First-principles studies on the electronic and contact properties of monolayer Ga2STe-metal contacts.

Monolayer (ML) Janus III-VI compounds have attracted the use of multiple competitive platforms for future-generation functional electronics, including non-volatile memories, field effect transistors, and sensors. In this work, the electronic and interfacial properties of ML Ga2STe-metal (Au, Ag, Cu, and Al) contacts are systematically investigated using first-principles calculations combined with the non-equilibrium Green's function method. The ML Ga2STe-Au/Ag/Al contacts exhibit weak electronic orbital hybridization at the interface, while the ML Ga2STe-Cu contact exhibits strong electronic orbital hybridization. The Te surface is more conducive to electron injection than the S surface in ML Ga2STe-metal contact. Quantum transport calculations revealed that when the Te side of the ML Ga2STe is in contact with Au, Ag and Cu electrodes, p-type Schottky contacts are formed. When in contact with the Al electrode, an n-type Schottky contact is formed with an electron SBH of 0.079 eV. When the S side of ML Ga2STe is in contact with Au and Al electrodes, p-type Schottky contacts are formed, and when it is in contact with Ag and Cu electrodes, n-type Schottky contacts are formed. Our study will guide the selection of appropriate metal electrodes for constructing ML Ga2STe devices.

Oxidative stress-induced neurotoxicity of quantum dots and influencing factors.

Quantum dots (QDs) have significant potential for treating and diagnosing CNS diseases. Meanwhile, the neurotoxicity of QDs has garnered attention. In this review, we focus on elucidating the mechanisms and consequences of CNS oxidative stress induced by QDs. First, we discussed the pathway of QDs transit into the brain. We then elucidate the relationship between QDs and oxidative stress from in vivo and in vitro studies. Furthermore, the main reasons and adverse outcomes of QDs leading to oxidative stress are discussed. In addition, the primary factors that may affect the neurotoxicity of QDs are analyzed. Finally, we propose potential strategies for mitigating QDs neurotoxicity and outline future perspectives for their development.

Oxymatrine alleviates high-fat diet/streptozotocin-induced non-alcoholic fatty liver disease in C57BL/6 J mice by modulating oxidative stress, inflammation and fibrosis.

Non-alcoholic fatty liver disease (NAFLD) represents a complex complication of type 2 diabetes mellitus (T2DM). Oxymatrine (OMT) is an alkaloid extracted from Sophora flavescens with broad pharmacological effects. However, there is currently a lack of research on OMT in the field of NAFLD. The present study aimed to explore the effects and underlying mechanisms of oxymatrine in treating T2DM with NAFLD. The T2DM mice model was induced by high-fat diet (HFD) combined with streptozotocin (STZ) injection in male C57BL/6 J mice. Animals were randomly divided into four groups (n = 8): Control group, DC group, OMT-L group (45 mg/kg i.g.), and OMT-H group (90 mg/kg, i.g.). The drug was administered once a day for 8 weeks. In addition, HepG2 hepatocytes were incubated with palmitic acid (PA) to establish a fatty liver cell model. Treated with OMT, the body weight and fasting blood glucose (FBG) of DC mice were reduced and the liver organ coefficient was significantly optimized. Meanwhile, OMT markedly enhanced the activities of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and also reduced malondialdehyde (MDA) levels. These biochemical alterations were accompanied by noticeable improvements in liver histopathology. Furthermore, OMT down-regulated the expression of NOD-like receptor protein 3 (NLRP3), interleukin-1ß (IL-1ß), transforming growth factor-ß1 (TGF-ß1) and collagen I significantly, highlighting its potential in modulating inflammatory and fibrotic pathways. In conclusion, OMT improved liver impairment effectively in diabetic mice by suppressing oxidative stress, inflammation and fibrosis. These results suggest that OMT may represent a novel therapy for NAFLD with diabetes.

