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Abstract Achieving precise and controllable hierarchical self-assembly of functional nanoclusters within crystal lattices to create distinct architectures is of immense significance, yet it creates considerable challenges. Here we successfully synthesized a silver nanowheel Ag40, along with its optically pure enantiomers S-/R-Ag40. Each species possesses an internal nanospace and exhibits host-guest interactions. These structures are constructed from primary building blocks (Ag9). By manipulating the surface anions and guest molecules, the nanowheels function as secondary building blocks, spontaneously organizing into complex double- and triple-helical crystalline superstructures or one-dimensional chains {Ag41} n through conformational matching and diverse noncovalent interactions. Moreover, we demonstrate that the water-mediated complex specifically assembled with uridine monophosphate nucleotides, resulting in chiral assemblies of Ag40 that exhibit chiroptical activity for specific recognition. Our findings provide insights into the efficient construction of assemblies with hollow frameworks and propose strategies for superstructure engineering by manipulating surface motifs.

Abstract Background Lung cancer (LC) occupies an important position in the lethality of cancer patients. Acquired resistance to gefitinib in lung adenocarcinoma (LUAD) seriously affects the therapeutic efficacy of LC. Thus, it is of major scientific and clinical significance to probe the mechanism of gefitinib resistance in LUAD for ameliorating the prognosis of patients. Methods The expression of miRNAs in gefitinib-resistant LUAD cells was validated using qRT-PCR. Cell viability was assessed through CCK-8, whereas cell death was examined through PI staining. Changes in the ferroptosis process were evaluated by detecting the intracellular Glutathione (GSH), Malondialdehyde (MDA), and Reactive Oxygen Species (ROS) levels. Downstream targets of miR-138-5p were verified via luciferase reporter and RNA pull-down assays. RIP and qRT-PCR were employed to evaluate pri-miR-138-5p binding to DiGeorge critical region 8 (DGCR8) and the pri-miR-138-5p m6A modification level. Additionally, the impact of fat mass and obesity-associated protein (FTO) on LUAD gefitinib sensitivity was assessed in vivo by constructing a xenograft model. Results We observed that miR-138-5p was notably diminished in gefitinib-resistant cells. Overexpression of miR-138-5p suppressed viability while facilitated cell death and intracellular ferroptosis in gefitinib-resistant cells. Moreover, lipocalin 2 (LCN2) was the downstream target of miR-138-5p. The biological functions of miR-138-5p on gefitinib-resistant cells was reversed by introduction of LCN2. FTO suppressed the binding of DGCR8 to pri-miR-138-5p through m6A modification, thereby restraining the processing of miR-138-5p. Meanwhile, silencing of FTO enhanced the sensitivity of LUAD to gefitinib treatment. Conclusion FTO suppressed the processing of miR-138-5p and then modulated the proliferation, death, and ferroptosis of gefitinib-resistant cells through the miR-138-5p/LCN2 pathway, which may put forward novel insights for clinically ameliorating the therapeutic effect of gefitinib in LUAD.

In this study, the groundwater hydrodynamics of two adjacent well sites were simulated under different pumping-injection ratios. The aim is to select an optimal pumping-injection ratio that can ensure the groundwater of the two well sites don't affect each other. In addition, the sulfur isotope composition of groundwater in the two well sites were analyzed to verify the simulated results. The results show that the flow velocity at different points outside the edge drilling hole decreases exponentially with the distance between the point and the edge hole. The streamline gradually extends outside of the borehole with the increase of leaching time. It is found that the optimal pumping-injection ratio is 1.003. In this case, the maximum distance between the moving front and the injection borehole is 28.44 m after leaching for 5 years. This indicates that the groundwater flow fields of the two well sites are well controlled. The significant difference in sulfur isotopes between the two well-sites further proves that the SO42− in the acid mining zone does not affect the groundwater in the zone leached by CO2+O2.

Fault-slip rockbursts are a major type of rockbursts in coal mine roadways, posing great hazards. Currently, there is a lack of systematic research on the entire process of fault-slip rockbursts, and prediction and prevention remain fundamental challenges. To achieve experimental simulation of fault-slip rockbursts, a testing system was developed, along with the development of low-strength high-brittleness similar simulation materials. A large-scale similar model containing faults and roadways was prepared, and a series of verification experiments were conducted, realizing the simulation of roadway shock failure and fault shear slip. The testing system is equipped with a triaxial six-face loading function, with a vertical loading capacity of 20 MPa and a model size of 1.50 m×0.75 m×0.75 m. The main frame innovatively adopts a key plate connection, ensuring high rigidity of the main frame. A honeycomb loading shell structure was invented, achieving oil cylinder group loading, which can meet the requirements of fault-slip rockburst simulation. A similar material suitable for fault-slip rockburst simulation was developed, which uses water glass as the binder, sodium fluosilicate as the curing agent, and talcum powder as the aggregate. The similar material has characteristics of both low strength and high brittleness, with a uniaxial compressive strength ranging from 3.44 to 7.81 MPa, an impact energy index of 9.2, and an elastic energy index of 8.83. Based on the test system and low-strength and high-brittleness materials, the bursting failure simulation of roadway under static load was realized, and the feasibility of simulating bursting failure of roadway using low-strength and high-brittleness materials was verified. The loading conditions of the critical equilibrium state of the roadway were obtained, with the continuous shedding of the roadway's side as a significant precursor characteristic of roadway damage. The shear slip of rough serrated faults was realized, confirming that the shear slip of rough faults would cause significant dynamic load disturbances to the roadway, obtaining a reasonable loading method for fault slip. The method of loading the top of the dynamic zone first and unloading the bottom later can achieve instantaneous slip of the fault and eliminate the influence on the static zone stress state.

D-mannose, essential for protein glycosylation, has been reported to have immunomodulatory effects and to maintain intestinal flora homeostasis. In addition to evaluating growth performance, we examined the impact of D-mannose on the structure of epithelial cells and apical junction complexes in the animal intestine. All 1800 grass carp (16.20 ± 0.01 g) were randomly divided into six treatments with six replicates of 50 fish each and fed with six different levels of D-mannose (0.52, 1.75, 3.02, 4.28, 5.50 and 6.78 g/kg diet) for 70 d. The study revealed that D-mannose increased feed intake (P 0.05). D-mannose supplementation at 1.75 g/kg increased crude protein content in fish and lipid production value (P

Objective: Hot air coupled with ultrasound and infrared irradiation were used for the drying of curdlan. The drying mechanism and quality change of curdlan were explored under the multi-physical fields, so as to developing the green drying technology of curdlan. Methods: Forced convective hot air alone, ultrasound-coupled forced convective hot air, infrared irradiation alone, and infrared-coupled forced convective hot air were used to dry curdlan. A mass transfer model considering temeprature change was constructed and the quality of the dried curdlan was comprehensively assessed. Results: Under the studied forced convective hot air drying conditions, it took around 40 min to dry the curdlan, and the required drying time was reduced to 36, 26 and 22 min for ultrasound-coupled hot air drying, infrared irradiation alone drying, and infrared-coupled hot air drying, respectively. The moisture transfer model coupled with the temperature change was able to accurately predict the change of the moisture content throughout drying. Under infrared drying coupled with convective hot air, the range of moisture effective diffusivity inside curdlan was 9.79×10−9 to 9.81×10−9 m2/s, and the surface mass transfer coefficient was 4.69×10−2 kg water/(m2·s), which were higher than those of the other treatment groups, followed by those under infrared irradiation alone drying, ultrasonic-coupled hot air drying, and hot air drying alone. Moreover, the gel strength, glucose content, the distribution of chemical functional groups on surface, crystal structure and thermal stability of curdlan samples dried by different methods were all similar. Conclusion: Taking all these results into consideration, infrared drying was regarded as an efficient method for drying curdlan compared to hot air drying and ultrasound-coupled hot air drying.

