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Abstract Ovarian cancer is an extremely malignant gynaecological tumour with a poor patient prognosis and is often associated with chemoresistance. Thus, exploring new therapeutic approaches to improving tumour chemosensitivity is important. The expression of transcription elongation factor B polypeptide 2 (TCEB2) gene is reportedly upregulated in ovarian cancer tumour tissues with acquired resistance, but the specific mechanism involved in tumour resistance remains unclear. In this study, we found that TCEB2 was abnormally highly expressed in cisplatin-resistant tumour tissues and cells. TCEB2 silencing also inhibited the growth and glycolysis of SKOV-3/cisplatin (DDP) and A2780/DDP cells. We further incubated human umbilical vein endothelial cells (HUVECs) with culture supernatants from cisplatin-resistant cells having TCEB2 knockdown. Results revealed that the migration, invasion, and angiogenesis of HUVECs were significantly inhibited. Online bioinformatics analysis revealed that the hypoxia-inducible factor-1A (HIF-1A) protein may bind to TCEB2, and TCEB2 silencing inhibited SKOV-3/DDP cell growth and glycolysis by downregulating HIF1A expression. Similarly, TCEB2 promoted HUVEC migration, invasion, and angiogenesis by upregulating HIF1A expression. In vivo experiments showed that TCEB2 silencing enhanced the sensitivity of ovarian cancer nude mice to cisplatin and that TCEB2 knockdown inhibited the glycolysis and angiogenesis of tumour cells. Our findings can serve as a reference for treating chemoresistant ovarian cancer.

Abstract Background This study investigated the clinical value of breast magnetic resonance imaging (MRI) radiomics for predicting axillary lymph node metastasis (ALNM) and to compare the discriminative abilities of different combinations of MRI sequences. Methods This study included 141 patients diagnosed with invasive breast cancer from two centers (center 1: n = 101, center 2: n = 40). Patients from center 1 were randomly divided into training set and test set 1. Patients from center 2 were assigned to the test set 2. All participants underwent preoperative MRI, and four distinct MRI sequences were obtained. The volume of interest (VOI) of the breast tumor was delineated on the dynamic contrast-enhanced (DCE) postcontrast phase 2 sequence, and the VOIs of other sequences were adjusted when required. Subsequently, radiomics features were extracted from the VOIs using an open-source package. Both single- and multisequence radiomics models were constructed using the logistic regression method in the training set. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and precision of the radiomics model for the test set 1 and test set 2 were calculated. Finally, the diagnostic performance of each model was compared with the diagnostic level of junior and senior radiologists. Results The single-sequence ALNM classifier derived from DCE postcontrast phase 1 had the best performance for both test set 1 (AUC = 0.891) and test set 2 (AUC = 0.619). The best-performing multisequence ALNM classifiers for both test set 1 (AUC = 0.910) and test set 2 (AUC = 0.717) were generated from DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging single-sequence ALNM classifiers. Both had a higher diagnostic level than the junior and senior radiologists. Conclusions The combination of DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging radiomics features had the best performance in predicting ALNM from breast cancer. Our study presents a well-performing and noninvasive tool for ALNM prediction in patients with breast cancer.

Abstract During follicular development, changes in the composition of the follicular fluid are synchronized with the development of oocytes. Our aim was to screen the key factors affecting oocyte maturation and optimize the in vitro culture protocol by understanding the changes of proteins and metabolites in follicular fluid. Follicles are divided into three groups according to their diameter (small follicle fluid (SFF): 10 mm

Abstract Purpose Benign prostatic hyperplasia (BPH) commonly impacts the quality of life in older men. However, there is lack of research on relationship between dietary niacin intake and the risk of BPH. The purpose of this study was to investigate the relationship between dietary niacin intake and the risk of BPH. Methods Data from the NHANES spanning 2003 to 2008 were utilized. BPH was determined using a self-report questionnaire, while dietary niacin intake was calculated based on the mean of two distinct diet interviews. Multivariate logistic regressions were performed to explore the association, supplemented with restricted cubic splines and subgroup analysis. Results A total of 700 males were enrolled, of which 653 men had BPH. After adjusting for all covariates, a high dietary intake of niacin was associated with an increased risk of BPH (OR: 1.04; 95%CI: 1.01–1.07). Furthermore, when the lowest dietary niacin intake is used as the reference, the highest tertile is associated with an increased risk of BPH (OR: 2.34, 95% CI: 1.24-4,42). Restricted cubic splines demonstrated a positive correlation between dietary niacin intake and BPH risk. Conclusions The study results demonstrated a positive association between dietary niacin intake and the risk of BPH in elderly men in the US. These findings underscore the importance of systematic assessment before supplementing micronutrients in elderly men.

