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Abstract Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan–Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan–Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P

Abstract Background The relationship between healthy lifestyle and frailty remains unclear. Healthy weight is crucial for overall well-being, but using body mass index (BMI) to evaluate weight management is inefficient. This study clarifies the association between healthy lifestyle or its factors (non-smoking, moderate drinking, healthy weight, healthy diet, sufficeint physical activity, and non-sedentary) and frailty, and the feasibility of using the weight-adjusted waist index (WWI) reflecting central obesity as an intermediate indicator. Methods This study included 4,473 participants from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). Healthy lifestyle quality was assessed by summing the scores of each healthy lifestyle factor. Frailty was assessed using a 49-item frailty index (FI), categorizing participants into robust, pre-frail, and frail. Logistic regression to investigate the association between healthy lifestyle or its factors, WWI, and frailty. Smooth curve fitting and threshold effect analyses were used to elucidate the nonlinear association. Subgroup and two other sensitivity analyses were conducted to confirm the stability of the results. A causal mediation model examined the proportion of frailty mediated by WWI. Results The study identified 13.98% of the participants as frail. Optimal healthy lifestyle and frailty were negatively associated (OR: 0.39, 95%CI: 0.27–0.58). Five healthy lifestyle factors (non-smoking, healthy weight, healthy diet, sufficient physical activity, and non-sedentary) were associated with a lower prevalence of frailty, with odds ratios (OR) ranging from 0.48 to 0.61. We also analyzed the association between a healthy lifestyle and WWI (OR: 0.32, 95%CI: 0.27–0.37), WWI and frailty (OR: 1.85, 95%CI: 1.59–2.16). A positive association between WWI and FI was observed beyond the inflection point (9.99) (OR: 0.03, 95%CI: 0.02–0.03). Subgroup and sensitivity analyses confirmed stable associations between healthy lifestyle, WWI, and frailty. WWI partially mediated the association between a healthy lifestyle and frailty (mediating ratio = 20.50–20.65%). Conclusions An optimal healthy lifestyle and positive healthy lifestyle factors are associated with a lower incidence of frailty. WWI may mediate the relationship between a healthy lifestyle and frailty.

Abstract This study aimed to investigate the therapeutic potential of human adipose‐derived mesenchymal stem cells (hADSCs) modified with recombinant adeno‐associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate‐buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control‐hADSCs group), or rAAV VEGF165 vector (VEGF165‐hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium‐binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165‐hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain‐derived neurotrophic factor (BDNF) and glial cell‐derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV‐VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.

Abstract The recent high death tolls caused by large earthquakes are a further indication that earthquakes remain one of the most destructive natural hazards in the world and can seriously threaten the achievement of disaster reduction goals. To effectively reduce the existing seismic risk, the limited available mitigation resources should be allocated to areas with the most severe potential risk. However, identifying localized concentrations of risk requires detailed studies. Here, we propose a strategy to delineate regional high seismic risk zone at a fine resolution and with high confidence. We demonstrate this strategy by using the seismic hazard and loss estimation results for earthquake scenarios with a magnitude of Mw 7.5 for the Jiaocheng fault of the Shanxi Rift System, China. Our analyses reveal that the delineated zone accounts for only ~7% of the regional land area but for ~85% of the total financial loss. We recommend prioritizing seismic risk mitigation measures in such high-risk zones, especially for densely populated cities in seismically active areas, to better meet the disaster risk reduction targets in the Sendai Framework.

Abstract The mid-Holocene climate optimum saw warm temperatures in large parts of China, but its impact on seasonal environmental changes is not fully understood yet. Here, we use high-resolution geochemical analyses of 7000 to 6000 year-old oyster shells from the Yangtze River Delta to reconstruct climatic and oceanographic patterns. The stable isotope (δ18O, δ13C) and clumped isotope data reflect prominent seasonal changes in temperature, precipitation, and river discharge. Summer months experienced warm temperatures and a distinct increase in rainfalls and river discharge. In contrast, winter months were characterized by a dry season, which might have been longer than today. Stable isotope data also indicate regular summer upwelling in the study area. These results partly disagree with available climate models raising doubts on the models’ reliability. Thus, our palaeo-proxy data offers the possibility to evaluate and correct climate models and thereby improve predictions for the future considering on-going global warming.

Objective: To evaluate whether improved progression-free survival (PFS) from radiotherapy (RT) translates into an overall survival (OS) benefit for diffuse large B-cell lymphoma (DLBCL). Methods: A systematic literature search identified randomized controlled trials (RCTs) and retrospective studies that compared combined-modality therapy (CMT) with chemotherapy (CT) alone. Weighted regression analyses were used to estimate the correlation between OS and PFS benefits. Cohen's kappa statistic assessed the consistency between DLBCL risk-models and PFS patterns. Furthermore, the benefit trend of RT was analyzed by fitting a linear regression model to the pooled hazard ratio (HR) according to the PFS patterns. Results: For both 7 RCTs and 52 retrospective studies, correlations were found between PFS HR (HRPFS) and OS HR (HROS) at trial level (r = 0.639–0.876), and between PFS and OS rates at treatment-arm level, regardless of CT regimens (r = 0.882–0.964). Incorporating RT into CT increased about 18% of PFS, and revealed a different OS benefit profile. Patients were stratified into four CT-generated PFS patterns (>80%, >60–80%, >40–60%, and ≤40%), which was consistent with risk-stratified subgroups (kappa > 0.6). Absolute gain in OS from RT ranged from ≤5% at PFS >80% to about 21% at PFS ≤40%, with pooled HROS from 0.70 (95% CI, 0.51–0.97) to 0.48 (95% CI, 0.36–0.63) after rituximab-based CT. The OS benefit of RT was predominant in intermediate- and high-risk patients with PFS ≤ 80%. Conclusion: We demonstrated a varied OS benefit profile of RT to inform treatment decisions and clinical trial design.

