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Abstract Aims/Introduction To evaluate the differences in cardiac autonomic function, cardiac structure and diastolic function between individuals with diabetic foot (DF) and those with diabetes but without DF. Materials and Methods A total of 413 individuals with DF and 437 without DF who underwent a 24‐h electrocardiogram Holter and a Doppler echocardiogram were included. The heart rate variability parameters to evaluate cardiac autonomic function, and the indices for the assessment of cardiac structure and left ventricular (LV) diastolic function, including left atrium, LV posterior wall thickness, interventricular septum and E/e′ ratio, were measured or calculated. Propensity score matching was used for the sensitivity analysis to minimize potential imbalance. Results In both the crude and propensity score matching analyses, significant differences were observed in heart rate variability between individuals with and without DF, as evidenced by lower standard deviation of the normal sinus interval, lower low‐frequency power/high‐frequency power ratio, lower standard deviation of the 5‐min average RR intervals, lower low‐frequency power, lower percentage of normal adjacent RR interval difference >50 ms, lower root mean square of successive RR interval differences and lower high‐frequency power (all P

Objective It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and dural adhesion are the essential reasons. There are always residual tumor cells maintained at the edge of dura. Dural resection is a key point to obtain a comfortable surgical margin for such cases. Whether such patients benefit from this risky surgical procedure is unknown. This study aims to understand better the oncological results, associated risks, and neurological function of this risky surgical procedure. Methods We retrospectively reviewed clinical data from six consecutive patients who registered spinal tumors in our institute and underwent dural resection during en bloc spinal resection from June 2013 to May 2020. The demographic and perioperative data, oncological outcomes, complications, and neurological status were collected and analyzed. Results All six patients were followed up for 24 to 46 months (mean follow‐up time: 32.8 months). Local recurrence was detected in one patient (1/6, 16.7%) at 36 months postoperatively and in five patients with no evidence of disease at the last follow up (survival rate 83.3%). Eleven complications occurred in four patients (66.7%), and the dural resection‐related complications included only four cases of cerebrospinal fluid leakage (CSFL), which accounted for 36.4% (4/11) of all complications. Neurologic status evaluated by the Frankel grade showed improvement of one grade in one case and deterioration of one to two grades in five patients immediately after surgery. All deterioration cases recovered to the preoperative level 6 months after the operation. Conclusion Dural resection is significant for patients with dura matter invaded by recurrent primary malignant or invasive benign spinal tumors with the purpose of clinical cure. This study demonstrated that in strictly selected cases, intentional dural resection could provide satisfying local control and long‐term disease‐free survival with acceptable complications and satisfying neurological function.

Abstract Aims The study aims to investigate exercise‐limiting factors in hypertrophic cardiomyopathy (HCM) using combined stress echocardiography and cardiopulmonary exercise test. Methods and results A symptom‐limited ramp bicycle exercise test was performed in the semi‐supine position on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Thirty‐six HCM patients (mean age 67 ± 6 years, 72% men, 18 obstructive HCM) were compared with age and sex‐matched 29 controls. At rest, compared with controls, E/E′ ratio (6.26 ± 2.3 vs. 14 ± 2.5, P

Abstract The accurate prediction of photovoltaic (PV) power is crucial for planning, constructing, and scheduling high‐penetration distributed PV power systems. Traditional point prediction methods suffer from instability and lack reliability, which can be effectively addressed through interval prediction. This study proposes a short‐term PV power interval prediction method based on the framework of sparrow search algorithm (SSA)‐variational mode decomposition (VMD)‐convolutional neural network (CNN)‐gate recurrent unit (GRU). First, PV data undergo similar day clustering based on permutation entropy and VMD is applied to solar radiation signals with high correlation. Then, the hyperparameters of GRU are optimized by SSA according to the comprehensive evaluation indicator of interval prediction proposed in this study. Subsequently, quantile prediction results are obtained based on CNN‐GRU using the optimal parameters from SSA optimization. Finally, the prediction interval is composed of multiple quantile prediction results. A MATLAB R2022b program is developed to compare different prediction methods. The results demonstrate that compared to single neural network methods, the proposed method effectively improves the coverage width‐based criterion. In the interval prediction of sunny and rainy similar days, the comprehensive evaluation indicators of the proposed method are only 54.3% and 37.4% of the single GRU, respectively, indicating significantly improved interval prediction accuracy.

Abstract Mixed‐flow pump is a typical pump using in low‐head cases of water lifting. The flow field pulsation is usually an important issue in the operation of mixed‐flow pumps and their pumping statins. Due to its large size, it is difficult to monitor the internal flow characteristics well, based on computational fluid dynamics, we use 5678 monitoring points which arranged in the impeller and fixed vane with using the high pulsation tracking network, and the pressure pulsation signals are analyzed by fast Fourier transform and variable mode decomposition to decompose the main frequency and intensity of the pressure pulsation signals, then analyze the energy dissipation with the entropy production rate (EPR). It is found that there are strong low‐frequency (0.416, 0.625, and 1.67 Hz) pressure pulsation near hub, and the pressure pulsation on the shroud is stronger than that on the hub (at least three times or more); there are strong and stable pressure pulsation (25 Hz) on the shroud generated by the rotor–stator interference (RSI); and the EPR in the flow field can be well combined with the signal. Reasonably allocating material strength and controlling the number of vanes and impellers to avoid producing a common multiple can avoid pressure pulsation caused by RSI and reduce energy dissipation. Therefore, it is very effective in improving the efficiency of this part. Under low flow conditions, the siphon outflow passage can predict the high‐frequency (45.833 Hz) attenuation area well through the phase signal decomposition of the signal, which has certain significance for improving its stability and efficiency.

Abstract Background Improving immunotherapy efficacy for EGFR‐negative lung adenocarcinoma (LUAD) patients remains a critical challenge, and the therapeutic effect of immunotherapy is largely determined by the tumor microenvironment (TME). Tumor‐associated macrophages (TAMs) are the top‐ranked immune infiltrating cells in the TME, and M2‐TAMs exert potent roles in tumor promotion and chemotherapy resistance. An M2‐TAM‐based prognostic signature was constructed by integrative analysis of single‐cell RNA‐seq (scRNA‐seq) and bulk RNA‐seq data to reveal the immune landscape and select drugs in EGFR‐negative LUAD. Methods M2‐TAM‐based biomarkers were obtained from the intersection of bulk RNA‐seq data and scRNA‐seq data. After consensus clustering of EGFR‐negative LUAD into different clusters based on M2‐TAM‐based genes, we compared the prognosis, clinical features, estimate scores, immune infiltration, and checkpoint genes among the clusters. Next, we combined univariate Cox and LASSO regression analyses to establish an M2‐TAM‐based prognostic signature. Results CCL20, HLA‐DMA, HLA‐DRB5, KLF4, and TMSB4X were verified as prognostic M2‐like TAM‐related genes by univariate Cox and LASSO regression analyses. IPS and TMB analyses revealed that the high‐risk group responded better to common immunotherapy. Conclusion The study shows the potential of the M2‐like TAM‐related gene signature in EGFR‐negative LUAD, explores the immune landscape based on M2‐like TAM‐related genes, and predict immunotherapy response of patients with EGFR‐negative LUAD, providing a new insight for individualized treatment.

