Catalytic activity of violet phosphorus-based nanosystems and the role of metabolites in tumor therapy.

Although nanocatalytic medicine has demonstrated its advantages in tumor therapy, the outcomes heavily relie on substrate concentration and the metabolic pathways are still indistinct. We discover that violet phosphorus quantum dots (VPQDs) can catalyze the production of reactive oxygen species (ROS) without requiring external stimuli and the catalytic substrates are confirmed to be oxygen (O2) and hydrogen peroxide (H2O2) through the computational simulation and experiments. Considering the short of O2 and H2O2 at the tumor site, we utilize calcium peroxide (CaO2) to supply catalytic substrates for VPQDs and construct nanoparticles together with them, named VPCaNPs. VPCaNPs can induce oxidative stress in tumor cells, particularly characterized by a significant increase in hydroxyl radicals and superoxide radicals, which cause substantial damage to the structure and function of cells, ultimately leading to cell apoptosis. Intriguingly, O2 provided by CaO2 can degrade VPQDs slowly, and the degradation product, phosphate, as well as CaO2-generated calcium ions, can promote tumor calcification. Antitumor immune activation and less metastasis are also observed in VPCaNPs administrated animals. In conclusion, our study unveils the anti-tumor activity of VPQDs as catalysts for generating cytotoxic ROS and the degradation products can promote tumor calcification, providing a promising strategy for treating tumors.

Multiprobe Amplification (MPA) with Melting Curve Analysis: A Highly Stable and Cost-Effective Platform for the Simultaneous Detection of Eight Potential Bacterial Bioterrorism Agents in Complex Samples.

We aimed to develop an efficient detection platform that can identify a larger number of suspicious samples in a single test, saving time, manpower, and material costs, and providing vital support to the public health system in coping with the current challenging and dynamic bioterrorism threat landscape, particularly in regions of turmoil and conflict. We have successfully developed a high-throughput, multitarget fluorescent array detection platform by effectively combining integrating multiprobe amplification (MPA) with melting curve analysis. Specifically, we have established reliable laboratory testing methods for eight highly pathogenic bacteria, including Bacillus anthracis, Yersinia pestis, Brucella spp., Burkholderia pseudomallei, Francisella tularensis, Vibrio cholerae, Salmonella typhi, and Staphylococcus aureus. Our method achieves sensitive and specific simultaneous detection of eight target bacteria in one well by optimizing the reaction conditions of MPA. In the assessment of 192 simulated environmental samples, both positive and negative coincidence rates were 100.00%. Among 48 simulated clinical samples, the positive coincidence rate reached 97.73%, while maintaining a perfect negative coincidence rate of 100.00%. Moreover, the detection platform holds immense potential for attaining a more comprehensive bioterrorism screening, and its high cost-effectiveness enables the provision of diverse and adaptable diagnostic methods for public health quarantine in underdeveloped countries and regions.

Detection and severity assessment of obstructive sleep apnea according to deep learning of single-lead electrocardiogram signals.

Developing a convenient detection method is important for diagnosing and treating obstructive sleep apnea. Considering availability and medical reliability, we established a deep-learning model that uses single-lead electrocardiogram signals for obstructive sleep apnea detection and severity assessment. The detection model consisted of signal preprocessing, feature extraction, time-frequency domain information fusion, and classification segments. A total of 375 patients who underwent polysomnography were included. The single-lead electrocardiogram signals obtained by polysomnography were used to train, validate and test the model. Moreover, the proposed model performance on a public dataset was compared with the findings of previous studies. In the test set, the accuracy of per-segment and per-recording detection were 82.55% and 85.33%, respectively. The accuracy values for mild, moderate and severe obstructive sleep apnea were 69.33%, 74.67% and 85.33%, respectively. In the public dataset, the accuracy of per-segment detection was 91.66%. A Bland-Altman plot revealed the consistency of true apnea-hypopnea index and predicted apnea-hypopnea index. We confirmed the feasibility of single-lead electrocardiogram signals and deep-learning model for obstructive sleep apnea detection and severity evaluation in both hospital and public datasets. The detection performance is high for patients with obstructive sleep apnea, especially those with severe obstructive sleep apnea.