The Moon and Mars are adjacent to Earth and are starting stations for human exploration of the Universe. An in-depth study of the lithospheric structure of the Moon and Mars can reveal the composition and structure of their crust and mantle systems and deepen our understanding of their origins and thermal evolution histories, providing essential references for studies of Earth's origin and evolution. With the vigorous international development of deep space exploration in recent years, the accuracy and resolution of gravity field models for the Moon and Mars have increased. Significant scientific advances have been made in the studies of lunar and Martian lithospheric structures based on gravity data. This article briefly introduces exploration plans and gravity field models for the Moon and Mars and elaborates on achievements in the lithospheric structures of the Moon and Mars by applying their gravity fields. Finally, we present a summary and outlook on research into the lithospheric structures of the Moon and Mars. Methods to overcome uncertainties in gravitational fields for studying the lithospheric structures of the Moon and Mars have been proposed. We hope that this review can assist in promoting gravity exploration on the Moon and Mars and research into their lithospheric structures.

To solve the problems of low accuracy, slow detection speed, and difficulty in deploying model parameters in surface defect detection of continuous casting production process, a lightweight surface defect detection algorithm YOLOv7-TSCR that integrates heavy parameterization and attention mechanism was proposed. Firstly, based on the Mish and SiLU activation functions and the SimAM attention mechanism, an improved high-efficiency layer aggregation module ELAN-S was constructed to effectively enhance the extraction of multi-scale defect features. Secondly, the C2f_RG module was designed to improve the feature fusion network, reducing the number of parameters while obtaining richer gradient flow information and enhancing feature fusion capabilities. Finally, based on the collected defect images from actual production, a dataset of casting defects was constructed and validated. The results show that YOLOv7-TSCR has significantly improved detection performance compared to other network models；With a reduced number of model parameters, the accuracy reaches 93.5%, the average accuracy increasesby 2.8%, and the detection speed reaches 120 FPS; The generalization comparison experiment on the NEU-DET public dataset proves that the algorithm has strong generalization. On the basis of ensuring high detection accuracy, the improved algorithm has a fast detection speed and a small number of parameters, which provides a technical reference for the efficient detection of surface defects in casting billets.

In early February 2024, severe low-temperature rainfall/snowfall and freezing weather events occurred in the eastern parts of Guizhou and the middle and lower reaches of the Yangtze River. Coinciding with the travel period of the Spring Festival, the event caused serious impacts on travel, energy supply guarantees, and people's daily lives. To reveal the exceptional characteristics of the weather event, observation data from the National Meteorological Information Center, NCEP/NCAR reanalysis data, and Huaihua dual-polarization radar data were used to analyze the characteristics and causes of rainfall/snowfall and freezing weather events. The results are as follows: (1) Severe freezing disasters lasting 4-6 days occurred in eastern Guizhou, northern and central parts of Hunan, eastern and southern parts of Hubei, and northern and western parts of Anhui. These disasters were primarily caused by two rounds of low-temperature rain and snow weather. The first round occurred around February 1 to 4, with the most severe period appearing on the 3rd. It was characterized by heavy snowfall and freezing rain, leading to rapid accumulation of snow and ice. The second round occurred from February 5 to 6, with freezing rain predominating in eastern Guizhou and northern and central parts of Hunan, and sleet predominating along the Yangtze River in Hubei and other areas, which sustained or further increased the ice accumulation. (2) The geopotential height anomaly of the mid to high latitudes in Asia showed a distribution of low in the west and high in the east, and the southern trough was active. Both provided important weather conditions for the low-temperature rain and snow weather. The strong southwest jet stream climbs along the front to form a tilted upward airflow, enhancing the precipitation intensity behind the front, and leading to the first round of the weather event. The weakening of the southern trough and the maintenance of the southern front area, the mid-to-low low-level jet, and the surface stationary front resulted in the second round of the weather event. (3) Affected by the formation and maintenance of the South China stationary front and the Yunnan-Guizhou stationary front, the range of inversion was wide, with a significant warm layer in the southern region of the Yangtze River, resulting in different phases of precipitation on the south and north sides of the Yangtze River. Meanwhile, there were significant differences in the vertical direction of the temperature and humidity fields on the north and south sides of the Yangtze River. When heavy snowfall dominated north of the Yangtze River, the temperature and humidity fields exhibited deep cold-wet characteristics, with a typical ice-phrase structure. However, when heavy freezing rain dominated south of the Yangtze River, the temperature and humidity fields exhibited a"strong warm-wet and cold-wet"feature. (4) The rapidly increasing amount of rainwater, ice, and snow formed strong wet snow and severe freezing rain on February 3-4. The low-level supercooled water of both light and heavy rain droplets coexisted in the southern region of the Yangtze River on the night of the 3rd day, while it was dominated by light rain on the night of the 5th day.

Abstract Background The metastasis of cancer cells is influenced by both their intrinsic characteristics and the tumor microenvironment (TME). However, the molecular mechanisms underlying pre-nodal metastases of breast cancer remain unclear. Methods We integrated a total of 216,963 cells from 54 samples across 6 single-cell datasets to profile the cellular landscape differences between primary tumors and pre-nodal metastases. Results We revealed three distinct metastatic epithelial cell subtypes (Epi1, Epi2 and Epi3), which exhibited different metastatic mechanisms. Specifically, the marker gene KCNK15 of the Epi1 subtype exhibited increased gene expression along the cell differentiation trajectory and was specifically regulated by the transcription factor ASCL1. In the Epi3 subtype, we highlighted NR2F1 as a regulator targeting the marker gene MUCL1. Additionally, we found that the Epi2 and Epi3 subtypes shared some regulons, such as ZEB1 and NR2C1. Similarly, we identified specific subtypes of stromal and immune cells in the TME, and discovered that vascular cancer-associated fibroblasts might promote capillary formation through CXCL9+ macrophages in pre-nodal metastases. All three subtypes of metastatic epithelial cells were associated with poor prognosis. Conclusions In summary, this study dissects the intratumoral heterogeneity and remodeling of the TME in pre-nodal metastases of breast cancer, providing novel insights into the mechanisms underlying breast cancer metastasis.