Symptom and comorbidity burden in hypertensive patients with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is an important but frequently overlooked risk factor for hypertension (HTN). The prevalence of hypertension is high in patients with OSA, but the differences in clinical symptoms and comorbidities between patients with OSA with hypertension and those with normal blood pressure have not been fully defined. Methods: This study retrospectively analyzed OSA patients diagnosed for the first time in Lihuili Hospital Affiliated to Ningbo University from 2016 to 2020. Patients were divided into an OSA group with hypertension and an OSA group without hypertension. The sociodemographic information, clinical symptoms, comorbidities, and polysomnography results of the two groups were compared. The independent risk factors associated with hypertension in patients with OSA were explored. Results: A total of 1108 patients with OSA initially diagnosed were included in the study, including 387 with hypertension and 721 without. Compared with OSA patients without hypertension, OSA patients with hypertension were older; had a higher body mass index (BMI) and Epworth sleepiness score (ESS); a higher incidence of nocturia; and a higher proportion of diabetes mellitus, coronary heart disease, and cerebrovascular disease. Multivariate analysis showed age (odds ratio [OR]:1.06, 95% confidence interval [CI]:1.04-1.08), BMI (OR:1.17, 95% CI:1.11-1.23), ESS score (OR:0.97, 95%CI: 0.94-1.00) and nocturia symptoms (OR:1.64, 95% CI:1.19-2.27) was independently associated with hypertension in OSA patients, and comorbid diabetes (OR: 3.86, 95% CI: 2.31-6.45), coronary heart disease (OR: 1.90, 95% CI:1.15-3.16), and ischemic stroke (OR: 3.69,95% CI:1.31-10.40) was independently associated with hypertension in OSA patients. Conclusion: Compared to OSA patients with normal blood pressure, OSA patients with hypertension had more significant daytime sleepiness, more frequent nocturnal urination, and a higher risk of diabetes, coronary heart disease, and cerebrovascular disease.

Changes in serum inflammatory factors after hip arthroplasty and analysis of risk factors for prosthesis loosening.

OBJECTIVE: To explore the relationship of serum levels of IL-1ß, IL-6, and TNF-α with prosthesis loosening after hip arthroplasty, and to establish a predictive model for prosthesis loosening. METHODS: We retrospectively analyzed the data of 501 patients who underwent hip arthroplasty in Xi'an International Medical Center Hospital from January 2020 to August 2022. Based on radiological diagnosis, the patients were divided into a prosthesis loosening group and a non-loosening group. Clinical data including postoperative serum levels of inflammatory cytokines were collected. Univariant analysis, Lasso regression, decision tree, and random forest models were used to screen feature variables. Based on the screening results, a nomogram model for predicting the risk of prosthesis loosening was established and then validated using ROC curve, and calibration curve, and other methods. RESULTS: There were 50 cases in the loosening group and 451 cases in the non-loosening group. Postoperative levels of IL-1ß, IL-6, and TNF-α were found to be significantly higher in the loosening group (P<0.0001). Univariant analysis showed that osteoporosis and postoperative infection were risk factors for prosthesis loosening (P<0.001). The machine learning algorithm identified osteoporosis, postoperative infection, IL-1ß, IL-6, and TNF-α as 5 relevant variables. The predictive model based on these 5 variables exhibited an area under the ROC curve of 0.763. The calibration curve and DCA curve verified the accuracy and practicality of the model. CONCLUSION: Serum levels of IL-1ß, IL-6, and TNF-α were significantly elevated in patients with postoperative prosthesis loosening. Osteoporosis, postoperative infection, and inflammatory cytokines are independent risk factors for prosthesis loosening. The predictive model we established through machine learning can effectively determine the risk of prosthesis loosening. Monitoring inflammatory cytokines and postoperative infections, combined with prevention of osteoporosis, can help reduce the risk of prosthesis loosening.

[Analysis of Spatio-temporal Distribution Characteristics and Influencing Factors of PM2.5 Concentration in Urban Agglomerations on the Northern Slope of Tianshan Mountains].