This study aimed to investigate the diagnostic utility of Magnetic Resonance Imaging (MRI) in detecting extracapsular extension (ECE) in prostate cancer (PCa). The data of 120 patients admitted to the hospital was retrieved and assessed. All patients underwent laparoscopic radical prostatectomy, and ECE status was determined by postoperative pathological examination. The results showed that 41 patients exhibited prostatic capsule invasion. Multiple logistic regression analysis identified Prostate-Specific Antigen (PSA) ≥10.4 ng/mL, biopsy Gleason score ≥7, clinical stage T2c, positive MRI findings, and Apparent Diffusion Coefficient (ADC) value < 0.75 × 10−3 mm2/s as significant risk factors for prostatic capsule invasion. The predictive model equation was Logit(P) = −1.325 + 0.469 × PSA ≥10.4 ng/mL + 0.865 × biopsy Gleason score ≥7 + 1.743 × positive MRI findings + 1.495 × ADC value < 0.75 × 10−3 mm2/s. The receiver operating characteristic (ROC) curve yielded an area under the curve (AUC) of 0.769 (95% Confidence Interval (CI): 0.681–0.856, p < 0.001). In conclusion, these results indicate that integrating MRI with clinical risk factors in the predictive model demonstrates robust performance in identifying prostatic capsule invasion, demonstrating promising ability to enhance diagnostic and therapeutic strategies for PCa management.

Abstract Background FGFR genomic aberrations occur in approximately 5–10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. Methods Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. Results Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7–63.6); the median progression-free survival was 5.6 months (95% CI, 3.6–12.7) and median overall survival was 40.2 months (95% CI, 12.4–not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5–57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). Conclusions Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. Trial registration This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.

Abstract Ovine contagious pustular dermatitis (ORF) is one of the main diseases of sheep and is a zoonotic disease caused by Ovine contagious pustular dermatitis virus (ORFV) infection, posing a significant constraint on sheep breeding industry and human health. The Tibetan medical formulation composed of Polygonum leucoides, Polygonum xanthoxylum and Acanthophora rotunda significantly regulated lymphocyte immune function following ORFV stimulation, although the mechanism remains unclear. In order to study the immunomodulatory effects and mechanism of three Tibetan medicinal extracts (Polygonum leucoides, Polygonum xanthoxylum, and Acanthophora rotunda) against ORFV in vitro, sheep peripheral blood lymphocytes were isolated in vitro and treated with different concentrations of Tibetan medicine compound extract solution after ORFV infection. The cytokine expression levels in lymphocytes were measured at 4 h, 8 h and 12 h. Additionally endogenous metabolites in lymphocytes at 0 h, 4 h, 8 h and 12 h were quantified by untargeted metabolomics method. The results showed that, the extracts could regulate the lymphocyte immune factors altered by ORFV, and regulate the lymphocyte immune function through cysteine and methionine metabolic pathways as well as the pyrimidine metabolic pathways, potentially alleviating the immune evasion induced by ORFV.

Abstract The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment, which remains an unmet clinical challenge. Herein, an injectable Tetra-PEG hydrogel that possesses rapid gelation, firm tissue adhesion, high mechanical strength, suitable degradability, and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets. Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing. In vivo experiments using an anticoagulated rat tooth extraction model show that the hydrogel significantly outperformed clinically used cotton and gelatin sponge in hemostatic efficacy, wound closure, alveolar ridge preservation, and in situ alveolar bone regeneration. Histomorphological evaluations reveal the mechanisms for accelerated bone repair through suppressed long-term inflammation, elevated collagen deposition, higher osteoblast activity, and enhanced angiogenesis. Together, our study highlights the clinical potential of the developed injectable Tetra-PEG hydrogel for treating anticoagulant-related post-extraction hemorrhage and improving socket healing.

Abstract Untethered miniature soft robots have significant application potentials in biomedical and industrial fields due to their space accessibility and safe human interaction. However, the lack of selective and forceful actuation is still challenging in revolutionizing and unleashing their versatility. Here, we propose a focused ultrasound-controlled phase transition strategy for achieving millimeter-level spatially selective actuation and Newton-level force of soft robots, which harnesses ultrasound-induced heating to trigger the phase transition inside the robot, enabling powerful actuation through inflation. The millimeter-level spatial resolution empowers single robot to perform multiple tasks according to specific requirements. As a concept-of-demonstration, we designed soft robot for liquid cargo delivery and biopsy robot for tissue acquisition and patching. Additionally, an autonomous control system is integrated with ultrasound imaging to enable automatic acoustic field alignment and control. The proposed method advances the spatiotemporal response capability of untethered miniature soft robots, holding promise for broadening their versatility and adaptability.

Objective The volume based procurement (VBP) program in China was initiated in 2022. The cost‐effectiveness of robotic arm assisted total knee arthroplasty is yet uncertain after the initiation of the program. The objective of the study was to investigate the cost‐effectiveness of robotic arm‐assisted total knee arthroplasty and the influence of the VBP program to its cost‐effectiveness in China. Methods The study was a Markov model‐based cost‐effectiveness study. Cases of primary total knee arthroplasty from January 2019 to December 2021 were included retrospectively. A Markov model was developed to simulate patients with advanced knee osteoarthritis. Manual and robotic arm‐assisted total knee arthroplasties were compared for cost‐effectiveness before and after the engagement of the VBP program in China. Probability and sensitivity analysis were conducted. Results Robotic arm‐assisted total knee arthroplasty showed better recovery and lower revision rates before and after initiation of the VBP program. Robotic arm‐based TKA was superior to manual total knee arthroplasty, with an increased effectiveness of 0.26 (16.87 vs 16.61) before and 0.52 (16.96 vs 16.43) after the application of Volume‐based procurement, respectively. The procedure is more cost‐effective in the new procurement system (17.13 vs 16.89). Costs of manual or robotic arm‐assisted TKA were the most sensitive parameters in our model. Conclusion Based on previous and current medical charging systems in China, robotic arm‐assisted total knee arthroplasty is a more cost‐effective procedure compared to traditional manual total knee arthroplasty. As the volume‐based procurement VBP program shows, the procedure can be more cost‐effective.

Dysregulated endoplasmic reticulum stress (ERS) is associated with recurrent spontaneous abortion (RSA) and is involved in the mechanisms that govern immune balance and vascular regulation at the maternal-fetal interface. The molecular intricacies of these mechanisms remain elusive. This study employed microarray and bioinformatics techniques to examine genetic abnormalities in endometrial tissues from RSA patients, with the objective of identifying potential ERS-related biomarkers. By integrating two publicly available microarray datasets, consisting of 88 RSA and 42 control samples, we conducted an extensive analysis, including differential expression, functional annotation, molecular interactions, and immune cell infiltration. Analysis of immune cell characteristics suggests an inflammatory immune imbalance as a potential contributor to RSA progression. Both innate and adaptive immunity were found to play roles in RSA development, with M1 macrophages constituting a significant proportion of immune infiltration. We identified five key ERS-associated genes (TMEM33, QRICH1, MBTPS2, ERN1, and BAK1) linked to immune-related mechanisms, with RT-qPCR results aligning with bioinformatics findings. Our research findings offer a fresh and comprehensive perspective on the ERS-related genes' pathways and interaction networks, offering significant insights for the advancement of innovative therapy techniques for RSA.

