Symmetric control of sister chromatid cohesion establishment.

Besides entrapping sister chromatids, cohesin drives other high-order chromosomal structural dynamics like looping, compartmentalization and condensation. ESCO2 acetylates a subset of cohesin so that cohesion must be established and only be established between nascent sister chromatids. How this process is precisely achieved remains unknown. Here, we report that GSK3 family kinases provide higher hierarchical control through an ESCO2 regulator, CRL4MMS22L. GSK3s phosphorylate Thr105 in MMS22L, resulting in homo-dimerization of CRL4MMS22L and ESCO2 during S phase as evidenced by single-molecule spectroscopy and several biochemical approaches. A single phospho-mimicking mutation on MMS22L (T105D) is sufficient to mediate their dimerization and rescue the cohesion defects caused by GSK3 or MMS22L depletion, whereas non-phosphorylable T105A exerts dominant-negative effects even in wildtype cells. Through cell fractionation and time-course measurements, we show that GSK3s facilitate the timely chromatin association of MMS22L and ESCO2 and subsequently SMC3 acetylation. The necessity of ESCO2 dimerization implicates symmetric control of cohesion establishment in eukaryotes.

In Situ Raman Spectroscopy Reveals Cytochrome c Redox-Controlled Modulation of Mitochondrial Membrane Permeabilization That Triggers Apoptosis.

The selective interaction of cytochrome c (Cyt c) with cardiolipin (CL) is involved in mitochondrial membrane permeabilization, an essential step for the release of apoptosis activators. The structural basis and modulatory mechanism are, however, poorly understood. Here, we report that Cyt c can induce CL peroxidation independent of reactive oxygen species, which is controlled by its redox states. The structural basis of the Cyt c-CL binding was unveiled by comprehensive spectroscopic investigation and mass spectrometry. The Cyt c-induced permeabilization and its effect on membrane collapse, pore formation, and budding are observed by confocal microscopy. Moreover, cytochrome c oxidase dysfunction is found to be associated with the initiation of Cyt c redox-controlled membrane permeabilization. These results verify the significance of a redox-dependent modulation mechanism at the early stage of apoptosis, which can be exploited for the design of cytochrome c oxidase-targeted apoptotic inducers in cancer therapy.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

BACKGROUND: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown. METHODS: Ischemic stroke was induced in wild-type (WT) or GPR65 knockout (GPR65-/-) mice by photothrombotic ischemia. Male mice were injected intraperitoneally with BTB09089 every other day at days 3, 7, or 14 poststroke. AAV-Syn-GPR65 (adenoassociated virus-synapsin-GPR65) was utilized to overexpress GPR65 in the peri-infarct cortical neurons of GPR65-/- and WT mice. Motor function was monitored by grid-walk and cylinder tests. The neurorestorative effects of BTB09089 were observed by immunohistochemistry, Golgi-Cox staining, and Western blotting. RESULTS: BTB09089 significantly promoted motor outcomes in WT but not in GPR65-/- mice, even when BTB09089 was delayed for 3 to 7 days. BTB09089 inhibited the activation of microglia and glial scar progression in WT but not in GPR65-/- mice. Meanwhile, BTB09089 reduced the decrease in neuronal density in WT mice, but this benefit was abolished in GPR65-/- mice and reemerged by overexpressing GPR65 in peri-infarct cortical neurons. Furthermore, BTB09089 increased the GAP43 (growth-associated protein-43) and synaptophysin puncta density, dendritic spine density, dendritic branch length, and dendritic complexity by overexpressing GPR65 in the peri-infarct cortical neurons of GPR65-/- mice, which was accompanied by increased levels of p-CREB (phosphorylated cAMP-responsive element-binding protein). In addition, the therapeutic window of BTB09089 was extended to day 14 by overexpressing GPR65 in the peri-infarct cortical neurons of WT mice. CONCLUSIONS: Our findings indicated that delayed BTB09089 treatment improved neurological functional recovery and brain tissue repair poststroke through activating neuronal GRP65. GPR65 overexpression may be a potential strategy to expand the therapeutic time window of GPR65 agonists for neurorehabilitation after ischemic stroke.