Abstract Monitoring the health of lithium batteries is a crucial undertaking in ensuring the safe and dependable functioning of electric vehicles. Data‐driven methods have been proved to be an effective method for identifying the complex degradation process of batteries. To augment the precision of predicting the remaining useful life (RUL), this paper introduces a pioneering architecture for a denoising autoencoder (DAE). This architecture integrates a stacked convolutional neural network with subsequent layers of bidirectional gated recurrent units within an encoder–decoder framework. The utilization of the DAE network is employed as a means to effectively capture and represent the intricate and nonlinear knowledge associated with degradation data acquired from measured sources. Simultaneously, the reconstruction loss is incorporated into the total loss to improve the accuracy and generalization of the prediction model. The efficacy of the proposed approach is substantiated through the utilization of data sets sourced from the NASA Ames Prognostics Data Repository. The comparative findings suggest that the proposed approach demonstrates an exceptional ability to achieve precise and robust estimation in predicting the RUL, surpassing other advanced methodologies.

Abstract Lithium (Li) oxyhalides have emerged as promising solid electrolyte candidates for all-solid-state batteries (ASSBs) due to their superior ionic conductivity and excellent cathode capability. However, the mechanism of Li transport in oxyhalides has remained unclear due to the complex nature of these compounds, which often comprise multiple phases such as crystalline and amorphous structures. Herein, a first-principles study using density functional theory and ab initio molecular dynamic simulation is performed to gain a theoretical insight into the structural behavior and conduction pathway in oxyhalide electrolytes. Li2.5ZrCl5.5O0.5 electrolyte, as a case of study, is comprehensively investigated by considering various phases. It’s revealed that the $${\rm{P}}\bar{3}{\rm{m}}1$$ P 3 ̅ m 1 phase is energetically more stable and exhibits one order of magnitude higher Li conductivity compared to the C2/m phase among potential crystalline phases (1.63 mS cm−1 versus 0.24 mS cm−1 at room temperature). Interestingly, an amorphous phase with even higher ionic conductivity (~40 mS cm−1) can be generated by creating LiCl-deficient Li-Zr-O-Cl compounds. The remarkably high ionic conductivity suggests that the amorphous structure is likely the dominant conducting pathway, facilitating fast Li transport due the weak bonding between Li and other atoms. Cl anion mobility is also observed in the amorphous phase through mean square displacement (MSD) calculation, although further analyses revealed this to be localized vibration. This study sheds light on the nature of oxychloride structures and promotes a deeper understanding of the superionic conduction mechanism in oxychlorides, which will contribute to the development of advanced solid electrolytes and ASSBs.

The heightened autonomy and robust adaptability inherent in a multi-robot system have proven pivotal in disaster search and rescue, agricultural irrigation, and environmental monitoring. This study addresses the coordination of multiple robots for the surveillance of various key target positions within an area. This involves the allocation of target positions among robots and the concurrent planning of routes for each robot. To tackle these challenges, we formulate a unified optimization model addressing both target allocation and route planning. Subsequently, we introduce an adaptive memetic algorithm featuring dual-level local search strategies. This algorithm operates independently among and within robots to effectively solve the optimization problem associated with surveillance. The proposed method’s efficacy is substantiated through comparative numerical experiments and simulated experiments involving diverse scales of robot teams and different target positions.

Abstract Background Testosterone deficiency (TD) and obesity are globally recognized health concerns, with a bidirectional causal relationship between them. And a newly discovered obesity indicator, the Weight-Adjusted-Waist Index (WWI), has been proposed, demonstrating superior adiposity identification capability compared to traditional body mass index (BMI) and waist circumference (WC) indicators. Therefore, we present the inaugural investigation into the associations of WWI with total testosterone levels and the risk of TD. Methods Data restricted to the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016 were analyzed. Only males aged > 20 years who completed body measures and underwent serum sex hormone testing were potentially eligible for analysis. Weighted multivariable linear regression and logistic regression analyses were employed to investigate the relationships between WWI and total testosterone levels, and the risk of TD, respectively. Smooth curve fittings and weighted generalized additive model (GAM) regression were conducted to examine the linear relationship among them. Additionally, subgroup analyses with interaction tests were performed to assess the stability of the results. Results Finally, a total of 4099 participants with complete data on testosterone and WWI were included in the formal analysis. The mean age of study participants was 46.74 ± 0.35 years with a TD prevalence of 25.54%. After adjusting all potential confounders, the continuous WWI displayed a negative linear relationship with total testosterone levels (β=-61.41, 95%CI: -72.53, -50.29, P 0.05). Conclusions This investigation firstly unveiled a negative linear association between WWI and total testosterone levels, coupled with a positive linear relationship with the prevalence of TD in U.S. male adults aged 20 years and older. Further studies are needed to validate the potential utility of WWI for the early identification and timely intervention of TD.

This study aimed to investigate the effect of different storage temperatures and methods for fresh tea leaves on the sensory quality, aroma components and biochemical components of broken black tea prepared from‘Yinghong 9’ tea leaves stored at 15, 25, 22–28 (room temperature) or 36–37 ℃ using sensory evaluation and headspace solid phase microextraction (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS). The results showed that storage of fresh tea leaves at 15 ℃ could enhance the fresh and brick taste, sweetness and sweet volatile compound contents of broken black tea, which was more favorable to the formation of the quality of broken black tea. However, storage at 36–37 ℃ of fresh tea leaves could significantly affect the sensory quality and quality components of broken black tea. These results provide a reference for fresh tea leaf management and the quality improvement of black broken tea.