Objectives: The study aimed to investigate the relationship between blood pressure (BP) levels and mortality among critically ill older adults in the intensive care unit (ICU), establish optimal BP target for this population, and assess the mediating effect of severe malnutrition on BP-related mortality. Methods: Data were extracted from the Medical Information Mart for Intensive Care IV version 2.2 database, focusing on critically ill patients aged 80 years and older. The analysis included various BP parameters, such as systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Results: The study cohort comprised 14,660 critically ill patients, of whom 1558 (10.6 %) experienced ICU mortality and 2493 (17.0 %) experienced in-hospital mortality. Lower BP levels (SBP ≤ 112 mmHg; DBP ≤ 53 mmHg; MAP ≤65 mmHg), were associated with an increased risk of both ICU and in-hospital mortality. Notably, only reduced SBP levels were linked to a higher risk of 1-year mortality, with an adjusted hazard ratio 1.13 (95 % confidence interval 1.05 to 1.23). Additionally, severe malnutrition was identified as a mediator in the relationship between low BP levels and ICU mortality, with BP levels positively correlated with prognostic nutritional indexes. Conclusion: Among critically ill older adults, lower BP levels are significantly associated with higher risks of ICU and in-hospital mortality, while reduced SBP levels are linked to 1-year mortality. These findings emphasize the importance of assessing nutritional status in older ICU patients with low BP levels to potentially mitigate mortality risk.

Aims: The relationship between sarcopenia and cognitive impairment in older adults remains contentious. This study investigates this association and examines the long-term prognosis for individuals with both conditions. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, this study focuses on the correlation between sarcopenia and cognitive impairment, as well as the extended prognosis for individuals managing these conditions. Results: The study cohort comprised 2890 participants, with 648 (22.4 %) diagnosed with sarcopenia. Multivariable logistic regression analysis identified a significant association between sarcopenia and an increased risk of cognitive impairment (adjusted odds ratio [aOR]: 1.68, 95 % confidence interval [CI]: 1.30–2.17). Over a median follow-up period of 48 months, 200 individuals (6.9 %) succumbed to cardiovascular and cerebrovascular diseases (CCVDs), including hypertension, congestive heart failure, coronary artery disease, and stroke, as well as Alzheimer's disease (AD). Participants had comorbid conditions such as CCVDs and diabetes mellitus. Kaplan–Meier survival analysis and the Cox proportional hazards model indicated that individuals with both sarcopenia and cognitive impairment had the highest mortality risk from CCVDs and AD (adjusted hazard ratio [aHR]: 2.73, 95 % CI: 1.48–5.02). Individuals with sarcopenia and comorbidities exhibited a higher mortality risk from CCVDs or AD compared to those without sarcopenia but with comorbidities (aHR: 2.71, 95 % CI: 1.37–5.37). Conclusion: Sarcopenia is independently associated with cognitive impairment. Older adults with both sarcopenia and cognitive impairment or concurrent comorbidities face increased mortality risks from CCVDs or AD compared to their healthy counterparts. Clinical implication: • Sarcopenia is associated with cognitive impairment. • Cognitive impairment and comorbidities increased the risk of mortality from CCVDs and AD for sarcopenia patients.

IntroductionUltrasound imaging has become a crucial tool in medical diagnostics, offering real-time visualization of internal organs and tissues. However, challenges such as low contrast, high noise levels, and variability in image quality hinder accurate interpretation. To enhance the diagnostic accuracy and support treatment decisions, precise segmentation of organs and lesions in ultrasound image is essential. Recently, several deep learning methods, including convolutional neural networks (CNNs) and Transformers, have reached significant milestones in medical image segmentation. Nonetheless, there remains a pressing need for methods capable of seamlessly integrating global context with local fine-grained information, particularly in addressing the unique challenges posed by ultrasound images.MethodsIn this paper, to address these issues, we propose DDTransUNet, a hybrid network combining Transformer and CNN, with a dual-branch encoder and dual attention mechanism for ultrasound image segmentation. DDTransUNet adopts a Swin Transformer branch and a CNN branch to extract global context and local fine-grained information. The dual attention comprising Global Spatial Attention (GSA) and Global Channel Attention (GCA) modules to capture long-range visual dependencies. A novel Cross Attention Fusion (CAF) module effectively fuses feature maps from both branches using cross-attention.ResultsExperiments on three ultrasound image datasets demonstrate that DDTransUNet outperforms previous methods. In the TN3K dataset, DDTransUNet achieves IoU, Dice, HD95 and ACC metrics of 73.82%, 82.31%, 16.98 mm, and 96.94%, respectively. In the BUS-BRA dataset, DDTransUNet achieves 80.75%, 88.23%, 8.12 mm, and 98.00%. In the CAMUS dataset, DDTransUNet achieves 82.51%, 90.33%, 2.82 mm, and 96.87%.DiscussionThese results indicate that our method can provide valuable diagnostic assistance to clinical practitioners.

Abstract Despite the proceeds in the management of acute myocardial infarction (AMI), the current therapeutic landscape still suffers from limited success in the clinic. Exaggerated inflammatory immune response and excessive oxidative stress are key pathological features aggravating myocardium damage. Herein, catalytic immunomodulatory nanocomplexes as anti‐AMI therapeutics to resolve reactive oxygen species (ROS)‐proinflammatory neutrophils‐specific‐inflammation is engineered. The nanocomplexes contain lyophilic S100A8/9 inhibitor ABR2575 in the core of nanoemulsions, which effectively disrupts the neutrophils‐S100A8/A9‐inflammation signaling pathway in the AMI microenvironment. Additionally, ROS scavenger ultrasmall CuxO nanoparticles are incorporated into the nanoemulsions via coordinating with SH groups of poly(ethylene glycol) (PEG)‐conjugated lipids, which mimic multiple enzymes, dramatically alleviating the oxidative stress damage to myocardial tissue. This combination strategy significantly suppresses the infiltration of pro‐inflammatory monocytes, macrophages, and neutrophils, as well as the secretion of inflammatory cytokines. Additionally, it potentially triggers cardiac Tert activation, which promotes myocardial function and decreases infarction size in preclinical murine AMI models. This approach offers a new nanomedicine for treating AMI, resulting in a dramatically enhanced therapeutic outcome.

Abstract Background There is no gold standard patient-reported outcome measure (PROM) in hand surgery. As a result, a diverse array of PROM instruments have been utilized across centers over time. Lack of score interchangeability limits the ability to compare or conglomerate scores when new instruments are introduced. Our aim was to develop a linkage for the PROMIS UE CAT v1.2 and PROMIS PF CAT scores and develop crosswalk tables for interconversion between these PROMs. Methods Retrospective review was conducted to identify adult (≥ 18y) patients seen by orthopaedic hand surgeons at a single academic tertiary care hospital who had completed PROMIS UE CAT v1.2 and PROMIS PF CAT score at the same visit. For those with multiple visits, only one randomly selected visit was included in the analyses. Pearson’s correlation was calculated to determine the linear relationship between the scores. Linkage from PF to UE was performed utilizing several commonly utilized equating models (identity, mean, linear, equipercentile and circle-arc methods). The performance of the models was assessed using intraclass correlation (ICC) between observed PROMIS UE CAT v1.2 and estimated PROMIS UE CAT v1.2 scores generated using the model as well as Root Mean Square Error (RMSE). The model chosen as the ‘best’ was further assessed for population invariance using root expected mean squared difference (REMSD) where

Abstract Background The gut microbiota and their hosts profoundly affect each other’s physiology and evolution. Identifying host-selected traits is crucial to understanding the processes that govern the evolving interactions between animals and symbiotic microbes. Current experimental approaches mainly focus on the model bacteria, like hypermutating Escherichia coli or the evolutionary changes of wild stains by host transmissions. A method called atmospheric and room temperature plasma (ARTP) may overcome the bottleneck of low spontaneous mutation rates while maintaining mild conditions for the gut bacteria. Results We established an experimental symbiotic system with gnotobiotic bee models to unravel the molecular mechanisms promoting host colonization. By in vivo serial passage, we tracked the genetic changes of ARTP-treated Snodgrassella strains from Bombus terrestris in the non-native honeybee host. We observed that passaged isolates showing genetic changes in the mutual gliding locus have a competitive advantage in the non-native host. Specifically, alleles in the orphan mglB, the GTPase activating protein, promoted colonization potentially by altering the type IV pili-dependent motility of the cells. Finally, competition assays confirmed that the mutations out-competed the ancestral strain in the non-native honeybee gut but not in the native host. Conclusions Using the ARTP mutagenesis to generate a mutation library of gut symbionts, we explored the potential genetic mechanisms for improved gut colonization in non-native hosts. Our findings demonstrate the implication of the cell mutual-gliding motility in host association and provide an experimental system for future study on host-microbe interactions. Video Abstract