Abstract Background Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength. However, current anti‐resorptive drugs carry a risk of various complications. The deep learning‐based efficacy prediction system (DLEPS) is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes. This study aimed to explore the protective effect and potential mechanisms of cinobufotalin (CB), a traditional Chinese medicine (TCM), on bone loss. Methods DLEPS was employed for screening anti‐osteoporotic agents according to gene profile changes in primary osteoporosis. Micro‐CT, histological and morphological analysis were applied for the bone protective detection of CB, and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells (hBMMSCs) were also investigated. The underlying mechanism was verified using qRT‐PCR, Western blot (WB), immunofluorescence (IF), etc. Results A safe concentration (0.25 mg/kg in vivo, 0.05 μM in vitro) of CB could effectively preserve bone mass in estrogen deficiency‐induced bone loss and promote osteogenic differentiation/function of hBMMSCs. Both BMPs/SMAD and Wnt/β‐catenin signaling pathways participated in CB‐induced osteogenic differentiation, further regulating the expression of osteogenesis‐associated factors, and ultimately promoting osteogenesis. Conclusion Our study demonstrated that CB could significantly reverse estrogen deficiency‐induced bone loss, further promoting osteogenic differentiation/function of hBMMSCs, with BMPs/SMAD and Wnt/β‐catenin signaling pathways involved.

Abstract Background Jiaohong pills (JHP) consist of Pericarpium Zanthoxyli (PZ) and Radix Rehmanniae, two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment. However, the precise mechanisms underlying the beneficial effects remain elusive. Here, research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease. Methods BV‐2 cell inflammation was induced by lipopolysaccharide. AD mice were administered amyloid‐β (Aβ). Behavioral experiments were used to evaluate learning and memory ability. The levels of nitric oxide (NO), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐10 (IL‐10) were detected using enzyme‐linked immunosorbent assay (ELISA). The protein expressions of inducible nitric oxide synthase (iNOS) and the phosphorylation level of mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐B (NF‐κB) were detected using Western blot. Nissl staining was used to detect neuronal degeneration. Results The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO, IL‐1β, TNF‐α, and iNOS; increased the expression level of IL‐10; and significantly decreased the phosphorylation levels of MAPK and NF‐κB. These inhibitory effects were further confirmed in the AD mouse model. Meanwhile, JHP improved learning and memory function in AD mice, reduced neuronal damage, and enriched the Nissl bodies in the hippocampus. Moreover, IL‐1β and TNF‐α in the cortex were significantly downregulated after JHP administration, whereas IL‐10 showed increased expression. Conclusions It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF‐κB signaling pathway.

Abstract To evaluate the effect of different decalcification solutions on the immunohistochemical staining of trichorhinophalangeal syndrome type 1 (TRPS1), and to provide a reliable basis for the accurate diagnosis of bone metastasis of breast cancer. Due to the limited biopsy samples of bone metastatic cancer, 20 cases of invasive breast cancer were selected to simulate bone metastatic biopsy, dividing into four groups: undecalcified group, 30% formic acid group, 10% hydrochloric acid group and 10% nitric acid group. Immunohistochemical staining was performed after treatment for 2, 6, 18 and 24 h. There was no change in the proportion and intensity of TRPS1 cells in the formic acid decalcification group within 18 h, but decreased significantly after 24 h. The staining intensity of TRPS1 and the proportion of stained cells were significantly decreased in the hydrochloric acid decalcification group since 2 h treatment. The percentage and intensity of positive cells in the nitric acid decalcification group changed little or no change within 6 h, and then gradually decreased with the extension of time. Another three invasive breast cancer samples were used to compare the effects of different decalcification solutions on the same case. In brief, we conclude that the effect of 30% formic acid decalcification on TRPS1 staining is small when the time is less than 18 h. 10% nitric acid decalcification should be controlled within 6 h, which has little effect on TRPS1 staining, and 10% hydrochloric acid decalcification will lead to significantly less positive TRPS1 staining, so it is not recommended for breast bone metastasis tissue decalcification.

Abstract Background The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F‐FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). Methods This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F‐FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index‐1 (HI‐1; standard deviation [SD] divided by SUVmean) and heterogeneity index‐2 (HI‐2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. Results The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI‐1 were significant prognostic factors for progression‐free survival (PFS), while MTV, HI‐2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI‐1 (p

Abstract Exposure to cigarette smoke directly damages the lungs and causes lung inflammation. The anti‐inflammatory properties of edible bird's nest (EBN) have been reported. We aimed to determine the effect of EBN on pneumonia in a mouse model exposed to cigarette smoke. Fifty BALB/c mice were randomly divided into control, model, positive drug, low‐dose EBN, and high‐dose EBN groups (n = 10 each). Except for the control group, the mice in each group were exposed to four cigarettes once a day for 8 days. In addition, we validated the effects of EBN on A549 cells and investigated the mechanism by which EBN alleviates lung inflammation. Edible bird's nest (EBN) could alleviate the structural damage of lung tissue and the smoke‐induced inflammatory response in mice. The best effect was observed at the high dose of EBN (0.019 g). The mice treated with EBN had a stronger ability than those in the model group to resist cigarette smoke stimulation, as indicated by a decrease in serum and lung inflammatory markers (interleukin 6 [IL‐6], tumor necrosis factor‐α [TNF‐α], and interleukin 8 [IL‐8]), an increase in serum interleukin 10 (IL‐10) levels, and a decrease in the expression of inflammasome NOD‐like receptor pyrin 3 (NLRP3). In addition, our cell experiments showed that EBN attenuated cigarette smoke‐induced pulmonary inflammation mainly by inhibiting the tumor necrosis factor receptor 1 (TNFR1)/nuclear factor‐kappa B (NF‐κB)/NLRP3 pathway. These findings provide theoretical evidence for the positive nutritional qualities of EBN for the lung by demonstrating that it inhibits the TNFR1/NF‐κB/NLRP3 signaling pathway, which prevents the development of cigarette smoke‐induced pulmonary inflammation.

Abstract Diabetic nephropathy (DN) is a primary diabetic complication ascribed to the pathological changes in renal microvessels. This study investigated the nuclear factor erythroid 2‐related factor 2 (Nrf2)/Kelch ECH associating protein (Keap1)/antioxidant response element (ARE) signaling pathway impact of chitooligosaccharides (COS) with a certain degree of polymerization (DP) on DN mouse models and high glucose‐damaged human kidney 2 (HK‐2) cells. The findings indicated that COS effectively reduced the renal function indexes (uric acid [UA], urinary albumin excretion rate [UAER], urine albumin‐to‐creatinine ratio [UACR], blood urea nitrogen [BUN], and creatinine [Cre]) of DN mice. It increased (p

Abstract The report of the 20th National Congress of the Communist Party of China pointed out that it is necessary to accelerate the construction of digital China, and actively develop equipment intelligence, digitalization, and high‐end equipment manufacturing. With the construction of a new round of digital China, the safety of digital technology and high‐end equipment is particularly important for power grid. Transformer is an important link of power grid operation. The destructive thermal failure of transformer has become a hot research issue in the power industry. At the same time, there are more and more power electronic equipment in the power grid, which makes the regulation and control more and more complicated. Taking a 1000 kVA oil‐immersed transformer as an example, the magnetic, current, and thermal multi field coupling numerical analysis method is first used to simulate and analyse the operation status of the transformer. By comparing the simulation results with the monitoring data results, the error of the results is controlled within 5%. Finally, the multi‐state characteristic parameters of the transformer are monitored through sensors, and the numerical simulation analysis results are integrated with the state monitoring results to build a transformer thermal life loss assessment system. The method in this paper can evaluate and analyse the running state of transformer in real time, which is of great significance for the power company to formulate the treatment measures.

