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Painting is the most fundamental kind of art, and is one important part of creative practice in art courses. In typical painting classes, students paint a picture independently with only a few theoretical explanations and may lack authentic experience of the painting topic. It would therefore be meaningful to construct a new painting form to enhance students' learning efficiency and creativity. Previous research indicated that high-quality collaboration and digital technology have the potential to enhance students' innovation in art courses. Therefore, in the current study, a virtual reality-based collaborative painting (VR-CP) approach was developed and applied to painting in a primary school art class to verify its effectiveness. A total of 45 fifth graders from China were recruited and randomly divided into an experimental group, with 21 students learning with the VR-CP approach, and 24 students in the control group, which adopted the conventional paper-and-brush collaborative painting (C-CP) approach. The results showed that the VR-CP approach can facilitate students' creative thinking behaviors of exploring, knowing what they want to do, analyzing ideas, and taking risks, as well as the development of product creative quality. It was found that the students learning with the VR-CP approach tended to demonstrate better collaboration levels and used more bidirectional-sharing strategies than the students learning with the C-CP approach.

Background: Painting is the foundational expression across all art forms and is one of the key creative practices for fostering students' aesthetic ability and creativity within fine arts courses. Collaborative painting in the form of socially shared regulation of learning (SSRL) can be recognized as an effective strategy for enhancing creativity in both individual and group work. However, the absence of contextual experiences and collaborative spaces poses challenges for students in cultivating their creativity in painting. Objectives: The present study explores students' creativity, socially shared regulation (SSR) and positive painting behaviours using an SSRL-based collaborative painting approach in the metaverse (Meta-CP). Methods: Via a quasi-experimental design, a total of 40 Chinese students in fifth grade were recruited and were randomly divided into an experimental group and a control group, with 20 students utilizing the Meta-CP approach, while the remaining 20 students followed the conventional SSRL-based paper-and-brush collaborative painting (C-CP) approach. The Meta-CP approach not only offers an authentic painting context and a collaborative space but also facilitates the collaborative process through the SSRL framework. The data collection included students' creative tendency, painting works and painting process. Results and Conclusions: The Meta-CP approach effectively enhances students' creativity concerning adventure, curiosity and imagination, as well as results in the creation of more distinctive and logical artistic works. Furthermore, the approach significantly improved the quality of students' SSR. Additionally, students utilizing the Meta-CP approach displayed more positive painting behaviours compared with those employing the C-CP approach.

Abstract Background Patients with type 2 diabetes mellitus (T2DM) are predisposed to cardiovascular disease (CVD). Bone mineral density (BMD) is linked to CVD, but most studies focused on women. Our analysis aims to explore the association of BMD and fracture with the prevalence of CVD in men with T2DM. Methods In this retrospective cross‐sectional study, 856 men with T2DM were enrolled. BMDs at the lumbar spine (L2‐4), femoral neck (FN), and total hip (TH) were measured by dual‐energy X‐ray absorptiometry (DXA). The CVD outcome was determined as the sum of the following conditions: congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction, the requirement for coronary artery revascularization, and stroke. The relationship between BMDs and CVD was investigated by restricted cubic spline curves and logistic regression models. Results A total of 163 (19.0%) patients developed CVD. The restricted cubic spline curve revealed a linear and negative association between FN‐BMD, TH‐BMD, and CVD. After full adjustments for confounding covariates, the odds ratios were 1.34 (95% confidence interval [CI] [1.11–1.61], p

Synthetic lethality is a phenomenon wherein the simultaneous deficiency of two or more genes results in cell death, while the deficiency of any individual gene does not lead to cell death. In recent years, synthetic lethality has emerged as a significant topic in the field of targeted cancer therapy, with certain drugs based on this concept exhibiting promising outcomes in clinical trials. Nevertheless, the presence of tumor heterogeneity and the intricate DNA repair mechanisms pose challenges to the effective implementation of synthetic lethality. This review aims to explore the concepts, development, and ethical quandaries surrounding synthetic lethality. Additionally, it will provide an in-depth analysis of the clinical application and underlying mechanism of synthetic lethality.

