Targeting Degradation of the Transcription Factor C/EBPß Reduces Lung Fibrosis by Restoring Activity of the Ubiquitin-Editing Enzyme A20 in Macrophages.

Although recent progress provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung epithelial injury results in injury-repairing response and inflammation, which drive the development of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing progressive accumulation of the transcription factor C/EBPß in alveolar macrophages (AMs) from PF patients and mice, which upregulated a number of immunosuppressive and profibrotic factors promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3ß (GSK-3ß) interacted with and phosphorylated A20 to suppress C/EBPß degradation. Ectopic expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3ß interaction accelerated C/EBPß degradation and showed potent therapeutic efficacy against experimental PF. Our study indicates that a regulatory mechanism of the GSK-3ß-A20-C/EBPß axis in AMs may be a potential target for treating PF and fibroproliferative lung diseases.

Dissecting the dynamic cellular transcriptional atlas of adult teleost testis development throughout the annual reproductive cycle.

Teleost testis development during the annual cycle involves dramatic changes in cellular compositions and molecular events. In this study, the testicular cells derived from adult black rockfish at distinct stages - regressed, regenerating and differentiating - were meticulously dissected via single-cell transcriptome sequencing. A continuous developmental trajectory of spermatogenic cells, from spermatogonia to spermatids, was delineated, elucidating the molecular events involved in spermatogenesis. Subsequently, the dynamic regulation of gene expression associated with spermatogonia proliferation and differentiation was observed across spermatogonia subgroups and developmental stages. A bioenergetic transition from glycolysis to mitochondrial respiration of spermatogonia during the annual developmental cycle was demonstrated, and a deeper level of heterogeneity and molecular characteristics was revealed by re-clustering analysis. Additionally, the developmental trajectory of Sertoli cells was delineated, alongside the divergence of Leydig cells and macrophages. Moreover, the interaction network between testicular micro-environment somatic cells and spermatogenic cells was established. Overall, our study provides detailed information on both germ and somatic cells within teleost testes during the annual reproductive cycle, which lays the foundation for spermatogenesis regulation and germplasm preservation of endangered species.

Deciphering dynamic interactions between spermatozoa and the ovarian microenvironment through integrated multi-omics approaches in viviparous Sebastes schlegelii.

The ovarian microenvironment plays a crucial role in ensuring the reproductive success of viviparous teleosts. However, the molecular mechanism underlying the interaction between spermatozoa and the ovarian microenvironment has remained elusive. This study aimed to contribute to a better understanding of this process in black rockfish (Sebastes schlegelii) using integrated multi-omics approaches. The results demonstrated significant upregulation of ovarian complement-related proteins and pattern recognition receptors, along with remodeling of glycans on the surface of spermatozoa at the early spermatozoa-storage stage (1 month after mating). As spermatozoa were stored over time, ovarian complement proteins were progressively repressed by tryptophan and hippurate, indicating a remarkable adaptation of spermatozoa to the ovarian microenvironment. Before fertilization, a notable upregulation of cellular junction proteins was observed. The study revealed that spermatozoa bind to ZPB2a protein through GSTM3 and that ZPB2a promotes spermatozoa survival and movement in a GSTM3-dependent manner. These findings shed light on a key mechanism that influences the dynamics of spermatozoa in the female reproductive tract, providing valuable insights into the molecular networks regulating spermatozoa adaptation and survival in species with internal fertilization.

Liquid Metal-Polymer Conductor-Based Conformal Cyborg Devices.

Gallium-based liquid metal (LM) exhibits exceptional properties such as high conductivity and biocompatibility, rendering it highly valuable for the development of conformal bioelectronics. When combined with polymers, liquid metal-polymer conductors (MPC) offer a versatile platform for fabricating conformal cyborg devices, enabling functions such as sensing, restoration, and augmentation within the human body. This review focuses on the synthesis, fabrication, and application of MPC-based cyborg devices. The synthesis of functional materials based on LM and the fabrication techniques for MPC-based devices are elucidated. The review provides a comprehensive overview of MPC-based cyborg devices, encompassing their applications in sensing diverse signals, therapeutic interventions, and augmentation. The objective of this review is to serve as a valuable resource that bridges the gap between the fabrication of MPC-based conformal devices and their potential biomedical applications.