Objective All‐inside and standard techniques with 4‐strand hamstrings graft have been widely used in anterior cruciate ligament (ACL) reconstruction. However, the graft diameter of less than 8 mm will significantly increase the rate of surgical failure, and the 6‐strand graft can solve this problem. The purpose of this study is to compare all‐inside ACL reconstruction using suspensory cortical button fixation on both tibia and femur with standard ACL reconstruction using suspensory femoral fixation and a bioabsorbable tibial interference screw with a 6‐strand hamstring tendon autograft in postoperative clinical outcomes. Methods From January 2020 to December 2020, 48 patients performed ACL reconstruction were divided into the all‐side group and the standard group according to the different surgical techniques. Magnetic resonance imaging (MRI) and subjective function scores was used to assess clinical outcomes at least 24 months following ACL reconstruction. MRI was used to measure the value of bone tunnel widening in articular and middle portions. Subjective function scores included the Lysholm knee score, the International Knee Documentation Committee (IKDC) score, the Knee Society Score (KSS) for pain and function, and KT‐1000. The t‐test was used assuming the distribution of the patients which follows the normal distribution and we used non‐parametric tests if these two conditions were not satisfied. Results At the final follow‐up, there were 22 patients in the all‐inside group and 24 patients in the standard group. No significant differences were found with respect to femoral tunnel widening and subjective function scores. However, a significant increase in tibial tunnel widening was found in the middle portion of the standard group (2.25 ± 0.74) compared to the all‐inside group (0.76 ± 0.24) (p

Abstract Background Androgenic alopecia (AGA) is the most common type of hair loss in men, and there are many studies on the treatment of hair loss by platelet‐rich plasma (PRP). The human scalp contains a huge microbiome, but its role in the process of hair loss remains unclear, and the relationship between PRP and the microbiome needs further study. Therefore, the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition. Methods We performed PRP treatment on 14 patients with AGA, observed their clinical efficacy, and collected scalp swab samples before and after treatment. The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3‐V4 region of the 16 s RNA gene and sequencing for bacterial identification. Results The results showed that PRP was effective in the treatment of AGA patients, and the hair growth increased significantly. The results of relative abundance analysis of microbiota showed that after treatment, g_Cutibacterium increased and g_Staphylococcus decreased, which played a stable role in scalp microbiota. In addition, g_Lawsonella decreased, indicating that the scalp oil production decreased after treatment. Conclusions The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

Abstract The rotor blades of an axial‐flow turbine are cantilever structures, and there is inevitably a gap between them and the casing. Due to factors such as rotor wear and unit vibration, the eccentricity of the impeller will change during the operation of the turbine, resulting in the impeller being affected by additional radial forces, which can even lead to rubbing or biting between the impeller and the casing. To monitor the eccentricity of the impeller and the additional radial forces in real time during the operation of the turbine, this study conducted numerical simulations of the internal flow of the turbine under different eccentricities of the impeller, and analyzed the characteristics of pressure pulsation and impeller radial force in the turbine using the variational mode decomposition method. The results showed that there was a good linear relationship between the eccentricity of the impeller and the amplitude of the frequency corresponding to the rotor in pressure pulsation at the monitoring point and the Alford force acting on the impeller. Based on this finding, we established mathematical formulas for the relationship between the pressure pulsation at the monitoring point and the eccentricity of the impeller, as well as the eccentricity of the impeller and the Alford force acting on it. According to these formulas, we only need to monitor the pressure pulsation during the operation of the turbine to realize the real‐time monitoring of the eccentricity of the impeller and the Alford force, which is of great significance for ensuring the safe and stable operation of the turbine.

Abstract Previous findings showed that anthocyanins from Lycium ruthenicum Murray (ACN) reduced HFD‐induced hypercholesterolemia by regulating gut microbiota, but the mechanism has not been fully understood. The objective of this research was to know whether the cholesterol‐lowering impact of ACN in HFD‐induced ApoE−/− mice is related to the gut microbiota‐bile acid (BA) metabolism. Twenty‐four male ApoE−/− mice were divided into three groups: the Control group, the HFD group, and the HFD + ACN group. Here, we showed that ACN intervention reduced HFD‐induced body weight serum concentrations of TC and LDL‐C and ameliorated lipid accumulation in the liver and adipose tissues. Besides, ACN altered gut microbiota composition in HFD‐fed ApoE−/− mice. Moreover, UHPLC–MS/MS analysis revealed that ACN intervention significantly increased the ratio of conjugated to unconjugated BAs in feces induced by HFD, attributed to the increase in conjugated BAs and decrease in unconjugated BAs. Finally, the correlation analysis indicated that the above changes in fecal BA profile were linked with an increase in Bifidobacterium, Allobaculum and a decrease in Ileibacterium, Helicobacter, Rikenellaceae_RC9_gut_group, Blautia, Odoribacter, and Colidextribacter. In summary, ACN could alleviate HFD‐induced hypercholesterolemia in ApoE−/− mice, which was associated with the improvement of gut microbiota and modulation of fecal BA profile.

Abstract The present study aimed to prepare and evaluate a new probiotic functional beverage, using single‐probiotic and compound probiotic fermentation on okara. Four different forms of fermentation microorganisms used were Lacticaseibacillus rhamnosus S24 (Lr), Lacticaseibacillus paracasei 6244 (Lp), Lactobacillus acidophilus 11,073 (La), and mixed fermentation (Lr + Lp + La). The physicochemical properties, antioxidant activity, flavor change, and storage period of fermented okara beverages with probiotics were investigated. The results showed that different fermentation schemes could significantly improve the physicochemical properties, antioxidant activity, and sensory quality of the okara beverages. The number of viable bacteria in the Lp group (3.53 × 108 CFU/mL), isoflavone content (0.514 μg/mL) were the highest; total phenol and flavonoid content were 3.32 and 5.68 times higher than in the CK group, respectively. DPPH and ABTS+ free radical scavenging rates were increased by 11.32% and 20%, respectively (p

Abstract This research aims to improve the utilization efficiency of parking facilities in residential areas. The real‐time and fixed‐time shared parking spot allocation models based on a time window constraint are proposed, respectively. The real‐time model adopts the dynamic response service mechanism, introducing a multi‐objective decision weighting method to construct the weighted evaluation function. Then, the 0–1 planning model with user optimization is established, utilizing branch‐bound algorithm for a solution. The fixed‐time model adopts the periodic service mechanism, where a rejection penalty factor is introduced to add penalty cost. Then, the 0–1 programming model with system optimization is constructed, where genetic annealing algorithm solves the large‐scale calculation problem. The results from this case study illustrate the fixed‐time allocation mode has more balanced utilization of parking facilities, whereas over‐utilization of preferred parking lots occurs in the real‐time model; additionally, when supply and demand are in balance, the fixed‐time model can obtain higher system revenues, reduce effective rejection rate by 9.43%, and increase resource utilization efficiency by 5.28%. In conclusion, the real‐time allocation mode reflects the advantage of a user's optimal allocation mode when supply is greater than demand; conversely, the fixed‐time allocation mode has the advantage of optimum system resources utilization efficiency.