Abstract The development of lithium (Li) metal batteries has been severely limited by the formation of lithium dendrites and the associated catastrophic failure and inferior Coulombic efficiency which caused by non‐uniform or insufficient Li+ supply across the electrode–electrolyte interface. Therefore, a rational strategy is to construct a robust electrolyte that can allow efficient and uniform Li+ transport to ensure sufficient Li+ supply and homogenize the Li plating/stripping. Herein, we report an ion‐percolating electrolyte membrane that acts as a stable Li+ reservoir to ensure a near‐single Li+ transference number (0.78) and homogenizes Li+ migration to eradicate dendrite growth, endowing Li//LFP cell with an ultrahigh average Coulombic efficiency (ca. 99.97%) after cycling for nearly half of a year and superior cycling stability when pairing with LiCoO2 with limited Li amount and LiNi0.8Mn0.1Co0.1O2. These estimable attributes demonstrate significant potential of utility value for the ion‐percolating electrolyte.

Abstract Objective Compared logistic regression (LR) with machine learning (ML) models, to predict the risk of ischemic stroke in an elderly population in China. Methods We applied 2208 records from the Rugao Longitudinal Ageing Study (RLAS) for ischemic stroke risk prediction assessment. Input variables included 103 phenotypes. For 3‐year ischemic stroke risk prediction, we compared the discrimination and calibration of LR model and ML methods, where ML methods include Random Forest (RF), Gaussian kernel Support Vector Machines (SVM), Multilayer perceptron (MLP), K‐Nearest Neighbors Algorithm (KNN), and Gradient Boosting Decision Tree (GBDT) to develop an ischemic stroke risk prediction model. Results Age, pulse, waist circumference, education level, β2‐microglobulin, homocysteine, cystatin C, folate, free triiodothyronine, platelet distribution width, QT interval, and QTc interval were significant induced predictors of ischemic stroke. For ischemic stroke prediction, the ML approach was able to tap more biochemical and ECG‐related multidimensional phenotypic indicators compared to the LR model, which placed more importance on general demographic indicators. Compared to the LR model, SVM provided the best discrimination and calibration (C‐index: 0.79 vs. 0.71, 11.27% improvement in model utility), with the best performance in both validation and test data. Conclusion In a comparison of LR with five ML models, the accuracy of ischemic stroke prediction was higher by combining ML with multiple phenotypes. Combined with other studies based on elderly populations in China, ML techniques, especially SVM, have shown good long‐term predictive performance, inspiring the potential value of ML use in clinical practice.

Objectives The transtibial pull‐out repair (TP) is a relatively new method for treating meniscal root tear; however, the clinical evaluation of its healing effect remains controversial. Due to ethical constraints and limitations of imaging techniques in humans, here we dynamically observe the healing effects of TP and TP with platelet‐rich plasma gel (PRG) at the histological level using an animal model. Methods Platelet‐rich plasma (PRP) and PRG of rabbits were prepared. Platelet‐derived growth factor (PDGF) and transforming growth factor‐β1 (TGF‐β1) levels in PRP and PRG were determined using an enzyme‐linked immunosorbent assay. A rabbit model of anterior horn tear of the medial meniscus and TP surgery were created. PRG was injected between the anterior horn of the medial meniscus and the tibial tunnel. Rabbits were divided into three groups: the anterior horn tear group (Tear group), the anterior horn tear + TP group (TP group), and the anterior horn tear + TP + PRG group (TP + PRG group). The healing effect was observed dynamically using histopathological studies and biomechanical experiments. Results The platelet content in PRP significantly increased to approximately 4.57 times that of whole blood. PDGF and TGF‐β1 concentrations in PRG increased to 2.46 and 4.15 times those in PRP, respectively. Hematoxylin and eosin (H&E) and Masson staining showed that the number of inflammatory cells in healing tissue decreased and the collagen fibers significantly increased in TP and TP + PRG groups at 4, 8, and 12 weeks postoperatively compared to those in Tear group. Neatly arranged, interlaced, and dense collagen fibers were found between the anterior horn and bone at 12 weeks. H&E and toluidine blue staining showed that the injury to the femoral condyle cartilage was alleviated. The healing performance in TP + PRG group was better and faster than that in TP group. The maximum tensile fracture strength of the meniscus progressively increased at 8 and 12 weeks postoperatively. Conclusions Anterior horn injury of the medial meniscus in rabbits can be repaired using the TP technique, and the addition of autologous PRG to the bone tunnel promotes early healing of the meniscus and bone postoperatively. Meanwhile, both treatments can reduce the secondary damage to the cartilage due to osteoarthritis.