Abstract Background Early pregnancy is a critical window for neural system programming; however, the association of first-trimester fetal size with children’s neurodevelopment remains to be assessed. This study aimed to explore the association between first-trimester fetal size and children’s neurodevelopment and to examine whether intrauterine accelerated growth could compensate for the detrimental effects of first-trimester restricted growth on childhood neurodevelopment. Methods The participants were from a birth cohort enrolled from March 2014 to March 2019 in Wuhan, China. A total of 2058 fetuses with crown to rump length (CRL) (a proxy of first-trimester fetal size) measurements in the first trimester and neurodevelopmental assessment at age 2 years were included. We measured the first-trimester CRL and defined three fetal growth patterns based on the growth rate of estimated fetal weight from mid to late pregnancy. The neurodevelopment was assessed using the Bayley Scales of Infant Development of China Revision at 2 years. Results Each unit (a Z score) increase of first-trimester CRL was associated with increased scores in mental developmental index (MDI) (adjusted beta estimate = 1.19, (95% CI: 0.42, 1.95), P = 0.03) and psychomotor developmental index (PDI) (adjusted beta estimate = 1.36, (95% CI: 0.46, 2.26), P

Abstract Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron. Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023)

BackgroundBone metastasis from prostate cancer severely impacts patient outcomes and quality of life. Anoikis, a form of programmed cell death triggered by the loss of cell-matrix interactions, plays a critical role in cancer progression. However, its precise relationship with prostate cancer-induced bone metastasis remains unclear. This study aims to elucidate this relationship, focusing on anoikis-related gene signatures, molecular pathways, and therapeutic implications.MethodsWe used the TCGA-PRAD dataset for training, with MSKCC and GSE70769 as validation cohorts. To evaluate immunotherapy efficacy, we examined IMvigor 210 and GSE91016 datasets, and GSE137829 provided single-cell insights into prostate cancer. Specific anoikis-related genes (ARGs) were identified, and Random Survival Forest analysis and multivariate Cox regression were employed to develop anoikis-linked features. The ‘clustanoikisProfilanoikis’ and ‘GSEA’ packages were used to explore potential ARG-related pathways.ResultsAnalyzing 553 samples from TCGA, 231 from MSKCC, 94 from GSE70769, and single-cell data from 6 prostate cancer patients (GSE137829), we constructed a prognostic model based on 9 ARGs. GSVA revealed upregulation of carcinogenic pathways, including epithelial-mesenchymal transition, E2F targets, and angiogenesis, with downregulation of metabolic pathways. Significant differences in somatic mutations were observed between cohorts, with a positive correlation between anoikis scores and tumor mutational burden (TMB). Immune landscape analysis suggested high-risk patients might benefit more from chemotherapy than immunotherapy based on their risk score. Single-cell analysis indicated overactivation of carcinogenic pathways in the high anoikis score group.ConclusionThis study elucidates the complex interplay between anoikis and bone metastasis in prostate cancer. Our findings highlight the critical role of anoikis in metastatic progression, enhancing the understanding of key biomarkers and molecular dynamics. The identified anoikis-related gene signatures and disrupted pathways offer promising avenues for predictive and therapeutic strategies in prostate cancer management.

As one of the developed genetically modified (GM) maize varieties in China, CC-2 has demonstrated promising commercial prospects during demonstration planting. The establishment of detection methods is a technical prerequisite for effective supervision and regulation of CC-2 maize. In this study, we have developed an event-specific quantification method that targets the junction region between the exogenous gene and the 5’ flanking genomic DNA (gDNA) of CC-2. The accuracy and precision of this method were evaluated across high, medium, and low levels of CC-2 maize content, revealing biases within ±25% and satisfactory precision data. Additionally, we determined the limits of quantification of the method to be 0.05% (equivalent to 20 copies) of the CC-2 maize. A collaborative trial further confirmed that our event-specific method for detecting CC-2 produces reliable, comparable, and reproducible results when applied to five different samples provided by various sources. Furthermore, we calculated the expanded uncertainty associated with determining the content level of CC-2 in these samples.

Background: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. Methods: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. Results: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. Conclusion: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.

ObjectiveExplore the clinical application value of urethral mucosal pretreatment at the tip of the prostate in preventing stress urinary incontinence (SUI) after thulium laser enucleation of the prostate (ThuLEP).MethodsEighty-seven patients with benign prostatic hyperplasia (BPH) treated with ThuLEP from June 2021 to December 2022 were divided into two groups. Of these, 42 patients (group A) underwent conventional ThuLEP and 45 patients (group B) were enucleated after pretreatment of the urethral mucosa. At the tip of the prostate, pretreatment of the urethral mucosa consisted of pushing the gland separately on both sides at the level of the verumontanum and cutting off the mucosa near the external urethral sphincter clockwise and counterclockwise. The perioperative and postoperative follow-up indicators [operation time, hemoglobin reduction, complications, Qmax, International Prostate Symptom Score (IPSS), quality of life (QoL), and post-void residual (PVR) volume] of the two groups of patients were collected and compared. All patients were followed up 1 month after surgery.ResultsAll 87 procedures were successfully completed. There was no significant difference in age and gland size between the two groups (P > 0.05). There was no significant difference between operating time and hemoglobin reduction in the two groups (P > 0.05). The Qmax, IPSS, QOL, and PVR volume were significantly improved postoperatively in both groups (P 0.05).ConclusionPretreatment of the urethral mucosa before ThuLEP for BPH significantly reduces the incidence of SUI after surgery. This technique, which preconditions the apical urethral mucosa of the prostate, is safe and effective, has few complications, and is worthy of clinical application.