Analysis of the spatial and temporal distribution characteristics and influencing factors of PM2.5 concentrations for the urban agglomeration on the northern slope of Tianshan Mountain is of positive significance for regional economic construction and environmental protection. The spatial and temporal distributions of PM2.5 concentrations in the Tianshan North Slope urban agglomeration from March to November 2015 to 2021 were obtained through the inversion of the MCD19A2 aerosol product combined with meteorological factors using a geographically weighted regression (GWR) model, followed by the analysis of change trends and influencing factors. The results were as follows:① the high PM2.5 concentrations in the study area were mainly distributed in the oasis city cluster between the northern foot of Tianshan Mountain and the Gurbantunggut Desert, showing the spatial distribution characteristics of being "low around and high in the middle" and "low in the west and high in the east." The annual average value of ρ(PM2.5) in the study area was 16.98 µg·m-3, with high values mainly concentrated in the urban part of Urumqi and decreasing towards Changji and Fukang. The monthly average ρ(PM2.5) distribution pattern was consistent with the annual average, but there were seasonal differences as follows:autumn (20.32 µg·m-3) > spring (18.25 µg·m-3) > summer (12.47 µg·m-3). The accumulation phenomenon was more pronounced in spring and winter. ② The study area's annual average PM2.5 concentration showed a decreasing trend from 2015 to 2021, and the average value from March to October also showed a decreasing trend, with only a slight increase in November. From the analysis of the spatial distribution of PM2.5 concentration trends, the decrease was concentrated in the urban parts of major cities, especially in the urban part of Urumqi and its surrounding areas, where the decrease was the largest and the change was the most drastic. ③ Temperature and air pressure were positively correlated with PM2.5 concentrations, whereas relative humidity, wind speed, atmospheric boundary layer height, and precipitation were negatively correlated with PM2.5 concentrations. The degree of influence of each factor was ranked from high to low as follows:atmospheric boundary layer height > relative humidity > air pressure > air temperature > wind speed > precipitation.

A hollow Ag/AgCl nanoelectrode for single-cell chloride detection.

This work reports the construction of a miniaturized Ag/AgCl nanoelectrode on a nanopipette, which is capable of dual-functions of single-cell drug infusion and chloride detection and is envisioned to promote the study of chloride-correlated therapeutic effects.

Computational dissection of genetic variation modulating the response of multiple photosynthetic phenotypes to the light environment.

BACKGROUND: The expression of biological traits is modulated by genetics as well as the environment, and the level of influence exerted by the latter may vary across characteristics. Photosynthetic traits in plants are complex quantitative traits that are regulated by both endogenous genetic factors and external environmental factors such as light intensity and CO2 concentration. The specific processes impacted occur dynamically and continuously as the growth of plants changes. Although studies have been conducted to explore the genetic regulatory mechanisms of individual photosynthetic traits or to evaluate the effects of certain environmental variables on photosynthetic traits, the systematic impact of environmental variables on the dynamic process of integrated plant growth and development has not been fully elucidated. RESULTS: In this paper, we proposed a research framework to investigate the genetic mechanism of high-dimensional complex photosynthetic traits in response to the light environment at the genome level. We established a set of high-dimensional equations incorporating environmental regulators to integrate functional mapping and dynamic screening of gene‒environment complex systems to elucidate the process and pattern of intrinsic genetic regulatory mechanisms of three types of photosynthetic phenotypes of Populus simonii that varied with light intensity. Furthermore, a network structure was established to elucidate the crosstalk among significant QTLs that regulate photosynthetic phenotypic systems. Additionally, the detection of key QTLs governing the response of multiple phenotypes to the light environment, coupled with the intrinsic differences in genotype expression, provides valuable insights into the regulatory mechanisms that drive the transition of photosynthetic activity and photoprotection in the face of varying light intensity gradients. CONCLUSIONS: This paper offers a comprehensive approach to unraveling the genetic architecture of multidimensional variations in photosynthetic phenotypes, considering the combined impact of integrated environmental factors from multiple perspectives.

Genome-Wide Network Analysis of Above- and Below-Ground Co-growth in Populus euphratica.

