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IntroductionNK cells are dysfunctional in myasthenia gravis (MG), but the mechanism is unclear. This study aims to measure associations and underlying mechanisms between the NK cells and the development of MG.MethodsTwenty healthy controls (HCs) and 53 MG patients who did not receive glucocorticoids and immunosuppressants were collected. According to the Myasthenia Gravis Foundation of America (MGFA) classification, MG patients were categorized into MGFA I group (n = 18) and MGFA II-IV group (n = 35). Flow cytometry, cell sorting, ELISA, mRNA-sequencing, RT-qPCR, western blot, and cell culture experiments were performed to evaluate the regulatory mechanism of exhausted NK cells.ResultsPeripheral NK cells in MGFA II-IV patients exhibit exhausted phenotypes than HCs, marked by the dramatic loss of total NK cells, CD56dimCD16− NK cells, elevated PD1 expression, reduced NKG2D expression, impaired cytotoxic activity (perforin, granzyme B, CD107a) and cytokine secretion (IFN-γ). Plasma IL-6 and IL-21 are elevated in MG patients and mainly derived from the aberrant expansion of monocytes and Tfh cells, respectively. IL-6/IL-21 cooperatively induced NK-cell exhausted signature via upregulating SOCS2 and inhibiting the phosphorylation of STAT5. SOCS2 siRNA and IL-2 supplement attenuated the IL-6/IL-21-mediated alteration of NK-cell phenotypes and function.DiscussionInhibition of IL-6/IL-21/SOCS2/STAT5 pathway and recovery of NK-cell ability to inhibit autoimmunity may be a new direction in the treatment of MG.

BackgroundPast studies have demonstrated that diabetic neuropathy is related to sarcopenia, but the further causal relation is still unclear. We sought to investigate the causal relationship by combining data from cross-sectional and Mendelian randomization (MR) studies.MethodsThe genome-wide association studies data were collected from the UK Biobank and the European Working Group on Sarcopenia to conduct a bi-directional two-sample MR study to explore the causality between diabetic neuropathy and relevant clinical traits of sarcopenia, including appendicular lean mass (ALM), walking speed and low hand grip strength. The inverse-variance weighted and various sensitivity analyses were used to obtain MR estimates. We also enrolled a total of 196 Type 2 diabetes patients from April 2021 to April 2024 and divided them into the Distal peripheral neuropathy (DPN) group (n=51) and non-DPN group (n=145) via vibration perception threshold (VPT) and neuropathy deficit score. Logistic regression and ROC curve analysis were used to investigate the relationship between DPN and relevant sarcopenia clinical features.ResultsAccording to a forward MR analysis, decreased walking speed (OR: 0.04, 95% confidence interval (CI): 0.01-0.16; P

ObjectivesConsidering the importance of mental health help-seeking, researchers have closely examined the relationship between mental health literacy (MHL) and help-seeking intention (HSI). Furthermore, the high impact of stigma and the potential value of social support on HSI have been recognised. However, the relationship between these variables has not been fully tested within the context of Chinese elite athletes. This study addressed this gap by examining the relationship between MHL and HSI. Furthermore, it explored the mediating effects of public stigma, self-stigma, and social support on the relationship between MHL and HSI among Chinese elite athletes.Methods450 Chinese elite athletes (Mage = 18.12, SD = 3.20, 46.2% female) self-reported their MHL, public stigma, self-stigma, social support, and HSI. Mediation analysis was conducted using the bootstrap approach of the PROCESS macro version 3.3 of SPSS 25.ResultsThe results showed a significant positive correlation between MHL and HSI (r = 0.348). The results also demonstrated that MHL was a predictor of HSI (β = 0.337, 95%CI [0.249, 0.425], p

Identifying priority conservation areas (PCAs) on the basis of ecosystem services (ESs) trade-offs is a crucial step in achieving optimal ecosystem management in the BTH, noting the complex spatio-temporal and scaling effects inherent in these ecosystems. A cross-scale quantification of spatial and temporal changes in ecosystem services and their correlations was conducted in the BTH. Furthermore, the Ordered Weighting Algorithm (OWA) was introduced to simulate a variety of scenarios in order to determine the PCAs and to explore the drivers of ES in the PCAs. The results indicated that Food supply (FS), Water yield (WY), and Soil retention (SR) in the BTH increased by 16.4 × 104t/hm2, 81.81 mm, and 37081.29 t/hm2, respectively. In contrast, Carbon storage (CS) and Habit quality (HQ) exhibited a decrease of 0.01 t/hm2 and 0.03. Spatially, the high-value areas of ESs at the county scale exhibited greater clustering. At the county scale, there were two trade-offs and eight synergies in 2000, and four trade-offs and six synergies by 2020. In contrast, at the raster scale, there were two trade-offs and eight synergies from 2000 to 2020. The mechanisms of change were similar and exhibited spatial heterogeneity. Scenario 6 represents the optimal priority conservation area, exhibiting the most balanced conservation efficiency of each ecosystem service. This scenario enables the simultaneous conservation of multiple ESs. The natural factors within the PCAs exert a stronger influence on ESs than socio-economic factors. The inclusion of interacting factor effects will enhance the explanatory power of the drivers. The findings of this study can serve as a theoretical foundation for cross-scale ecosystem service management decisions.