Background: Exposure to endocrine-disrupting chemicals (EDCs) has been found to be associated with growth and developmental abnormalities in children. However, the potential mechanisms by which exposure to EDCs during pregnancy increases the risk of obesity in children remain unclear. Objective: We aimed to explore associations between prenatal EDC exposure and the body mass index (BMI) of children at age two, and to further explore the potential impact of DNA methylation (DNAm). Method: This study included 285 mother–child pairs from a birth cohort conducted in Wuhan, China. The BMI of each child was assessed at around 24 months of age. The concentrations of sixteen EDCs at the 1st, 2nd, and 3rd trimesters were measured using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer. The research utilized general linear models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to assess the association between prenatal EDC exposure and childhood BMI z-scores (BMIz). Cord blood DNAm was measured using the Human Methylation EPIC BeadChip array. An epigenome-wide DNAm association study related to BMIz was performed using robust linear models. Mediation analysis was then applied to explore potential mediators of DNAm. Results: Urinary concentrations of seven EDCs were positively associated with BMIz in the 1st trimester, which remained significant in the WQS model. A total of 641 differential DNAm positions were associated with elevated BMIz. Twelve CpG positions (annotated to DUXA, TMEM132C, SEC13, ID4, GRM4, C2CD2, PRAC1&PRAC2, TSPAN6 and DNAH10) mediated the associations between urine BP-3/BPS/MEP/TCS and elevated BMIz (P

To achieve all-organic polymer with high dielectric performances, we have designed a novel side-chain liquid crystalline polymer (P7) with strong polar mesogen of (Z)-4-(2-cyano-2-phenylvinyl)benzonitrile (CSCN) attached to polycyclooctene backbone. The bis-cyano-substituted CSCN is board-shaped and exhibits a large dipole moment (8.54 D) which tilts ∼34.2° away from its molecular long axis. Consequently, CSCN shows unique dual molecular anisotropy: one from biaxial shape anisotropy and the other from polarization anisotropy. The complex phase behaviors of P7 were investigated employing mainly the techniques of differential scanning calorimetry and X-ray diffraction. Four liquid crystal (LC) phases are identified as K0, K1, K2 and K3, which are SmA, highly-ordered biaxial SmA, B5-like and B7-like, respectively, with the thermal stability increased in sequence. The experimental results indicate that the different LC phases are arisen from the competition and balance between π-π stacking and dipole-dipole interaction. While the face-to-face π-π stacking is dominant in K0 and K1, optimizing the dipole-dipole interaction causes the CSCN mesogens within the smectic layer to tilt and rotate, resulting in K2 and K3. We further investigated the dielectric properties of P7 films using polarization-electric field loops test. The dielectric constant (εr) of P7 is found to be LC structure dependent, which is increased when the LC phase is varied from K0 to K3. With an average εr of 9.7 achieved in K3 and the low dielectric loss (tan δ = 0.001), P7 film offers a promising material in advanced applications like energy storage and electronic devices.

There are frequent high-temperature geotherm disasters in the tunnels of China's western mountainous regions. The surrounding rock fissure water in the tunnels and underground water contain a great amount of corrosive salt. As a result, the lining concrete may suffer accelerated damage due to the combined attack of hot-humid environment and sulfate ions. In this context, the physical and mechanical properties of cement-based materials for shotcrete use are studied under different temperatures by simulating the interaction environment of hot-humid and sulfate, and the microscopic erosion mechanism and mesoscopic damage characteristics are analyzed. The results show that: at 20 °C and 90 °C, the relative compressive strength of cement-based materials first increases and then decreases with the increase of erosion time, but it decreases rapidly at 55 °C and loses compressive ability after 60 days; the expansion process of cement-based materials at 20 °C is divided into two stages: the ''latent period'' and the ''significant expansion period'', and the expansion velocity is greatly increased at 55 °C, while there is no significant expansion period at 90 °C; the high temperature of 55 °C will greatly increase the erosion reaction rate of sulfate, and the damage process of cement-based materials is greatly accelerated, but the high temperature of 90 °C will hinder the formation of ettringite, and significantly delay the damage of cement-based materials; different from the failure mode of layer-by-layer spalling at the end under the erosion environment of 20 °C, the specimen at 55 °C shows the failure mode of central fracture.