Tree growth is the consequence of developmental interactions between above- and below-ground compartments. However, a comprehensive view of the genetic architecture of growth as a cohesive whole is poorly understood. We propose a systems biology approach for mapping growth trajectories in genome-wide association studies viewing growth as a complex (phenotypic) system in which above- and below-ground components (or traits) interact with each other to mediate systems behavior. We further assume that trait-trait interactions are controlled by a genetic system composed of many different interactive genes and integrate the Lotka-Volterra predator-prey model to dissect phenotypic and genetic systems into pleiotropic and epistatic interaction components by which the detailed genetic mechanism of above- and below-ground co-growth can be charted. We apply the approach to analyze linkage mapping data of Populus euphratica, which is the only tree species that can grow in the desert, and characterize several loci that govern how above- and below-ground growth is cooperated or competed over development. We reconstruct multilayer and multiplex genetic interactome networks for the developmental trajectories of each trait and their developmental covariation. Many significant loci and epistatic effects detected can be annotated to candidate genes for growth and developmental processes. The results from our model may potentially be useful for marker-assisted selection and genetic editing in applied tree breeding programs. The model provides a general tool to characterize a complete picture of pleiotropic and epistatic genetic architecture in growth traits in forest trees and any other organisms.

The Global Leadership Initiative on Malnutrition criteria for diagnosis of malnutrition and outcomes prediction in emergency abdominal surgery.

OBJECTIVES: Malnutrition has adverse postoperative outcomes, especially in emergency surgery. Among the numerous tools for nutritional assessment, this study aims to investigate malnutrition diagnosed by Global Leadership Initiative on Malnutrition criteria and the Global Leadership Initiative on Malnutrition predictive value for outcomes after emergency abdominal surgery. METHODS: This was a prospective observational study. Among the 468 patients undergoing emergency abdominal surgery admitted to a department of emergency surgery from June 2020 to December 2021, 53 patients were not eligible for enrollment, and 19 patients had missing data. Thus, the final number of participants was 396. Muscle mass was evaluated by skeletal muscle index at the third lumbar vertebra on computed tomography scans, and the lower quartile was defined as the threshold of muscle mass reduction. The associations of Global Leadership Initiative on Malnutrition, Global Leadership Initiative on Malnutrition (muscle mass reduction excluded), and skeletal muscle index with in-hospital mortality, postoperative complications, and postoperative stay were evaluated using χ2. In addition, confounding factors were screened, regression models were established, and the Global Leadership Initiative on Malnutrition predictive value was analyzed for clinical outcome. Ethical approval was obtained from the appropriate department. RESULTS: Malnutrition was observed in 19.9% of the total 396 patients based on the Global Leadership Initiative on Malnutrition and in 12.4% on the Global Leadership Initiative on Malnutrition (muscle mass reduction excluded). Sarcopenia by skeletal muscle index was found in 24.7% of patients. Univariate analysis indicated that in-hospital mortality, postoperative complications, infective complication rate, and postoperative hospital stay were significantly higher in malnourished and sarcopenic patients. Multivariate analysis found that malnutrition diagnosed by the Global Leadership Initiative on Malnutrition was predictive for complications, infective complications, and postoperative stay (total postoperative complications: odds ratio = 3.620; 95% CI, 1.635-8.015; P = 0.002; infective complications: odds ratio = 3.127; 95% CI, 1.194-8.192; P = 0.020; and postoperative stay: regression coefficient = 2.622; P = 0.022). The Global Leadership Initiative on Malnutrition (muscle mass reduction excluded) identified postoperative complications and postoperative stay (total postoperative complications: odds ratio = 3.364; 95% CI, 1.247-9.075; P = 0.017 and postoperative stay: regression coefficient = 3.547; P = 0.009). Sarcopenia by skeletal muscle index was a risk factor for postoperative complications (odds ratio = 3.366; 95% CI, 1.587-7.140; P = 0.002). CONCLUSION: The Global Leadership Initiative on Malnutrition and Global Leadership Initiative on Malnutritison (muscle mass reduction excluded) had predictive value for adverse clinical outcomes due to malnutrition in patients undergoing emergency abdominal surgery.

Targeting Diverse Wounds and Scars: Recent Innovative Bio-design of Microneedle Patch for Comprehensive Management.

Wounds and the subsequent formation of scars constitute a unified and complex phased process. Effective treatment is crucial; however, the diverse therapeutic approaches for different wounds and scars, as well as varying treatment needs at different stages, present significant challenges in selecting appropriate interventions. Microneedle patch (MNP), as a novel minimally invasive transdermal drug delivery system, has the potential for integrated and programmed treatment of various diseases and has shown promising applications in different types of wounds and scars. In this comprehensive review, the latest applications and biotechnological innovations of MNPs in these fields are thoroughly explored, summarizing their powerful abilities to accelerate healing, inhibit scar formation, and manage related symptoms. Moreover, potential applications in various scenarios are discussed. Additionally, the side effects, manufacturing processes, and material selection to explore the clinical translational potential are investigated. This groundwork can provide a theoretical basis and serve as a catalyst for future innovations in the pursuit of favorable therapeutic options for skin tissue regeneration.