Abstract Aims The clinical application of doxorubicin (DOX), a potent anthracycline anticancer drug that effectively treats various malignancies, is limited by its side effects, such as cardiomyopathy. Apurinic/apyrimidinic endonuclease 1/redox factor‐1 (APE1/Ref‐1) is a multifunctional protein that can be secreted and is a promising target for the reduction of DOX‐induced inflammation and oxidative stress. We aimed to investigate the protective role of secretory APE1/Ref‐1 against DOX‐induced cardiac injury. Methods and results Designated adenoviral preprotrypsin‐leading sequence APE1/Ref‐1 (Ad‐PPTLS‐APE1/Ref‐1) was used to overexpress secretory APE1/Ref‐1 and assess its role in preventing DOX‐induced cardiomyopathy in vitro. Our findings revealed that exposure to secretory APE1/Ref‐1 significantly decreased N‐terminal pro‐B‐type natriuretic peptide levels in DOX‐treated H9C2 cells. In addition, secretory APE1/Ref‐1 reduced the severity of cardiomyocyte injury and apoptosis in both in vitro and in vivo DOX‐induced cardiotoxicity models. The observed cardioprotective effects of secretory APE1/Ref‐1 were mediated via inhibition of the p53 signalling pathway and enhancement of cell viability through attenuation of oxidative stress in DOX‐treated cardiomyocytes. Conclusions Our study provides evidence that secretory APE1/Ref‐1 has the potential to inhibit DOX‐induced cardiac toxicity by inhibiting oxidative stress and p53 related apoptosis both in vitro and in vivo. These findings suggest that secretory APE1/Ref‐1 supplementation is a promising strategy to attenuate DOX‐induced cardiomyocyte damage in a preclinical model. Further clinical investigations are essential to validate the therapeutic efficacy and safety of the intervention in human subjects.

Abstract Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor‐specific CD8+ T cells and their recruitment to tumor microenvironment. However, cDC1s are often underrepresented in the microenvironment. Systemic administration of Fms‐like tyrosine kinase 3 ligand, a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to cDC1 expansion in the periphery and recruitment into the microenvironment. FLT3 pathway stimulation using GS‐3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T‐cell mediated antitumor activity. This was a first‐in‐human, placebo‐controlled study of GS‐3583 in healthy participants to evaluate the safety, pharmacokinetics (PK), and pharmacodynamic (PD) of escalating single doses (75–2000 μg) of GS‐3583. Each dose cohort enrolled 8–12 healthy participants who received GS‐3583 or placebo as single IV infusion at 3:1 ratio. As part of the PD evaluation, the changes in the number of cDC1 cells were investigated. GS‐3583 was well‐tolerated in healthy participants up to the highest evaluated dose (2000 μg). There have been no serious or grade III or higher adverse events. PK analysis suggested a dose‐dependent increase in GS‐3583 exposure with target‐mediated disposition characteristics at low doses. PD analysis shows that administration of GS‐3583 resulted in transient, dose‐dependent increases in cDC1 cells that returned to baseline within 3 weeks of drug administration. The pharmacokinetics and pharmacodynamics of GS‐3583 following single dosing were characterized in this study which enabled subsequent phase Ib assessments in patients with advanced solid tumors.

Abstract Sand rice (Agriophyllum squarrosum), widely distributed in Central Arid Asia and prevalent in the sand dunes of northern China, presents a promising potential as a climate‐resilient crop. The plasticity of hypocotyl growth is the key trait for sand rice to cope with wind erosion and sand burial, ensure seedling emergence, and determine plant architecture. In this study, we assessed the overall hypocotyl phenotype of six sand rice elite lines, which were collected from different regions of northern China, and selected by our group over past decade through common garden trials. Significant phenotypic variations were observed in thousand‐seed weight (TSW), seedling emergence percentage, hypocotyl length and diameter, and seedling fresh weight among the lines. The elite line Aerxiang (AEX) exhibited excellent agronomic performance with superior and synchronous emergence, and high survival percentage, distinguishing itself as a prime candidate for further large‐scale cultivation. Contrastingly, the lines from the arid regions showed markedly lower performance. Partial Least Squares Path Modeling (PLSPM) was used to assess the impact of seed provenance climate factors, including annual mean temperature (AMT) and annual mean precipitation (AMP), on trait variability among lines. The findings indicate a significant correlation between climate factors and hypocotyl length, highlighting the intricate adaptation of sand rice to local climate. The comprehensive understanding of the mechanisms behind phenotypic variations offers valuable insights for sand rice de novo domestication and innovative germplasm resources, and lays the foundation for ecological restoration in sandy areas.

Abstract The small mammalian fauna plays pivotal roles in ecosystem dynamics and as crucial biodiversity indicators. However, recent research has raised concerns about the decline of mammalian species due to climate change. Consequently, significant attention is directed toward studying various big flagship mammalian species for conservation. However, small mammals such as the hog badgers (Mustelidae: Arctonyx) remain understudied regarding the impacts of climate change in Asia. The present study offers a comprehensive analysis of climate change effects on two mainland hog badger species, utilizing ensemble species distribution modeling. Findings reveal concerning outcomes, as only 52% of the IUCN extent is deemed suitable for the Great Hog Badger (Arctonyx collaris) and a mere 17% is ideal for the Northern Hog Badger (Arctonyx albogularis). Notably, projections suggest a potential reduction of over 26% in suitable areas for both species under future climate scenarios, with the most severe decline anticipated in the high‐emission scenario of SSP585. These declines translate into evident habitat fragmentation, particularly impacting A. collaris, whose patches shrink substantially, contrasting with the relatively stable patches of A. albogularis. However, despite their differences, niche overlap analysis reveals an intriguing increase in overlap between the two species, indicating potential ecological shifts. The study underscores the importance of integrating climate change and habitat fragmentation considerations into conservation strategies, urging a reassessment of the IUCN status of A. albogularis. The insights gained from this research are crucial for improving protection measures by ensuring adequate legal safeguards and maintaining ecological corridors between viable habitat patches, which are essential for the conservation of hog badgers across mainland Asia. Furthermore, emphasizing the urgency of proactive efforts, particularly in countries with suitable habitats can help safeguard these small mammalian species and their ecosystems from the detrimental impacts of climate change.

Abstract Background Depressive symptoms are frequently observed in patients with primary biliary cholangitis (PBC). The role of depressive symptoms on cirrhosis has not been fully noticed in PBC. We aimed to establish a risk model for cirrhosis that took depressive symptoms into account. Methods Depressive symptoms were assessed by the 17‐item Hamilton Depression Rating Scale (HAMD‐17). HAMD‐17 score was analyzed in relation to clinical parameters. Least absolute shrinkage and selection operator (Lasso)‐logistic regression and decision tree models were used to explore the effect of depressive symptoms on cirrhosis. Results The rate of depressive symptom in patients with PBC (n = 162) was higher than in healthy controls (n = 180) (52.5% vs. 16.1%; p

Abstract Polyethers play a crucial role in the development of anticancer drugs. To enhance the anticancer efficacy and reduce the toxicity of these compounds, thereby advancing their application in cancer treatment, herein, guided by the structure‐activity relationships of aglycone polyethers, novel aglycone polyethers are rationally redesigned with potentially improved efficacy and reduced toxicity against tumors. To realize the biosynthesis of the novel aglycone polyethers, the gene clusters and the post‐polyketide synthase tailoring pathways for aglycone polyethers endusamycin and lenoremycin are identified and subjected to combinatorial biosynthesis studies, resulting in the creation of a novel aglycone polyether termed End‐16, which demonstrates significant potential for treating bladder cancer (BLCA). End‐16 demonstrates the ability to suppress the proliferation, migration, invasion, and cellular protrusions formation of BLCA cells, as well as induce cell cycle arrest in the G1 phase in vitro. Notably, End‐16 exhibits superior inhibitory activity and fewer side effects against BLCA compared to the frontline anti‐BLCA drug cisplatin in vivo, thereby warranting further preclinical studies. This study highlights the significant potential of integrating combinatorial biosynthesis strategies with rational design to create unnatural products with enhanced pharmacological properties.