Abstract The digital economy is an essential engine of the innovation-driven development strategy and plays a valuable role in promoting the high-quality development of the regional economy. Based on the panel data of 286 cities in mainland China with the help of the digital economy strategic plans issued by local governments as a quasi-natural experiment, we use the multi-temporal double-difference (DID) method to examine the impact of the digital economy on the urban innovation level. Findings show that the digital economy can significantly improve the urban innovation level. After a series of robustness tests, such as parallel trend test, updating sample and period, and repeated placebo test, the innovation-driving effect generated by the development of the digital economy remains significant. Results of the mechanism analysis indicate that the digital economy enhances the level of innovation through upgrading industrial structures. In addition, we find through the heterogeneity test that the digital economy has a stronger effect on improving the quality of innovation. Meanwhile, the innovation output in the Middle Eastern region is more significantly affected by the “Digital China” strategy than the Western region. Therefore, we should accelerate the implementation of the local digital economy development strategy to realize the high-quality development of the regional economy.

Abstract Acute liver injury is the basis of the pathogenesis of diverse liver diseases. However, the mechanism underlying liver injury is complex and not completely understood. In our study, we revealed that CERK, which phosphorylates ceramide to produce ceramide-1-phosphate (C1P), was the sphingolipid pathway-related protein that had the most significantly upregulated expression during acute liver injury. A functional study confirmed that CERK and C1P attenuate hepatic injury both in vitro and in vivo through antioxidant effects. Mechanistic studies have shown that CERK and C1P positively regulate the protein expression of NRF2, which is a crucial protein that helps maintain redox homeostasis. Furthermore, our results indicated that C1P disrupted the interaction between NRF2 and KEAP1 by competitively binding to KEAP1, which allowed for the nuclear translocation of NRF2. In addition, pull-down assays and molecular docking analyses revealed that C1P binds to the DGR domain of KEAP1, which allows it to maintain its interaction with NRF2. Importantly, these findings were verified in human primary hepatocytes and a mouse model of hepatic ischemia‒reperfusion injury. Taken together, our findings demonstrated that CERK-mediated C1P metabolism attenuates acute liver injury via the binding of C1P to the DGR domain of KEAP1 and subsequently the release and nuclear translocation of NRF2, which activates the transcription of cytoprotective and antioxidant genes. Our study suggested that the upregulation of CERK and C1P expression may serve as a potential antioxidant strategy to alleviate acute liver injury.

Abstract Background Osteosarcoma is a diverse and aggressive bone tumor. Driver genes regulating osteosarcoma initiation and progression remains incompletely defined. Zinc finger protein 692 (ZNF692), a kind of Krüppel C2H2 zinc finger transcription factor, exhibited abnormal expression in different types of malignancies and showed a correlation with the clinical prognosis of patients as well as the aggressive characteristics of cancer cells. Nevertheless, its specific role in osteosarcoma is still not well understood. Methods We investigated the dysregulation and clinical significance of ZNF692 in osteosarcoma through bioinformatic method and experimental validation. A range of in vitro assays, including CCK-8, colony formation, EdU incorporation, wound healing, and transwell invasion tests, were conducted to assess the impact of ZNF692 on cell proliferation, migration, and invasion in osteosarcoma. A xenograft mouse model was established to evaluate the effect of ZNF692 on tumor growth in vivo. Western blot assay was used to measure the protein levels of MEK1/2, P-MEK1/2, ERK1/2, and P-ERK1/2 in cells that had been genetically modified to either reduce or increase the expression of ZNF692. The relationship between ZNF692 and tyrosine kinase non-receptor 2 (TNK2) were validated by qRT-PCR, chromatin immunoprecipitation and luciferase reporter assays. Results Expression of ZNF692 was increased in both human osteosarcoma tissues and cell lines. Furthermore, the expression of ZNF692 served as an independent predictive biomarker in osteosarcoma. The results of the survival analysis indicated that increased expression of ZNF692 was associated with worse outcome. Downregulation of ZNF692 inhibits the proliferation, migration, and invasion of osteosarcoma cells, whereas upregulation of ZNF692 has the opposite impact. Western blot assay indicates that reducing ZNF692 decreases phosphorylation of MEK1/2 and ERK1/2, whereas increasing ZNF692 expression enhances their phosphorylation. U0126, a potent inhibitor specifically targeting the MEK/ERK signaling pathway, partially counteracts the impact of ZNF692 overexpression on the proliferation, migration, and invasion of osteosarcoma cells. In addition, ZNF692 specifically interacts with the promoter region of TNK2 and stimulates the transcription of TNK2 in osteosarcoma cells. Forcing the expression of TNK2 weakens the inhibitory impact of ZNF692 knockdown on P-MEK1/2 and P-ERK1/2. Similarly, partly inhibiting TNK2 counteracts the enhancing impact of ZNF692 overexpression on the phosphorylation of MEK1/2 and ERK1/2. Functional tests demonstrate that the suppressive effects of ZNF692 knockdown on cell proliferation, migration, and invasion are greatly reduced when TNK2 is overexpressed. In contrast, the reduction of TNK2 hinders the ability of ZNF692 overexpression to enhance cell proliferation, migration, and invasion. Conclusion ZNF692 promotes the proliferation, migration, and invasion of osteosarcoma cells via the TNK2-dependent stimulation of the MEK/ERK signaling pathway. The ZNF692-TNK2 axis might potentially function as a possible predictive biomarker and a promising target for novel therapeutics in osteosarcoma.

Abstract To address the surrounding rock control problems in high-stressed deep mining roadways, we used Suncun Coal Mine with maximum mining depth in China as the engineering background to analyze failure laws of surrounding rock of gob-side entry driving. Combined with field tests of anchor grouting parameters, we carried out numerical simulation with multi factors. The evolution of surrounding rock stress and displacement under different pressure relief parameters were clarified. On the basis, we proposed an integrated control method for the comprehensive pressure relief for coal and rock mass and anchor grouting reinforcement in deep mining roadway. We used geomechanical model test to compare gob-side entry driving method and this new method. The results showed that this new method can reduce average stress at the working face by 15.8% and peak stress of roadway shoulder by 12.5%. We applied this method in the field, which reduced roadway deformation by 535 mm.

Abstract Nonlinear transport is a unique functionality of noncentrosymmetric systems, which reflects profound physics, such as spin-orbit interaction, superconductivity and band geometry. However, it remains highly challenging to enhance the nonreciprocal transport for promising rectification devices. Here, we observe a light-induced giant enhancement of nonreciprocal transport at the superconducting and epitaxial CaZrO3/KTaO3 (111) interfaces. The nonreciprocal transport coefficient undergoes a giant increase with three orders of magnitude up to 105 A−1 T−1. Furthermore, a strong Rashba spin-orbit coupling effective field of 14.7 T is achieved with abundant high-mobility photocarriers under ultraviolet illumination, which accounts for the giant enhancement of nonreciprocal transport coefficient. Our first-principles calculations further disclose the stronger Rashba spin-orbit coupling strength and the longer relaxation time in the photocarrier excitation process, bridging the light-property quantitative relationship. Our work provides an alternative pathway to boost nonreciprocal transport in noncentrosymmetric systems and facilitates the promising applications in opto-rectification devices and spin-orbitronic devices.