Erbin accelerates TFEB-mediated lysosome biogenesis and autophagy and alleviates sepsis-induced inflammatory responses and organ injuries.

Mounting attention has been focused on defects of the autophagy-lysosomal pathway in sepsis, however, the precise mechanisms governing the autophagy-lysosomal process in sepsis are poorly known. We have previously reported that Erbin deficiency aggravated the inflammatory response and organ injuries caused by sepsis. In the present study, we found that Erbin knockout impaired the autophagy process in both muramyl dipeptide (MDP)-induced bone marrow-derived macrophages (BMDMs) and sepsis mouse liver and lung, as detected by the accumulation of LC3-II and SQSTM1/p62, and autophagosomes. Pretreatment with autophagy inhibitor chloroquine (CQ) further aggravated inflammatory response and organ injuries in vivo and in vitro sepsis model. We also observed that the impaired lysosomal function mediated autophagic blockade, as detected by the decreased expression of ATP6V, cathepsin B (CTSB) and LAMP2 protein. Immunoprecipitation revealed that the C-terminal of Erbin (aa 391-964) interacts with the N-terminal of transcription factor EB (TFEB) (aa 1-247), and affects the stability of TFEB-14-3-3 and TFEB-PPP3CB complexes and the phosphorylation status of TFEB, thereby promote the nucleus translocation of TFEB and the TFEB target genes transcription. Thus, our study suggested that Erbin alleviated sepsis-induced inflammatory responses and organ injuries by rescuing dysfunction of the autophagy-lysosomal pathway through TFEB-14-3-3 and TFEB-PPP3CB pathway.

Exposure to organochlorine pesticides and polychlorinated biphenyls, adherence to an ideal cardiovascular health, and arterial stiffness among Chinese adults.

This study aimed to assess the relationships between exposure to individual organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their mixture and arterial stiffness and explore whether adherence to an ideal cardiovascular health (CVH) could mitigate these associations. The cross-sectional study enrolled 1437 Chinese adults between March and May 2019 in Wuhan, China. OCPs and PCBs concentrations were measured using solid phase extraction coupled with gas chromatography-tandem mass spectrometry. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). CVH was determined by three behavioral and four biological metrics and categorized as ideal, intermediate, and poor CVH. We applied generalized linear model and weighted quantile sum (WQS) regression to evaluate the associations of exposure to individual OCPs or PCBs and their mixture with baPWV, respectively. We found that participants with detectable levels of heptachlor epoxide, PCB-153, and PCB-180 had higher baPWV (ß: 34.25, 95% CI 14.28-54.22; ß: 27.64, 95% CI 7.90-47.38; and ß: 30.51, 95% CI 10.68-50.35) than those with undetectable levels. In WQS regression, the mixture of OCPs and PCBs was related to a higher baPWV (ß: 24.93, 95% CI 2.70-47.15). Compared with participants with ideal CVH and undetectable OCPs or PCBs levels, those with poor CVH and detectable OCPs or PCBs levels had the highest increase in baPWV (heptachlor epoxide: ß: 147.94, 95% CI 112.52-183.55; PCB-153: ß: 150.22, 95% CI 115.40-185.04; PCB-180: ß: 147.02, 95% CI 111.66-182.38). Our findings suggested that individual OCPs, PCBs, and their mixture exposure were positively associated with arterial stiffness, and adherence to an ideal CVH may mitigate the adverse effect.

Alternative splicing of histone demethylase Kdm6bb mediates temperature-induced sex reversal in the Nile tilapia.