Electrically pumped topological laser with valley edge modes.

Quantum cascade lasers are compact, electrically pumped light sources in the technologically important mid-infrared and terahertz region of the electromagnetic spectrum1,2. Recently, the concept of topology3 has been expanded from condensed matter physics into photonics4, giving rise to a new type of lasing5-8 using topologically protected photonic modes that can efficiently bypass corners and defects4. Previous demonstrations of topological lasers have required an external laser source for optical pumping and have operated in the conventional optical frequency regime5-8. Here we demonstrate an electrically pumped terahertz quantum cascade laser based on topologically protected valley edge states9-11. Unlike topological lasers that rely on large-scale features to impart topological protection, our compact design makes use of the valley degree of freedom in photonic crystals10,11, analogous to two-dimensional gapped valleytronic materials12. Lasing with regularly spaced emission peaks occurs in a sharp-cornered triangular cavity, even if perturbations are introduced into the underlying structure, owing to the existence of topologically protected valley edge states that circulate around the cavity without experiencing localization. We probe the properties of the topological lasing modes by adding different outcouplers to the topological cavity. The laser based on valley edge states may open routes to the practical use of topological protection in electrically driven laser sources.

PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

Natural variation of domestication-related genes contributed to latitudinal expansion and adaptation in soybean.

Soybean is a major source of protein and edible oil worldwide. Originating from the Huang-Huai-Hai region, which has a temperate climate, soybean has adapted to a wide latitudinal gradient across China. However, the genetic mechanisms responsible for the widespread latitudinal adaptation in soybean, as well as the genetic basis, adaptive differentiation, and evolutionary implications of theses natural alleles, are currently lacking in comprehensive understanding. In this study, we examined the genetic variations of fourteen major gene loci controlling flowering and maturity in 103 wild species, 1048 landraces, and 1747 cultivated species. We found that E1, E3, FT2a, J, Tof11, Tof16, and Tof18 were favoured during soybean improvement and selection, which explained 75.5% of the flowering time phenotypic variation. These genetic variation was significantly associated with differences in latitude via the LFMM algorithm. Haplotype network and geographic distribution analysis suggested that gene combinations were associated with flowering time diversity contributed to the expansion of soybean, with more HapA clustering together when soybean moved to latitudes beyond 35°N. The geographical evolution model was developed to accurately predict the suitable planting zone for soybean varieties. Collectively, by integrating knowledge from genomics and haplotype classification, it was revealed that distinct gene combinations improve the adaptation of cultivated soybeans to different latitudes. This study provides insight into the genetic basis underlying the environmental adaptation of soybean accessions, which could contribute to a better understanding of the domestication history of soybean and facilitate soybean climate-smart molecular breeding for various environments.

Diagnostic Performance of Noninvasive Coronary Computed Tomography Angiography-Derived FFR for Coronary Lesion-Specific Ischemia Based on Deep Learning Analysis.