Health disparities in cervical cancer: Estimating geographic variations of disease burden and association with key socioeconomic and demographic factors in the US.

BACKGROUND: Despite advances in cervical cancer (CC) prevention, detection, and treatment in the US, health disparities persist, disproportionately affecting underserved populations or regions. This study analyzes the geographical distribution of both CC and recurrent/metastatic CC (r/mCC) in the US and explores potential risk factors of higher disease burden to inform potential strategies to address disparities in CC and r/mCC. METHODS: We estimated CC screening rates, as well as CC burden (number of patients with CC diagnosis per 100,000 eligible enrollees) and r/mCC burden (proportion of CC patients receiving systemic therapy not in conjunction with surgery or radiation), at the geographic level between 2017-2022 using administrative claims. Data on income and race/ethnicity were obtained from US Census Bureau's American Community Survey. Brachytherapy centers were proxies for guideline-conforming care for locally advanced CC. Associations among demographic, socioeconomic, and healthcare resource variables, with CC and r/mCC disease burden were assessed. RESULTS: Between 2017-2022, approximately 48,000 CC-diagnosed patients were identified, and approximately 10,000 initiated systemic therapy treatment. Both CC and r/mCC burden varied considerably across the US. Higher screening was significantly associated with lower CC burden only in the South. Lower income level was significantly associated with lower screening rates, higher CC and r/mCC burden. Higher proportion of Hispanic population was also associated with higher CC burden. The presence of ≥1 brachytherapy center in a region was significantly associated with a reduction in r/mCC burden (2.7%). CONCLUSION: CC and r/mCC disparities are an interplay of certain social determinants of health, behavior, and race/ethnicity. Our findings may inform targeted interventions for a geographic area, and further highlight the importance of guideline-conforming care to reduce disease burden.

Correlation of dietary inflammation index and dietary pattern with mild cognitive impairment in patients with type 2 diabetes.

OBJECTIVE: We aimed to determine the dietary patterns associated with mild cognitive impairment (MCI) in type 2 diabetes (T2DM) and the correlation of dietary inflammatory index (DII) with MCI. METHODS: The Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. A semi-quantitative food frequency questionnaire was used to collect dietary data and calculate DII. Dietary patterns were determined by reduced-rank regression (RRR), grouping dietary pattern scores and DII into quartiles, with logistic regression for correlation analysis. Dose-response relationships between dietary pattern scores, DII and diabetic MCI were explored using restricted cubic splines (RCS). A mediation analysis was performed to investigate whether DII mediates the association between dietary patterns and MCI. RESULTS: In the "Mediterranean-style dietary pattern", the multivariable-adjusted odds ratio of having MCI was 0.37 (95% CI: 0.20-0.68; p for trend=0.002) in the highest versus lowest quartiles of the dietary score. In the "high-meat and low-vegetable pattern", the multivariable-adjusted odds ratio of having MCI was 6.84 (95% CI: 3.58-13.10; p for trend<0.001) in the highest versus lowest quartiles of the dietary score. In the "Western-style dietary pattern", the multivariable-adjusted odds ratio of having MCI was 2.48 (95% CI: 1.38-4.46; p for trend=0.001). The multivariable-adjusted odds ratio of having MCI was 3.99 (95% CI: 2.14-7.42; p for trend<0.001) in the highest versus lowest quartiles of DII. There is a non-linear dose-response relationship between the "high-meat and low-vegetable pattern" score and the prevalence of MCI, as well as the DII and the prevalence of MCI. The DII partially mediated the impact of the "Mediterranean-style dietary pattern" and the "high-meat and low-vegetable pattern" on MCI. CONCLUSION: In T2DM patients, greater adherence to the "Mediterranean-style dietary pattern" is associated with a lower probability of having MCI. However, excessive consumption of meat, especially red meat and processed meat, combined with a lack of vegetable intake, is associated with a higher probability of having MCI. Greater adherence to the "Western-style dietary pattern" is associated with a higher probability of having MCI. In addition, a pro-inflammatory diet is associated with a higher probability of having MCI, and DII partially mediates the impact of dietary patterns on MCI.