In underground engineering with complex conditions, the bolt (cable) anchorage support system is in an environment where static and dynamic stresses coexist, under the action of geological conditions such as high stresses and strong disturbances and construction conditions such as the application of high prestress. It is essential to study the support components performance under dynamic-static coupling conditions. Based on this, a multi-functional anchorage support dynamic-static coupling performance test system (MAC system) is developed, which can achieve 7 types of testing functions, including single component performance, anchored net performance, anchored rock performance and so on. The bolt and cable mechanical tests are conducted by MAC system under different prestress levels. The results showed that compared to the non-prestress condition, the impact resistance performance of prestressed bolts (cables) is significantly reduced. In the prestress range of 50–160 kN, the maximum reduction rate of impact energy resisted by different types of bolts is 53.9%–61.5% compared to non-prestress condition. In the prestress range of 150–300 kN, the impact energy resisted by high-strength cable is reduced by 76.8%–84.6% compared to non-prestress condition. The MAC system achieves dynamic-static coupling performance test, which provide an effective means for the design of anchorage support system.

Abstract Purpose Hepatocellular carcinoma (HCC) has a poor prognosis, and alpha-fetoprotein (AFP) is widely used to evaluate HCC. However, the proportion of AFP-negative individuals cannot be disregarded. This study aimed to establish a nomogram of risk factors affecting the prognosis of patients with AFP-negative HCC and to evaluate its diagnostic efficiency. Patients and methods Data from patients with AFP-negative initial diagnosis of HCC (ANHC) between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database for model establishment and validation. We randomly divided overall cohort into the training or validation cohort (7:3). Univariate and multivariate Cox regression analysis were used to identify the risk factors. We constructed nomograms with overall survival (OS) and cancer-specific survival (CSS) as clinical endpoint events and constructed survival analysis by using Kaplan-Meier curve. Also, we conducted internal validation with Receiver Operating Characteristic (ROC) analysis and Decision curve analysis (DCA) to validate the clinical value of the model. Results This study included 1811 patients (1409 men; 64.7% were Caucasian; the average age was 64 years; 60.7% were married). In the multivariate analysis, the independent risk factors affecting prognosis were age, ethnicity, year of diagnosis, tumor size, tumor grade, surgery, chemotherapy, and radiotherapy. The nomogram-based model related C-indexes were 0.762 (95% confidence interval (CI): 0.752–0.772) and 0.752 (95% CI: 0.740–0.769) for predicting OS, and 0.785 (95% CI: 0.774–0.795) and 0.779 (95% CI: 0.762–0.795) for predicting CSS. The nomogram model showed that the predicted death was consistent with the actual value. The ROC analysis and DCA showed that the nomogram had good clinical value compared with TNM staging. Conclusion The age(HR:1.012, 95% CI: 1.006–1.018, P-value

Background Critically ill patients in the intensive care unit (ICU) often experience dysglycaemia. However, studies investigating the link between acute kidney injury (AKI) and dysglycaemia, especially in those with and without diabetes mellitus (DM), are limited.Methods We used the Medical Information Mart for Intensive Care IV database to investigate the association between AKI within 7 days of admission and subsequent dysglycaemia. The primary outcome was the occurrence of dysglycaemia (both hypoglycemia and hyperglycemia) after 7 days of ICU admission. Logistic regression analyzed the relationship between AKI and dysglycaemia, while a Cox proportional hazards model estimated the long-term mortality risk linked to the AKI combined with dysglycaemia.Results A cohort of 20,008 critically ill patients were included. The AKI group demonstrated a higher prevalence of dysglycaemia, compared to the non-AKI group. AKI patients had an increased risk of dysglycaemia (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.41–1.65), hypoglycemia (aOR 1.56, 95% CI 1.41–1.73), and hyperglycemia (aOR 1.53, 95% CI 1.41–1.66). In subgroup analysis, compared to DM patients, AKI showed higher risk of dysglycaemia in non-DM patients (aOR: 1.93 vs. 1.33, Pint

The elastic modulus is a basic parameter reflecting the deformation resistance and energy concentration characteristics of rock. The traditional testing method of the rock elastic modulus needs to core the surrounding rock and testing it in the laboratory, which has difficulty reflecting the rock mechanical properties under the engineering site environment, and uncontrolled broken surrounding rock is difficult to core for testing. Digital drilling technology provides a new idea for in situ testing of the rock’s elastic modulus. The key is to establish a quantitative relationship between the elastic modulus and drilling data. In this paper, the relationship between rock cutting energy density and drilling data is established, and a series of rock digital drilling tests are carried out. The response law of the drilling data and cutting energy density to the rock elastic modulus is clarified. The inversion model of the rock elastic modulus while drilling (DP-E model) is established. The verification test results indicate that the average difference rate of the test results based on the DP-E model is 7.06% compared with the compression test method, which verifies the effectiveness of the model. This study provides a theoretical basis for in situ testing of the rock elastic modulus.

Introduction: The reason why some people with severe mental illness (SMI) maintain positive self-identity, while some are affected by the stigmatized environment is unclear. Aims: To describe the status of individual stigma and explore the relationship between self-stigma, stigma resistance and related variables in people with SMI. Methods: A cross-sectional study was conducted from April 2021 to March 2022. The Chinese version of Internalized Stigma of Mental Illness Scale and Stigma Resistance Scale were used to assess individual stigma. Perceived public stigma, psychological capital, stigma stress appraisal and coping orientations were also measured by scales. Data was provided by 422 patients with schizophrenia or bipolar disorder, from one psychiatric hospital and four community healthcare centers in China. A structural equation model was applied for analysis. Results: The total mean scores of self-stigma and stigma resistance were (2.06 ± 0.65), and (3.95 ± 0.84). Perceived public stigma was the primary condition for constructing individual stigma, which indirectly affected self-stigma (β = 0.268) and stigma resistance (β = −0.145). Stigma stress appraisal mediated the transformation of public stigma into individual, which had direct and indirect effects on self-stigma (β = 0.417, 0.166), and an indirect effect on stigma resistance (β = −0.374). Secrecy positively affected self-stigma (β = 0.117), while positive coping positively affected stigma resistance (β = 0.380). Psychological capital significantly directly impacted individual stigma. Conclusions: Findings highlighted how public stigma determines the degree to which patients with SMI deal with stigma stress appraisal, and how this influences individuals. Anti-stigma programs and interventions to improve individuals' psychological capital and coping capabilities should be emphasized.

In this paper, the influence of micro scale and nanoscale limestone powder (LP) on plastic viscosity of ultra-high performance concrete (UHPC) mixture was investigated. Moreover, a novel method for analyzing water film on particle surfaces has been presented based on low-field nuclear magnetic resonance technology (LF NMR). Results showed that approximately 95% of free water in UHPC slurry is adsorbed on the surface of particles, while the rest is filled in capillaries and macropores. Moreover, rheological properties of UHPC are related to particle size of limestone powder. Micro scale limestone powder (LP1) could reduce the heat release during early hydration of UHPC, increase the fluidity, but has no significant effect on the water film thickness. The plastic viscosity of UHPC mixed with 10% mass fraction of LP1 will decrease by 22.8%, the flowability will increase from 235 mm to 270 mm, and the compressive strength will remain unchanged at 160 MPa. However, nanoscale limestone powder (LP2) increases the heat release of UHPC and significantly reduces its fluidity. A 10% mass fraction of LP2 will reduce the water film thickness of the UHPC by 23.5%, increase the plastic viscosity by 38.5%, and reduce the flowability to 210 mm. Meanwhile, the compressive strength of UHPC will decrease if the mass fraction of LP2 exceeds 5%.