Sex determination in many fish species is remarkably plastic and temperature sensitive. Nile tilapia display a genetic sex-determination system (XX/XY). However, high-temperature treatment during critical thermosensitive periods can induce XX females into XXm pseudo-males, and this phenomenon is termed temperature-induced sex reversal (TISR). To investigate the molecular mechanism of TISR in Nile tilapia, we performed Iso-seq analysis and found a dramatic effect of high temperature on gene alternative splicing (AS). Kdm6bb histone demethylase showed a novel AS at intron 5 that generates Kdm6bb_tv1 transcripts without intron 5 and Kdm6bb_tv2 with intron 5. Kdm6bb_tv1 encodes a full-length protein while Kdm6bb_tv2 encodes a truncated protein. Expression analysis revealed that intron 5 splicing of Kdm6bb is male and gonad biased at larval stage, and only gonad biased at adult stage. High-temperature treatment induced intron 5 splicing in the gonads of XX and XY fish, resulting in increased Kdm6bb_tv1 expression. To directly test the role of Kdm6bb_tv1 in Nile tilapia TISR, we knocked out expression of Kdm6bb_tv1. However, Kdm6bb_tv1-/- homozygous mutants showed embryonic lethality. Overexpression of Kdm6bb_tv1, but not Kdm6bb_tv2, induced sex reversal of XX females into pseudo-males. Overexpression of Kdm6bb_tv1, as with high-temperature treatment, modified the promotor region of Gsdf and Dmrt1 by demethylating the trimethylated lysine 27 of histone 3 (H3K27me3), thereby increasing expression. Collectively, these studies demonstrate that AS of Kdm6bb intron 5 increases the expression of Kdm6bb_tv1, which acts as a direct link between high temperature and activation of Gsdf and Dmrt1 expression, leading to male sex determination.

Interfacial electronic states and self-formed asymmetric Schottky contacts in polar α-In2Se3/Au contacts.

In recent years, the two-dimensional (2D) semiconductor α-In2Se3 has great potential for applications in the fields of electronics and optoelectronics due to its spontaneous iron electrolysis properties. Through ab initio electronic structure calculations and quantum transport simulations, the interface properties and transport properties of α-In2Se3/Au contacts with different polarization directions are studied, and a two-dimensional α-In2Se3 asymmetric metal contact design is proposed. When α-In2Se3 is polarized upward, it forms an n-type Schottky contact with Au. While when α-In2Se3 is polarized downward, it forms a p-type Schottky contact with Au. More importantly, significant rectification effect is found in the asymmetric Au/α-In2Se3/Au field-effect transistor. The carrier transports under positive and negative bias voltages are found to be dominated by thermionic excitation and tunneling, respectively. These findings provide guidance for the further design of 2D α-In2Se3-based transistors.

Reverse Lumbar Pedicle Screw in Oblique Lateral Interbody Fusion: A Novel Concept to Restrict Cage Subsidence.

OBJECTIVE: Cage subsidence is a common morbidity after oblique lumbar interbody fusion (OLIF), with risk of compromising clinical and radiographic outcomes. The study aims to describe an innovative reverse lumbar pedicle screw (RLPS) technique in OLIF and compare its effect on restricting cage subsidence with classical lateral fixation (LF) in radiological and clinical evaluation. METHOD: Consecutive patients having undergone single-level OLIF-LF/RLPS from 2018 to 2020 were retrospectively reviewed. In OLIF-RLPS, the upper entry point was determined at the intersection between one horizontal line (1 cm above inferior endplate) and one vertical line (dissecting anterior and middle thirds of the vertebra) while the inferior entry point between one horizontal line (5 mm below superior endplate) and the same vertical line. Trajectories were from vertebrae reverse into contralateral pedicle. Radiological evaluation included disc height (DH) and segmental lordosis (SL); cage subsidence was evaluated by DH loss. Clinical assessment included visual analogue scale (VAS) and Oswestry disability index (ODI). Student t or Mann-Whitney U test was used for continuous variation according to normality analysis while Chi-square test for category variation. RESULTS: A total of 29 patients had been enrolled in the study including 14 cases in the RLPS group and 15 cases in the LF group. The DH in the OLIF-RLPS group had increased from the preoperative 9.07 ± 1.73 mm to 13.73 ± 1.83 mm postoperatively, without significant difference compared with the OLIF-LF group during the perioperative, but decreased to 12.53 ± 1.74 mm in 3 months and maintained at 12.00 ± 1.45 mm in 12 months, significantly higher than the OLIF-LF group (p < 0.05). At the last follow-up, 7.1% (1/14) cases in the OLIF-RLPS group had shown subsidence of grade I, significantly less than 46.7% (7/15) cases in the OLIF-LF group. Pain and disability had improved similarly in two groups, without significant difference detected between two groups at the last follow-up. CONCLUSION: RLPS technique with modified entry points and prolonged trajectory could effectively restrict cage subsidence in OLIF postoperatively compared with traditional lateral fixation.