Nuclear Quantum Effects Accelerate Charge Separation and Recombination in g-C3N4/TiO2 Heterojunctions.

We combined ring-polymer molecular dynamics (MD) and ab initio MD with nonadiabatic MD to study the effects of nuclear quantum effects (NQEs) on interlayer electron transfer and electron-hole recombination at the g-C3N4/TiO2 interface. Our simulations indicate that NQEs significantly affect electron transfer and electron-hole recombination dynamics, accelerating both processes. NQEs deform the g-C3N4 layer and expedite the movement of carbon and nitrogen atoms, thus, enhancing charge delocalization and interlayer coupling. This improved overlap between electronic state wave functions enhances nonadiabatic couplings, facilitating electron transfer and recombination. In addition to the enhanced nonadiabatic couplings accelerating electron transfer, the presence of NQEs narrows the energy gap and delays decoherence by mitigating overall fluctuations, because of restricted TiO2 movements overwhelming enhanced g-C3N4 fluctuations, thereby making the recombination faster. This work provides valuable insights into NQEs in light-element systems and contributes to guiding the development of highly efficient photocatalysts.

Visual Detection of LPS at the Femtomolar Level Based on Click Chemistry-Induced Gold Nanoparticles Electrokinetic Accumulation.

Lipopolysaccharide (LPS) presents a significant threat to human health. Herein, a novel method for detecting LPS was developed by coupling hybridization chain reaction (HCR), gold nanoparticles (AuNPs) agglutination (AA) triggered by a Cu(I)-catalyzed azide-alkyne cycloaddition click chemistry (CuAAC), and electrokinetic accumulation (EA) in a microfluidic chip, termed the HCR-AA-EA method. Thereinto, the LPS-binding aptamer (LBA) was coupled with the AuNP-coated Fe3O4 nanoparticle, which was connected with the polymer of H1 capped on CuO (H1-CuO) and H2-CuO. Upon LPS recognition by LBA, the polymers of H1- and H2-CuO were released into the solution, creating a "one LPS-multiple CuO" effect. Under ascorbic acid reduction, CuAAC was initiated between the alkyne and azide groups on the AuNPs' surface; then, the product was observed visually in the microchannel by EA. Finally, LPS was quantified by the integrated density of AuNP aggregates. The limit of detections were 29.9 and 127.2 fM for water samples and serum samples, respectively. The levels of LPS in the injections and serum samples by our method had a good correlation with those from the limulus amebocyte lysate test (r = 0.99), indicating high accuracy. Remarkably, to popularize our method, a low-cost, wall-power-free portable device was developed, enabling point-of-care testing.

RAAS in diabetic retinopathy: mechanisms and therapies.

Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.

Effects of flaxseed oil supplementation on metaphase II oocyte rates in IVF cycles with decreased ovarian reserve: a randomized controlled trial.

Background: This study was designed to explore the effects of flaxseed oil on the metaphase II (MII) oocyte rates in women with decreased ovarian reserve (DOR). Methods: The women with DOR were divided into a study group (n = 108, flaxseed oil treatment) and a control group (n = 110, no treatment). All patients were treated with assisted reproductive technology (ART). Subsequently, the ART stimulation cycle parameters, embryo transfer (ET) results, and clinical reproductive outcomes were recorded. The influencing factors affecting the MII oocyte rate were analyzed using univariate analysis and multivariate analysis. Results: Flaxseed oil reduced the recombinant human follicle-stimulating hormone (r-hFSH) dosage and stimulation time and increased the peak estradiol (E2) concentration in DOR women during ART treatment. The MII oocyte rate, fertilization rate, cleavage rate, high-quality embryo rate, and blastocyst formation rate were increased after flaxseed oil intervention. The embryo implantation rate of the study group was higher than that of the control group (p = 0.05). Additionally, the female age [odds ratio (OR): 0.609, 95% confidence interval (CI): 0.52-0.72, p < 0.01] was the hindering factor of MII oocyte rate, while anti-Müllerian hormone (AMH; OR: 100, 95% CI: 20.31-495, p < 0.01), peak E2 concentration (OR: 1.00, 95% CI: 1.00-1.00, p = 0.01), and the intake of flaxseed oil (OR: 2.51, 95% CI: 1.06-5.93, p = 0.04) were the promoting factors for MII oocyte rate. Conclusion: Flaxseed oil improved ovarian response and the quality of oocytes and embryos, thereby increasing the fertilization rate and high-quality embryo rate in DOR patients. The use of flaxseed oil was positively correlated with MII oocyte rate in women with DOR. Clinical trial number: https://www.chictr.org.cn/, identifier ChiCTR2300073785.