ObjectiveTo explore the potential causal relationship between obesity and IgA nephropathy through Mendelian randomization. MethodsSummary-level data from genome-wide association studies of obesity-related shapes (body mass index, percentage body fat, waist circumference & waist-to-hip ratio) and IgA nephropathy were acquired. Inverse variance weighted analysis was utilized as a primary analytical method with weighted median and MR-Egger regression supplementing the results. Sensitivity analyses were performed for testing the reliability of the results of Mendelian randomization. ResultsThe results of two-sample Mendelian randomization indicated that, according to forward inverse variance weighted analysis, BMI （OR=1.193, 95%CI：1.104～1.289, P

Abstract Background The purpose of this study was to explore the relevant risk factors associated with biliary complications (BCs) in patients with end-stage hepatic alveolar echinococcosis (HAE) following ex vivo liver resection and autotransplantation (ELRA) and to establish and visualize a nomogram model. Methods This study retrospectively analysed patients with end-stage HAE who received ELRA treatment at the First Affiliated Hospital of Xinjiang Medical University between August 1, 2010 and May 10, 2023. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize the feature variables for predicting the incidence of BCs following ELRA. Multivariate logistic regression analysis was used to develop a prognostic model by incorporating the selected feature variables from the LASSO regression model. The predictive ability, discrimination, consistency with the actual risk, and clinical utility of the candidate prediction model were evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Internal validation was performed by the bootstrapping method. Results The candidate prediction nomogram included predictors such as age, hepatic bile duct dilation, portal hypertension, and regular resection based on hepatic segments. The model demonstrated good discrimination ability and a satisfactory calibration curve, with an area under the ROC curve (AUC) of 0.818 (95% CI 0.7417–0.8958). According to DCA, this prediction model can predict the risk of BCs occurrence within a probability threshold range of 9% to 85% to achieve clinical net benefit. Conclusions A prognostic nomogram with good discriminative ability and high accuracy was developed and validated to predict BCs after ELRA in patients with end-stage HAE.

Abstract Background WHO stated the environment is an important factor affecting the development of hospice care. The environment is the sum of factors affecting behavior besides the individual factors. Currently, a scale to comprehensively assess the hospice environment of nurse is still lacking. This study aimed to develop an instrument to investigate the environmental factors affecting hospice care of nurses. Methods Literature review and a semi-structured interview were conducted to form the items pool of the Hospice Care Environment Scale. Two rounds of Delphi expert consultation were conducted by 16 experts to revise the scale dimensions and entries to form the Hospice Care Environment Scale. A psychometric evaluation was then performed among 530 oncology nurses in a large tertiary oncology hospital in Hubei Province. The 500 valid questionnaires were randomly divided into two groups in a 1:1 ratio, sample 1 (n1 = 250) for item screening and sample 2 (n2 = 250) for quality evaluation of the resulting scale. Item analysis, reliability analysis, validity analysis and acceptability analysis were performed. Result The Hospice Care Environment Scale consists of two dimensions and 13 entries. The Cronbach’s α coefficient of the Hospice Care Environment Scale was 0.970, and the Cronbach’s α coefficient of the two dimensions were 0.952 and 0.969, respectively, with the Item-content validity index and average Scale- content validity index of the scale was both 1.000. The validation factor analysis showed the standardized path coefficients of each item were basically above 0.5, and the factor structure model was stable and suitable. The average completion time of the scale was about 3 min, which had good feasibility. Conclusion The Hospice Care Environment Scale to assess the environment of hospice care services, has good content and construct validity and reliability. This scale can provide guidance to evaluate the hospice care environment.