Background: The noninvasive computed tomography angiography-derived fractional flow reserve (CT-FFR) can be used to diagnose coronary ischemia. With advancements in associated software, the diagnostic capability of CT-FFR may have evolved. This study evaluates the effectiveness of a novel deep learning-based software in predicting coronary ischemia through CT-FFR. Methods: In this prospective study, 138 subjects with suspected or confirmed coronary artery disease were assessed. Following indication of 30%-90% stenosis on coronary computed tomography (CT) angiography, participants underwent invasive coronary angiography and fractional flow reserve (FFR) measurement. The diagnostic performance of the CT-FFR was determined using the FFR as the reference standard. Results: With a threshold of 0.80, the CT-FFR displayed an impressive diagnostic accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), positive predictive value (PPV), and negative predictive value (NPV) of 97.1%, 96.2%, 97.7%, 0.98, 96.2%, and 97.7%, respectively. At a 0.75 threshold, the CT-FFR showed a diagnostic accuracy, sensitivity, specificity, AUC, PPV, and NPV of 84.1%, 78.8%, 85.7%, 0.95, 63.4%, and 92.8%, respectively. The Bland-Altman analysis revealed a direct correlation between the CT-FFR and FFR (p < 0.001), without systematic differences (p = 0.085). Conclusions: The CT-FFR, empowered by novel deep learning software, demonstrates a strong correlation with the FFR, offering high clinical diagnostic accuracy for coronary ischemia. The results underline the potential of modern computational approaches in enhancing noninvasive coronary assessment.

Alkane-Strengthened Viscoelasticity in Micellar Solutions of Surface-Active Ionic Liquids and Their Potential Application in Enhanced Oil Recovery.

Wormlike micelles (WLMs) are highly sensitive to alkanes, resulting in structural destruction and loss of viscosity. Therefore, the study of WLMs against alkanes holds great significant importance. Surface-active ionic liquids have shown increasing promise for different situations for customizing molecular structures with the specialty of flexible functional assembly. In this paper, we found that WLMs constructed from the long-chain fatty acid surface-active ionic liquid (N,N-dimethylbenzylamine-oleic acid, abbreviated as BD-OA) exhibit strengthened viscoelasticity with the introduction of alkanes, expanding the resistance range to alkane damage. Here, the rheological behavior, microstructure, and dissipative particle dynamics (DPD) simulations of BD-OA WLMs were investigated at macro-, micro-, and mesoscopic scales, before (and after) the introduction of alkane. Our findings confirm the structural transformation of the micellar system from WLMs to lamellar micelles with higher viscoelasticity after alkane induction. The rearrangement of the micelle configuration may be attributed to the infiltration of alkane molecules into the fence layer formed by the BD-OA WLMs, leading to an increase in the boundary accumulation parameter and ultimately resulting in the formation of lower curvature lamellar micelles. More importantly, the against alkanes BD-OA WLMs have exhibited excellent in enhanced oil recovery, which has a promise for substituting common oil-displacing agents in tertiary oil recovery processes.

Good Cycling Stabilities of Sn/SnO2/C/S Composite Electrodes with Introduced Active Tin Atoms in Li-S Batteries.

Polysulfides are easily dissolved in the electrolyte of Li-S batteries after long cycles. Sn atom modification electrodes are beneficial for improving cycling stabilities of Li-S batteries. However, the influence of Sn atoms on the structure and electrochemical performance of SnO2/C composite materials is not explored. Sn/SnO2/C composite materials are developed as sulfur carriers in Li-S batteries in our work. In addition, the cycling stability mechanism of Sn/SnO2/C/S composite electrodes is also elucidated. Results show that introduced Sn/SnO2/C/S composite electrodes display good cycling stability (420.1 mAh·g-1 at 1C after 1000 cycles) in Li-S batteries. The sulfur load of Sn/SnO2/C/S composite electrodes is 80 wt % (2 mg-1·cm-2). The introduction of Sn into Sn/SnO2/C/S composite electrodes plays three roles. The first role is to enhance the structural stability of SnO2. The second role is to help adsorb active sulfur ions. The last role is to promote the electron transportation ability during the initial discharging/charging process. Sn/SnO2/C/S composite electrodes are beneficial for inhibiting the dissolution of polysulfides in electrolytes after long cycles.

Insights into the Efficient Release of the Polyacrylamide Drag Reducer via a pH-Responsive Inverse Polymer Emulsion.