Abstract Currently, there is still debate over the effectiveness of transcranial direct current stimulation (tDCS) in treating obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and anxiety disorders (ADs). To investigate the immediate and long-term effectiveness of tDCS in these diseases, we conducted a systematic review and quantitative analysis of existing literature on the treatment of OCD, PTSD, and ADs with tDCS. Following the PRISMA guidelines, we searched seven electronic databases and systematically retrieved articles published from May 2012 to June 2024 that compared the effects of active tDCS with sham stimulation in the treatment of these disorders. We included primary outcome measures such as the change scores in disorder-specific and general anxiety symptoms before and after treatment, as well as secondary outcomes such as changes in disorder-specific and general anxiety symptoms at follow-up. We also assessed the impact of tDCS on depressive symptoms. Fifteen papers met the eligibility criteria. Overall, the results of meta-analysis indicated that tDCS had a high effect in improving specific symptoms (SMD = −0.73, 95% CI: −1.09 to −0.37) and general anxiety symptoms (SMD = −0.75; 95% CI: −1.23 to −0.26) in OCD, PTSD and ADs, with effects lasting up to 1 month and showing a moderate effect size. Furthermore, tDCS demonstrated immediate and significant alleviation of depressive symptoms in these diseases. This study concludes that tDCS can serve as a non-invasive brain stimulation technology for treating these disorders, and the therapeutic effects can be maintained for a period of time.

Abstract Objective To elucidate the impact and predictive value of the Triglyceride Glucose Index (TyG) and the ratio of Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) in identifying the risk of diabetes progression in Chinese individuals with prediabetes. Methods This longitudinal study enrolled 15,012 prediabetic adults from the Rich Healthcare Group between 2010 and 2016. Diabetes was defined as self-reported diabetes or a fasting glucose level ≥ 7.0 mmol/L. The Cox proportional hazards models was utilized to assess the relationship between the two indices and the risk of developing diabetes. The predictive efficacy of the two markers was gauged by the area under the curve (AUC). Results Over a median follow-up period of 2.87 years, 1,730 (11.5%) prediabetic participants developed diabetes. The adjusted hazard ratios for the top quartile of the TyG index and the TG/HDL-C ratio were 2.03 (95% confidence interval [CI]: 1.71–2.40) and 2.59 (95% CI: 2.20–3.05), respectively, compared to the lowest quartile. A significant trend of increasing diabetes risk with higher quartiles of both indices was observed. The AUC for the adjusted prediction model for prediabetes-to-diabetes transition was 0.726 for the TyG index and 0.710 for the TG/HDL-C ratio. The difference in AUCs was statistically significant (P = 0.03). Conclusions The baseline TyG index or TG/HDL-C ratio was significantly associated with an increased risk of diabetes in prediabetic individuals. The TyG index demonstrated superior predictive accuracy, underscoring its importance in preventing diabetes in prediabetic individuals.

In 60Co based computed tomography (CT) of carbon components，reducing the number of sampling angles can significantly shorten detection time and improve detection efficiency. However，for conventional analytical reconstruction algorithms，sparse angle reconstruction images contain a large amount of noise and artifacts，which interfere with the detection of defects in the images and affect the quality evaluation of the inspected components by the detection system under fast detection conditions. This article proposes a sparse angle CT image reconstruction method based on neuralnetwork，which uses an untrained encoding decoding neural network to optimize the projection error of the reconstructed image，and uses the ADAM algorithm to optimize the total variation prior of the image. Compared with traditional deep learning reconstruction algorithms，this method does not require training sample sets and has stronger generalization ability and robustness. The results of simulation and practical experiments show that compared to traditional analytical and reconstruction algorithms，this method significantly improves the quality of reconstructed images，while retaining the detailed information of the detected components，and significantly suppresses artifacts and noise in the reconstructed images retaining image details and texture. This work can effectively improve image quality，eliminate the interference of artifacts on the identification of defects in graphics，and improve the ability to recognize defects in carbon components for the detection system.

Abstract Xanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot in Brassica vegetables, which can induce the host plant to produce salicylic acid and 4-hydroxybenzoic acid (4-HBA) during infection. Xcc was previously shown to sense and degrade host plant-derived 4-HBA via the sensor PobR and a PobA-dependent pathway. The degradation of 4-HBA is associated with Xcc virulence in cabbage. The present study generated a reporter strain XC1::PpobA-gusA to monitor pobA transcription. 4-HBA-like compounds were screened for their ability to interfere with pobA transcription. Benzoic acid (BA) was found to efficiently decrease pobA transcription in a dose-dependent manner. Xcc neither produced nor degraded BA; however, the exogenous addition of BA to the 4-HBA-containing Xcc culture significantly decreased the 4-HBA degradation rate. Furthermore, addition of BA into the Xcc culture did not significantly affect the transcription of pobA or pobR; however, addition of BA into the 4-HBA-containing culture significantly decreased the transcription of both genes. Isothermal titration calorimetry and an electrophoretic mobility shift assay revealed that BA binds to PobR with a moderate affinity, which interfered with the binding of 4-HBA/PobR complex to the pobA promoter and thereby inhibiting pobA transcription and 4-HBA degradation. The endogenous BA level of the infected cabbage leaves increased in response to Xcc infection. In the presence of BA, the virulence of Xcc on cabbage decreased significantly. Taken together, these results suggest that cabbage utilizes BA to interfere with 4-HBA degradation, thereby reducing Xcc virulence. Thus, BA has the potential to be developed as a bactericide against Xcc infection.

Abstract N-Myc is a key driver of neuroblastoma and neuroendocrine prostate cancer (NEPC). One potential way to circumvent the challenge of undruggable N-Myc is to target the protein homeostasis (proteostasis) system that maintains N-Myc levels. Here, we identify heat shock protein 70 (HSP70) as a top partner of N-Myc, which binds a conserved “SELILKR” motif and prevents the access of E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1), possibly through steric hindrance. When HSP70’s dwell time on N-Myc is increased by treatment with the HSP70 allosteric inhibitor, STUB1 is in close proximity with N-Myc and becomes functional to promote N-Myc ubiquitination on the K416 and K419 sites and forms polyubiquitination chains linked by the K11 and K63 sites. Notably, HSP70 inhibition significantly suppressed NEPC tumor growth, increased the efficacy of aurora kinase A (AURKA) inhibitors, and limited the expression of neuroendocrine-related pathways.