For studying the corrosion behavior and mechanism of tubing in high temperature and pressure vapor-liquid phase of H2S/CO2 coexistence system, the dynamic corrosion simulation experiment of P110 steel for oil casing in CO2/H2S coexisting system was carried out using the high temperature autoclave. The uniform corrosion rates and pitting corrosion rates of samples were calculated by the weight loss method, and the corrosion behavior characteristics of P110 steel in liquid phase and gas phase of CO2/H2S coexistence system were analyzed and studied by XRD, SEM/EDS and 3D optical profile microscope. Results showed that the uniform corrosion rate and pitting corrosion rate of P110 steel in the liquid phase environment were 0.026 3 and 0.208 1 mm/a, respectively, which were higher than the uniform corrosion rate(0.014 8 mm/a) and pitting corrosion rate(0.156 9 mm/a) of P110 steel in the gas phase environment. Moreover, the corrosion products formed on the surface of P110 steel in the liquid phase environment were mainly red-brown powdery loose FeCO3, and the corrosion products formed on the surface of P110 steel in the gas phase were mainly FeCO3 and black-brown dense and uniform FeS. FeS inhibited the further corrosion of the base material from corrosive medium of CO2, H2S and Cl. Besides, the corrosion of P110 steel in liquid and gas phases was mainly uniform corrosion, with localized pitting and a tendency towards localized corrosion.

Abstract Objective Cystic echinococcosis (CE) represents a profoundly perilous zoonotic disease. The advent of viral macrogenomics has facilitated the exploration of hitherto uncharted viral territories. In the scope of this investigation, our objective is to scrutinize disparities in the intestinal microbiotic ecosystems of canines dwelling in elevated terrains and those afflicted by Echinococcus infection, employing the tool of viral macrogenomics. Methods In this study, we collected a comprehensive total of 1,970 fecal samples from plateau dogs infected with Echinococcus, as well as healthy control plateau dogs from the Yushu and Guoluo regions in the highland terrain of China. These samples were subjected to viral macrogenomic analysis to investigate the viral community inhabiting the canine gastrointestinal tract. Results Our meticulous analysis led to the identification of 136 viral genomic sequences, encompassing eight distinct viral families. Conclusion The outcomes of this study hold the potential to enhance our comprehension of the intricate interplay between hosts, parasites, and viral communities within the highland canine gut ecosystem. Through the examination of phage presence, it may aid in early detection or assessment of infection severity, providing valuable insights into Echinococcus infection and offering prospects for potential treatment strategies.

Abstract Background To evaluate the hemodynamic characteristics of normal upper extremity arteries from the brachial artery to the fingertip arterioles. Methods We analyzed the characteristics and changes in the regularities of ultrasonic parameters in the upper extremity arteries of 104 healthy volunteers using color Doppler flow imaging and Angio Planewave UltraSensitive™ imaging. The measured ultrasonic parameters included the vessel diameter, blood-flow spectrum waveform, peak systolic velocity, end-diastolic velocity, resistance index, pulsatility index, ratio of PSV to EDV, blood-flow volume, along with systolic acceleration of each BA, radial artery, superficial palmar arch artery, palmar proper digital artery, and third-grade artery arch of the fingernail bed. Results From BA to FN3AA, the diameter, PSV, RI, S/D, VFlow, and slope of the artery significantly decreased (P

Abstract Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.

Abstract Exploring novel diagnostic and therapeutic biomarkers is extremely important for osteosarcoma. YME1 Like 1 ATPase (YME1L), locating in the mitochondrial inner membrane, is key in regulating mitochondrial plasticity and metabolic activity. Its expression and potential functions in osteosarcoma are studied in the present study. We show that YME1L mRNA and protein expression is significantly elevated in osteosarcoma tissues derived from different human patients. Moreover, its expression is upregulated in various primary and immortalized osteosarcoma cells. The Cancer Genome Atlas database results revealed that YME1L overexpression was correlated with poor overall survival and poor disease-specific survival in sarcoma patients. In primary and immortalized osteosarcoma cells, silencing of YME1L through lentiviral shRNA robustly inhibited cell viability, proliferation, and migration. Moreover, cell cycle arrest and apoptosis were detected in YME1L-silenced osteosarcoma cells. YME1L silencing impaired mitochondrial functions in osteosarcoma cells, causing mitochondrial depolarization, oxidative injury, lipid peroxidation and DNA damage as well as mitochondrial respiratory chain complex I activity inhibition and ATP depletion. Contrarily, forced YME1L overexpression exerted pro-cancerous activity and strengthened primary osteosarcoma cell proliferation and migration. YME1L is important for Akt-S6K activation in osteosarcoma cells. Phosphorylation of Akt and S6K was inhibited after YME1L silencing in primary osteosarcoma cells, but was strengthened with YME1L overexpression. Restoring Akt-mTOR activation by S473D constitutively active Akt1 mitigated YME1L shRNA-induced anti-osteosarcoma cell activity. Lastly, intratumoral injection of YME1L shRNA adeno-associated virus inhibited subcutaneous osteosarcoma xenograft growth in nude mice. YME1L depletion, mitochondrial dysfunction, oxidative injury, Akt-S6K inactivation, and apoptosis were detected in YME1L shRNA-treated osteosarcoma xenografts. Together, overexpressed YME1L promotes osteosarcoma cell growth, possibly by maintaining mitochondrial function and Akt-mTOR activation.