Purification, crystallization and preliminary crystallographic analysis of Chlamydophila pneumoniae AP endonuclease IV.

Base excision is a crucial DNA repair process mediated by endonuclease IV in nucleotide excision. In Chlamydia pneumoniae, CpendoIV is the exclusive AP endonuclease IV, exhibiting DNA replication error-proofreading capabilities, making it a promising target for anti-chlamydial drug development. Predicting the structure of CpendoIV, molecular docking with DNA was performed, analyzing complex binding sites and protein surface electrostatic potential. Comparative structural studies were conducted with E. coli EndoIV and DNA complex containing AP sites.CpendoIV was cloned, expressed in E. coli, and purified via Ni-NTA chelation and size-exclusion chromatography. Low NaCl concentrations induced aggregation during purification, while high concentrations enhanced purity.CpendoIV recognizes and cleaving AP sites on dsDNA, and Zn2+ influences the activity. Crystallization was achieved under 8% (v/v) Tacsimate pH 5.2, 25% (w/v) polyethylene glycol 3350, and 1.91 Å resolution X-ray diffraction data was obtained at 100 K. This research is significant for provides a deeper understanding of CpendoIV involvement in the base excision repair process, offering insights into Chlamydia pneumoniae.

Decoding epitranscriptomic regulation of viral infection: mapping of RNA N6-methyladenosine by advanced sequencing technologies.

Elucidating the intricate interactions between viral pathogens and host cellular machinery during infection is paramount for understanding pathogenic mechanisms and identifying potential therapeutic targets. The RNA modification N6-methyladenosine (m6A) has emerged as a significant factor influencing the trajectory of viral infections. Hence, the precise and quantitative mapping of m6A modifications in both host and viral RNA is pivotal to understanding its role during viral infection. With the rapid advancement of sequencing technologies, scientists are able to detect m6A modifications with various quantitative, high-resolution, transcriptome approaches. These technological strides have reignited research interest in m6A, underscoring its significance and prompting a deeper investigation into its dynamics during viral infections. This review provides a comprehensive overview of the historical evolution of m6A epitranscriptome sequencing technologies, highlights the latest developments in transcriptome-wide m6A mapping, and emphasizes the innovative technologies for detecting m6A modification. We further discuss the implications of these technologies for future research into the role of m6A in viral infections.

Functional analysis of the ube3a response in Japanese flounder (Paralichthys olivaceus) to CSBV infection.

Ube3a is a member of the E3 ubiquitin ligase HECTc family, and its role has been established in neurodevelopmental disorders. However, studies on its role in Japanese flounder are scarce. Thus, in this study, the ube3a of Japanese flounder was cloned, and its role in conferring resistance against Chinook salmon bafnivirus (CSBV) was analyzed. Japanese flounder ube3a encoded a protein containing 834 amino acids. Interestingly, its homology with the Atlantic halibut was determined to be 94%. In addition, there were differential expressions of ube3a in different tissues of Japanese flounder, with the highest expression level observed in the fin, followed by the gills and skin (P ≤ 0.05). Subcellular localization analysis revealed that Ube3a is a cytoplasmic protein. We established an in vitro CSBV infection model using Japanese flounder gill cell line (FG). After ube3a overexpression, the viral load was significantly lower than that of the control group (P ≤ 0.05). Contrastingly, after incubation of FG cells with an E3 ubiquitin ligase inhibitor, the viral load was significantly higher than in the control group (P ≤ 0.01). Then, the expression levels of nf-κb, traf3, and tnf-α after incubation with an E3 ubiquitin ligase inhibitor were examined. The results demonstrated that ube3a may exerted a significant antiviral effect in Japanese flounder via the ubiquitination pathway.