Spinel Nanostructures for the Hydrogenation of CO2 to Methanol and Hydrocarbon Chemicals.

Composite oxides have been widely applied in the hydrogenation of CO/CO2 to methanol or as the component of bifunctional oxide-zeolite for the synthesis of hydrocarbon chemicals. However, it is still challenging to disentangle the stepwise formation mechanism of CH3OH at working conditions and selectively convert CO2 to hydrocarbon chemicals with narrow distribution. Here, we investigate the reaction network of the hydrogenation of CO2 to methanol over a series of spinel oxides (AB2O4), among which the Zn-based nanostructures offer superior performance in methanol synthesis. Through a series of (quasi) in situ spectroscopic characterizations, we evidence that the dissociation of H2 tends to follow a heterolytic pathway and that hydrogenation ability can be regulated by the combination of Zn with Ga or Al. The coordinatively unsaturated metal sites over ZnAl2Ox and ZnGa2Ox originating from oxygen vacancies (OVs) are evidenced to be responsible for the dissociative adsorption and activation of CO2. The evolution of the reaction intermediates, including both carbonaceous and hydrogen species at high temperatures and pressures over the spinel oxides, has been experimentally elaborated at the atomic level. With the integration of a series of zeolites or zeotypes, high selectivities of hydrocarbon chemicals with narrow distributions can be directly produced from CO2 and H2, offering a promising route for CO2 utilization.

In Situ Monitoring of Membrane Protein Electron Transfer via Surface-Enhanced Resonance Raman Spectroscopy.

In situ analysis of membrane protein-ligand interactions under physiological conditions is of significance for both fundamental and applied science, but it is still a big challenge due to the limits in sensitivity and selectivity. Here, we demonstrate the potential of surface-enhanced resonance Raman spectroscopy (SERRS) for the investigation of membrane protein-protein interactions. Lipid biolayers are successfully coated on silver nanoparticles through electrostatic interactions, and a highly sensitive and biomimetic membrane platform is obtained in vitro. Self-assembly and immobilization of the reduced cytochrome b5 on the coated membrane are achieved and protein native biological functions are preserved. Owing to resonance effect, the Raman fingerprint of the immobilized cytochrome b5 redox center is selectively enhanced, allowing for in situ and real-time monitoring of the electron transfer process between cytochrome b5 and their partners, cytochrome c and myoglobin. This study provides a sensitive analytical approach for membrane proteins and paves the way for in situ exploration of their structural basis and functions.

Anisotropic Galvanomagnetic Effects in Single Cubic Crystals: A Theory and Its Verification.

A theory of anisotropic galvanomagnetic effects in single cubic crystals and its experimental verifications are presented for the current in the (001) plane. In contrast to the general belief that galvanomagnetic effects in single crystals are highly sensitive to many internal and external effects and have no universal features, the theory predicts universal angular dependencies of longitudinal and transverse resistivity and various characteristics when magnetization rotates in the (001) plane, the plane perpendicular to the current, and the plane containing the current and [001] direction. The universal angular dependencies are verified by experiments on Fe_{30}Co_{70} single cubic crystal film. The findings provide new avenues for fundamental research and applications of galvanomagnetic effects, because single crystals offer advantages over polycrystalline materials for band structure and crystallographic orientation engineering.

Subrelativistic Alternating Phase Focusing Dielectric Laser Accelerators.

We demonstrate a silicon-based electron accelerator that uses laser optical near fields to both accelerate and confine electrons over extended distances. Two dielectric laser accelerator (DLA) designs were tested, each consisting of two arrays of silicon pillars pumped symmetrically by pulse front tilted laser beams, designed for average acceleration gradients 35 and 50 MeV/m, respectively. The DLAs are designed to act as alternating phase focusing (APF) lattices, where electrons, depending on the electron-laser interaction phase, will alternate between opposing longitudinal and transverse focusing and defocusing forces. By incorporating fractional period drift sections that alter the synchronous phase between ±60° off crest, electrons captured in the designed acceleration bucket experience half the peak gradient as average gradient while also experiencing strong confinement forces that enable long interaction lengths. We demonstrate APF accelerators with interaction lengths up to 708 µm and energy gains up to 23.7±1.07 keV FWHM, a 25% increase from starting energy, demonstrating the ability to achieve substantial energy gains with subrelativistic DLA.