Abstract Dental pulp stem cells (DPSC) have shown osteogenic and bone regenerative potential. Improving the in situ bone regeneration potential of DPSC is crucial for their application as seed cells during bone defect reconstruction in clinics. This study aimed to develop DPSC-derived organoid-like microspheroids as effective seeds for bone tissue engineering applications. DPSC osteogenic microspheroids (70 μm diameter) were cultured in a polydimethylsiloxane-mold-based agarose-gel microwell-culture-system with or without cannabidiol (CBD)-treatment. Results of in vitro studies showed higher osteogenic differentiation potential of microspheroids compared with 2D-cultured-DPSC. CBD treatment further improved the osteogenic differentiation potential of microspheroids. The effect of CBD treatment in the osteogenic differentiation of microspheroids was more pronounced compared with that of CBD-treated 2D-cultured-DPSC. Microspheroids showed a higher degree of bone regeneration in nude mice calvarial bone defect compared to 2D-cultured-DPSC. CBD-treated microspheroids showed the most robust in situ bone regenerative potential compared with microspheroids or CBD-treated 2D-cultured-DPSC. According to mRNA sequencing, bioinformatic analysis, and confirmation study, the higher osteogenic potential of CBD-treated microspheroids was mainly attributed to WNT6 upregulation. Taken together, DPSC microspheroids have robust osteogenic potential and can effectively translate the effect of in vitro osteoinductive stimulation during in situ bone regeneration, indicating their application potential during bone defect reconstruction in clinics.

Abstract Wearable devices especially smartwatches are widely used in our daily life. With their increased use, a large amount of sensitive data are collected, stored, and managed in those devices. To protect sensitive data, encryption is often used but, traditional encryption is vulnerable to a novel coercive attack in which the adversary can capture the device’s user and coerce the user to disclose the decryption key. To defend against the coercive attack, Plausibly Deniable Encryption (PDE) has been designed which can allow the victim user to deny the existence of hidden sensitive data. The PDE systems have been explored broadly for smartphones. However, the PDE systems which are suitable for wearable devices are still missing in the literature. In this work, we have designed MobiWear, the first PDE system specifically designed for wearable devices. By leveraging PDE, image steganography as well as watermarking, MobiWear ensures plausible deniability and can be easily deployed at the application layer. In addition, MobiWear relies on sensors equipped with the wearable devices to enter passwords, accommodating the wearable devices which have small-size screens and are inconvenient for entering plaintext. Security analysis and experimental evaluation using a real-world prototype (ported to an LG G smartwatch) show that MobiWear can ensure the deniability with a small computational overhead as well as a tiny degradation of the perceived quality of the image.

Abstract Background Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), which accounts for approximately one-fifth of all BCs, are highly invasive with a high rate of recurrence and a poor prognosis. Several studies have shown that growth factor receptor-bound protein 7 (GRB7) might be a potential therapeutic target for tumor diagnosis and prognosis. Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated. The aim of this study was to investigate the biological function and regulatory mechanism of GRB7 in HER2+ BC. Methods Bioinformatics analysis was performed using the TCGA, GEO and CancerSEA databases to evaluate the clinical significance of GRB7. RT quantitative PCR, western blot and immunofluorescence were conducted to assess the expression of GRB7 in BC cell lines and tissues. MTT, EdU, colony formation, wound healing, transwell, and xenograft assays were adopted to explore the biological function of GRB7 in HER2+ BC. RNA sequencing was performed to analyze the signaling pathways associated with GRB7 in SK-BR-3 cells after the cells were transfected with GRB7 siRNA. Chromatin immunoprecipitation analysis (ChIP) and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of GRB7 in HER2+ BC. Results GRB7 was markedly upregulated and associated with poor prognosis in BC, especially in HER2+ BC. Overexpression of GRB7 increased the proliferation, migration, invasion, and colony formation of HER2+ BC cells, while depletion of GRB7 had the opposite effects in HER2+ BC cells and inhibited xenograft growth. ChIP-PCR and luciferase reporter assay revealed that TCF12 directly bound to the promoter of the GRB7 gene to promote its transcription. GRB7 facilitated HER2+ BC epithelial-mesenchymal transition (EMT) progression by interacting with Notch1 to activate Wnt/β-catenin pathways and other signaling (i.e., AKT, ERK). Moreover, forced GRB7 overexpression activated Wnt/β-catenin to promote EMT progression, and partially rescued the inhibition of HER2+ BC proliferation, migration and invasion induced by TCF12 silencing. Conclusions Our work elucidates the oncogenic role of GRB7 in HER2+ BC, which could serve as a prognostic indicator and promising therapeutic target.

Abstract Background At present, the guidelines for urology recommend percutaneous nephrolithotomy (PCNL) as the preferred treatment for staghorn renal calculi (SRC). However, for complete SRC, it has been questioned by clinicians and patients due to high residual stone rate, complications, repeated hospitalizations and high treatment cost. Anatrophic nephrolithotomy (ANL) is a traditional and classic method for the treatment of SRC. Due to its high trauma and high technical requirements, it is difficult to carry out in primary hospitals, and gradually replaced by PCNL. The purpose of this study is to compare the efficacy of PCNL and ANL in the treatment of complete SRC. Methods Overall, 238 patients with complete SRC were divided into mini-PCNL in lateral supine position group, (n = 190) and ANL group (n = 94) according to treatment for a retrospective cohort study. The calculi parameters, renal function index, comorbidities of calculi, surgical complications, length and frequency of hospitalization, treatment costs, results of postoperative satisfaction survey were compared between the two groups. Results The risk of the residual stone rate after mini-PCNL in lateral supine position was 239 times (OR = 238.667, P

Abstract This paper provides an in-depth discussion on the comprehensive requirements analysis, design implementation, algorithm optimization, and experimental evaluation of an electric power marketing information system, aiming to build a modern information system that is efficient, secure, and user-friendly. In the requirements analysis phase, the importance of business process optimization, data management analysis, security compliance, system integration and scalability is emphasized, while the diversified needs of end customers are considered. For the design and implementation part, the system architecture is based on microservices and cloud-native technologies to ensure high performance and security; and modularized development is achieved through Spring Boot, Vue.js and other technology stacks. For algorithm optimization, LSTM is used for power demand prediction and anomaly detection by combining integrated learning and self-encoder, which improves the prediction accuracy and anomaly identification capability. Experimental evaluation shows that the system demonstrates good performance, security and scalability in cloud computing environment, and the cost-effectiveness is significantly better than traditional deployment.