The enormous demand for petroleum consumption has resulted in the shortage of fossil resources, prompting the need to explore unconventional reservoirs. Polyacrylamide emulsion drag reducers are capable of inhibiting the turbulence of fracturing fluids for enhancing the reservoir stimulation results, but the poor dissolution efficiency of polyacrylamide emulsion drag reducers is the primary limitation to their large-scale application. Here, a pH-responsive ionic liquid surfactant, oleic acid/cyclohexanediamine (HOA/HMDA), is synthesized by using oleic acid (HOA) and cyclohexanediamine (HMDA). HOA/HMDA shows a remarkable pH-responsive behavior due to the pH-induced deconstruction of the HOA/HMDA structure. Interestingly, the HOA/HMDA-stabilized monomer emulsion exhibits an obvious pH-induced emulsion structure transformation behavior. In addition, the HOA/HMDA-stabilized monomer emulsion possesses excellent dynamic and storage stability, supporting the inverse emulsion polymerization of the polymer P(AM/AMPS/AA). The obtained P(AM/AMPS/AA) polymer inverse emulsions maintained stability for 30 days. Our finding proposes that the structure of the P(AM/AMPS/AA) polymer inverse emulsions changes with pH stimulation, which is capable of facilitating the release of polymers. P(AM/AMPS/AA) is released from the P(AM/AMPS/AA) polymer inverse emulsions within 30 s at a pH value of 12.06, along with a drag reduction rate of 62.54%. Obviously, the HOA/HMDA-stabilized P(AM/AMPS/AA) polymer inverse emulsions eliminate the contradiction between the stability and release of polyacrylamide emulsion drag reducers, which is promising for meeting the demands of reservoir stimulation.

Genome-wide identification, characterization and expression profiling of TLR family genes in Chromileptesaltivelis.

Toll-like receptors (TLRs) represent a prominent category of pattern recognition receptors that have been extensively investigated for their pivotal role in combating pathogen incursions. Despite this, there has been a notable absence of comprehensive identification and exploration of the immune response associated with the TLR family genes in C. altivelis. This study successfully identified and named fourteen genes as Catlr1-1, Catlr1-2, Catlr2-1, Catlr2-2, Catlr3, Catlr5, Catlr7, Catlr8, Catlr9, Catlr13-1, Catlr13-2, Catlr18, Catlr21, and Catlr22. A series of bioinformatic analysis were performed, encompassing analysis of protein properties, examination of gene structures, evolutionary assessments, and prediction of protein tertiary structures. The expression patterns of Catlr genes were analyzed in five immune tissues: liver, spleen, kidney, gill, and intestine, in both healthy and bacterial stimulated-fish. The results showed that different tissue and different genes showed differed expression patterns after V. harveyi infection, indicating the involvement of all Catlr members in mounting immune responses following infection in various tissues. Additionally, histological evaluations of immune tissues unveiled varying levels of damage. In conclusion, this investigation into the TLR gene family offers novel information that contribute to a more profound comprehension of the immune response mechanisms in C. altivelis.

Exploring the underlying mechanisms of enteritis impact on golden pompano (Trachinotus ovatus) through multi-omics analysis.