Visible Light-Induced 1,2-Diphenyldisulfane-Mediated Defluoroborylation of Polyfluoroarenes.

A green and practical protocol of defluoroborylation of polyfluoroarenes with stable and readily accessible NHC-borane was developed, using 1,2-diphenyldisulfane as a hydrogen atom transfer (HAT) and single electron transfer (SET) reagent precursor under visible-light irradiation, leading to the concise formation of value-added fluorinated organoboron scaffolds. Mechanism studies revealed the method underwent a boryl radical addition reaction with polyfluoroarene, followed by successive single electron transfer pathways and defluorination of the C-F bond to offer the targeted product. This unprecedented platform relies on 1,2-diphenyldisulfane and base without using expensive photocatalysts, highlighting the methodology has promising application value to prepare borylated polyfluoroarene compounds.

Meta-analysis of the association between interleukin-17 and ischemic cardiovascular disease.

BACKGROUND: Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD. METHODS: We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis. RESULTS: A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53-2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies. CONCLUSION: Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD.

Exposures to drinking water disinfection byproducts and kidney function in Chinese women.

BACKGROUND: Disinfection byproducts (DBPs), the ubiquitous contaminants in drinking water, have been shown to impair renal function in experimental studies. However, epidemiological evidence is sparse. OBJECTIVE: To investigate exposures to DBPs in associations with renal function among women. METHODS: A total of 920 women from December 2018 to January 2020 were abstracted from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort study in Wuhan, China. Urine samples were gathered at baseline recruitment and analyzed for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. Serum uric acid (UA), creatinine, and estimated glomerular filtration rate (eGFR) were measured as indicators of renal function. Multivariate linear regression and restricted cubic spline (RCS) models were conducted to assess urinary DCAA and TCAA concentrations in associations with renal function indicators. Stratified analyses by age and body mass index (BMI) were also performed. RESULTS: We found null evidence of urinary TCAA in associations with renal function indicators. However, elevated urinary DCAA tertiles were related to decreased eGFR (ß = -1.78%, 95% CI: 3.21%, -0.36%, comparing the upper vs. lower tertile; P for trend = 0.01). This inverse association still existed when urinary DCAA concentration was treated as a continuous variable, and the dose-response relationship was linear based on the RCS model (P for overall association = 0.002 and P for non-linear associations = 0.44). In the stratified analyses, we found an association of urinary DCAA concentration with decreased UA level among women <30 years but an association with increased UA level among women ≥30 years (P for interaction = 0.04). CONCLUSION: Urinary DCAA but not TCAA was associated with impaired renal function among women undergoing assisted reproductive technology.

CAR-T cell therapeutic avenue for fighting cardiac fibrosis: Roadblocks and perspectives.

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR-T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR-T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR-T cell therapy, and considers future outlooks for research development.

Knocking Down HN1 Blocks Helicobacter pylori-Induced Malignant Phenotypes in Gastric Mucosal Cells and Inhibits Gastric Cancer Cell Proliferation, Cytoskeleton Remodeling, and Migration.