Abstract Background Due to the great heterogeneity of gastric cancer (GC), the prognosis of patients within a stage is very different. Therefore, it is necessary to identify the high risk factors for postoperative recurrence and metastasis and take appropriate therapeutic strategies to improve the prognosis of patients. In this study, we aimed to explore the prognostic significance of preoperative and postoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19 − 9 (CA19-9) and carbohydrate antigen 72 − 4 (CA72-4) in patients with stage I, II and III GC who underwent radical gastrectomy. Methods A total of 580 patients who underwent curative surgical resection and had not received neoadjuvant chemotherapy were included in this study. The relationship between clinicopathological features and recurrence was analysed. Survival analysis was performed by Kaplan–Meier curve. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors in GC patients. Results Among patients with stage III GC, the recurrence free survival (RFS) and overall survival (OS) of patients with CA19-9>35 U/mL were significantly lower than those with CA19-9 ≤ 35 U/mL; CA19-9 was always a significant independent marker. CEA and CA72-4 were sometime useful to predict RFS or OS alternatively in the pre- or postoperative period. The only other independent significant factors for prognosis in our study were lymph node metastases for RFS and postoperative adjuvant chemotherapy for OS. Conclusion Preoperative and postoperative CA19-9 values are independent risk factors for predicting prognosis in stage III GC after curative gastrectomy.

Andrias davidianus (Chinese giant salamander, CGS) is the largest and oldest extant amphibian species in the world and is a source of prospective functional food in China. However, the progress of functional peptides mining was slow due to lack of reference genome and protein sequence data. In this study, we illustrated full-length transcriptome sequencing to interpret the proteome of CGS meat and obtain 10703 coding DNA sequences. By functional annotation and amino acid composition analysis, we have discovered various genes related to signal transduction, and 16 genes related to longevity. We have also found vast variety of functional peptides through protein coding sequence (CDS) analysis by comparing the data obtained with the functional peptide database. Val-Pro-Ile predicted by the CDS analysis was released from the CGS meat through enzymatic hydrolysis, suggesting that our approach is reliable. This study suggested that transcriptomic analysis can be used as a reference to guide polypeptide mining in CGS meat, thereby providing a powerful mining strategy for the bioresources with unknown genomic and proteomic sequences.

Abstract External cycling regenerating nitrogen oxides (NOx ≡ NO + NO2) from their oxidative reservoir, NOz, is proposed to reshape the temporal–spatial distribution of NOx and consequently hydroxyl radical (OH), the most important oxidant in the atmosphere. Here we verify the in situ external cycling of NOx in various environments with nitrous acid (HONO) as an intermediate based on synthesized field evidence collected onboard aircraft platform at daytime. External cycling helps to reconcile stubborn underestimation on observed ratios of HONO/NO2 and NO2/NOz by current chemical model schemes and rationalize atypical diurnal concentration profiles of HONO and NO2 lacking noontime valleys specially observed in low-NOx atmospheres. Perturbation on the budget of HONO and NOx by external cycling is also found to increase as NOx concentration decreases. Consequently, model underestimation of OH observations by up to 41% in low NOx atmospheres is attributed to the omission of external cycling in models.

Abstract Background Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer and chemoresistance. DNA damage repair contributes to the proliferation of cancer cells and resistance to chemotherapy-induced apoptosis. However, the role of circRNAs in the regulation of DNA damage repair needs clarification. Methods RNA sequencing analysis was applied to identify the differentially expressed circRNAs. qRT-PCR was conducted to confirm the expression of hsa_circ_0007919, and CCK-8, FCM, single-cell gel electrophoresis and IF assays were used to analyze the proliferation, apoptosis and gemcitabine (GEM) resistance of pancreatic ductal adenocarcinoma (PDAC) cells. Xenograft model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor growth and DNA damage in vivo. RNA sequencing and GSEA were applied to confirm the downstream genes and pathways of hsa_circ_0007919. FISH and nuclear-cytoplasmic RNA fractionation experiments were conducted to identify the cellular localization of hsa_circ_0007919. ChIRP, RIP, Co-IP, ChIP, MS-PCR and luciferase reporter assays were conducted to confirm the interaction among hsa_circ_0007919, FOXA1, TET1 and the LIG1 promoter. Results We identified a highly expressed circRNA, hsa_circ_0007919, in GEM-resistant PDAC tissues and cells. High expression of hsa_circ_0007919 correlates with poor overall survival (OS) and disease-free survival (DFS) of PDAC patients. Hsa_circ_0007919 inhibits the DNA damage, accumulation of DNA breaks and apoptosis induced by GEM in a LIG1-dependent manner to maintain cell survival. Mechanistically, hsa_circ_0007919 recruits FOXA1 and TET1 to decrease the methylation of the LIG1 promoter and increase its transcription, further promoting base excision repair, mismatch repair and nucleotide excision repair. At last, we found that GEM enhanced the binding of QKI to the introns of hsa_circ_0007919 pre-mRNA and the splicing and circularization of this pre-mRNA to generate hsa_circ_0007919. Conclusions Hsa_circ_0007919 promotes GEM resistance by enhancing DNA damage repair in a LIG1-dependent manner to maintain cell survival. Targeting hsa_circ_0007919 and DNA damage repair pathways could be a therapeutic strategy for PDAC.

(1) Background: This study seeks to employ a machine learning (ML) algorithm to forecast the risk of distant metastasis (DM) in patients with T1 and T2 gallbladder cancer (GBC); (2) Methods: Data of patients diagnosed with T1 and T2 GBC was obtained from SEER, encompassing the period from 2004 to 2015, were utilized to apply seven ML algorithms. These algorithms were appraised by the area under the receiver operating characteristic curve (AUC) and other metrics; (3) Results: This study involved 4371 patients in total. Out of these patients, 764 (17.4%) cases progressed to develop DM. Utilizing a logistic regression (LR) model to identify independent risk factors for DM of gallbladder cancer (GBC). A nomogram has been developed to forecast DM in early T-stage gallbladder cancer patients. Through the evaluation of different models using relevant indicators, it was discovered that Random Forest (RF) exhibited the most outstanding predictive performance; (4) Conclusions: RF has demonstrated high accuracy in predicting DM in gallbladder cancer patients, assisting clinical physicians in enhancing the accuracy of diagnosis. This can be particularly valuable for improving patient outcomes and optimizing treatment strategies. We employ the RF algorithm to construct the corresponding web calculator.

Abstract Knowledge of aerosol radiative effects in the Tibetan Plateau (TP) is limited due to the lack of reliable aerosol optical properties, especially the single scattering albedo (SSA). We firstly reported in situ measurement of SSA in Lhasa using a cavity enhanced albedometer (CEA) at λ = 532 nm from 22nd May to 11th June 2021. Unexpected strong aerosol absorbing ability was observed with an average SSA of 0.69. Based on spectral absorptions measured by Aethalometer (AE33), black carbon (BC) was found to be the dominated absorbing species, accounting for about 83% at λ = 370 nm, followed by primary and secondary brown carbon (BrCpri and BrCsec). The average direct aerosol radiative forcing at the top of atmosphere (DARFTOA) was 2.83 W/m2, indicating aerosol warming effect on the Earth‐atmosphere system. Even though aerosol loading is low, aerosol heating effect plays a significant role on TP warming due to strong absorbing ability.

BackgroundGlioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy.MethodsWe identified genes associated with immunotherapy resistance through an analysis of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. Subsequently, qRT-PCR and western blot analyses were conducted to measure the mRNA and protein levels of TBC1 Domain Family Member 1 (TBC1D1), respectively. Additionally, Gene Set Enrichment Analysis (GSEA) was employed to reveal relevant signaling pathways, and the expression of TBC1D1 in immune cells was analyzed using single-cell RNA sequencing (scRNA-seq) data from GEO database. Tumor Immune Dysfunction and Exclusion (TIDE) database was utilized to assess T-cell function, while Tumor Immunotherapy Gene Expression Resource (TIGER) database was employed to evaluate immunotherapy resistance in relation to TBC1D1. Furthermore, the predictive performance of molecules on prognosis was assessed using Kaplan-Meier plots, nomograms, and ROC curves.ResultsThe levels of TBC1D1 were significantly elevated in tumor tissue from glioma patients. Furthermore, high TBC1D1 expression was observed in macrophages compared to other cells, which negatively impacted T cell function, impaired immunotherapy response, promoted treatment tolerance, and led to poor prognosis. Inhibition of TBC1D1 was found to potentially synergistically enhance the efficacy of immunotherapy and prolong the survival of cancer patients with gliomas.ConclusionHeightened expression of TBC1D1 may facilitate an immunosuppressive microenvironment and predict a poor prognosis. Blocking TBC1D1 could minimize immunotherapy resistance in cancer patients with gliomas.