Abstract Objective Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. Methods Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). Results The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. Conclusion The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Abstract Diabetic retinopathy (DR), a well-known microvascular complication of diabetes mellitus, remains the main cause of vision loss in working-age adults worldwide. Up to now, there is a shortage of information in the study regarding the contributing factors of DR in diabetes. Accumulating evidence has identified glycemic variability (GV), referred to fluctuations of blood glucose levels, as a risk factor for diabetes-related complications. Recent reports demonstrate that GV plays an important role in accounting for the susceptibility to DR development. However, its exact role in the pathogenesis of DR is still not fully understood. In this review, we highlight the current landscape and relevant mechanisms of GV in DR, as well as address the mechanism-based therapeutic strategies, aiming at better improving the quality of DR management in clinical practice.

Abstract Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.

Abstract Background The atherogenic index of plasma (AIP) is a critical metric for predicting cardiovascular outcomes. However, its associations with cardiovascular disease mortality (CVM) and all-cause mortality (ACM) remain unclear. This study aims to elucidate the relationship between baseline AIP levels and CVM and ACM among a broad cohort of US adults. Methods Utilizing data from the National Health and Nutrition Examination Survey (2005–2018), we analyzed 18,133 adults aged ≥ 18. Baseline triglycerides and high-density lipoprotein cholesterol levels were measured to calculate the AIP. Mortality outcomes were determined through linkage with the National Death Index database, with follow-up through December 31, 2019. Multivariable Cox proportional hazard models examined the associations between baseline AIP and mortality risks. Additionally, restricted cubic splines were utilized to investigate potential non-linear relationships, with subgroup analyses conducted across strata defined by age, gender, body mass index, diabetes, hypertension, and metabolic syndrome to assess variability in these associations. Results Over a median 95.0-month follow-up, there were 1870 all-cause deaths and 579 cardiovascular disease-related deaths. Our findings indicate a J-shaped association between the AIP and ACM (threshold = 0.0905); specifically, when baseline AIP exceeded 0.0905, a significant positive association with ACM emerged (hazard ratio, HR (95% confidence interval, CI): 1.61(1.08–2.37)). However, after adjusting for confounders, the relationship between AIP and CVM was not statistically significant (HR 1.31, 95% CI 0.93–1.86). Notably, in the 40–60-year age group, AIP was significantly positively associated with ACM and CVM, with HRs and 95% CIs of 1.51 (1.08v2.10) and 2.63 (1.39–4.98), respectively. Conclusions A J-shaped relationship was observed between baseline AIP levels and ACM within the general US population, with a threshold of 0.0905. Moreover, AIP could potentially be an effective predictor for future ACM or CVM, particularly among individuals aged 40–60. Further investigation is warranted to corroborate these findings.

Limited cells and factors, inadequate mechanical properties, and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds. Herein, we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure. The hydrogel scaffold possesses the characteristics of extracellular matrix; Meanwhile, the fabricated hybrid double network structure by polyacrylamide and CaCl2-crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability. Furthermore, the O2 generated by CaO2 nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8, which can significantly promote cell viability and proliferation in vitro, as well as angiogenesis and osteogenic differentiation with the assistance of Zn2+. More significantly, the synergy of O2 and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need, which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect in vivo. Overall, this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative.

Abstract Background Anti-vascular endothelial growth factor monoclonal antibody (anti-VEGF) or immune checkpoint inhibitors (ICIs) combined with chemotherapy are commonly administered to cancer patients. Although cancer patients receiving anti-VEGF or ICIs have been reported to experience an increased risk of acute kidney injury (AKI), comparative studies on the AKI incidence have not been evaluated. Methods Cancer patients receiving anti-VEGF or ICIs were retrospectively selected from the hospital information system of the First Affiliated Hospital of Wenzhou Medical University between Jan, 2020 and Dec, 2022 and were divided into two groups according to the treatment regimen: anti-VEGF group and ICIs group. The baseline characteristics were propensity-score matched. The primary outcome was sustained AKI. A comparison of cumulative incidence of sustained AKI was performed by Kaplan-Meier curves and log-rank test. Risks for outcomes were assessed using Cox proportional regression. Results A total of 1581 cancer patients receiving anti-VEGF (n = 696) or ICIs (n = 885) were included in the primary analysis. The ICIs group had a higher cumulative incidence of sustained AKI within one year than the anti-VEGF group (26.8% vs. 17.8%, P 35 g/l) was an important risk factor for a lower incidence of sustained AKI in the anti-VEGF group (HR 0.5; 95%CI 0.3 to 0.9; P = 0.027) and the ICIs group (HR 0.3; 95%CI 0.2 to 0.5; P

Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a major cause of malignant tumors and cancer-related deaths in China, accounting for approximately 85% of all cancer cases in the country. Several guidelines have been used to diagnose and treat liver cancer. However, these guidelines provide a broad definition for classifying advanced liver cancer, with an emphasis on a singular approach, without considering treatment options for individual patients. Therefore, it is necessary to establish a comprehensive and practical expert consensus, specifically for China, to enhance the diagnosis and treatment of HCC using the Delphi method. The classification criteria were refined for Chinese patients with HCC, and the corresponding optimal treatment regimen recommendations were developed. These recommendations took into account various factors, including tumor characteristics, vascular tumor thrombus grade, distant metastasis, liver function status, portal hypertension, and the hepatitis B virus replication status of patients with primary HCC, along with treatment prognosis. The findings and recommendations provide detailed, scientific, and reasonable individualized diagnosis and treatment strategies for clinicians.