VGLUT2 and APP family: unraveling the neurobiochemical mechanisms of neurostimulation therapy to STZ-induced diabetes and neuropathy.

Diabetic Peripheral Neuropathy (DPN) poses an escalating threat to public health, profoundly impacting well-being and quality of life. Despite its rising prevalence, the pathogenesis of DPN remains enigmatic, and existing clinical interventions fall short of achieving meaningful reversals of the condition. Notably, neurostimulation techniques have shown promising efficacy in alleviating DPN symptoms, underscoring the imperative to elucidate the neurobiochemical mechanisms underlying DPN. This study employs an integrated multi-omics approach to explore DPN and its response to neurostimulation therapy. Our investigation unveiled a distinctive pattern of vesicular glutamate transporter 2 (VGLUT2) expression in DPN, rigorously confirmed through qPCR and Western blot analyses in DPN C57 mouse model induced by intraperitoneal Streptozotocin (STZ) injection. Additionally, combining microarray and qPCR methodologies, we revealed and substantiated variations in the expression of the Amyloid Precursor Protein (APP) family in STZ-induced DPN mice. Analyzing the transcriptomic dataset generated from neurostimulation therapy for DPN, we intricately explored the differential expression patterns of VGLUT2 and APPs. Through correlation analysis, protein-protein interaction predictions, and functional enrichment analyses, we predicted the key biological processes involving VGLUT2 and the APP family in the pathogenesis of DPN and during neurostimulation therapy. This comprehensive study not only advances our understanding of the pathogenesis of DPN but also provides a theoretical foundation for innovative strategies in neurostimulation therapy for DPN. The integration of multi-omics data facilitates a holistic view of the molecular intricacies of DPN, paving the way for more targeted and effective therapeutic interventions.

TET1 inhibits liver fibrosis by blocking hepatic stellate cell activation.

Hepatic stellate cells (HSCs) are critical regulator contributing to the onset and progression of liver fibrosis. Chronic liver injury triggers HSCs to undergo vast changes and trans-differentiation into a myofibroblast HSCs, the mechanism remains to be elucidated. This study investigated that the involvement of hydroxymethylase TET1 (ten-eleven translocation 1) in HSC activation and liver fibrosis. It is revealed that TET1 levels were downregulated in the livers in mouse models of liver fibrosis and patients with cirrhosis, as well as activated HSCs in comparison to quiescent HSCs. In vitro data showed that the inhibition of TET1 promoted the activation HSC, whereas TET1 overexpression inhibited HSC activation. Moreover, TET1 could regulate KLF2 (Kruppel-like transcription factors) transcription by promoting hydroxymethylation of its promoter, which in turn suppressed the activation of HSCs. In vivo, it is confirmed that liver fibrosis was aggravated in Tet1 knockout mice after CCl4 injection, accompanied by excessive activation of primary stellate cells, in contrast to wild-type mice. In conclusion, we suggested that TET1 plays a significant role in HSC activation and liver fibrosis, which provides a promising target for anti-fibrotic therapies.

SST: a snore shifted-window transformer method for potential obstructive sleep apnea patient diagnosis.

Objective.Obstructive sleep apnea (OSA) is a high-incidence disease that is seriously harmful and potentially dangerous. The objective of this study was to develop a noncontact sleep audio signal-based method for diagnosing potential OSA patients, aiming to provide a more convenient diagnostic approach compared to the traditional polysomnography (PSG) testing.Approach.The study employed a shifted window transformer model to detect snoring audio signals from whole-night sleep audio. First, a snoring detection model was trained on large-scale audio datasets. Subsequently, the deep feature statistical metrics of the detected snore audio were used to train a random forest classifier for OSA patient diagnosis.Main results.Using a self-collected dataset of 305 potential OSA patients, the proposed snore shifted-window transformer method (SST) achieved an accuracy of 85.9%, a sensitivity of 85.3%, and a precision of 85.6% in OSA patient classification. These values surpassed the state-of-the-art method by 9.7%, 10.7%, and 7.9%, respectively.Significance.The experimental results demonstrated that SST significantly improved the noncontact audio-based OSA diagnosis performance. The study's findings suggest a promising self-diagnosis method for potential OSA patients, potentially reducing the need for invasive and inconvenient diagnostic procedures.