Shales of the Wufeng-Longmaxi formations in the basin-margin transition zone of southeastern Chongqing, China are characterized by high organic matter content and a significant presence of pyrite development. By examining numerous scanning electron microscope (SEM) images and considering the crystal and aggregate characteristics of minerals, we identified four types of pyrite in the study area: euhedral crystals, irregular aggregates, framboidal aggregates, and metasomatized organisms. Among these types, framboidal aggregates are the most prevalent. The formation mechanism of framboidal pyrite can be categorized into inorganic and organic origins. As inferred from the pyrite characteristics in the study area, the formation mechanism of the metasomatized organisms aligns with the biologically induced mineralization mode of organic origin, whereas the framboidal aggregates are more associated with the biologically controlled mineralization mode of organic origin. This underscores a close relationship between the pyrite formation and organic matter, which in turn indicates that an organic origin is more consistent with the pyrite characteristics observed in this study area. The pyrite morphology can reflect reactive iron concentration. Euhedral pyrite crystals tend to form under a low reactive iron concentration, whereas the formation of framboidal pyrite requires a high reactive iron concentration. Additionally, the type and grain size of pyrite aggregates can reflect variations in the redox conditions of the depositional environment. Pyrite produces positive effects on reservoir storage space, with intercrystalline organic pores, intercrystalline pores, and mold pores associated with pyrite contributing greatly to the storage spaces.

Abstract. Background:. Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. Methods:. The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4+) T-cell counts, CD8+ T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results:. The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6–6.5 copies/reaction) with linearity over a 5-log10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8–16.6 copies/reaction) with linearity over a 3-log10-unit range. Total HIV DNA in CD4+ T cells was positively associated with integrated HIV DNA (r = 0.76, P

Background The repair and reconstruction of medial meniscus posterior root tears (MMPRTs) is an important issue in the field of orthopedic sports medicine. This study reports the first application of arthroscopic linear chain fixation for the treatment of MMPRTs. Case presentation A 78‐year‐old female patient presented with a 1.5‐month history of right knee pain accompanied by a locked facet joint. The patient underwent surgery with the new linear chain fixation method. In this method, the suture and the loop part of the buckle‐strap titanium plate were combined into a linear chain mechanical complex, and the tension of the posterior root stump was gradually increased by pulling on the two attachment lines at the external mouth of the tibial tunnel. The postoperative Lysholm score was 89, and the visual analogue scale score was 0.9, indicating a significant improvement in knee joint function. At the 7‐month and 1‐year post‐surgery follow‐up, physical and MRI examinations confirmed satisfactory healing of the MMPRTs. Conclusion This surgical approach offers several benefits, including a simplified instrumentation setup, preservation of natural anatomical structures, and reliable residual stump fixation. It has the potential for clinical implementation.

Abstract Background Endoplasmic reticulum stress (ERS) acts critical roles on cell growth, proliferation, and metastasis in various cancers. However, the relationship between ERs and lung squamous cell carcinoma (LUSC) prognoses still remains unclear. Methods The consensus clustering analysis of ERS-related genes and the differential expression analysis between clusters were investigated in LUSC based on TCGA database. Furthermore, ERS-related prognostic risk models were constructed by LASSO regression and Cox regression analyses. Then, the predictive effect of the risk model was evaluated by Kaplan–Meier, Cox regression, and ROC Curve analyses, as well as validated in the GEO cohort. According to the optimal threshold, patients with LUSC were divided into high- and low- risk groups, and somatic mutations, immune cell infiltration, chemotherapy response and immunotherapy effect were systematically analyzed. Results Two ERS-related clusters were identified in patients with LUSC that had distinct patterns of immune cell infiltration. A 5-genes ERS-related prognostic risk model and nomogram were constructed and validated. Kaplan–Meier curves and Cox regression analysis showed that ERS risk score was an independent prognostic factor (p

Abstract The noncentrosymmetric ferromagnetic Weyl semimetal CeAlSi with simultaneous space-inversion and time-reversal symmetry breaking provides a unique platform for exploring novel topological states. Here, by employing multiple experimental techniques, we demonstrate that ferromagnetism and pressure can serve as efficient parameters to tune the positions of Weyl nodes in CeAlSi. At ambient pressure, a magnetism-facilitated anomalous Hall/Nernst effect (AHE/ANE) is uncovered. Angle-resolved photoemission spectroscopy (ARPES) measurements demonstrated that the Weyl nodes with opposite chirality are moving away from each other upon entering the ferromagnetic phase. Under pressure, by tracing the pressure evolution of AHE and band structure, we demonstrate that pressure could also serve as a pivotal knob to tune the positions of Weyl nodes. Moreover, multiple pressure-induced phase transitions are also revealed. These findings indicate that CeAlSi provides a unique and tunable platform for exploring exotic topological physics and electron correlations, as well as catering to potential applications, such as spintronics.