Abstract Background There is currently a lack of comprehensive prevalence information on arthritis and its various classifications among adults in the U.S., particularly given the notable absence of detailed data regarding the Asian population. We examined the trends in the prevalence of arthritis, including osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and other types of arthritis, among U.S. adults by race between 2011 and 2018. Methods We analyzed data from the National Health and Nutrition Examination Survey (NHANES), spanning from 2011 to 2018. Our study focused on a nationally representative sample of U.S. adults aged 20 and older. Participants who answered “y es” to the research question “Doctors ever said you had arthritis?” were classified as having arthritis. Further classification into specific diseases was based on responses to the question “Which type of arthritis was it?” with options including “OA or degenerative arthritis, ” “RA, ” “PsA, ” or “Other. ” Results We analyzed 22,566 participants from NHANES (2011–2018), averaging 44.8 years, including 10,927 males. The overall arthritis prevalence rose significantly from 22.98% (95% CI: 21.47–24.55%) in 2011–12 to 27.95% (95% CI: 26.20–29.76%) in 2017–18 (P for trend

Abstract Background Blood homocysteine (Hcy) level has become a sensitive indicator in predicting the development of cardiovascular disease. Studies have shown an association between individual mineral intake and blood Hcy levels. The effect of mixed minerals’ intake on blood Hcy levels is unknown. Methods Data were obtained from the baseline survey data of the Shanghai Suburban Adult Cohort and Biobank(SSACB) in 2016. A total of 38273 participants aged 20–74 years met our inclusion and exclusion criteria. Food frequency questionnaire (FFQ) was used to calculate the intake of 10 minerals (calcium, potassium, magnesium, sodium, iron, zinc, selenium, phosphorus, copper and manganese). Measuring the concentration of Hcy in the morning fasting blood sample. Traditional regression models were used to assess the relationship between individual minerals’ intake and blood Hcy levels. Three machine learning models (WQS, Qg-comp, and BKMR) were used to the relationship between mixed minerals’ intake and blood Hcy levels, distinguishing the individual effects of each mineral and determining their respective weights in the joint effect. Results Traditional regression model showed that higher intake of calcium, phosphorus, potassium, magnesium, iron, zinc, copper, and manganese was associated with lower blood Hcy levels. Both Qg-comp and BKMR results consistently indicate that higher intake of mixed minerals is associated with lower blood Hcy levels. Calcium exhibits the highest weight in the joint effect in the WQS model. In Qg-comp, iron has the highest positive weight, while manganese has the highest negative weight. The BKMR results of the subsample after 10,000 iterations showed that except for sodium, all nine minerals had the high weights in the joint effect on the effect of blood Hcy levels. Conclusion Overall, higher mixed mineral’s intake was associated with lower blood Hcy levels, and each mineral contributed differently to the joint effect. Future studies are available to further explore the mechanisms underlying this association, and the potential impact of mixed minerals’ intake on other health indicators needs to be further investigated. These efforts will help provide additional insights to deepen our understanding of mixed minerals and their potential role in health maintenance.

Abstract Fine particulate matter produced during the rapid industrialization over the past decades can cause significant harm to human health. Twin-fluid atomization technology is an effective means of controlling fine particulate matter pollution. In this paper, the influences of the main parameters on the droplet size, effective atomization range and sound pressure level (SPL) of a twin-fluid nozzle (TFN) are investigated, and in order to improve the atomization performance, a multi-objective synergetic optimization algorithm is presented. A multi-physics coupled acoustic-mechanics model based on the discrete phase model (DPM), large eddy simulation (LES) model, and Ffowcs Williams-Hawkings (FW-H) model is established, and the numerical simulation results of the multi-physics coupled acoustic-mechanics method are verified via experimental comparison. Based on the analysis of the multi-physics coupled acoustic-mechanics numerical simulation results, the effects of the water flow on the characteristics of the atomization flow distribution were obtained. A multi-physics coupled acoustic-mechanics numerical simulation result was employed to establish an orthogonal test database, and a multi-objective synergetic optimization algorithm was adopted to optimize the key parameters of the TFN. The optimal parameters are as follows: A gas flow of 0.94 m3/h, water flow of 0.0237 m3/h, orifice diameter of the self-excited vibrating cavity (SVC) of 1.19 mm, SVC orifice depth of 0.53 mm, distance between SVC and the outlet of nozzle of 5.11 mm, and a nozzle outlet diameter of 3.15 mm. The droplet particle size in the atomization flow field was significantly reduced, the spray distance improved by 71.56%, and the SPL data at each corresponding measurement point decreased by an average of 38.96%. The conclusions of this study offer a references for future TFN research.

Abstract Hydrocarbon contamination, including contamination with polycyclic aromatic hydrocarbons (PAHs), is a major concern in Antarctica due to the toxicity, recalcitrance and persistence of these compounds. Under the Antarctic Treaty, nonindigenous species are not permitted for use in bioremediation at polluted sites in the Antarctic region. In this study, three bacterial consortia (C13, C15, and C23) were isolated from Antarctic soils for phenanthrene degradation. All isolated bacterial consortia demonstrated phenanthrene degradation percentages ranging from 45 to 85% for 50 mg/L phenanthrene at 15 ℃ within 5 days. Furthermore, consortium C13 exhibited efficient phenanthrene degradation potential across a wide range of environmental conditions, including different temperature (4–30 ℃) and water availability (without polyethylene glycol (PEG) 6000 or 30% PEG 6000 (w/v)) conditions. Sequencing analysis of 16S rRNA genes revealed that Pseudomonas and Pseudarthrobacter were the dominant genera in the phenanthrene-degrading consortia. Moreover, six cultivable strains were isolated from these consortia, comprising four strains of Pseudomonas, one strain of Pseudarthrobacter, and one strain of Paeniglutamicibacter. These isolated strains exhibited the ability to degrade 50 mg/L phenanthrene, with degradation percentages ranging from 4 to 22% at 15 ℃ within 15 days. Additionally, the constructed consortia containing Pseudomonas spp. and Pseudarthrobacter sp. exhibited more effective phenanthrene degradation (43–52%) than did the individual strains. These results provide evidence that Pseudomonas and Pseudarthrobacter can be potential candidates for synergistic phenanthrene degradation at low temperatures. Overall, our study offers valuable information for the bioremediation of PAH contamination in Antarctic environments.