Abstract Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2‐hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two‐step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re‐epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual‐enhanced cell and tissue penetration and multistep interventions.

Abstract This study investigated the ability of a sarcopenia screening test to predict mortality among cancer inpatients. We conducted a prospective study of patients admitted to the oncology ward of a teaching hospital in southern Taiwan. Over a 5‐month period, 82 patients were enrolled for evaluation and were followed for 3 years. All participants received a comprehensive assessment at the time of admission, including Eastern Cooperative Oncology Group (ECOG) performance status, cognitive ability, nutrition index, body mass index, and short physical performance battery (SPPB). Age, ECOG performance status, dementia, SPPB score, and albumin level were associated with sarcopenia. Of the enrolled participants, 53 (64.6%) were diagnosed with sarcopenia. Patients with sarcopenia were associated with worse overall survival (OS) than patients without sarcopenia (28.8% vs. 82%, p = 0.01). Metastasis (hazard ratio [HR]: 5.166; 95% confidence interval [CI]: 1.358–19.656) and albumin level (HR: 4.346; 95% CI: 1.493–12.654) were independent and significant predictors of OS for the whole study population. Age was a predictor of 2‐year all‐cause mortality among patients aged ≥65 years but not among those aged

Abstract Photocatalytic CO2 reduction is considered as a promising strategy for CO2 utilization and producing renewable energy, however, it remains challenge in the improvement of photocatalytic performance for wide‐band‐gap photocatalyst with controllable product selectivity. Herein, the sulfur‐doped In(OH)3 (In(OH)xSy‐z) nanocubes are developed for selective photocatalytic reduction of CO2 to CH4 under simulated light irradiation. The CH4 yield of the optimal In(OH)xSy‐1.0 can be enhanced up to 39 times and the CH4 selectivity can be regulated as high as 80.75% compared to that of pristine In(OH)3. The substitution of sulfur atoms for hydroxyl groups in In(OH)3 enhances the visible light absorption capability, and further improves the hydrophilicity behavior, which promotes the H2O dissociation into protons (H*) and accelerates the dynamic proton‐feeding CO2 hydrogenation. In situ DRIFTs and DFT calculation confirm that the non‐metal sulfur sites significantly weaken the over‐potential of the H2O oxidation and prevent the formation of ·OH radicals, enabling the stabilization of *CHO intermediates and thus facilitating CH4 production. This work highlights the promotion effect of the non‐metal doping engineering on wide‐band‐gap photocatalysts for tailoring the product selectivity in photocatalytic CO2 reduction.

Abstract Constrained by a limited understanding of the structure and luminescence mechanisms of carbon dots (CDs), achieving precise enhancement of their photoluminescence (PL) performance without altering the emission wavelength and color remains a challenge. In this work, a deuterated CD is first achieved by simply replacing the reaction solvent from H2O to D2O. The substitution of D atoms for H atoms is not limited on the surface but also within the internal structure of CDs. Deuteration affects the formation of the π‐conjugated network structure by altering the content of sp2 carbon and sp3 carbon, ultimately inducing a reconstruction for energy level structure of CDs. Both the intrinsic state and surface state emission, including quantum yield, emission intensity and lifetime, are significantly enhanced after deuteration. It benefits from the reduction in non‐radiative transitions, since the lowered vibrational frequencies of D atoms and optimized local energy level distribution in CDs structure. The deuterated CDs are applied in the fabrication of white‐light‐emitting diodes to show their application potential. This work provides a highly versatile route for improving and controlling photoluminescence performance of CDs and has opportunities to guide the development of CDs for practical applications.

Abstract Targeted delivery of glutamine metabolism inhibitors holds promise for cholangiocarcinoma therapy, yet effective delivery vehicles remain a challenge. This study reports the development of a biomimetic nanosystem, termed R‐CM@MSN@BC, integrating mesoporous organosilicon nanoparticles with reactive oxygen species‐responsive diselenide bonds for controlled release of the glutamine metabolism inhibitor bis‐2‐(5‐phenylacetamido‐1,3,4‐thiadiazol‐2‐yl) ethyl sulfide (BPTES) and the photosensitizer Ce6. Erythrocyte membrane coating, engineered with Arg‐Gly‐Asp (RGD) peptides, not only enhanced biocompatibility but also improved tumor targeting and tissue penetration. Upon laser irradiation, R‐CM@MSN@BC executed both photodynamic and glutamine‐metabolic therapies, inducing necroptosis in tumor cells and triggering significant immunogenic cell death. Time‐of‐flight mass cytometry analysis revealed that R‐CM@MSN@BC can remodel the immunosuppressive tumor microenvironment by polarizing M1‐type macrophages, reducing infiltration of M2‐type and CX3CR1+ macrophages, and decreasing T cell exhaustion, thereby increasing the effectiveness of anti‐programmed cell death ligand 1 immunotherapy. This strategy proposed in this study presents a viable and promising approach for the treatment of cholangiocarcinoma.

Abstract Knowing the impacts of global climate change on the habitat suitability distribution of Limassolla leafhoppers contributes to understanding the feedback of organisms on climate change from a macroecological perspective, and provides important scientific basis for protecting the ecological environment and biodiversity. However, there is limited knowledge on this aspect. Thus, our study aimed to address this gap by analyzing Asian habitat suitability and centroid shifts of Limassolla based on 19 bioclimatic variables and occurrence records. Selecting five ecological niche models with the outstanding predictive performance (Maxlike, generalized linear model, generalized additive model, random forest, and maximum entropy) along with their ensemble model from 12 models, the current habitat suitability of Limassolla and its future habitat suitability under two Shared Socio‐economic Pathways (SSP1‐2.6 and SSP5‐8.5) in the 2050s and 2090s were predicted. The results showed that the prediction results of the five models are generally consistent. Based on ensemble model, 11 potential biodiversity hotspots with high suitability were identified. With climate change, the suitable range of Limassolla will experience both expansion and contraction. In SSP5‐8.52050s, the expansion area is 118.56 × 104 km2, while the contraction area is 25.40 × 104 km2; in SSP1‐2.62090s, the expansion area is 91.71 × 104 km2, and the contraction area is 26.54 × 104 km2. Furthermore, the distribution core of Limassolla will shift toward higher latitudes in the northeast direction, and the precipitation of warmest quarter was found to have the greatest impact on the distribution of Limassolla. Our research results supported our four hypotheses. Finally, this research suggests establishing ecological reserves in identified contraction to prevent habitat loss, enhancing the protection of biodiversity hotspots, and pursuing a sustainable development path with reduced emissions.