Abstract Background In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Methods CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. Results Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)‑like population. Moreover, hyperthermia substantially improved the sensitivity of radiation‑resistant NPC cells and CSC‑like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti‑tumor‑killing activity of hyperthermia against NPC cells and CSC‑like cells, whereas ectopic expression of Cirbp compromised tumor‑killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC‑like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. Conclusion Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Abstract Light engineering of correlated states in topological materials provides a new avenue of achieving exotic topological phases inaccessible by conventional tuning methods. Here we demonstrate a light control of correlation gaps in a model charge-density-wave (CDW) and polaron insulator (TaSe4)2I recently predicted to be an axion insulator. Our ultrafast terahertz photocurrent spectroscopy reveals a two-step, non-thermal melting of polarons and electronic CDW gap via the fluence dependence of a longitudinal circular photogalvanic current. This helicity-dependent photocurrent reveals continuous ultrafast phase switches from the polaronic state to the CDW (axion) phase, and finally to a hidden Weyl phase as the pump fluence increases. Additional distinctive attributes aligning with the light-induced switches include: the mode-selective coupling of coherent phonons to the polaron and CDW modulation, and the emergence of a non-thermal chiral photocurrent above the pump threshold of CDW-related phonons. The demonstrated ultrafast chirality control of correlated topological states here holds large potentials for realizing axion electrodynamics and advancing quantum-computing applications.

Abstract Background The tumor immune microenvironment can influence the prognosis and treatment response to immunotherapy. We aimed to develop a non-invasive radiomic signature in high-grade glioma (HGG) to predict the absolute density of tumor-associated macrophages (TAMs), the preponderant immune cells in the microenvironment of HGG. We also aimed to evaluate the association between the signature, and tumor immune phenotype as well as response to immunotherapy. Methods In this retrospective setting, total of 379 patients with HGG from three independent cohorts were included to construct a radiomic model named Radiomics Immunological Biomarker (RIB) for predicting the absolute density of M2-like TAM using the mRMR feature ranking method and LASSO classifier. Among them, 145 patients from the TCGA microarray cohort were randomly allocated into a training set (N=101) and an internal validation set (N=44), while the immune-phenotype cohort (N=203) and the immunotherapy-treated cohort (N=31, patients from a prospective clinical trial treated with DC vaccine) recruited from Huashan Hospital were used as two external validation sets. The immunotherapy-treated cohort was also used to evaluate the relationship between RIB and immunotherapy response. Radiogenomic analysis was performed to find functional annotations using RNA sequencing data from TAM cells. Results An 11-feature radiomic model for M2-like TAM was developed and validated in four datasets of HGG patients (area under the curve = 0.849, 0.719, 0.674, and 0.671) using MRI images of post contrast enhanced T1-weighted (T1CE). Patients with high RIB scores had a strong inflammatory response. Four hub-genes (SLC7A7, RNASE6, HLA-DRB1 and CD300A) expressed by TAM were identified to be closely related to the RIB, providing important evidence for biological interpretation. Only individuals with a high RIB score were shown to have survival benefits from DC vaccine [DC vaccine vs. Placebo: median progression-free survival (mPFS), 10.0 mos vs. 4.5 mos, HR=0.17, P=0.0056, 95%CI=0.041-0.68; median overall survival (mOS), 15.0 mos vs. 7.0 mos, HR=0.17, P =0.0076, 95%CI=0.04-0.68]. Multivariate analyses also confirmed that treatment by DC vaccine was an independent factor for improved survival in the high RIB score group. However, in the low RIB score group, DC vaccine was not associated with improved survival. Furthermore, a radiomic nomogram based on the RIB score and clinical factors could efficiently predict the 1-, 2-, and 3-year survival rates, as confirmed by ROC curve analysis (AUC for 1-, 2- and 3-year survival: 0.705, 0.729 and 0.684, respectively). Conclusions The radiomic model could allow for non-invasive assessment of the absolute density of TAM from MRI images in HGG patients. Of note, our RIB model is the first immunological radiomic model confirmed to have the ability to predict survival benefits from DC vaccine in gliomas, thereby providing a novel tool to inform treatment decisions and monitor patient treatment course by radiomics.

The extra-interfacial manifestations induced by the waveguide resonance properties of monolayer colloidal crystals (MCCs) have been well discovered by symmetrically probing their reflectance spectra. To clearly analyze the origin of the resonance peaks in the spectra obtained by reflection probing, experimental and calculated values were compared and the results for monolayers with different arrangement structures were compared. The different contributions to the resonance modes by different light bands entering the MCC were elucidated. In addition, the experimental results visualize that changing the incident angle, lattice and polarization can effectively modulate the wavelength position and intensity of the characteristic peaks induced by the resonance of the monolayer waveguide.

ABSTRACTEpstein-Barr virus (EBV) infection in humans is ubiquitous and associated with various diseases. Remodeling of the immune microenvironment is the primary cause of EBV infection and pathogenesis; however, the underlying mechanism has not been fully elucidated. In this study, we used whole-transcriptome RNA-Seq to detect mRNAs, long non-coding RNAs (lncRNA), and microRNA (miRNA) profiles in the control group, 3 days, and 28 days after EBV infection, based on the tree shrew model that we reported previously. First, we estimated the proportion of 22 cell types in each sample using CIBERSORT software and identified 18 high-confidence DElncRNAs related to immune microenvironment regulation after EBV infection. Functional enrichment analysis of these differentially expressed lncRNAs primarily focused on the autophagy, endocytosis, and ferroptosis signalling pathways. Moreover, EBV infection affects miRNA expression patterns, and many miRNAs are silenced. Finally, three competing endogenous RNA regulatory networks were built using lncRNAs that significantly correlated with immune cell types, miRNAs that responded to EBV infection, and potentially targeted the mRNA of the miRNAs. Among them, MRPL42-AS-5 might act as an hsa-miR-296-5p “sponge” and compete with target mRNAs, thus increasing mRNA expression level, which could induce immune cell infiltration through the cellular senescence signalling pathway against EBV infection. Overall, we conducted a complete transcriptomic analysis of EBV infection in vivo for the first time and provided a novel perspective for further investigation of EBV-host interactions.

