels) for each indicator. A support-vector-machine recurrence-feature-elimination method was used to identify the most discriminative feature subset. RESULTS: The dynamic graph-theory indicators with a 3-s window width and 50% moving step achieved the highest classification performance, with an average accuracy of 95.2%. Notably, mean, median, and inter-quartile-range indicators in this condition reached 100% accuracy, with the least number of selected features. The distribution of selected features showed a preference for the frontal region and the Beta sub-band. CONCLUSIONS: A window width of 3 s and a 50% moving step emerged as optimal parameters for dynamic graph-theory analysis. Anomalies in dynamic local graph-theory indicators in the frontal lobe and Beta sub-band may serve as valuable biomarkers for diagnosing autism spectrum disorders.

Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function.

Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.

Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.

Whole genome resequencing reveals genomic regions related to red plumage in ducks.

Plumage color is a characteristic trait of ducks that originates as a result of natural and artificial selection. As a conspicuous phenotypic feature, it is a breed characteristic. Previous studies have identified some genes associated with the formation of black and white plumage in ducks. However, studies on the genetic basis underlying the red plumage phenotype in ducks are limited. Here, genome-wide association analysis (GWAS) and selection signal detection (Fst, θπ ratio, and cross-population composite likelihood ratio [XP-CLR]) were conducted to identify candidate regions and genes underlying duck plumage color phenotype. Selection signal detection revealed 29 overlapping genes (including ENPP1 and ULK1) significantly associated with red plumage color in Ji'an Red ducks. ENSAPLG00000012679, ESRRG, and SPATA5 were identified as candidate genes associated with red plumage using GWAS. Selection signal detection revealed that 19 overlapping genes (including GMDS, PDIA6, and ODC1) significantly correlated with light brown plumage in Brown Tsaiya ducks. GWAS to narrow down the significant regions further revealed nine candidate genes (AKT1, ATP6V1C2, GMDS, LRP4, MAML3, PDIA6, PLD5, TMEM63B, and TSPAN8). Notably, in Brown Tsaiya ducks, GMDS, ODC1, and PDIA6 exhibit significantly differentiated allele frequencies among other feather-colored ducks, while in Ji'an Red ducks, ENSAPLG00000012679 has different allele frequency distributions compared with that in other feather-colored ducks. This study offers new insights into the variation and selection of the red plumage phenotype using GWAS and selective signals.

Significant genomic introgression from grey junglefowl (Gallus sonneratii) to domestic chickens (Gallus gallus domesticus).

BACKGROUND: Chicken is one of the most numerous and widely distributed species around the world, and many studies support the multiple ancestral origins of domestic chickens. The research regarding the yellow skin phenotype in domestic chickens (regulated by BCO2) likely originating from the grey junglefowl serves as crucial evidence for demonstrating the multiple origins of chickens. However, beyond the BCO2 gene region, much remains unknown about the introgression from the grey junglefowl into domestic chickens. Therefore, in this study, based on whole-genome data of 149 samples including 4 species of wild junglefowls and 13 local domestic chicken breeds, we explored the introgression events from the grey junglefowl to domestic chickens. RESULTS: We successfully detected introgression regions besides BCO2, including two associated with growth trait (IGFBP2 and TKT), one associated with angiogenesis (TIMP3) and two members of the heat shock protein family (HSPB2 and CRYAB). Our findings suggest that the introgression from the grey junglefowl may impact the growth performance of chickens. Furthermore, we revealed introgression events from grey junglefowl at the BCO2 region in multiple domestic chicken breeds, indicating a phenomenon where the yellow skin phenotype likely underwent strong selection and was retained. Additionally, our haplotype analysis shed light on BCO2 introgression event from different sources of grey junglefowl into domestic chickens, possibly suggesting multiple genetic flows between the grey junglefowl and domestic chickens. CONCLUSIONS: In summary, our findings provide evidences of the grey junglefowl contributing to the genetic diversity of domestic chickens, laying the foundation for a deeper understanding of the genetic composition within domestic chickens, and offering new perspectives on the impact of introgression on domestic chickens.

IFNT-induced IRF1 enhances bovine endometrial receptivity by transactivating LIFR.