Abstract Background The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as “fit” by comprehensive geriatric assessment (CGA). Methods A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of “fit” (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). Results One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). Conclusion This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. Trial registration The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Balancing the strength, ductility and Elastic modulus of β-Ti alloys is still a great challenge for medical implantation, extremely limiting its further applications. Herein, we prepared a fine-grain β-type Ti–24Nb–4Zr-2.5Mn alloy with high performance by adding CaB6 deoxidizer via mechanical alloying and spark plasma sintering. The effects of CaB6 addition on the microstructure and mechanical properties were systematically investigated, and the results show that adding a trace amount of CaB6 will form in-situ nano-sized CaTiO3 particles and micro-sized (Ti,Nb)B2 solid solution whiskers, which can significantly refine the grain size and inhibit the grain boundary movement and dislocation motion, thus improving the comprehensive mechanical properties of Ti–24Nb–4Zr-2.5Mn alloys. With a trace addition of 0.1 wt% CaB6, the Ti–24Nb–4Zr-2.5Mn alloy exhibits an excellent combination of high strength of ∼971 MPa, good ductility of ∼17.8% and low elastic modulus of ∼79.1 GPa. This work may provide a new methodology to prepare high-performance biomedical Ti alloys.

Convolutional Neural Network (CNN) is widely used for image target classifications in Synthetic Aperture Radar (SAR), but the lack of mechanism transparency prevents it from meeting the practical application requirements, such as high reliability and trustworthiness. The Class Activation Mapping (CAM) method is often used to visualize the decision region of the CNN model. However, existing methods are primarily based on either channel-level or space-level class activation weights, and their research progress is still in its infancy regarding more complex SAR image datasets. Based on this, this paper proposes a CNN model visualization method for SAR images, considering the feature extraction ability of neurons and their current network decisions. Initially, neuronal activation values are used to visualize the capability of neurons to learn a target structure in its corresponding receptive field. Further, a novel CAM-based method combined with channel-wise and spatial-wise weights is proposed, which can provide the foundation for the decision-making process of the trained CNN models by detecting the crucial areas in SAR images. Experimental results showed that this method provides interpretability analysis of the model under different settings and effectively expands the application of CNNs for SAR image visualization.

Abstract This study aimed to analyze peripheral blood lymphocyte subsets in lupus nephritis (LN) patients and use machine learning (ML) methods to establish an effective algorithm for predicting co-infection in LN. This study included 111 non-infected LN patients, 72 infected LN patients, and 206 healthy controls (HCs). Patient information, infection characteristics, medication, and laboratory indexes were recorded. Eight ML methods were compared to establish a model through a training group and verify the results in a test group. We trained the ML models, including Logistic Regression, Decision Tree, K-Nearest Neighbors, Support Vector Machine, Multi-Layer Perceptron, Random Forest, Ada boost, Extreme Gradient Boosting (XGB), and further evaluated potential predictors of infection. Infected LN patients had significantly decreased levels of T, B, helper T, suppressor T, and natural killer cells compared to non-infected LN patients and HCs. The number of regulatory T cells (Tregs) in LN patients was significantly lower than in HCs, with infected patients having the lowest Tregs count. Among the ML algorithms, XGB demonstrated the highest accuracy and precision for predicting LN infections. The innate and adaptive immune systems are disrupted in LN patients, and monitoring lymphocyte subsets can help prevent and treat infections. The XGB algorithm was recommended for predicting co-infection in LN.

Abstract The deep coalbed methane (CBM) resources are widely developed in the Linxing Block. However, the evaluation of CBM geological areas suitable for CBM exploitation remains unexplored, hindering further development. This research optimizes the key geological parameters that influence the development of deep CBM from the perspectives of resource and development conditions. The evaluation system for deep CBM recoverability has been established, and the multi-fuzzy evaluation method has been used to perform the quantitative evaluation of recoverability. The results indicate that the resource conditions of No.8 + 9 coal seam are superior to those of No.4 + 5 coal seam. Favorable resource conditions are predominantly concentrated in the northeast and specific southern portions of the research area. Favorable development conditions for both coal seams are mostly concentrated in the northeastern area. Based on the classification standard of recoverable favorable areas, the Level II area is crucial for the development of No.4 + 5 coal seam. This area is primarily distributed in the northeast of the research area., Both Level I and Level II areas for the No. 8 + 9 coal seam are situated in the northeast. The Level III area is earmarked for deep CBM production and shows potential for exploration. Further analysis reveals that the resource conditions in the favorable area are generally superior to the development conditions. These areas are classified as Class A, including categories such as I-A, II-A, and III-A, indicating relatively complex reservoir transformation.

Abstract Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value

Summary: Claudin18.2 has been recently recognized as a potential therapeutic target for gastric/gastroesophageal junction or pancreatic cancer. Here, we develop a Claudin18.2-directed antibody-drug conjugate (ADC), CMG901, with a potent microtubule-targeting agent MMAE (monomethyl auristatin E) and evaluate its preclinical profiles. In vitro studies show that CMG901 binds specifically to Claudin18.2 on the cell surface and kills tumor cells through direct cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and bystander killing activity. In vivo pharmacological studies show significant antitumor activity in patient-derived xenograft (PDX) models. Toxicity studies show that the major adverse effects related to CMG901 are reversible hematopoietic changes attributed to MMAE. The highest non-severely toxic dose (HNSTD) is 6 mg/kg in cynomolgus monkeys and 10 mg/kg in rats once every 3 weeks. CMG901’s favorable preclinical profile supports its entry into the human clinical study. CMG901 is currently under phase 3 investigation in patients with advanced gastric/gastroesophageal junction adenocarcinoma expressing Claudin18.2 (NCT06346392).

Ureteral endometriosis accounts for about 5 % of urologic endometriosis, with a peak incidence in the age group of 30–35 years, usually with unilateral onset. Because of its insidious onset, often combined with asymptomatic loss of renal function, and the ineffectiveness of medications, surgery is the gold standard of treatment.Thus, here we report a case of ureteral endometriosis with severe hydronephrosis to raise awareness of this condition.