The combination of photodynamic therapy (PDT)-immunotherapy has brought much hope for cancer patients. However, the hypoxia tumor microenvironment (TME) can regulate tumor angiogenesis and inhibit immune response, thus limiting the therapeutic effects. In this paper, engineered cyanobacteria-M2-like tumor-associated macrophages (TAMs) targeting peptide modified Fe3O4 nanoparticles hybrid system (ECyano@Fe3O4-M2pep) was constructed for alleviating hypoxia and relieving immune suppression to achieve synergistic cancer PDT-immunotherapy. With the irradiation of red laser, oxygen was produced by the photosynthesis of ECyano to alleviate the hypoxia TME. Then, ECyano could secret 5-aminolevulinic acid (5-ALA) under the induction of theophylline for controllable PDT. In the process of PDT, the disulfide bond between ECyano and Fe3O4-M2pep was broken in response to reactive oxygen species (ROS), and then Fe3O4-M2pep was released to target M2-like TAMs, corresponding by the polarization of M2-like TAMs to M1-like TAMs for the killing of tumor cells. Compared with other groups, ECyano@Fe3O4-M2pep + theophylline + laser (ECyano@Fe3O4-M2pep + T + L) group displayed the lowest tumor volume (159.3 mm3) and the highest M1/M2 ratio (1.25- fold). We believe that this hybrid system will offer a promising way for the biomedical application of bacterial therapy.

BackgroundTestosterone deficiency (TD) is closely associated with cardiovascular diseases (CVD). We intended to explore the association of Life’s Essential 8 (LE8), the recently updated measurement of cardiovascular health, with the prevalence of TD among US male adults.MethodsThe population-based cross-sectional study selected male adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. According to the American Heart Association definitions, the LE8 score was measured on a scale of 0–100, and divided into health behavior and health factor scores, simultaneously. Furthermore, these scores were categorized into low (0–49), moderate (50–79), and high (80–100) classifications. TD is defined as a total testosterone level below 300ng/dL. Correlations were investigated by weighted multivariable logistic regression, and the robustness of the results were verified by subgroup analysis.ResultsA total of 4971 male adults with an average age of 47.46 ± 0.41 years were eligible for the final analyses, of whom 1372 were determined to have TD. The weighted mean LE8 score of the study population was 68.11 ± 0.41. After fully adjusting potential confounders, higher LE8 scores were significantly associated with low risk of TD (odd ratio [OR] for each 10-point increase, 0.79; 95% CI, 0.71–0.88) in a linear dose-response relationship. Similar patterns were also identified in the association of health factor scores with TD (OR for each 10-point increase, 0.74; 95% CI, 0.66–0.83). These results persisted when LE8 and health factor scores was categorized into low, moderate, and high groups. The inversed association of LE8 classifications and TD remained statistically significant among older, obese, and men without CVD.ConclusionsLE8 and its health factor subscales scores were negatively associated with the presence of TD in linear fashions. Promoting adherence to optimal cardiovascular health levels may be advantageous to alleviate the burden of TD.

Abstract Hydrogen‐bonded organic frameworks (HOFs) are emerging porous materials that show high structural flexibility, mild synthetic conditions, good solution processability, easy healing and regeneration, and good recyclability. Although these properties give them many potential multifunctional applications, their frameworks are unstable due to the presence of only weak and reversible hydrogen bonds. In this work, the development history and synthesis methods of HOFs are reviewed, and categorize their structural design concepts and strategies to improve their stability. More importantly, due to the significant potential of the latest HOF‐related research for addressing energy and environmental issues, this work discusses the latest advances in the methods of energy storage and conversion, energy substance generation and isolation, environmental detection and isolation, degradation and transformation, and biological applications. Furthermore, a discussion of the coupling orientation of HOF in the cross‐cutting fields of energy and environment is presented for the first time. Finally, current challenges, opportunities, and strategies for the development of HOFs to advance their energy and environmental applications are discussed.

Organizational climate has been shown to be an important factor associated with teachers’ job satisfaction. However, the internal mechanism between them is unclear. The purpose of this study was to investigate whether the relationship between kindergarten organizational climate and kindergarten teachers’ job satisfaction was affected by occupational stress and emotional labor. This study employed a questionnaire survey method to gather data from 1,091 kindergarten teachers nationwide. It conducted an analysis of the current status of kindergarten organizational climate and the job satisfaction of kindergarten teachers, elucidating the relationship between the two and the underlying mechanisms. Additionally, a chain mediation model was constructed. The findings indicated that: (1) organizational climate, kindergarten teachers’ occupational stress and emotional labor all significantly predict kindergarten teachers’ job satisfaction directly (2) organizational climate could indirectly influence kindergarten teachers’ job satisfaction through three pathways: the separate mediating effect of occupational stress and emotional labor, and the chain mediating effect on both. The research findings highlight the significance of kindergarten organizational climate, occupational stress, and emotional labor in augmenting the job satisfaction of kindergarten teachers, offering valuable insights for the improvement of kindergarten teacher job satisfaction.