Abstract Background To investigate the influence of osteophytes on postoperative gap balancing, and to work out a predictive model of the relationship between osteophyte size and gap gaining in primary total knee replacement. Methods One hundred and ten patients were enrolled in the study. Pre- and postoperative radiographs were collected and analyzed. They were assigned to the training dataset and test dataset randomly at a ratio of 9:1 by using the statistical package R (version 4.0.5). Size and marginal distances of osteophytes, planned bone cut planes, predicted bone cuts and joint gaps were labeled on the preoperative standing anteroposterior and lateral views, while actual bone cuts and joint gaps were recorded on the postoperative plain films, respectively. Statistical analysis was performed. Results Actual joint gaps were significantly related to the distances of medial and lateral predictive bone cutting lines, bone cut thickness on tibial side and posterior condylar, as well as size and marginal distances of osteophytes (P

Abstract Background Prostate cancer is a disease that seriously troubles men. However, there are some inevitable limitations in interventional therapy for prostate cancer patients at present, most of which are caused by low selectivity and high toxic side effects due to unclear drug targets. In this study, we identified the target protein of Curcusone C with anti-prostate cancer potential activity and verified its target and mechanism of action. Methods Click chemistry-activity based proteomics profiling (CC-ABPP) method was used to find target protein of Curcusone C against prostate cancer. Competitive CC-ABPP, drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) methods were used to verifying the target protein. Moreover, potential mechanism was validated by western blot in vitro and by hematoxylin-eosin (HE) staining, detection of apoptosis in tumor tissue (TUNEL), and immunohistochemical (IHC) in vivo. Results We found that poly(rC)-binding protein 2 (PCBP2) was the target protein of Curcusone C. In addition, Curcusone C might disrupt the Bax/Bcl-2 balance in PC-3 cells by inhibiting the expression of the target protein PCBP2, thereby inducing mitochondrial damage and activation of the mitochondrial apoptosis pathway, and ultimately inducing apoptosis of prostate cancer cells. Conclusions Curcusone C is a potential compound with anti-prostate cancer activity, and this effect occurs by targeting the PCBP2 protein, which in turn may affect the TGF/Smad signaling pathway and Bax/Bcl-2 balance. Our results laid a material and theoretical foundation for Curcusone C, to be widely used in anti-prostate cancer.

Abstract Lung cancer is a leading cause of cancer-related deaths, and the most common type is lung adenocarcinoma (LUAD). LUAD is frequently diagnosed in people who never smoked, patients are always diagnosed at advanced inoperable stages, and the prognosis is ultimately poor. Thus, there is an urgent need for the development of novel targeted therapeutics to suppress LUAD progression. In this study, we demonstrated that the expression of DNA replication and sister chromatid cohesion 1 (DSCC1) was higher in LUAD samples than normal tissues, and the overexpression of DSCC1 or its coexpressed genes were highly correlated with poor outcomes of LUAD patients, highlighting DSCC1 might be involved in LUAD progression. Furthermore, the expression of DSCC1 was positively correlated with multiple genetic mutations which drive cancer development, including TP53, TTN, CSMD, and etc. More importantly, DSCC1 could promote the cell proliferation, stemness, EMT, and metastatic potential of LUAD cells. In addition, DSCC1 interacted with HSP90AB1 and promoted the progression of LUAD via regulating ER stress. Meanwhile, DSCC1 expression negatively correlated with immune cell infiltration in lung cancer, and DSCC1 positively regulated the expression of PD-L1 in LUAD cells. Collectively, this study revealed that DSCC1 is a novel therapeutic target to treat LUAD and a biomarker for predicting the efficiency of PD-1/PD-L1 blockade treatment.

The nutritional status of preschool children in economically underdeveloped multi-ethnic areas is a global concern. This study aimed to examine the effect of a 2.2-year cluster randomized clinical trial that provided customized nutritious breakfast and nutrition education to preschool children in Linxia County, China. A total of 578 children aged 3 to 6 years were enrolled. After the intervention, the incidence of undernourishment was significantly lower in the intervention group compared to the control group (8.73% vs. 9.92%, OR = 0.01 [95%CI 0.00, 0.39], p = 0.014). Additionally, children with non-Muslim dietary habits had a lower incidence of undernourishment compared to those with Muslim dietary habits (OR = 0.05 [95%CI 0.00, 0.88]; p = 0.010). The intervention group also had a lower prevalence rate of wasting (OR = 0.02 [95%CI 0.00, 0.40]; p = 0.011) and a higher mean BMI-for-age Z-score (β = 1.05 [95%CI 0.32, 1.77]; p = 0.005) compared to the control group. These findings suggest that providing nutritious breakfast and nutrition education is an effective strategy to improve the nutrition and health of preschool children, particularly in economically disadvantaged regions and among children with Muslim dietary habits.

Artificial intelligence and the Internet of Things (IoT) have brought great convenience to people’s everyday lives. With the emergence of edge computing, IoT devices such as unmanned aerial vehicles (UAVs) can process data instantly at the point of generation, which significantly decreases the requirement for on-board processing power and minimises the data transfer time to enable real-time applications. Meanwhile, with federated learning (FL), UAVs can enhance their intelligent decision-making capabilities by learning from other UAVs without directly accessing their data. This facilitates rapid model iteration and improvement while safeguarding data privacy. However, in many UAV applications such as UAV logistics, different UAVs may perform different tasks and cover different areas, which can result in heterogeneous data and add to the problem of non-independent and identically distributed (Non-IID) data for model training. To address such a problem, we introduce a novel cloud–edge–end collaborative FL framework, which organises and combines local clients through clustering and aggregation. By employing the cosine similarity, we identified and integrated the most appropriate local model into the global model, which can effectively address the issue of Non-IID data in UAV logistics. The experimental results showed that our approach outperformed traditional FL algorithms on two real-world datasets, CIFAR-10 and MNIST.

Cultivated peanut (Arachis hypogaea L.) is a key oil- and protein-providing legume crop of the world. It is full of nutrients, and its nutrient profile is comparable to that of other nuts. Peanut is a unique plant as it showcases a pegging phenomenon, producing flowers above ground, and after fertilization, the developing peg enters the soil and produces seeds underground. This geocarpic nature of peanut exposes its seeds to soil pathogens. Peanut seeds are protected by an inedible pericarp and testa. The pericarp- and testa-specific promoters can be effectively used to improve the seed defense. We identified a pericarp- and testa-abundant expression gene (AhN8DT-2) from available transcriptome expression data, whose tissue-specific expression was further confirmed by the qRT-PCR. The 1827bp promoter sequence was used to construct the expression vector using the pMDC164 vector for further analysis. Quantitative expression of the GUS gene in transgenic Arabidopsis plants showed its high expression in the pericarp. GUS staining showed a deep blue color in the pericarp and testa. Cryostat sectioning of stained Arabidopsis seeds showed that expression is only limited to seed coat (testa), and staining was not present in cotyledons and embryos. GUS staining was not detected in any other tissues, including seedlings, leaves, stems, and roots, except for some staining in flowers. Under different phytohormones, this promoter did not show an increase in expression level. These results indicated that the AhN8DT-2 promoter drives GUS gene expression in a pericarp- and testa-specific manner. The identified promoter can be utilized to drive disease resistance genes, specifically in the pericarp and testa, enhancing peanut seed defense against soil-borne pathogens. This approach has broader implications for improving the resilience of peanut crops and other legumes, contributing to sustainable agricultural practices and food security.