[Comparison on blood-prostate barrier permeability of tanshinone extract and corresponding major monomers].

In this study, the transmittance of tanshinone Ⅱ_A(Tan Ⅱ_A) and cryptotanshinone(CTS) through the blood-prostate barrier and their distributions in the prostate tissue were compared between tanshinone extract(Tan E) treatment group and the corresponding monomer composition group under the equivalent dose conversion in vitro and in vivo. First, the human prostate epithelial cell line RWPE-1 was cultured in vitro for 21 days for the establishment of a blood-prostate barrier model, and the transmission of Tan Ⅱ_A and CTS through the barrier model was investigated after administration of Tan E and corresponding single active components. Second, SD rats were administrated with 700 mg·kg~(-1) Tan E, 29 mg·kg~(-1) CTS, and 50 mg·kg~(-1) Tan Ⅱ_A by gavage, and plasma and prostate tissue samples were collected at the time points of 2, 4, 8, 12, and 24 h. The Tan Ⅱ_A and CTS concentrations in the samples were determined. The results showed that in the cell model, the cumulative transmission amounts of CTS and Tan Ⅱ_A in the extract at each time point were higher than those of the corresponding single active components(P<0.01). In rats, after the administration of Tan E, the concentrations of Tan Ⅱ_A and CTS in rat plasma and prostate were higher than those of the corresponding single active components. This study demonstrated that the coexisting components in Tan E promoted the penetration of its main pharmacological components Tan Ⅱ_A and CTS through the blood-prostate barrier. The findings provide a theoretical and experimental basis for the application of Tan E in the clinical treatment of prostate-related diseases.

Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy.

The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and pseudotyped SARS-CoV-2 viruses. RBCEVs competitively inhibit this interaction and block TIM-1-mediated viral entry into cells. We further extend the therapeutic efficacy of this antiviral treatment by loading antisense oligonucleotides (ASOs) designed to target conserved regions of key SARS-CoV-2 genes into RBCEVs. We establish that ASO-loaded RBCEVs are efficiently taken up by cells in vitro and in vivo to suppress SARS-CoV-2 replication. Our findings indicate that this RBCEV-based SARS-CoV-2 therapeutic displays promise as a potential treatment capable of inhibiting SARS-CoV-2 entry and replication.

Efficient Proton Conductor Based on Bismuth Oxide Clusters and Polyoxometalates.

Developing new solid-state electrolyte materials for improving the proton conductivity remains an important challenge. Herein, a novel two-dimensional layered solid-state proton conductor Bi2O2-SiW12 nanocomposite, based on silicotungstic acid (H4SiW12O40) and Bi(NO3)3·5H2O, was synthesized and characterized. The composite consists of a layered cation framework [Bi2O2]2+ and interlayer-embedded counteranionic [SiW12O40]4-, which forms continuous hydrogen bond (O-H···O) networks through the interaction of adjacent oxygen atoms on the surface of the [Bi2O2]2+ and oxygen atoms of the H4SiW12O40. Facile proton transfer along these pathways endows the Bi2O2-SiW12 (30:1) nanocomposite with an excellent proton conductivity of 3.61 mS cm-1 at 90 °C and 95% relative humidity, indicating that the nanocomposite has good prospects as a highly efficient proton conductor.

Association between female-specific reproductive factors and leukocyte telomere length.

STUDY QUESTION: What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)? SUMMARY ANSWER: Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL. WHAT IS KNOWN ALREADY: Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear. STUDY DESIGN, SIZE, DURATION: This population-based study included 224 965 women aged 40-69 years from the UK Biobank between 2006 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for potential confounders, early menarche (<12 years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45 years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30 years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20 years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.