INSM1 expression in primary and metastatic neuroendocrine neoplasms at distinct locations.

BACKGROUND: Insulinoma-associated protein 1 (INSM1) has been reported as a valuable marker for neuroendocrine neoplasms (NENs). The aims of this study were to evaluate any change in INSM1 expression between primary and metastatic NENs in distinct locations, as well as the expression of INSM1 at different differentiation levels. Furthermore, we would also investigate the significance of INSM1 expression in non-neuroendocrine neoplasms (non-NENs). METHODS: We collected 78 cases with primary NENs and 16 cases with metastatic NENs. An addition 7 cases of non-NENs with neuroendocrine (NE) differentiation and 84 cases of other non-NENs, respectively, were included as controls. RESULTS: In our cohort, 82% of primary NENs and 88% of metastatic NENs expressed INSM1 with no difference between them. There was no difference in the expression of INSM1 in the lung and digestive system, and its staining pattern was independent of tumor differentiation or location. The proportion of INSM1 -positive in non-NENs with NE differentiation was significantly higher than that in other non-NENs. INSM1 sensitivity for primary NENs (82%) was comparable to Chromogranin A (82%), less than that of Synaptophysin (96%) and CD56 (94%); specificity was higher (96% vs 94%, 82%, and 89%, respectively). The sensitivity of INSM1 for well differentiated NENs was significantly higher than that of poorly differentiated NENs (100% vs 79%). CONCLUSIONS: INSM1 is a useful neuroendocrine marker in primary and metastatic NENs, helping to identify primary NENs with different degrees of differentiation. The expression of INSM1 was independent of tumor location. It should be with caution to interpret the expression of INSM1 in non-NENs that morphologically resemble NENs.

Pediococcus acidilactici reduces tau pathology and ameliorates behavioral deficits in models of neurodegenerative disorders.

BACKGROUND: Alzheimer's disease (AD), affecting many elders worldwide, is characterized by A-beta and tau-related cognitive decline. Accumulating evidence suggests that brain iron accumulation is an important characteristic of AD. However, the function and mechanism of the iron-mediated gut-brain axis on AD is still unclear. METHODS: A Caenorhabditis elegans model with tau-overexpression and a high-Fe diet mouse model of cognitive impairment was used for probiotic function evaluation. With the use of qPCR, and immunoblotting, the probiotic regulated differential expression of AD markers and iron related transporting genes was determined. Colorimetric kits, IHC staining, and immunofluorescence have been performed to explore the probiotic mechanism on the development of gut-brain links and brain iron accumulation. RESULTS: In the present study, a high-Fe diet mouse model was used for evaluation in which cognitive impairment, higher A-beta, tau and phosphorylated (p)-tau expression, and dysfunctional phosphate distribution were observed. Considering the close crosstalk between intestine and brain, probiotics were then employed to delay the process of cognitive impairment in the HFe mouse model. Pediococcus acidilactici (PA), but not Bacillus subtilis (BN) administration in HFe-fed mice reduced brain iron accumulation, enhanced global alkaline phosphatase (AP) activity, accelerated dephosphorylation, lowered phosphate levels and increased brain urate production. In addition, because PA regulated cognitive behavior in HFe fed mice, we used the transgenic Caenorhabditis elegans with over-expressed human p-tau for model, and then PA fed worms became more active and longer lived than E.coli fed worms, as well as p-tau was down-regulated. These results suggest that brain iron accumulation influences AD risk proteins and various metabolites. Furthermore, PA was shown to reverse tau-induced pathogenesis via iron transporters and AP-urate interaction. CONCLUSIONS: PA administration studies demonstrate that PA is an important mediator of tau protein reduction, p-tau expression and neurodegenerative behavior both in Caenorhabditis elegans and iron-overload mice. Finally, our results provide candidates for AP modulation strategies as preventive tools for promoting brain health. Video Abstract.