Abstract Background Patients with myocardial infarction (MI) frequently experience a heightened incidence of depression, thereby increasing the risk of adverse cardiovascular events. Consequently, early detection and intervention in depressive symptoms among patients with MI are imperative. Shexiang Baoxin Pills (SBP), a Chinese patent medicine employed for the treatment of MI, exhibits diverse mechanisms targeting this condition. Nevertheless, its therapeutic efficacy on postmyocardial infarction depressive symptoms remains unclear. The aim of this study is to investigate the effectiveness and mechanism of SBP in managing depression during acute myocardial infarction (AMI). Methods A rat model combining MI and depression was established, and the rats were randomly divided into four groups: the model (MOD) group, SBP group, Fluoxetine (FLX) group, and Sham group. After 28 days of drug intervention, cardiac function was assessed using echocardiography while behavior was evaluated through sucrose preference test (SPT), forced swimming test (FST), and open‐field test (OFT). Additionally, levels of inflammatory factors in serum and hippocampus were measured along with NLRP3 inflammasome‐related protein expression via Western blotting and immunofluorescence. Results SBP can enhance cardiac function in rats with AMI and depression, while significantly ameliorating depressive‐like behavior. Compared to the Sham group, levels of IL‐1β, IL‐18, TNF‐α, and other inflammatory factors were markedly elevated in the MOD group. However, expressions of these inflammatory factors were reduced to varying degrees following treatment with SBP or FLX. Analysis of NLRP3 inflammasome‐related proteins in the hippocampus revealed a significant upregulation of IL‐1β, IL‐18, NLRP3, ASC, caspase‐1, and GSDMD in the MOD group; conversely, these measures were significantly attenuated after SBP intervention. Conclusion We have observed a significant amelioration in depression‐like behavior upon SBP administration during the treatment of AMI, suggesting that this effect may be attributed to the inhibition of NLRP3‐mediated pyroptosis. (The main findings are summarized in the graphical abstract in the supplementary file.)

ABSTRACT Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).

Abstract The coral reef microbiome plays a vital role in the health and resilience of reefs. Previous studies have examined phage therapy for coral pathogens and for modifying the coral reef microbiome, but defence systems against coral‐associated bacteria have received limited attention. Phage defence systems play a crucial role in helping bacteria fight phage infections. In this study, we characterized a new defence system, Hma (HmaA‐HmaB‐HmaC), in the coral‐associated Halomonas meridiana derived from the scleractinian coral Galaxea fascicularis. The Swi2/Snf2 helicase HmaA with a C‐terminal nuclease domain exhibits antiviral activity against Escherichia phage T4. Mutation analysis revealed the nickase activity of the nuclease domain (belonging to PDD/EXK superfamily) of HmaA is essential in phage defence. Additionally, HmaA homologues are present in ~1000 bacterial and archaeal genomes. The high frequency of HmaA helicase in Halomonas strains indicates the widespread presence of these phage defence systems, while the insertion of defence genes in the hma region confirms the existence of a defence gene insertion hotspot. These findings offer insights into the diversity of phage defence systems in coral‐associated bacteria and these diverse defence systems can be further applied into designing probiotics with high‐phage resistance.

Abstract Aim To determine how nurses' experiences with the coronavirus disease (COVID‐19) pandemic affected their knowledge, awareness, and compliance related to the use of personal protective equipment (PPE) during the COVID‐19 pandemic in South Korea. Design A descriptive cross‐sectional study. Methods A total of 247 nurses in South Korea participated in this study between May 10 and 19, 2023. An online self‐report questionnaire was used to collect data on demographic and occupational characteristics, COVID‐19 experience, knowledge, awareness, and compliance related to the use of PPE. Factors affecting compliance were analysed using hierarchical multiple linear regression. Results Mean age of the nurses was 31.92, and 94.3% were women. Most had a bachelor's degree or higher and the mean clinical experience as a nurse was 6.45 years. Knowledge of the use of PPE was 8.45 out of 10, awareness was 3.52 out of 5, and compliance was 4.28 out of 5. Knowledge and awareness were correlated with compliance related to PPE use. Awareness (β = 0.234, p

Abstract White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno‐associated virus delivery of vascular endothelial growth factor‐C (VEGF‐C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF‐C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.

Abstract Integrating multiple single‐cell datasets is essential for the comprehensive understanding of cell heterogeneity. Batch effect is the undesired systematic variations among technologies or experimental laboratories that distort biological signals and hinder the integration of single‐cell datasets. However, existing methods typically rely on a selected dataset as a reference, leading to inconsistent integration performance using different references, or embed cells into uninterpretable low‐dimensional feature space. To overcome these limitations, a reference‐free method, Beaconet, for integrating multiple single‐cell transcriptomic datasets in original molecular space by aligning the global distribution of each batch using an adversarial correction network is presented. Through extensive comparisons with 13 state‐of‐the‐art methods, it is demonstrated that Beaconet can effectively remove batch effect while preserving biological variations and is superior to existing unsupervised methods using all possible references in overall performance. Furthermore, Beaconet performs integration in the original molecular feature space, enabling the characterization of cell types and downstream differential expression analysis directly using integrated data with gene‐expression features. Additionally, when applying to large‐scale atlas data integration, Beaconet shows notable advantages in both time‐ and space‐efficiencies. In summary, Beaconet serves as an effective and efficient batch effect removal tool that can facilitate the integration of single‐cell datasets in a reference‐free and molecular feature‐preserved mode.

Abstract The photoreceptor cilium is vital for maintaining the structure and function of the retina. However, the molecular mechanisms underlying the photoreceptor cilium integrity and retinal homeostasis are largely unknown. Herein, it is shown that kinesin family member 11 (KIF11) localizes at the transition zone (connecting cilium) of the photoreceptor and plays a crucial role in orchestrating the cilium integrity. KIF11 depletion causes malformations of both the photoreceptor ciliary axoneme and membranous discs, resulting in photoreceptor degeneration and the accumulation of drusen‐like deposits throughout the retina. Mechanistic studies show that the stability of KIF11 is regulated by an interplay between its UFMylation and ubiquitination; UFMylation of KIF11 at lysine 953 inhibits its ubiquitination by synoviolin 1 and thereby prevents its proteasomal degradation. The lysine 953‐to‐arginine mutant of KIF11 is more stable than wild‐type KIF11 and also more effective in reversing the ciliary and retinal defects induced by KIF11 depletion. These findings identify a critical role for KIF11 UFMylation in the maintenance of photoreceptor cilium integrity and retinal homeostasis.

Abstract High‐entropy oxides (HEOs) have garnered significant attention within the realm of rechargeable batteries owing to their distinctive advantages, which encompass diverse structural attributes, customizable compositions, entropy‐driven stabilization effects, and remarkable superionic conductivity. Despite the brilliance of HEOs in energy conversion and storage applications, there is still lacking a comprehensive review for both entry‐level and experienced researchers, which succinctly encapsulates the present status and the challenges inherent to HEOs, spanning structural features, intrinsic properties, prevalent synthetic methodologies, and diversified applications in rechargeable batteries. Within this review, the endeavor is to distill the structural characteristics, ionic conductivity, and entropy stabilization effects, explore the practical applications of HEOs in the realm of rechargeable batteries (lithium‐ion, sodium‐ion, and lithium‐sulfur batteries), including anode and cathode materials, electrolytes, and electrocatalysts. The review seeks to furnish an overview of the evolving landscape of HEOs‐based cell component materials, shedding light on the progress made and the hurdles encountered, as well as serving as the guidance for HEOs compositions design and optimization strategy to enhance the reversible structural stability, electrical properties, and electrochemical performance of rechargeable batteries in the realm of energy storage and conversion.