Enteritis posed a significant health challenge to golden pompano (Trachinotus ovatus) populations. In this research, a comprehensive multi-omics strategy was implemented to elucidate the pathogenesis of enteritis by comparing both healthy and affected golden pompano. Histologically, enteritis was characterized by villi adhesion and increased clustering after inflammation. Analysis of the intestinal microbiota revealed a significant increase (P < 0.05) in the abundance of specific bacterial strains, including Photobacterium and Salinivibrio, in diseased fish compared to the healthy group. Metabolomic analysis identified 5479 altered metabolites, with significant impacts on terpenoid and polyketide metabolism, as well as lipid metabolism (P < 0.05). Additionally, the concentrations of several compounds such as calcitetrol, vitamin D2, arachidonic acid, and linoleic acid were significantly reduced in the intestines of diseased fish post-enteritis (P < 0.05), with the detection of harmful substances such as Efonidipine. In transcriptomic profiling, enteritis induced 68 upregulated and 73 downregulated genes, predominantly affecting steroid hormone receptor activity (P < 0.05). KEGG pathway enrichment analysis highlighted upregulation of SQLE and CYP51 in steroidogenesis, while the HSV-1 associated MHC1 gene exhibited significant downregulation. Integration of multi-omics results suggested a potential pathogenic mechanism: enteritis may have resulted from concurrent infection of harmful bacteria, specifically Photobacterium and Salinivibrio, along with HSV-1. Efonidipine production within the intestinal tract may have blocked certain calcium ion channels, leading to downregulation of MHC1 gene expression and reduced extracellular immune recognition. Upregulation of SQLE and CYP51 genes stimulated steroid hormone synthesis within cells, which, upon binding to G protein-coupled receptors, influenced calcium ion transport, inhibited immune activation reactions, and further reduced intracellular synthesis of anti-inflammatory substances like arachidonic acid. Ultimately, this cascade led to inflammation progression, weakened intestinal peristalsis, and villi adhesion. This study utilized multi-level omics detection to investigate the pathological symptoms of enteritis and proposed a plausible pathogenic mechanism, providing innovative insights into enteritis verification and treatment in offshore cage culture of golden pompano.

Si anode with high initial Coulombic efficiency, long cycle life, and superior rate capability by integrated utilization of graphene and pitch-based carbon.

A variety of strategies have been developed to enhance the cycling stability of Si-based anodes in lithium-ion batteries. Although significant progress has been made in enhancing the cycling stability of Si-based anodes, the low initial Coulombic efficiency (ICE) remains a significant challenge to their commercial application. Herein, pitch-based carbon (C) coated Si nanoparticles (NPs) were wrapped by graphene (G) to obtain Si@C/G composite with a small specific surface area of 11.3 m2g-1, resulting in a high ICE of 91.2% at 500 mA g-1. Moreover, the integrated utilization of graphene and soft carbon derived from the low-cost petroleum pitch strongly promotes the electrical conductivity, structure stability, and reaction kinetics of Si NPs. Consequently, the synthesized Si@C/G with a Si loading of 54.7% delivers large reversible capacity (1191 mAh g-1at 500 mA g-1), long cycle life over 200 cycles (a capacity retention of 87.1%), and superior rate capability (952 mAh g-1at 1500 mA g-1). When coupled with a homemade LiNi0.8Co0.1Mn0.1O2(NCM811) cathode in a full cell, it exhibits a promising cycling stability for 200 cycles. This work presents an innovative approach for the manufacture of Si-based anode materials with commercial application.

Rerouting phytosterol degradation pathway for directed androst-1,4-diene-3,17-dione microbial bioconversion.

Steroid-based drugs are now mainly produced by the microbial transformation of phytosterol, and a two-step bioprocess is adopted to reach high space-time yields, but byproducts are frequently observed during the bioprocessing. In this study, the catabolic switch between the C19- and C22-steroidal subpathways was investigated in resting cells of Mycobacterium neoaurum NRRL B-3805, and a dose-dependent transcriptional response toward the induction of phytosterol with increased concentrations was found in the putative node enzymes including ChoM2, KstD1, OpccR, Sal, and Hsd4A. Aldolase Sal presented a dominant role in the C22 steroidal side-chain cleavage, and the byproduct was eliminated after sequential deletion of opccR and sal. Meanwhile, the molar yield of androst-1,4-diene-3,17-dione (ADD) was increased from 59.4 to 71.3%. With the regard of insufficient activity of rate-limiting enzymes may also cause byproduct accumulation, a chromosomal integration platform for target gene overexpression was established supported by a strong promoter L2 combined with site-specific recombination in the engineered cell. Rate-limiting steps of ADD bioconversion were further characterized and overcome. Overexpression of the kstD1 gene further strengthened the bioconversion from AD to ADD. After subsequential optimization of the bioconversion system, the directed biotransformation route was developed and allowed up to 82.0% molar yield with a space-time yield of 4.22 g·L-1·day-1. The catabolic diversion elements and the genetic overexpression tools as confirmed and developed in present study offer new ideas of M. neoaurum cell factory development for directed biotransformation for C19- and C22-steroidal drug intermediates from phytosterol. KEY POINTS: • Resting cells exhibited a catabolic switch between the C19- and C22-steroidal subpathways. • The C22-steroidal byproduct was eliminated after sequential deletion of opccR and sal. • Rate-limiting steps were overcome by promoter engineering and chromosomal integration.