IntroductionInflammatory bowel disease (IBD) is a chronic disease involving multiple genes, and the current available targeted drugs for IBD only deliver moderate efficacy. Whether there is a single gene that systematically regulates IBD is not yet known. MiR-146a plays a pivotal role in repression of innate immunity, but its function in the intestinal inflammation is sort of controversy, and the genetic regulatory networks regulated by miR-146a in IBD has not been revealed.MethodsRT-qPCR was employed to detect the expression of miR-146a in IBD patients and in a mouse IBD model induced by dextran sulfate sodium (DSS), and then we generated a miR-146a knock-out mouse line with C57/Bl6N background. The disease activity index was scored in DSS-treated miR-146a deficiency mice and their wild type (WT) littermates. Bulk RNA-sequencing, RT-qPCR and immunostaining were done to illustrate the downstream genetic regulatory networks of miR-146a in flamed colon. Finally, the modified miR-146a mimics were used to treat DSS-induced IBD in miR-146a knock-out and WT IBD mice.ResultsWe showed that the expression of miR-146a in the colon was elevated in dextran sulfate sodium (DSS)-induced IBD mice and patients with IBD. DSS induced dramatic body weight loss and more significant rectal bleeding, shorter colon length, and colitis in miR-146a knock-out mice than WT mice. The miR-146a mimics alleviated DSS-induced symptoms in both miR-146a-/- and WT mice. Further RNA sequencing illustrated that the deficiency of miR-146a de-repressed majority of DSS-induced IBD-related genes that cover multiple genetic regulatory networks in IBD, and supplementation with miR-146a mimics inhibited the expression of many IBD-related genes. Quantitative RT-PCR or immunostaining confirmed that Ccl3, Saa3, Csf3, Lcn2, Serpine1, Serpine2, MMP3, MMP8, MMP10, IL1A, IL1B, IL6, CXCL2, CXCL3, S100A8, S100A9, TRAF6, P65, p-P65, and IRAK1 were regulated by miR-146a in DSS induced IBD. Among them, MMP3, MMP10, IL6, IL1B, S100A8, S100A9, SERPINE1, CSF3, and IL1A were involved in the active stage of IBD in humans.DiscussionOur date demonstrated that miR-146a acts as a top regulator in C57/BL6N mice to systematically repress multiple genetic regulatory networks involved in immune response of intestine to environment factors, and combinatory treatment with miR-146a-5p and miR-146a-3p mimics attenuates DSS-induced IBD in mice through down-regulating multiple genetic regulatory networks which were increased in colon tissue from IBD patients. Our findings suggests that miR-146a is a top inhibitor of IBD, and that miR-146a-5p and miR-146a-3p mimics might be potential drug for IBD.

BackgroundEngaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual’s positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect.MethodsBased on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200–499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM.ResultsThe core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts.ConclusionAs HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.

Injectable poly (methyl methacrylate) (PMMA) bone cements are widely used in orthopaedics to stabilize fractures and for implant fixation. However, bacterial attachment to bone cements leads to significant complications that can create a need for implant revision. Common attempts at reducing bacterial attachment are through the addition of antibiotics or antibacterial nanometals to the bone cements. However, clinical data is inconclusive on the effectiveness of antibiotic-loaded bone cements and a negative osteoblastic response has been reported for certain additive concentrations. There is therefore a need for an additive that can positively affect osteoblastic behaviour while inhibiting bacterial attachment. Silicon nitride (Si3N4) could be such an additive, with initial studies showing promise in achieving antipathogenic properties. The aim of this study was hence to investigate the possibility of creating a bone cement that can support osteoblast growth while reducing bacterial attachment by introducing silicon nitride powders into an injectable PMMA cement. To this end, commercially available bone cements were doped with 5%, 10% and 20% weight/weight (w/w) of Si3N4. Their mechanical properties were examined through compression testing and their radiopacity was evaluated through fluoroscopy imaging. The samples that fulfilled compressive strength requirements had their biological properties tested using Staphylococcus epidermidis bacteria for antibacterial properties and MC3T3-E1 preosteoblasts for the examination of cytotoxicity. Bone cements that were doped with up to 20% w/w Si3N4 were radiopaque (only 13% reduction in optical density compared to radiopaque controls) and retained their compressive strength (85.35 ± 2.1 MPa compared to 83.4 ± 1.9 MPa for the commercial cements), while significantly reducing bacterial attachment by more than 90% compared to commercial cements and achieving a similar level of preosteoblast metabolic activity. This study supports further evaluation of Si3N4 as an additive to injectable bone cements as a way to create mechanically stable, radiopaque, bacteriostatic bone cements that could improve osteointegration.