Helicobacter pylori (H. pylori) is implicated in the aberrant proliferation and malignant transformation of gastric mucosal cells, heightening the risk of gastric cancer (GC). HN1 is involved in the development of various tumors. However, precise mechanistic underpinnings of HN1 promoting GC progression in H. pylori remain elusive. The study collected 79 tissue samples of GC patients, including 47 with H. pylori-positive GC and 32 H. pylori-negative controls. Using human gastric epithelial cells (GES-1) and human gastric adenocarcinoma cells (HGC-27), the effect of overexpression / knocking down of HN1 and H. pylori infection was evaluated on cell function (proliferation, migration, apoptosis), cytoskeleton, and expression of cell malignant phenotype factors that promote the malignant biological behavior of cancer cells. The expression of HN1 in GC tissues is higher than that in paracancerous tissue and is closely related to infiltration, lymphatic metastasis, distant metastasis, survival, and H. pylori infection. Downregulation of HN1 effectively hinders the ability of H. pylori strains 26695 and SS1 to promote migration of GES-1 and HGC-27 cells, while lowering the expression of key indicators associated with malignant phenotype. Downregulated GSK3B, ß-catenin, and Vimentin after knockdown Integrinß1, but HN1 expression remained largely unchanged, when HN1 and Integrinß1 were knocked down, GSK3B, ß-catenin, and Vimentin expression were considerably reduced. Our research demonstrated the crucial role of HN1 in H. pylori-induced acquisition of a malignant phenotype in GES-1 cells. Knockdown of HN1 blocked the pathogenic mechanism of H. pylori-induced GC and downregulated the expression of GSK3Β, ß-catenin and Vimentin via Integrin ß1.

Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Deep learning methods for fully automated dental age estimation on orthopantomograms.

OBJECTIVES: This study aimed to use all permanent teeth as the target and establish an automated dental age estimation method across all developmental stages of permanent teeth, accomplishing all the essential steps of tooth determination, tooth development staging, and dental age assessment. METHODS: A three-step framework for automatically estimating dental age was developed for children aged 3 to 15. First, a YOLOv3 network was employed to complete the tasks of tooth localization and numbering on a digital orthopantomogram. Second, a novel network named SOS-Net was established for accurate tooth development staging based on a modified Demirjian method. Finally, the dental age assessment procedure was carried out through a single-group meta-analysis utilizing the statistical data derived from our reference dataset. RESULTS: The performance tests showed that the one-stage YOLOv3 detection network attained an overall mean average precision 50 of 97.50 for tooth determination. The proposed SOS-Net method achieved an average tooth development staging accuracy of 82.97% for a full dentition. The dental age assessment validation test yielded an MAE of 0.72 years with a full dentition (excluding the third molars) as its input. CONCLUSIONS: The proposed automated framework enhances the dental age estimation process in a fast and standard manner, enabling the reference of any accessible population. CLINICAL RELEVANCE: The tooth development staging network can facilitate the precise identification of permanent teeth with abnormal growth, improving the effectiveness and comprehensiveness of dental diagnoses using pediatric orthopantomograms.

Effectiveness of abdominal sandbag training in enhancing diaphragm muscle function and exercise tolerance in patients with chronic respiratory failure.

BACKGROUND: Chronic respiratory failure is a common cause of ventilator dependence in the intensive care unit (ICU). The causes of chronic respiratory failure include primary disease or complications, such as ICU-acquired weakness. Traditional practice requires patients to remain immobile and bedridden; however, recent evidence suggests that early adequate exercise promotes recovery without increasing risks. In this study, we explored the efficacy of planned progressive abdominal sandbag training in promoting the successful withdrawal of patients with chronic respiratory failure from mechanical ventilation. METHODS: This study was conducted between April 2019 and November 2020. Patients were recruited and divided into two groups: abdominal sandbag training group and control group (no training). The training group participated in a 3-month daily pulmonary rehabilitation program, which involved a 30-min session of progressive sandbag loading on the upper abdomen as a form of diaphragmatic resistant exercise. The pressure support level of the ventilator was adjusted to maintain a tidal volume of 8 mL/kg. To investigate the effect of abdominal sandbag training on patients with chronic respiratory failure, we compared tidal volume, shallow breathing index, maximum respiratory pressure, and diaphragm characteristics between the training and control groups. RESULTS: This study included 31 patients; of them, 17 (54.8 %) received abdominal sandbag training and 14 (45.2 %) did not. No significant between-group difference was found in baseline characteristics. Compared with the control group, the training group exhibited considerable improvements in ventilation-related parameters (p < 0.001): the tidal volume markedly increased (p = 0.012), rapid shallow breathing index declined (p = 0.016), and maximum respiratory pressure increased (p < 0.001) in the training group. The diaphragm motion value (p = 0.048) and diaphragm thickness (p = 0.041) were greater in the training group than in the control group. Nine patients (52.9 %) in the training group were removed from the ventilator compared with 1 (7.1 %) in the control group (p = 0.008). CONCLUSIONS: Abdominal sandbag training may be beneficial for patients dependent on a ventilator. The training improves the function of the diaphragm muscle, thereby increasing tidal volume and reducing the respiratory rate and rapid shallow breathing index, thus facilitating withdrawal from ventilation. This training approach may also improve the thickness and motion of the diaphragm and the rate of ventilator detachment.