A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation.

The Hippo pathway has important roles in organ development, tissue homeostasis and tumour growth. Its downstream effector TAZ is a transcriptional coactivator that promotes target gene expression through the formation of biomolecular condensates. However, the mechanisms that regulate the biophysical properties of TAZ condensates to enable Hippo signalling are not well understood. Here using chemical crosslinking combined with an unbiased proteomics approach, we show that FUS associates with TAZ condensates and exerts a chaperone-like effect to maintain their proper liquidity and robust transcriptional activity. Mechanistically, the low complexity sequence domain of FUS targets the coiled-coil domain of TAZ in a phosphorylation-regulated manner, which ensures the liquidity and dynamicity of TAZ condensates. In cells lacking FUS, TAZ condensates transition into gel-like or solid-like assembles with immobilized TAZ, which leads to reduced expression of target genes and inhibition of pro-tumorigenic activity. Thus, our findings identify a chaperone-like function of FUS in Hippo regulation and demonstrate that appropriate biophysical properties of transcriptional condensates are essential for gene activation.

Insulin resistance is associated with the presence and severity of retinopathy in patients with type 2 diabetes.

BACKGROUND: To assess the relationship between novel insulin resistance (IR) indices and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: This is a cross-sectional study involving 2211 patients. The study outcomes were DR events. The study exposures were IR indices including estimated glucose disposal rate (eGDR), natural logarithm of glucose disposal rate (lnGDR), metabolic insulin resistance score (METS-IR), triglyceride glucose index-body mass index (TyG-BMI), triglyceride glucose index-waist-to-hip ratio (TyG-WHR), and triglyceride/high-density lipoprotein cholesterol(TG/HDL-c ratio). We used binary and multivariate ordered logistic regression models to estimate the association between different IR indices and the presence and severity of DR. Subject work characteristic curves were used to assess the predictive power of different IR indices for DR. RESULTS: DR was present in 25.4% of participants. After adjusting for all covariates, per standard deviation (SD) increases in eGDR (ratio [OR] 0.38 [95% CI 0.32-0.44]), lnGDR (0.34 [0.27-0.42]) were negatively associated with the presence of DR. In contrast, per SD increases in METS-IR (1.97 [1.70-2.28]), TyG-BMI (1.94 [1.68-2.25]), TyG-WHR (2.34 [2.01-2.72]) and TG/HDL-c ratio (1.21 [1.08-1.36]) were positively associated with the presence of DR. eGDR was strongly associated with severity of DR. Of all variables, eGDR had the strongest diagnostic value for DR (AUC = 0.757). CONCLUSIONS: Of the six IR indices, eGDR was significantly associated with the presence and severity of DR in patients with type 2 diabetes. eGDR has a good predictive value for DR. Thus, eGDR maybe a stronger marker of DR.

Resolving the Puzzle of Charge Carrier Lifetime in ZnO by Revisiting the Role of Oxygen Vacancy.

Zinc oxide (ZnO) is a wide bandgap prototypical n-type semiconductor due to the presence of intrinsic oxygen vacancies (VO). The VO can readily transfer to the most energetically favorable +2 charged VO (VO2+) by losing two electrons mediated by the metastable VO1+ defect. Nevertheless, the influence of charged VO on the charge dynamics in ZnO and the underlying mechanisms remain elusive. By performing nonadiabatic molecular dynamics simulations of the charge trapping and recombination processes, we show that both VO1+ and VO2+ slow down the nonradiative electron-hole recombination via assisted defect states and, thus, extending charge carrier lifetime compared to pristine ZnO. Our study contributes to identifying the different recombination pathways that take place in VO1+ and VO2+ of n-type ZnO systems, providing useful guidance for designing high-performance ZnO-based devices.