Abstract Background The clinical staging of non‐small cell lung cancer (NSCLC) is well known to be related to their prognosis. However, there is usually a discrepancy between clinical staging and pathological staging. There are few analyses of clinical staging accuracy in patients with NSCLC. We compared the concordance rate between clinical and pathological staging of NSCLC and evaluated factors affecting the accuracy in real‐world data. Methods Altogether, 811 patients with primary NSCLC who had undergone curative lung resection surgery in Severance Hospital from January 2019 to December 2020 were retrospectively reviewed. We used the eighth edition of the American Joint Committee on Cancer TNM staging. Results Among 811 patients, endobronchial ultrasound (EBUS) and positron emission tomography (PET‐CT) were performed in 31.6% and 96.7%, respectively. The concordance rates between clinical and pathological TNM staging, T factor, and N factor, were 68.7%, 77.7%, and 85.8%, respectively. With multivariable logistic regression analysis, current smokers (OR 0.49; 95% CI: 0.32–0.76, p = 0.001) and a higher clinical stage (p

Abstract With the application of new technologies for coal mine gas control, it has been increasingly urgent to apply the fixed‐point closed sampling (FPCS) technology for accurate measurement of coal seam gas content. In this study, gas desorption during FPCS was analyzed. In addition, gas desorption experiments and COMSOL simulations were conducted on coal particles. Furthermore, the gas desorption law during FPCS was compared with that under atmospheric pressure. The results show that Sun's formula can effectively characterize the gas desorption law during FPCS, and the i value remains unchanged when the gas desorption curve is fitted with Sun's formula. On this basis, a specific method for calculating gas loss during FPCS by using Sun's formula was proposed. The research findings are expected to provide a theoretical basis for accurate measurement of coal seam gas content by means of FPCS.

Objective Glucocorticoid (GC) overuse is strongly associated with steroid‐induced osteonecrosis of the femoral head (SINFH). However, the underlying mechanism of SINFH remains unclear. This study aims to investigate the effect of dexamethasone (Dex)‐induced oxidative stress on osteocyte apoptosis and the underlying mechanisms. Methods Ten patients with SINFH and 10 patients with developmental dysplasia of the hips (DDH) were enrolled in our study. Sixty rats were randomly assigned to the Control, Dex, Dex + N‐Acetyl‐L‐cysteine (NAC), Dex + Dibenziodolium chloride (DPI), NAC, and DPI groups. Magnetic resonance imaging (MRI) was used to examine edema in the femoral head of rats. Histopathological staining was performed to assess osteonecrosis. Immunofluorescence staining with TUNEL and 8‐OHdG was conducted to evaluate osteocyte apoptosis and oxidative damage. Immunohistochemical staining was carried out to detect the expression of NOX1, NOX2, and NOX4. Viability and apoptosis of MLO‐Y4 cells were measured using the CCK‐8 assay and TUNEL staining. 8‐OHdG staining was conducted to detect oxidative stress. 2′,7′‐Dichlorodihydrofluorescein diacetate (DCFH‐DA) staining was performed to measure reactive oxygen species (ROS). The expression of NOX1, NOX2, and NOX4 in MLO‐Y4 cells was analyzed by Western blotting. Multiple comparisons were performed using one‐way analysis of variance (ANOVA). Results In patients and the rat model, hematoxylin–eosin (HE) staining revealed a significantly higher rate of empty lacunae in the SINFH group than in the DDH group. Immunofluorescence staining indicated a significant increase in TUNEL‐positive cells and 8‐OHdG‐positive cells in the SINFH group compared to the DDH group. Immunohistochemical staining demonstrated a significant increase in the expression of NOX1, NOX2, and NOX4 proteins in SINFH patients compared to DDH patients. Moreover, immunohistochemical staining showed a significant increase in the proportion of NOX2‐positive cells compared to the Control group in the femoral head of rats. In vitro, Dex significantly inhibited the viability of osteocyte cells and induced apoptosis. After Dex treatment, the intracellular ROS level increased. However, Dex treatment did not alter the expression of NOX proteins in vitro. Additionally, NAC and DPI inhibited the generation of intracellular ROS and partially alleviated osteocyte apoptosis in vivo and in vitro. Conclusion This study demonstrates that GC promotes apoptosis of osteocyte cells through ROS‐induced oxidative stress. Furthermore, we found that the increased expression of NOXs induced by GC serves as an important source of ROS generation.

Homologous recombination (HR) repair for DNA double‐strand breaks (DSBs) is critical for maintaining genome stability and conferring the resistance of tumor cells to chemotherapy. Nuclear PTEN which contains both phosphatidylinositol 3,4,5‐trisphosphate 3‐phosphatase and protein phosphatase plays a key role in HR repair, but the underlying mechanism remains largely elusive. We find that SUMOylated PTEN promotes HR repair but represses nonhomologous end joining (NHEJ) repair by directly dephosphorylating TP53‐binding protein 1 (53BP1). During DNA damage responses (DDR), tumor suppressor ARF (p14ARF) was phosphorylated and then interacted efficiently with PTEN, thus promoting PTEN SUMOylation as an atypical SUMO E3 ligase. Interestingly, SUMOylated PTEN was subsequently recruited to the chromatin at DSB sites. This was because SUMO1 that was conjugated to PTEN was recognized and bound by the SUMO‐interacting motif (SIM) of breast cancer type 1 susceptibility protein (BRCA1), which has been located to the core of 53BP1 foci on chromatin during S/G2 stage. Furthermore, these chromatin‐loaded PTEN directly and specifically dephosphorylated phosphothreonine‐543 (pT543) of 53BP1, resulting in the dissociation of the 53BP1 complex, which facilitated DNA end resection and ongoing HR repair. SUMOylation‐site‐mutated PTENK254R mice also showed decreased DNA damage repair in vivo. Blocking the PTEN SUMOylation pathway with either a SUMOylation inhibitor or a p14ARF(2‐13) peptide sensitized tumor cells to chemotherapy. Our study therefore provides a new mechanistic understanding of PTEN in HR repair and clinical intervention of chemoresistant tumors.

Abstract Vehicular trajectory data collected by connected automated vehicles (CAVs) is minimal due to the low penetration rates (PRs) of CAVs, and fail to capture the characteristics of traffic flow. This study proposes a fully sampled trajectory reconstruction method for mixed traffic flow with regular vehicles (RVs), connected vehicles (CVs), and CAVs based on car‐following behaviour. Firstly, considering the minimum safety distance constraints between vehicles, an optimization model for minimizing the impact on the acceleration of the known vehicles is developed to obtain the number of inserted RVs. Secondly, the speed of the inserted RVs is estimated based on the traffic flow model. Then, an optimization model is proposed to determine the position of each inserted RV. Finally, numerical simulation is designed to investigate the influence of traffic density and PRs of CAVs and CVs. Results show that the proposed method can better reconstruct the vehicle trajectory on the freeway under the different traffic densities in a congested state. The MAPE of the number and position of inserted RVs is less than 10.7% and 0.37%, respectively. In addition, the proposed method performs well even if the PRs of CAVs and CVs are extremely low.