Abstract In the three-dimensional $$\mathcal{N}$$ = 6 Chern-Simons matter (ABJM) theory, the integrand for the logarithm of the scattering amplitude admits a decomposition in terms of negative geometries, which implies that all the infrared divergences concentrate in the last loop integration. We compute the infrared-finite functions that arise from performing a three-loop integration over the four-loop integrand for the logarithm of the four-point amplitude, for which we use the method of differential equations. Our results provide a direct computation of the four-loop cusp anomalous dimension of the theory, in agreement with the current all-loop integrability-based proposal. We find an apparent simplicity in the leading singularities of the integrated results, provided one works in the frame in which the unintegrated loop variable goes to infinity. Finally, our results suggest an alternating sign pattern for the integrated negative geometries in the Euclidean region.

Abstract Background Whether asthma patients could benefit from home monitoring for fractional exhaled nitric oxide (flow of 50 mL/s, FeNO50) is unknown. We explore the application value of home monitoring FeNO50 in daily asthma management. Methods Twenty-two untreated, uncontrolled asthma patients were selected. Medical history, blood and sputum samples, pulmonary function, Asthma Control Test (ACT), and other clinical data of the subjects were collected. All subjects underwent daily monitoring for four weeks using a FeNO50 monitor and mobile spirometry (mSpirometry). The diurnal differences and dynamic changes were described. Compare the effect-acting time and the relative plateau of treatment between FeNO50 and mSpirometry monitoring. Results In the first two weeks, the morning median (IQR) level of FeNO50 was 44 (35, 56) ppb, which was significantly higher than the evening median level [41 (32, 53) ppb, P = 0.028]. The median (IQR) effect-acting time assessed by FeNO50 was 4 (3, 5) days, which was significantly earlier than each measure of mSpirometry (P < 0.05). FeNO50 reached the relative plateau significantly earlier than FEV1 (15 ± 2 days vs. 21 ± 3 days, P < 0.001). After treatment, the daily and weekly variation rates of FeNO50 showed a gradually decreasing trend (P < 0.05). The ACT score, sputum eosinophils, and blood eosinophils also significantly improved (P ≤ 0.01). Conclusions The daily home monitoring of FeNO50 in asthmatic patients showed significant circadian rhythm, and the sensitivity of FeNO50 in evaluating the response to treatment was higher than mSpirometry. The daily and weekly variation rates of FeNO50 change dynamically with time, which may be used to assess the condition of asthma.

Abstract Objectives While surgery plays a crucial role in treating papillary thyroid carcinoma (PTC), the potential effects of subsequent TSH suppression therapy on prognosis should not be overlooked. This study aims to investigate the factors that influence postoperative TSH suppression therapy in patients with PTC. Methods This study was a retrospective cohort study conducted at our hospital. It included 268 patients who underwent surgery and were pathologically diagnosed with PTC between February 2019 and February 2021. The selected patients received postoperative TSH suppression therapy. Based on the TSH level measured 12 months after surgery, the patients were divided into two groups: TSH level conforming group (n = 80) and non-conforming group (n = 188). We then compared the general clinical data, clinicopathological characteristics, preoperative laboratory test indicators, postoperative levothyroxine sodium tablet dosage, follow-up frequency, and thyroid function-related indicators between the two groups of patients. The correlation between the observed indicators and the success of TSH suppression therapy was further analyzed, leading to the identification of influencing factors for TSH suppression therapy. Results There were no statistically significant differences in general clinical data and clinicopathological characteristics between the two groups of patients (P > 0.05). The proportion of patients with preoperative TSH ≥ 2.0 mU/L was higher in the non-conforming group compared to the TSH level conforming group (P