Rational design of ROS scavenging and fluorescent gold nanoparticles to deliver siRNA to improve plant resistance to Pseudomonas syringae.

Bacterial diseases are one of the most common issues that result in crop loss worldwide, and the increasing usage of chemical pesticides has caused the occurrence of resistance in pathogenic bacteria and environmental pollution problems. Nanomaterial mediated gene silencing is starting to display powerful efficiency and environmental friendliness for improving plant disease resistance. However, the internalization of nanomaterials and the physiological mechanisms behind nano-improved plant disease resistance are still rarely understood. We engineered the polyethyleneimine (PEI) functionalized gold nanoparticles (PEI-AuNPs) with fluorescent properties and ROS scavenging activity to act as siRNA delivery platforms. Besides the loading, protection, and delivery of nucleic acid molecules in plant mature leaf cells by PEI-AuNPs, its fluorescent property further enables the traceability of the distribution of the loaded nucleic acid molecules in cells. Additionally, the PEI-AuNPs-based RNAi delivery system successfully mediated the silencing of defense-regulated gene AtWRKY1. Compared to control plants, the silenced plants performed better resistance to Pseudomonas syringae, showing a reduced bacterial number, decreased ROS content, increased antioxidant enzyme activities, and improved chlorophyll fluorescence performance. Our results showed the advantages of AuNP-based RNAi technology in improving plant disease resistance, as well as the potential of plant nanobiotechnology to protect agricultural production.

Association between bacterial vaginosis with human papillomavirus in the United States (NHANES 2003-2004).

BACKGROUND: The balance of vaginal microecology is closely related to human papillomavirus (HPV) infection and cervical lesions. This study aims to investigate the relationship between bacterial vaginosis (BV) and HPV infection. METHODS: In total, 1,310 individuals from the National Health and Nutrition Examination Survey (NHANES, 2003-2004) were included in this study. Logistic regression and subgroup analyses were used to examine the association between BV and HPV infection. RESULTS: A significant positive association was observed between BV and HPV infection in women after adjustment for other confounders (OR = 1.47, 95% confidence interval [CI]: 1.15-1.88). In subgroup analyses, we have found this positive correlation was most prominent among Mexican Americans (OR = 1.83, 95% CI: 1.08-3.08) and non-Hispanic blacks (OR = 1.81, 95% CI: 1.08-3.04). CONCLUSIONS: This cross-sectional study demonstrated a positive association between BV and HPV infection in women.

Relationships between nine neuropsychiatric disorders and cervical cancer: insights from genetics, causality and shared gene expression patterns.