Interferon-τ (IFN-τ) participates in the establishment of endometrial receptivity in ruminants. However, the precise mechanisms by which IFN-τ establishes bovine endometrial receptivity remain largely unknown. Interferon regulatory factor 1 (IRF1) is a classical interferon-stimulated gene (ISG) induced by type I interferon, including IFN-τ. Leukemia inhibitory factor receptor (LIFR) is a transmembrane receptor for leukemia inhibitory factor (LIF), which is a key factor in regulating embryo implantation in mammals. This study aimed to investigate the roles of IRF1 and LIFR in the regulation of bovine endometrial receptivity by IFN-τ. In vivo, we found IRF1 and LIFR were upregulated in the bovine endometrial luminal epithelium on Day 18 of pregnancy compared to Day 18 of the estrous cycle. In vitro, IFN-τ could upregulate IRF1, LIFR, and endometrial receptivity markers (LIF, HOXA10, ITGAV, and ITGB3) expression, downregulate E-cadherin expression and reduce the quantity of microvilli of bovine endometrial epithelial cells (bEECs). Overexpression of IRF1 had similar effects to IFN-τ on endometrial receptivity, and interference of LIFR could block these effects, suggesting the positive effects of IRF1 on endometrial receptivity were mediated by LIFR. Dual luciferase reporter assay verified that IRF1 could transactivate LIFR transcription by binding to its promoter. In conclusion, IFN-τ can induce IRF1 expression in bovine endometrial epithelial cells, and IRF1 upregulates LIFR expression by binding to LIFR promoter, contributing to the enhancement of bovine endometrial receptivity.

Preference for primary care in Chinese homebound patients.

OBJECTIVE: This study aims to describe the preference for primary healthcare (PHC) and investigate associated factors among homebound residents in both rural and urban areas of China. It provides valuable insights to facilitate the rational allocation of healthcare resources and promote the utilization of PHC. METHODS: In this nationally representative cross-sectional study, we utilized the most recent data (2020) from the China Family Panel Studies (CFPS). Participants were recruited from 25 provincial-level administrative regions in both rural and urban areas of China. Homebound patients were asked to provide details about their individual characteristics, variables related to family caregiving, and preferences for PHC. Multivariable logistic models were used to analyze potential factors associated with preference for PHC. Estimates of association were reported as odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: The study found that 58.43% of rural patients reported a preference for PHC, while 42.78% of urban patients favored PHC. Compared to rural participants who did not received inpatient care in the past year, those who received inpatient care in the past year had 67% lower odds of choosing PHC (OR:0.33, 95% CI:0.19-0.59); Compared to rural participants who did not received family caregiving when ill, those who received family caregiving when ill had 59% lower odds of choosing PHC (OR: 0.41, 95% CI:0.21-0.77). Correspondingly, Compared to urban participants who did not received inpatient care in the past year, those who had received inpatient care in the past year had 75% lower odds of choosing PHC (OR: 0.25, 95% CI: 0.10-0.56); Compared to urban participants who did not received family caregiving when ill, those who received family caregiving when ill had 73% lower odds of choosing PHC (OR: 0.27, 95% CI: 0.11-0.63); Compared to urban participants who with agricultural Hukou, those with Non-agricultural Hukou had 61% lower odds of choosing PHC (OR: 0.39, 95% CI:0.18-0.83); Compared to urban participants living in the eastern part of mainland China, those living in the central part of China had 188% higher odds of choosing PHC (OR: 2.88, 95% CI: 1.14-7.29). CONCLUSION: Policymakers should focus on tailoring PHC to vulnerable populations and prioritizing family-based public health strategies for enhancing homebound patients' perceptions of PHC. Furthermore, further study is needed on whether the Hukou registration system affects the barriers that homebound patients experience in choosing healthcare providers.

Deficiency of diacylglycerol Kinase ζ promotes Beclin1-mediated autophagy via the mTOR/TFEB signaling pathway: Relevance to maladaptive cardiac hypertrophy.

The activation Gq protein-coupled receptors (GPCRs) is a crucial factor contributing to maladaptive cardiac hypertrophy, and dysregulation of autophagy is implicated in its prohypertrophic effects. Previous studies have shown that diacylglycerol kinase zeta (DGKζ) can suppress cardiac hypertrophy by inhibiting the diacylglycerol (DAG)-PKC pathway in response to mechanical strain or growth agonists such as endothelin-1 (ET-1). However, the involvement of DGKζ in autophagy regulation remains poorly understood. In this study, we aimed to investigate the role of DGKζ in autophagy regulation during maladaptive cardiac hypertrophy. We found that Beclin1-mediated autophagy was involved in the development of maladaptive cardiac hypertrophy and dysfunction in response to prohypertrophic challenges of transverse aortic constriction (TAC) or ET-1. Deficiency of DGKζ promoted Beclin1-mediated autophagy, aggravated adverse cardiac remodeling, and cardiac dysfunction, which could be ameliorated by genetic deletion of Beclin1 or TFEB. Mechanistically, the deficiency of DGKζ disrupted the activation of AKT/mTOR signaling, the association between mTOR and TFEB, and favored the nuclear translocation of TFEB from the cytoplasm, leading to enhanced activation of Beclin1-mediated autophagy through ULK1/Beclin1 signaling and TFEB-dependent Beclin1 transcription. Taken together, these results suggest that the mechanisms by which DGKζ alleviates pathological cardiac hypertrophy may involve the regulation of Beclin1-mediated autophagy through the mTOR/TFEB signaling pathway.