Deposition pattern and path-planning deposition strategy have significant impacts on the deformation and residual stress of components during a wire-arc additive manufacturing (WAAM) process. This work comparatively addressed the influence of weaving and non-weaving deposition patterns on the distributions of residual stress and warping deformation during a single-bead-on-plate WAAM process. Further, four path strategies with different deposition sequences (in-out and out-in) and deposition directions (alternate and consistent) were designed for a weaving WAAM process of disc part, and their impacts on temperature history, warping deformation, and residual stress were comparatively analyzed through thermal-mechanical coupling finite element (FE) method. Simulation and experiment results manifest that, compared to the non-weaving pattern, the weaving deposition pattern results in more uniform deformation and lower residual stress on the deposited plate due to wider and shallower molten pool. Comparison results for the four deposition path strategies in the weaving WAAM process of disc part suggest that the out-in deposition sequence exhibits faster heat dissipation and uniform temperature field during the cooling stage, resulting in reduced warping deformation and residual stress on the workpiece. Moreover, uniform deformation is observed across path strategies employing alternate deposition direction. The out-in alternate deposition path strategy was identified as the optimal choice for the weaving WAAM process of disc part. Finally, physical experiments validated the simulated warping deformation of disc parts under different deposition path strategies. This work contributes to the design and optimization of weaving WAAM process for disc-shaped components.

Superplastic forming is considered a highly efficient technique for shaping intricate components from titanium matrix composites (TMCs). In this work, high-temperature TMCs with 5 vol% (TiBw + TiCp) reinforcements underwent superplastic tensile tests at various temperatures and strain rates. The results demonstrated that at all deformation temperatures (900 °C–1050 °C) and strain rates (5 × 10−3 s−1 to 10−4 s−1), the elongation of composite sheets surpassed 100%. The strain rate of 10−3 s−1 and a temperature of 1000 °C were found to yield the maximum elongation of 328.1%. At 900 °C, the matrix grains maintain a lamellar morphology during the main stage of deformation, and dynamic recovery (DRV) is the primary mechanism of matrix softening. At 1000 °C, wide-range dynamic recrystallization (DRX) takes place, and grain boundary slip coordinated by grain rotation is the main mechanism of deformation. At 1050 °C, the matrix grains undergo DRX and grow rapidly by migration, and the number of grain boundaries decreases dramatically, resulting in poor superplastic qualities. In the early stages of superplastic deformation, micropores sprout at the triple grain boundaries and at the interfaces between the reinforcements and the matrix. As the deformation proceeds, the micropores extend along the tensile direction and connect with each other to form cavity stringers (CS). The distance between the CS rapidly narrows as the stretching process continues, and eventually the CS links horizontally to form cavity coalescence (CC). Micropore dilatation around the reinforcements causes debonding and cavitation, leading to material failure.

Abstract In systems exhibiting the non-Hermitian skin effect (NHSE), the bulk spectrum under open boundary conditions (OBC) significantly differs from that of its periodic counterpart. This disparity renders the conventional bulk-boundary correspondence (BBC) inapplicable. Here we propose an intuitive approach called doubling and swapping to restore the BBC, using the non-Hermitian Su-Schrieffer-Heeger model as an example. Explicitly, we construct a modified system free of NHSE by swapping the asymmetric intracell hoppings in every second primitive unit cell. Importantly, this change does not alter the OBC spectrum. As a result, the modified periodic system can serve as the bulk for defining topological invariants that accurately predict edge states and topological phase transitions. The basic principle is applicable to many other systems. By extending the study to disordered systems in which the asymmetric hoppings are randomly swapped, we show that two types of winding numbers can also be defined to account for the NHSE and topological edge states, respectively.

Abstract The goal of blind image super-resolution (BISR) is to recover the corresponding high-resolution image from a given low-resolution image with unknown degradation. Prior related research has primarily focused effectively on utilizing the kernel as prior knowledge to recover the high-frequency components of image. However, they overlooked the function of structural prior information within the same image, which resulted in unsatisfactory recovery performance for textures with strong self-similarity. To address this issue, we propose a two stage blind super-resolution network that is based on kernel estimation strategy and is capable of integrating structural texture as prior knowledge. In the first stage, we utilize a dynamic kernel estimator to achieve degradation presentation embedding. Then, we propose a triple path attention groups consists of triple path attention blocks and a global feature fusion block to extract structural prior information to assist the recovery of details within images. The quantitative and qualitative results on standard benchmarks with various degradation settings, including Gaussian8 and DIV2KRK, validate that our proposed method outperforms the state-of-the-art methods in terms of fidelity and recovery of clear details. The relevant code is made available on this link as open source.