ObjectivesTo evaluate the intima-media thickness (IMT) and elasticity of the carotid artery in non-obese polycystic ovary syndrome (PCOS) patients using a quantitative technique for vascular elasticity measurement and to explore the influencing factors.MethodsSixty non-obese patients without metabolic and cardiovascular diseases who were diagnosed with PCOS in the Women and Children’s Hospital of Chongqing Medical University from January to December 2022 were prospectively selected (case group), and 60 healthy volunteers matched for body mass index were included as the control group. Body weight, height, heart rate, blood pressure, and waist-to-hip ratio were recorded. Fasting blood samples were drawn from the elbow vein to measure hormone levels including total testosterone (TT), sex hormone-binding globulin (SHBG), fasting plasma glucose (FPG), fasting insulin (FINS), lipids, and homocysteine (Hcy). The insulin resistance index (HOMA-IR) and free androgen index (FAI) were calculated. Ultrasound elastography was used to measure the IMT and elastic function parameters of the right carotid artery, including vessel diameter, wall displacement, stiffness coefficient, and pulse wave velocity. Differences in various parameters between the two groups were analyzed, and correlations between the carotid stiffness coefficient and other serological indicators were assessed using Spearman correlation analysis.ResultsNo significant differences in age, body mass index, heart rate, systolic blood pressure, and diastolic blood pressure were observed between the two groups (all P>0.05), while the waist-to-hip ratio (WHR) was higher in the case group than in the control group (P0.05), and serum FINS, HOMA-IR, and Hcy levels were significantly higher in the case group than in the control group (all P0.05). The carotid artery displacement in the case group was significantly smaller than that in the control group (P

Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multi-disciplinary team (MDT) and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.

Summary: Stapokibart (CM310) is a humanized IL-4Rα monoclonal antibody currently undergoing phase 3 trials for type 2 inflammatory diseases. In contrast to dupilumab, which bound exclusively to human IL-4Rα, stapokibart demonstrated cross-species reactivity to IL-4Rα from human, cynomolgus monkey, and rat. Stapokibart exhibited comparable blocking activity to dupilumab. Epitope mapping revealed that stapokibart bound to distinct sites on IL-4Rα compared to dupilumab. In vitro assays showed that stapokibart was comparable or numerically superior in blocking IL-4Rα-mediated signaling compared to dupilumab. In vivo studies further demonstrated that stapokibart effectively inhibited the progression of type 2 inflammation. Pharmacokinetic studies revealed a circulating half-life of approximately 298–351 h in cynomolgus monkeys and 55–142 h in rats for stapokibart. Toxicity studies indicated a favorable safety profile in cynomolgus monkeys and rats. The preclinical evaluation of stapokibart supports its clinical development.

Ureteral metastasis of prostate cancer is extremely rare, with less than 50 cases at present. Kidney cancer with prostate cancer is also rare, and ureteral metastasis with prostate cancer is difficult to diagnose. Especially if there are no symptoms of hematuria, the ureteral mass should be clearly understood. Although there is no error in the diagnosis and treatment process in this case, there are still many points worth considering, such as whether unilateral nephroperectomy should be performed if there is no kidney cancerHere, we report a case of renal cancer complicated with prostate cancer and ureteral metastasis.

Purpose: This study explored whether a free-breathing mean heart dose (FB-MHD) of 4 Gy is a reliable dose threshold for selecting left breast cancer patients after modified radical mastectomy suitable for deep inspiration breath-hold (DIBH) and developed anatomical indicators to predict FB-MHD for rapid selection. Materials and methods: Twenty-three patients with left breast cancer treated with DIBH were included to compare FB and DIBH plans. The patients were divided into the high-risk (FB-MHD ≥ 4 Gy) and low-risk (FB-MHD

The lignocellulose reinforced composites are commonly used sustainable materials with good mechanical and physical properties. Aiming to properly dispose and recover the potential value of discarded lignocellulose reinforced composites, the pyrolysis behaviour and kinetics of reed straw processing residual/polylactic acid (RSPR/PLA) composites, a typical 3D printing material, was investigated. Based on the TG-FTIR results, the synergistic effects between RSPR and PLA during the pyrolysis process were clarified. Compared with the FTIR spectra of PLA, the absorption peaks of CO and CO2 disappear in the FTIR spectra of RSPR/PLA composite, which indicates RSPR provides additional free radicals for the free radical reaction of PLA, and further promoting the decomposition. The apparent activation energy of the RSPR/PLA composite pyrolysis was calculated by two iso-conversional methods including Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS). The average Ea of the RSPR/PLA composite (122.6 kJ mol−1 (FWO) and 117.9 kJ mol−1 (KAS)) was lower than that of solo pyrolysis of RSPR (138.5 kJ mol−1 (FWO) and 135.4 kJ mol−1 (KAS)) and the pure PLA (197.0 kJ mol−1 (FWO) and 196.6 kJ mol−1 (KAS)). The master plot method results suggested the pyrolysis of RSPR/PLA composite followed the one-dimensional (D1) diffusion model. This work provides an environmentally friendly strategy to effective thermo-chemical upgrading of the value of discarded lignocellulose reinforced composite material.

The contamination of soil and water with high levels of heavy metals (HMs) has emerged as a significant obstacle to agricultural productivity and overall crop quality. Certain HMs, although serving as essential micronutrients, are required in smaller quantities for plant growth. However, when present in higher concentrations, they become very toxic. Several studies have shown that to balance out the harmful effects of HMs, complex systems are needed at the molecular, physiological, biochemical, cellular, tissue, and whole plant levels. This could lead to more crops being grown. Our review focused on HMs’ resources, occurrences, and agricultural implications. This review will also look at how plants react to HMs and how they affect seed performance as well as the benefits that HMs provide for plants. Furthermore, the review examines HMs’ transport genes in plants and their molecular, biochemical, and metabolic responses to HMs. We have also examined the obstacles and potential for HMs in plants and their management strategies.

For patients with repeated stenosis of autologous arteriovenous fistula, percutaneous transluminal angioplasty (PTA) or bare metal stent placement had limited efficacy. Rapamycin was reported to inhibit neointimal hyperplasia and keep blood vessels patent. In this study, we reported a case with refractory stenosis, i.e., a short duration of patency maintenance after each repeated PTA, which was treated with a rapamycin-eluting stent (RES). The RES extended the patency duration from 4 to 5 months on average to 14 months. The stent was used to maintain dialysis for over 30 months. RES may be an effective way to treat refractory stenosis and salvage limited vascular resources.