Effect of Protein Supplementation Combined With Resistance Training in Gait Speed in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We aimed to evaluate the effectiveness of the combination of protein supplementation and resistance training (RT), compared with RT alone or combined with a placebo, in improving gait speed. METHODS: We searched PubMed, Web of Science, Cochrane Library, and SPORTDiscus databases, and 18 randomized controlled trials with 1,147 older participants were included for meta-analysis. Data were pooled as the effect sizes (Hedges' g) with 95% confidence interval (CI) of the gait speed (in meters per second). The random-effect meta-analysis, subgroup analyses, meta-regression, and sensitivity analysis were conducted. RESULTS: The combination of protein supplementation and RT significantly improved gait speed (Hedges' g: 0.52 m/s, 95% confidence interval [0.17, 0.86], p = .005; I2 = 86.5%) compared with the RT alone. The subgroup analyses revealed that the significant improvement in gait speed postprotein intervention plus RT was observed only in participants who consumed protein after RT (Hedges' g: 0.90 m/s, 95% confidence interval [0.46, 1.33], p = .001; I2 = 79.6%). The pooled result did not significantly change after excluding any single study at one time or excluding smaller studies with large effect sizes. CONCLUSIONS: Protein supplementation combined with RT could significantly improve the gait speed of older adults compared with RT alone. This positive effect is more pronounced in people who consume protein after RT.

Magnetic superhydrophobic cellulose nanofibril based aerogel with rope-ladder like structure incorporating both superelasticity and excellent oil absorption.

Achieving an equilibrium between exceptional oil absorption and remarkable elasticity has emerged as a formidable challenge for magnetic porous materials designed for oil absorption. Here, we propose an original, magnetic and superhydrophobic cellulose nanofibril (CNF) based aerogel system with a rope-ladder like skeleton by to greatly improve the issue. Within this system, CNF as the skeleton was combined with multiwalled carbon nanotubes (MWCNT)@Fe3O4 as the magnetic and enhanced component, both methyltrimethoxysilane (MTMS) and acetonitrile-extracted lignin (AEL) as the soft-hard associating constituents. The resultant CNF based aerogel shows a rope-ladder like pore structure to contribute to high elasticity and excellent oil absorption (28.34-61.09 g/g for various oils and organic solvents) under the synergistic effect of Fe3O4@MWCNT, AEL and MTMS, as well as good specific surface area (27.97 m2/g), low density (26.4 mg/cm3). Notably, despite the introduced considerable proportion (0.5 times of mass-CNF) of Fe3O4@MWCNT, the aerogel retained an impressive compression-decompression rate (88%) and the oil absorption efficiency of above 87% for various oils due to the soft-hard associating structure supported by both MTMS and AEL. This study provides a prospective strategy to balance between high elasticity and excellent oil absorption of CNF based aerogel doping inorganic particles.

Effect of ultrasonic frequency on the structural and functional properties of pea protein isolation.

BACKGROUND: Pea protein, as a by-product of peas (Pisum sativum L.), is rich in a variety of essential amino acids that can meet the body's protein needs and is a valuable source of protein. Since the function of pea protein is closely related to its structure, pea protein has been subjected to different modifications in recent years to improve its application in food and to develop new products. RESULTS: The effects of sonication frequency (primary and secondary time) on pea protein isolate's (PPI's) structural and functional properties were investigated. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that different sonication frequencies at the same power (600 W) treatment had no effect on PPI's molecular weight. Fourier-transform infrared spectroscopy revealed that treatment at different sonication frequencies caused secondary structural changes in PPI. The particle size distribution, foaming, stability, surface hydrophobicity, emulsification, and oxidation resistance of PPI were improved after primary and secondary sonication, but secondary sonication was not more effective than primary sonication for an extended period of time. CONCLUSION: Overall, ultrasound is able to improve the structural and functional properties of pea proteins within a suitable range. It provides a theoretical basis for elucidating the modification of the structure and function of plant proteins by ultrasound and lays the foundation for the development of plant proteins in food applications as well as development. © 2023 Society of Chemical Industry.