Abstract Purpose This study aimed to evaluate the feasibility of 11C-CFT PET brain imaging in Parkinson’s Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice. Methods Thirty-two patients with Parkinson’s disease (PD) performing 11C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference. Results The overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P

Abstract Study objective To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. Design A prospective, randomized, controlled trial study. Setting A tertiary university hospital. Patients A total of 130 patients with moderate (American Fertility Society [AFS] score of 5–8) and severe (AFS score of 9–12) intrauterine adhesions were recruited. Interventions 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). Measurements and main results The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P

Abstract Exciton–polaritons (polaritons) resulting from the strong exciton–photon interaction stimulates the development of novel low-threshold coherent light sources to circumvent the ever-increasing energy demands of optical communications1–3. Polaritons from bound states in the continuum (BICs) are promising for Bose–Einstein condensation owing to their theoretically infinite quality factors, which provide prolonged lifetimes and benefit the polariton accumulations4–7. However, BIC polariton condensation remains limited to cryogenic temperatures ascribed to the small exciton binding energies of conventional material platforms. Herein, we demonstrated room-temperature BIC polariton condensation in perovskite photonic crystal lattices. BIC polariton condensation was demonstrated at the vicinity of the saddle point of polariton dispersion that generates directional vortex beam emission with long-range coherence. We also explore the peculiar switching effect among the miniaturized BIC polariton modes through effective polariton−polariton scattering. Our work paves the way for the practical implementation of BIC polariton condensates for integrated photonic and topological circuits.

Abstract Background Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa. Methods Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed. Results PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice. Conclusion Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.

Abstract Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.

Objective To explore the predictive value of monocyte-to-high-density lipoprotein (HDL) ratio (MHR) for all-cause mortality in maintenance hemodialysis (MHD) patients. Methods From November 2014 to November 2020, 100 MHD patients admitted into Blood Purification Center were recruited. At the end of the study, 24 patients died and 76 survived. The inter-group differences of general profiles, laboratory parameters, MHR, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein (CRP)-to-albumin ratio (CAR) were compared. The influencing factors of death were analyzed by Logistics regression. Based upon the level of median MHR, they were divided into two groups of high MHR (n=50) and low MHR (n=50). Survival analysis was conducted by the Kaplan-Meier method. Receiver operating characteristic (ROC) curve was plotted for assessing the predictive values of the relevant parameters for all-cause death. Results Patients were older in death group than those in survival group [77.00(71.25, 85.75) years vs 64.00(52.25, 73.75) years, P

Abstract Sugarcane is a vital crop with significant economic and industrial value. However, the cultivated sugarcane’s ultra-complex genome still needs to be resolved due to its high ploidy and extensive recombination between the two subgenomes. Here, we generate a chromosomal-scale, haplotype-resolved genome assembly for a hybrid sugarcane cultivar ZZ1. This assembly contains 10.4 Gb genomic sequences and 68,509 annotated genes with defined alleles in two sub-genomes distributed in 99 original and 15 recombined chromosomes. RNA-seq data analysis shows that sugar accumulation-associated gene families have been primarily expanded from the ZZSO subgenome. However, genes responding to pokkah boeng disease susceptibility have been derived dominantly from the ZZSS subgenome. The region harboring the possible smut resistance genes has expanded significantly. Among them, the expansion of WAK and FLS2 families is proposed to have occurred during the breeding of ZZ1. Our findings provide insights into the complex genome of hybrid sugarcane cultivars and pave the way for future genomics and molecular breeding studies in sugarcane.

The Pan-Eurasian Experiment Modelling Platform (PEEX-MP) is one of the key blocks of the PEEX Research Programme. The PEEX MP has more than 30 models and is directed towards seamless environmental prediction. The main focus area is the Arctic-boreal regions and China. The models used in PEEX-MP cover several main components of the Earth’s system, such as the atmosphere, hydrosphere, pedosphere and biosphere, and resolve the physical-chemical-biological processes at different spatial and temporal scales and resolutions. This paper introduces and discusses PEEX MP multi-scale modelling concept for the Earth system, online integrated, forward/inverse, and socioeconomical modelling, and other approaches with a particular focus on applications in the PEEX geographical domain. The employed high-performance computing facilities, capabilities, and PEEX dataflow for modelling results are described. Several virtual research platforms (PEEX-View, Virtual Research Environment, Web-based Atlas) for handling PEEX modelling and observational results are introduced. The overall approach allows us to understand better physical-chemical-biological processes, Earth’s system interactions and feedbacks and to provide valuable information for assessment studies on evaluating risks, impact, consequences, etc. for population, environment and climate in the PEEX domain. This work was also one of the last projects of Prof. Sergej Zilitinkevich, who passed away on 15 February 2021. Since the finalization took time, the paper was actually submitted in 2023 and we could not argue that the final paper text was agreed with him.