The production of high purity steel is a major issue for iron and steel enterprises. Obtaining bubbles with controllable size and dispersed distribution in liquid steel is an important method for removing fine inclusions and producing high-quality steel. Microheterogeneous purification of molten steel technology is a carbonate decomposition reaction-based process that generates fine bubbles and slag droplets to eradicate small inclusions. On this basis, composite spheres (powders) with various metallurgical functions are designed, and industrial field tests are carried out at ANSTEEL. The results show that the microheterogeneous purification of molten steel is a low-cost, high-efficiency, simple, and easy molten steel purification technology. The carbonate composite sphere (powder) can cause dispersion, microbubbles, and slag droplets in the molten steel. Its size is 0.02–0.2 mm, and the size distribution and slag droplet composition can be controlled. Rapid dephosphorization and slag-forward movement can be achieved by feeding composite balls during converter tapping. For low phosphorus steel, the minimum phosphorus content can reach 0.002% (in mass, the same below) and the dephosphorization efficiency is >50%. The slag-forward movement process can reduce the temperature drop during molten steel transmission, promote rapid slag formation in ladle furnace (LF) refining, increase the LF heating rate by 2 °C·min–1, and shorten the refining LF treatment cycle by 3–5 min. The addition of composite spheres in the Rheinstahl–Heraeus (RH) refining process can remove fine inclusions and provide deep desulfurization. The inclusion of free molten steel in the interstitial can be effectively removed. Compared to conventional inclusion removal technology, the number of the oxide inclusions can be reduced, and the inclusion size becomes finer. The total oxygen (mass fraction) in the as-cast slab can approach 5×10−6 using this novel technology, and the steel production cost per ton can be reduced by 5–12 RMB. The sulfur content of ultralow carbon nonoriented silicon steel can be consistently controlled below 0.002%, and the desulfurization efficiency is >50%. Recently, the advancement of this process has piqued the attention of metallurgical workers, and some new technologies have emerged and matured. Based on the principle of microheterogeneous purification of molten steel process, this paper introduces the latest progress of microheterogeneous purification of molten steel technology in detail, summarizes the characteristics and mechanism of microheterogeneous removal of fine inclusions, desulfurization, dephosphorization, slag migration, and RH rapid decarbonization, and looks forward to the problems to be solved in the engineering field and the future developments.

Abstract The role of angiotensin receptor blocker in wound healing and cutaneous fibrosis has become a hotspot in recent years. We have developed a losartan cream that is comparable to triamcinolone ointment in inhibiting scarring. Considering the effects of chitosan and asiaticoside on wound healing and scarring, we added them to the losartan cream this time and improved the formula, expecting to get a better anti-scarring effect. The effects of creams were investigated on mouse scar model with triamcinolone ointment, onion extract gel, and commercial asiaticoside cream set as positive controls. A preliminary exploration of the mechanism involved in TGF-β/Smad pathway was performed in vivo and in vitro. With all results of anti-scarring, the compound losartan cream (containing chitosan, asiaticoside, and losartan) shows the best effect, followed by the chitosan asiaticoside cream. The treatment of the compound losartan cream inhibited expression of TGF-β1, collagen, and Smads, and decreased phosphorylation of Smad in vivo. These inhibitory effects were also confirmed in vitro. Our findings indicated that the compound losartan cream could inhibit scarring via TGF-β/Smad pathway. This cream might be an effective option for scar treatment.