BACKGROUND: Neuropsychiatric disorders and cervical cancer exert substantial influences on women's health. Furthermore, neuropsychiatric disorders frequently manifest as common symptoms in cancer patients, potentially increasing the risk of malignant neoplasms. This study aimed to identify neuropsychiatric disorders that are genetically and causally related to cervical cancer and to investigate the molecular mechanisms underlying these associations. METHODS: GWAS data related to nine neuropsychiatric disorders, namely, schizophrenia, bipolar disorder, autism spectrum disorder, Parkinson's disease, anxiety, Alzheimer's disease, mood disorders, depression, and alcohol dependence, were obtained to calculate heritability (h2) and genetic correlation (rg) with cervical cancer using linkage disequilibrium score regression (LDSC). Mendelian randomization (MR) analysis of the two cohorts was employed to assess the causal effects. Shared gene expression pattern analysis was subsequently conducted to investigate the molecular mechanism underlying these significant associations. RESULTS: Anxiety, mood disorders, depression, and alcohol dependence were genetically correlated with cervical cancer (all adjusted P < 0.05). Only depression was causally related to cervical cancer in both the discovery (ORIVW: 1.41, PIVW = 0.02) and replication cohorts (ORIVW: 1.80, PIVW = 0.03) in the MR analysis. Gene expression pattern analysis revealed that 270 genes related to depression and cervical cancer, including tumour necrosis factor (TNF), were significantly upregulated in cervical cancer patients, while vascular endothelial growth factor A (VEGFA), transcription factor AP-1 (JUN), and insulin-like growth factor I (IGF-I) were associated with prognosis in cervical cancer patients (all P < 0.05). These overlapping genes implicated the involvement of multiple biological mechanisms, such as neuron death, the PI3K-Akt signalling pathway, and human papillomavirus infection. CONCLUSIONS: Genetic, causal and molecular evidence indicates that depression increases the risk of cervical cancer. The TNF, VEGFA, JUN, and IGF-1 genes and the neuron death, PI3K-Akt, and human papillomavirus infection signalling pathways may possibly explain this association.

SirT7-mediated transcription of fascin in hyperglycemic glomerular endothelial cells contributes to EndMT in diabetic nephropathy.

Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide. It is reported that the endothelial-to-mesenchymal transition (EndMT) in glomerular endothelial cells plays an important role in DN. As a specific form of epithelial-to-mesenchymal transition, EndMT may involve common regulators of epithelial-to-mesenchymal transition. Fascin has been shown to mediate epithelial-to-mesenchymal transition. In addition, SirT7 has been confir med to contribute to inflammation in hyperglycemic endothelial cells via the modulation of gene transcription. In this study, we speculate that SirT7 modulates fascin transcription and is thus involved in EndMT in hyperglycemic glomerular endothelial cells. Our data indicate that α-smooth muscle actin (α-SMA) and fascin levels are increased, while CD31 levels are decreased in the kidneys of DN rats. Consistently, our cellular experiments reveal that high glucose treatment elevates fascin levels and induces EndMT in human glomerular endothelial cells (HGECs). Moreover, silencing of fascin inhibits EndMT in hyperglycaemic HGECs. In addition, SirT7 is found to be decreased in hyperglycemic cells and in the kidneys of DN mice. Moreover, the inhibition of SirT7 increases fascin level and mediates EndMT. An increase in SirtT7 expression decreases fascin expression, inhibits EndMT, and improves renal function in hyperglycemic cells and DN mice. SirT7 is found to bind to the promoter region of fascin. In summary, the present study indicates that SirT7 transcribes fascin to contribute to hyperglycemia-induced EndMT in DN patients.

Deterministic Magnetization Switching via Tunable Noncollinear Spin Configurations in Canted Magnets.

Spin obit torque (SOT) driven magnetization switching has been used widely for encoding consumption-efficient memory and logic. However, symmetry breaking under a magnetic field is required to realize the deterministic switching in synthetic antiferromagnets with perpendicular magnetic anisotropy (PMA), which limits their potential applications. Herein, we report all electric-controlled magnetization switching in the antiferromagnetic Co/Ir/Co trilayers with vertical magnetic imbalance. Besides, the switching polarity could be reversed by optimizing the Ir thickness. By using the polarized neutron reflection (PNR) measurements, the canted noncollinear spin configuration was observed in Co/Ir/Co trilayers, which results from the competition of magnetic inhomogeneity. In addition, the asymmetric domain walls demonstrated by micromagnetic simulations result from introducing imbalance magnetism, leading to the deterministic magnetization switching in Co/Ir/Co trilayers. Our findings highlight a promising route to electric-controlled magnetism via tunable spin configuration, improve our understanding of physical mechanisms, and significantly promote industrial applications in spintronic devices.