Abstract Aim To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). Methods The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. Results Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493–0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482–0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. Conclusions Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Abstract Background Elevated central venous pressure (CVP) is deemed as a sign of right ventricular (RV) dysfunction. We aimed to characterize the echocardiographic features of RV in septic patients with elevated CVP, and quantify associations between RV function parameters and 30-day mortality. Methods We retrospectively reviewed a cohort of septic patients with CVP ≥ 8 mmHg in a tertiary hospital intensive care unit. General characteristics and echocardiographic parameters including tricuspid annular plane systolic excursion (TAPSE), pulmonary vascular resistance (PVR) as well as prognostic data were collected. Associations between RV function parameters and 30-day mortality were assessed using Cox regression models. Results Echocardiography was performed in 244 septic patients with CVP ≥ 8 mmHg. Echocardiographic findings revealed that various types of abnormal RV function can occur individually or collectively. Prevalence of RV systolic dysfunction was 46%, prevalence of RV enlargement was 34%, and prevalence of PVR increase was 14%. In addition, we collected haemodynamic consequences and found that prevalence of systemic venous congestion was 16%, prevalence of RV-pulmonary artery decoupling was 34%, and prevalence of low cardiac index (CI) was 23%. The 30-day mortality of the enrolled population was 24.2%. In a Cox regression analysis, TAPSE (HR:0.542, 95% CI:0.302–0.972, p = 0.040) and PVR (HR:1.384, 95% CI:1.007–1.903, p = 0.045) were independently associated with 30-day mortality. Conclusions Echocardiographic findings demonstrated a high prevalence of RV-related abnormalities (RV enlargement, RV systolic dysfunction and PVR increase) in septic patients with elevated CVP. Among those echocardiographic parameters, TAPSE and PVR were independently associated with 30-day mortality in these patients.

Osteosarcoma (OS) is a rare but aggressive malignancy. Despite previous reports, molecular characterization of this disease is not well understood, and little is known regarding OS in Chinese patients. Herein, we analyzed the genomic signatures of 73 Chinese OS cases. TP53, NCOR1, LRP1B, ATRX, RB1, and TFE3 were the most frequently mutated gene in our OS cohort. In addition, the genomic analysis of Western OS patients was performed. Notably, there were remarkable disparities in mutational landscape, base substitution pattern, and tumor mutational burden between the Chinese and Western OS cohorts. Specific molecular mechanisms, including DNA damage repair (DDR) gene mutations, copy number variation (CNV) presence, aneuploidy, and intratumoral heterogeneity, were associated with disease progression. Additionally, 30.1% of OS patients carried clinically actionable alterations, which were mainly enriched in PI3K, MAPK, DDR, and RTK signaling pathways. A specific molecular subtype incorporating DDR alterations and CNVs was significantly correlated with distant metastasis‐free survival and event‐free survival, and this correlation was observed in all subgroups with different characteristics. These findings comprehensively elucidated the genomic profile and revealed novel prognostic factors in OS, which would contribute to understanding this disease and promoting precision medicine of this population.

Abstract Aims A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well‐known HR‐lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF. Methods and results This multicentre, single‐arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment‐emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor–neprilysin inhibitor (ARNI) or beta‐blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P

One strain of Hanseniaspora uvarum YT-35 was screened from fermented sediment of wild cherry. Hanseniaspora uvarum YT-35 and commercial Saccharomyces cerevisiae were used as coculture for manufacture of fermented wild cherry beverage. The dynamics of microbial populations, reducing sugars and ethanol were analyzed at different stages of fermentation using single-strain fermentation with 2 strains of bacteria as a control. Meanwhile, the organic acids and volatile aromatic compounds of the fermented beverages were detected by high-performance liquid chromatography (HPLC) and headspace solid-phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS). The results showed that H. uvarum YT-35 dominated in the pre-fermentation stage of co-culture. Compared with single fermentation with S. cerevisiae, the coculture fermentation resulted in lower ethanol content (3.51 g/L). Notably, HPLC results revealed that coculture fermented beverage reduced the yield of citric, malic and quinic acids and increased the yield of glacial acetic acid. HS-SPME/GC-MS results revealed that coculture fermented beverage produced more volatile compounds of esters, such as ethyl caproate, methyl benzoate and isoamyl octanoate and showed enhanced contents of ethyl laurate, ethyl octanoate, phenyl ethyl alcohol, benzyl alcohol, octanoic acid and lauric acid. Meanwhile, clustering analysis revealed that coculture fermentation were correlated with the greatest number of volatile aroma compounds in the fermented wild cherry beverage. This study provides scientific basis and theoretical guidance for the research of coculture strains with different metabolic potential in improving the quality of fruit juice fermented beverage.