The future query of moving objects involves predicting their future positions based on their current locations and velocities to determine whether they will appear in a specified area. This technique is crucial for positioning and navigation, and its importance in our daily lives has become increasingly evident in recent years. Nonetheless, the growing volume of data renders traditional index structures for moving objects, such as the time-parameterized R-tree (TPR-tree), inefficient due to their substantial storage overhead and high query costs. Recent advancements in learned indexes have demonstrated a capacity to significantly reduce storage overhead and enhance query efficiency. However, most existing research primarily addresses static data, leaving a gap in the context of future queries for moving objects. We propose a novel future query technique for moving objects based on a learned index (FurMoLi for short). FurMoLi encompasses four key stages: firstly, a data partition through clustering based on velocity and position information; secondly, a dimensionality reduction mapping two-dimensional data to one dimension; thirdly, the construction of a learned index utilizing piecewise regression functions; and finally, the execution of a future range query and future KNN query leveraging the established learned index. The experimental results demonstrate that FurMoLi requires 4 orders of magnitude less storage overhead than TPR-tree and 5 orders of magnitude less than B+-tree for moving objects (Bx-tree). Additionally, the future range query time is reduced to just 41.6% of that for TPR-tree and 34.7% of that for Bx-tree. For future KNN queries, FurMoLi’s query time is only 70.1% of that for TPR-tree and 47.4% of that for Bx-tree.

Crosslinked polyethylene (XLPE) is an important polyethylene modification material which is widely used in high-voltage direct current (HVDC) transmission systems. Low-density polyethylene (LDPE) was used as a matrix to improve the thermal and electrical properties of XLPE composites through the synergistic effect of a crosslinking agent and nanopore structure molecular sieve, TS-1. It was found that the electrical and thermal properties of the matrices were different due to the crosslinking degree and crosslinking efficiency, and the introduction of TS-1 enhanced the dielectric constants of the two matrices to 2.53 and 2.54, and the direct current (DC) resistivities were increased to 3 × 1012 and 4 × 1012 Ω·m, with the enhancement of the thermal conductivity at different temperatures. As the applied voltage increases, the DC breakdown field strength is enhanced from 318 to 363 kV/mm and 330 to 356 kV/mm. The unique nanopore structure of TS-1 itself can inhibit the injection and accumulation in the internal space of crosslinked polyethylene composites, and the pore size effect of the filler can limit the development of electron impact ionization, inhibit the electron avalanche breakdown, and improve the strength of the external applied electric field (breakdown field) that TS-1/XLPE nanocomposites can withstand. This provides a new method for the preparation of nanocomposite insulating dielectric materials for HVDC transmission systems with better performance.

Abstract Respiratory syncytial virus (RSV) is a nonsegmented, negative strand RNA virus that has caused severe lower respiratory tract infections of high mortality rates in infants and the elderly, yet no effective vaccine or antiviral therapy is available. The RSV genome encodes the nucleoprotein (N) that forms helical assembly to encapsulate and protect the RNA genome from degradation, and to serve as a template for transcription and replication. Previous crystal structure revealed a decameric ring architecture of N in complex with the cellular RNA (N-RNA) of 70 nucleotides (70-nt), whereas cryo-ET reconstruction revealed a low-resolution left-handed filament, in which the crystal monomer structure was docked with the helical symmetry applied to simulate a nucleocapsid-like assembly of RSV. However, the molecular details of RSV nucleocapsid assembly remain unknown, which continue to limit our complete understanding of the critical interactions involved in the nucleocapsid and antiviral development that may target this essential process during the viral life cycle. Here we resolve the near-atomic cryo-EM structure of RSV N-RNA that represents roughly one turn of the helical assembly that unveils critical interaction interfaces of RSV nucleocapsid and may facilitate development of RSV antiviral therapy.

Abstract Background Studies reported that kelch-like protein 3 (KLHL3)-Cullin3(CUL3) E3 ligase ubiquitinated with-no-lysine kinase 4 (WNK4). Impaired WNK4 ubiquitination plays a key role in Familial hyperkalemic hypertension (FHHt, also called pseudohypoaldosteronism type II) which results from overaction of thiazide-sensitive sodium chloride cotransport (NCC). In addition, researchers have also found that dietary potassium deficiency activates NCC along the renal distal convoluted tubule (DCT). However, the underlying mechanism remains unclear about the relationship between potassium and WNK4. Methods In the present study, we conducted in vitro and in vivo experiments to confirm that KLHL3-dependent WNK4 degradation is affected by potassium through the neddylation and autophagy pathway. In vitro, the WNK4 and KLHL3 plasmids were cotransfected into HEK293 cell lines by lipofectamine 2000, and then incubated with different potassium concentrations (1mmol/L and 10mmol/L) for 24 h, and further treated with MLN4924 or the autophagy inhibitor or both of MLN4924 and the autophagy inhibitor for another 24 h respectively. In vivo, we created mice that were fed with low or high potassium diets and then were injected MLN4924 in the experimental groups. The expression of WNK4, pWNK4, KLHL3, NEDD8, LC3 ,and P62 was detected by western blotting in vitro and vivo experiments. Results We found that the abundance and phosphorylation of WNK4 increase when neddylation is inhibited both in vitro and vivo. Furthermore, the abundance of pWNK4, WNK4, NEDD8, and KLHL3 was increased in the low potassium (LK) group. Inhibiting autophagy can ameliorate the effect of potassium on the abundance and activity of WNK4 to some extent. Conclusion These findings suggest a complex regulation of potassium in the degradation of WNK4. Low potassium can activate WNK4, which may be related to neddylation and autophagy, but the mechanism needs to be further studied.

Abstract Background Increasing evidence suggests a vital role of the pre-metastatic niche in the formation of distant metastasis of many cancers. However, how the pre-metastatic niche is formed and promotes pulmonary metastasis of hepatocellular carcinoma (HCC) remains unknown. Methods Orthotopic liver tumor models and RNA-Seq were used to identify dysregulated genes in the pre-metastatic lung. Il1b knockout (Il1b −/− ) mice and lentivirus-mediated gene knockdown/overexpression were utilized to demonstrate the role of interleukin 1 beta (IL-1β)/serum amyloid A3 (SAA3) in the pre-metastatic niche formation and pulmonary metastasis. The potential molecular mechanisms were investigated by RNA-Seq, real-time quantitative PCR (qPCR), western blotting, immunohistochemistry (IHC), flow cytometry, luciferase reporter assay, double immunofluorescent staining and H&E staining. Results Accumulation of myeloid cells and upregulation of IL-1β were observed in the pre-metastatic lung of orthotopic liver tumor models. Myeloid cells accumulation and pulmonary metastasis were suppressed in Il1b −/− mice and Il1r1-silencing mice. Mechanistically, SAA3 and matrix metallopeptidase 9 (MMP9) were identified as potential downstream targets of IL-1β. Overexpression of SAA3 in the lungs of Il1b −/− mice restored myeloid cells accumulation and pulmonary metastasis of the orthotopic HCC xenografts. Moreover, alveolar macrophages-derived IL-1β dramatically enhanced SAA3 expression in alveolar epithelial cells in an NF-κB dependent manner and increased MMP9 levels in an autocrine manner. Furthermore, SAA3 recruited myeloid cells to the lung without affecting the expression of MMP9 in myeloid cells. Conclusions Our study suggests a key role of pulmonary IL-1β and SAA3 in creating a permissive lung pre-metastatic niche by enhancing MMP9 expression and recruiting myeloid cells, respectively, thus promoting pulmonary metastasis of HCC.