Abstract Background Magnetic resonance (MR)‐guided ultra‐hypofractionated radiotherapy with whole‐pelvic irradiation (UHF‐WPRT) is a novel approach to radiotherapy for patients with high‐risk (HR) and very high‐risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF‐WPRT might inevitably result in longer on‐couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF‐WPRT on a 1.5‐Tesla MR‐Linac. Methods Ten patients with clinical stage T3a‐4N0‐1M0‐1c PCa, who consecutively received UHF‐WPRT, were enrolled prospectively. The contours of the target and organ‐at‐risks on the position verification‐MR (PV‐MR), beam‐on 3D‐MR(Bn‐MR), and post‐MR (after radiotherapy delivery) were derived from the pre‐MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses. Results In total, we collected 188 MR scans (50 pre‐MR, 50 PV‐MR, 44 Bn‐MR, and 44 post‐MR scans). With median 59 min, the mean prostate clinical target volume (CTV)‐V100% was 98.59% ± 2.74%, and the mean pelvic CTVp‐V100% relative percentages of all scans was 99.60% ± 1.18%. The median V29 Gy change in the rectal wall was −2% (−18% to 20%). With a median follow‐up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion UHF‐RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt‐To‐Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam‐on phase was clinically acceptable based on the 3D‐MR–based dosimetry analysis. Clinical trial registration Chinese Clinical Trial Registry ChiCTR2000033382.

Abstract There has been no consensus yet regarding the precise initial timing and duration of the late Mesozoic extensional tectonics in the South‐eastern China Block. This work focusses on the growth strata of the Early Cretaceous red beds in the South‐eastern China Block to determine the late Mesozoic tectonics and the precise timing of the initiation and duration of extensional tectonics in this area. Field observation of several terrigenous basins shows that the dip angles of the Cretaceous red beds have varied from moderate to gentle from basin edges to interiors (or centres). The visible and estimated thickness within a single bed increases slightly downwards from the upper to the lower part. These characteristics indicate that the sedimentary area of these beds has undergone an extensional process with expansion and deepening of the sedimentary basins. Rotation of the border surfaces (limbs) and downward warping of the hanging walls or retreat of the footwalls of listric normal faults causes three types of extensional growth (or syntectonic) strata in the deposits of different basins. Dating of the volcanic rocks related to the growth beds reveals that the sedimentary basins were enlarged and deepened when the Early Cretaceous strata were deposited in the South‐eastern China Block from ca 140 to 137 Ma. Regionally, under the influence of Palaeo‐Pacific plate rollback since ca 140 Ma, the South‐eastern China Block stress field has led to lithospheric uplift and pull‐apart structures near the surface, causing the half‐graben basins to receive sedimentation. Although the extensional event was interrupted by a short compressional event during 120 to 105 Ma, with the oceanward retreat of the trench, the area of extension gradually enlarged and rejuvenated south‐eastwards until the end of the Cretaceous. This Cretaceous extension event of the South‐eastern China Block must belong to a worldwide geological event with global significance.

Abstract Background Radiomics is increasingly utilized to distinguish pulmonary nodules between lung adenocarcinoma (LUAD) and tuberculosis (TB). However, it remains unclear whether different segmentation criteria, such as the inclusion or exclusion of the cavity region within nodules, affect the results. Methods A total of 525 patients from two medical centers were retrospectively enrolled. The radiomics features were extracted according to two regions of interest (ROI) segmentation criteria. Multiple logistic regression models were trained to predict the pathology: (1) The clinical model relied on clinical‐radiological semantic features; (2) The radiomics models (radiomics+ and radiomics−) utilized radiomics features from different ROIs (including or excluding cavities); (3) the composite models (composite+ and composite−) incorporated both above. Results In the testing set, the radiomics+/− models and the composite+/− models still possessed efficient prediction performance (AUC ≥ 0.94), while the AUC of the clinical model was 0.881. In the validation set, the AUC of the clinical model was only 0.717, while that of the radiomics+/− models and the composite+/− models ranged from 0.801 to 0.825. The prediction performance of all the radiomics+/− and composite+/− models were significantly superior to that of the clinical model (p 0.05). Conclusions The present study established a machine learning‐based radiomics strategy for differentiating LUAD from TB lesions. The ROI segmentation including or excluding the cavity region may exert no significant effect on the predictive ability.

Abstract Radar‐based human activity recognition is considered as a competitive solution for the elderly care health monitoring problem, compared to alternative techniques such as cameras and wearable devices. However, raw radar signals are often contaminated with noise, clutter, and other artifacts that significantly impact recognition performance, which highlights the importance of prepossessing techniques that enhance radar data quality and improve classification model accuracy. In this study, two different human activity classification models incorporated with pre‐processing techniques have been proposed. The authors introduce wavelet denoising methods into a cyclostationarity‐based classification model, resulting in a substantial improvement in classification accuracy. To address the limitations of conventional pre‐processing techniques, a deep neural network model called Double Phase Cascaded Denoising and Classification Network (DPDCNet) is proposed, which performs end‐to‐end signal‐level classification and achieves state‐of‐the‐art accuracy. The proposed models significantly reduce false detections and would enable robust activity monitoring for older individuals with radar signals, thereby bringing the system closer to a practical implementation for deployment.

Abstract Ruthenium (Ru) has been recognized as a prospective candidate to substitute platinum catalysts in water‐splitting‐based hydrogen production. However, minimizing the Ru contents, optimizing the water dissociation energy of Ru sites, and enhancing the long‐term stability are extremely required, but still face a great challenge. Here, we report on creating tungsten oxide‐anchored Ru clusters (Ru–WOx) with electron‐rich and anti‐corrosive microenvironments for efficient and robust seawater splitting. Benefiting from the abundant oxygen vacancy structure in tungsten oxide support, the Ru–WOx exhibits strong Ru–O and Ru–W bonds at the interface. Our study elucidates that the strong Ru–O bonds in Ru–WOx may accelerate the water dissociation kinetics, and the Ru–W bonds will lead to the strong metal–support interaction and electrons transfer from W to Ru. The optimal Ru–WOx catalysts exhibit a low overpotential of 29 and 218 mV at the current density of 10 mA cm−2 in alkaline and seawater media, respectively. The outstanding long‐term stability discloses that the Ru–WOx catalysts own efficient corrosion resistance in seawater electrolysis. We believe that this work offers new insights into the essential roles of electron‐rich and anti‐corrosive microenvironments in Ru‐based catalysts and provide a new pathway to design efficient and robust cathodes for seawater splitting.

Abstract Formulas containing intact cow milk protein are appropriate alternatives when human milk (HM) is not feasible. However, for babies with a physician‐diagnosed cow milk protein allergy (CMPA), hydrolyzed formulas are needed. We conducted a 3‐month, open‐label, nonrandomized concurrent controlled trial (ChiCTR2100046909) between June 2021 and October 2022 in Qingdao City, China. In this study, CMPA toddlers were fed with a partially hydrolyzed formula containing synbiotics (pHF, n = 43) and compared with healthy toddlers fed a regular intact protein formula (IF, n = 45) or HM (n = 21). The primary endpoint was weight gain; the secondary endpoints were changes in body length and head circumference of both CMPA and healthy toddlers after 3‐month feeding; and the exploratory outcomes were changes in gut microbiota composition. After 3 months, there were no significant group differences for length‐for‐age, weight‐for‐age, or head circumference‐for‐age Z scores. In the gut microbiota, pHF feeding increased its richness and diversity, similar to those of IF‐fed and HM‐fed healthy toddlers. Compared with healthy toddlers, the toddlers with CMPA showed an increased abundance of phylum Bacteroidota, Firmicutes, class Clostridia, and Bacteroidia, and a decreased abundance of class Negativicutes, while pHF feeding partly eliminated these original differences. Moreover, pHF feeding increased the abundance of short‐chain fatty acid producers. Our data suggested that this pHF partly simulated the beneficial effects of HM and shifted the gut microbiota of toddlers with CMPA toward that of healthy individuals. In conclusion, this synbiotic‐containing pHF might be an appropriate alternative for toddlers with CMPA.