Abstract Objective Intervertebral disc degeneration (IVDD) is a major cause of morbidity and disability. Our study aimed to investigate the potential of cartilage oligomeric matrix protein (COMP) and ADAMTS7 (A disintegrin and metalloproteinases with thrombospondin motifs 7) as biomarkers for IVDD together with their functional relationship. Methods IVD tissues and peripheral blood samples were collected from IVDD rabbit models over 1–4 weeks. Tissues and blood samples were also collected from clinical patients those were stratified into four equal groups according to Pfirrmann IVDD grading (I–V) with baseline data collected for each participant. COMP and ADAMTS7 expression were analyzed and biomarker characteristics were assessed using linear regression and receiver operating curve (ROC) analyses. Results COMP and ADAMTS7 expression increased in tissues and serum during IVDD progression. Serum COMP (sCOMP) and serum ADAMTS7 (sADAMTS7) levels increased in a time-dependent manner following IVD damage in the rabbit model while significant positive correlations were detected between sCOMP and sADAMTS7 and Pfirrmann grade in human subjects. ROC analysis showed that combining sCOMP and sADAMTS7 assay results produced an improved diagnostic measure for IVDD compared to individual sCOMP or sADAMTS7 tests. In vitro assays conducted on human cell isolates revealed that COMP prevented extracellular matrix degradation and antagonized ADAMTS7 expression although this protective role was uncoupled under microenvironmental conditions mimicking IVDD. Conclusions Increases in circulating COMP and ADAMTS7 correlate with IVDD progression and may play regulatory roles. Assays for sCOMP and/or sADAMTS7 levels can discriminate between healthy subjects and IVDD patients, warranting further clinical assessment.

Abstract Diffuse myocardial fibrosis is associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). Dual-energy CT (DECT) can noninvasively assess myocardial fibrosis by quantification of extracellular volume (ECV) fraction. This study evaluated the association between ECV measured by DECT and clinical outcomes in patients with HFpEF. 125 hospitalized HFpEF patients were enrolled in this retrospective cohort study. ECV was measured using DECT with late iodine enhancement. The composite endpoint was defined as HFpEF hospitalization and all-cause mortality during the follow-up. During the median follow-up of 10.4 months, 34 patients (27.20%) experienced the composite outcomes, including 5 deaths; and 29 HFpEF hospitalizations. The higher DECT-ECV group had higher rates of composite outcomes than the low ECV group (log-rank X 2 = 6.818, P = 0.033). In multivariate Cox regression analysis, the ECV (HR 1.17, 95% CI 1.06–1.30, P = 0.001) and NT-pro BNP (HR 2.83, 95% CI 1.16–6.88, P = 0.022) were independent risk factors for the adverse outcomes. Myocardial ECV measured using DECT was an independent risk factor for adverse outcomes in patients with HFpEF.

Abstract Methylation of the promoters of SHOX2 and RASSF1A (LungMe®) exhibits promise as a potential molecular biomarker for diagnosing lung cancer. This study sought to assess the aberrant methylation of SHOX2 and RASSF1A in broncho-exfoliated cells (BEC) and compare it with conventional cytology, histology examination, immunohistochemistry, and serum tumor markers to evaluate the overall diagnostic efficiency for lung cancer. This study recruited 240 patients, including 185 malignant cases and 55 benign cases. In our observation, we noted a slight reduction in the detection sensitivity, however, the ΔCt method exhibited a significant enhancement in specificity when compared to Ct judgment. Consequently, the ΔCt method proves to be a more appropriate approach for interpreting methylation results. The diagnostic sensitivity of cytology and histology was in ranged from 20.0%-35.1% and 42.9%-80%, respectively, while the positive detection rate of LungMe® methylation ranged from 70.0% to 100%. Additionally, our findings indicate a higher prevalence of SHOX2( +) among patients exhibiting medium and high expression of Ki67 (P

Abstract Background Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. Methods This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b–3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 μg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. Discussion This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. Trial registration ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.