Polar Aromatic Two-dimensional Dion-Jacobson Halide Perovskites for Efficient Photocatalytic H2 Evolution.

Polar materials with spontaneous polarization (Ps) have emerged as highly promising photocatalysts for efficient photocatalytic H2 evolution owing to the Ps-enhanced photogenerated carrier separation. However, traditional inorganic polar materials often suffer from limitations such as wide band gaps and poor carrier transport, which hinders their photocatalytic H2 evolution efficiency. Here, we rationally synthesized a series of isostructural two-dimensional (2D) aromatic Dion-Jacobson (DJ) perovskites, namely (2-(2-Aminoethyl)pyridinium)PbI4 (2-APDPI), (3-(2-Aminoethyl)pyridinium)PbI4 (3-APDPI), and (4-(2-Aminoethyl)pyridinium)PbI4 (4-APDPI), where 2-APDPI and 4-APDPI crystalize in polar space groups with piezoelectric constants (d33) of approximately 40 pm V-1 and 3-APDPI adopts a centrosymmetric structure. Strikingly, owing to the Ps-facilitated separation of photogenerated carriers, polar 2-APDPI and 4-APDPI exhibit a 3.9- and 2.8-fold increase, respectively, in photocatalytic H2 evolution compared to the centrosymmetric 3-APDPI. As a pioneering study, this work provides an efficient approach for exploring new polar photocatalysts and highlights their potential in promoting photocatalytic H2 evolution.

Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer.

BACKGROUND: Cancer-testis antigens (CTAs) are often expressed in tumor and testicular tissues but not in other normal tissues. To date, there has been no comprehensive study of the expression and clinical significance of CTA genes associated with endometrial cancer (EC) development. Additionally, the clinical relevance, biological role, and molecular mechanisms of the CTA gene TTK protein kinase (TTK) in EC are yet to be fully understood. METHODS: Using bioinformatics methods, we comprehensively investigated the genomic, transcriptomic, and epigenetic changes associated with aberrant TTK overexpression in EC samples from the TCGA database. We further investigated the mechanisms of the lower survival associated with TTK dysregulation using single-cell data of EC samples from the GEO database. Cell functional assays were used to confirm the biological roles of TTK in EC cells. RESULTS: We identified 80 CTA genes that were more abundant in EC than in normal tissues, and high expression of TTK was significantly linked with lower survival in EC patients. Furthermore, ROC analysis revealed that TTK could accurately distinguish stage I EC tissues from benign endometrial samples, suggesting that TTK has the potential to be a biomarker for early EC detection. We found TTK overexpression was more prevalent in EC patients with high-grade, advanced tumors, serous carcinoma, and TP53 alterations. Furthermore, in EC tissue, TTK expression showed a strong positive correlation with EMT-related genes. With single-cell transcriptome data, we identified a proliferative cell subpopulation with high expression of TTK and known epithelial-mesenchymal transition (EMT)-related genes and transcription factors. When proliferative cells were grouped according to TTK expression levels, the overexpressed genes in the TTKhigh group were shown to be functionally involved in the control of chemoresistance. Utilizing shRNA to repress TTK expression in EC cells resulted in substantial decreases in cell proliferation, invasion, EMT, and chemoresistance. Further research identified microRNA-21 (miR-21) as a key downstream regulator of TTK-induced EMT and chemoresistance. Finally, the TTK inhibitor AZ3146 was effective in reducing EC cell growth and invasion and enhancing the apoptosis of EC cells generated by paclitaxel. CONCLUSION: Our findings establish the clinical significance of TTK as a new biomarker for EC and an as-yet-unknown carcinogenic function. This present study proposes that the therapeutic targeting of TTK might provide a viable approach for the treatment of EC.