AimThis study investigated the association between nerve conduction velocity (NCV) and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM).MethodsThis study retrospectively collected medical data of T2DM patients who underwent dual-energy X-ray absorptiometry and nerve conduction study at the Shanghai Ruijin Hospital, Shanghai, China. The primary outcome was the total hip BMD T-score. The main independent variables were motor nerve conduction velocities (MCVs), sensory nerve conduction velocities (SCVs), and composite Z-scores of MCV and SCV. T2DM patients were divided into total hip BMD T-scores < -1 and total hip BMD T-scores ≥ -1 groups. The association between the primary outcome and main independent variables was evaluated by Pearson bivariate correlation and multivariate linear regression.Results195 female and 415 male patients with T2DM were identified. In male patients with T2DM, bilateral ulnar, median, and tibial MCVs and bilateral sural SCVs were lower in the total hip BMD T-score < -1 group than T-score ≥ -1 group (P < 0.05). Bilateral ulnar, median, and tibial MCVs, and bilateral sural SCVs showed positive correlations with total hip BMD T-score in male patients with T2DM (P < 0.05). Bilateral ulnar and tibial MCVs, bilateral sural SCVs, and composite MCV SCV and MSCV Z-scores were independently and positively associated with total hip BMD T-score in male patients with T2DM, respectively (P < 0.05). NCV did not show significant correlation with the total hip BMD T-score in female patients with T2DM.ConclusionNCV showed positive association with total hip BMD in male patients with T2DM. A decline in NCV indicates an elevated risk of low BMD (osteopenia/osteoporosis) in male patients with T2DM.

Abstract Background There is no consensus on whether triplet regimen is better than doublet regimen in the first‐line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. Methods This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non‐inferiority in progression‐free survival (PFS) for XELOX as compared with EOX on an intention‐to‐treat basis. Results Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5‐6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0‐6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812‐1.203; Pnon‐inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health‐related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. Conclusions This non‐inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first‐line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

The hole-transporting layer (HTL), a pivotal component of perovskite solar cells (PSCs), can significantly improve device performance. The unique light-harvesting and charge-transport capabilities of porphyrin derivatives have facilitated their adoption in solar cell applications, showcasing their potential as holetransporting materials for PSCs. This study introduces an electrochemical polymerization method to deposit thin films of three distinct porphyrins as HTLs in PSCs. These polymerized films demonstrate exceptional thermal stability, with nickel-centered porphyrin films highly enhancing the power conversion efficiency, attributed to optimal energetic alignment and effective contact properties. Crucially, devices utilizing this approach exhibit outstanding long-term stability, maintaining 88% of their initial efficiency after 2200-hour storage under ambient conditions. This performance highlights the considerable promise of porphyrin-based materials in photovoltaic applications, suggesting that electrochemical polymerization could lead the way in developing efficient and durable PSCs. The innovative use of electrochemical polymerization represents a noteworthy contribution to the field, opening new avenues for the development of efficient and stable PSCs. [ABSTRACT FROM AUTHOR]

Oleanolic acid (OA) and ursolic acid (UA) possess anti-inflammatory, antioxidative, antiprotozoal, antimutagenic and anticancer properties and are the main bioactive compounds in the fruit of Ligustrum lucidum Ait. The aim of this paper was to study the method of separating the whole fruit into the main ingredients containing OA and UA for the later effective extraction with reduced organic solvents and easy separation and purification. In the present study, the sarcocarps and exocarps were separated from the whole fruits (designated exo-sarcocarps, the mass percentages (w/w, dry weight basis), 33.1%), testae (13.5%) and cores (48.7%) by using methods separated. The contents of OA and UA in whole fruits, exo-sarcocarps, testae and cores were analyzed. The OA and UA extraction yields were highest in exo-sarcocarps vs. yields from whole fruits, testae or cores. The spective yields of OA and UA from exo-sarcocarps were 24.34 ± 2.09 and 7.82 ± 0.09 mg/g; these yields were about 4 times higher than OA yields and about 4 times higher than UA yields from fruit.

Abstract Background Alzheimer’s disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6′-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis. Methods NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2′-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively. Results DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice. Conclusions Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

Chlorophyll derivatives can be applied in bio-solar cells, but their excited-state dynamics are not fully understood in this context. Here pump–probe time-resolved absorption spectroscopy measurements of chlorophyll derivatives reveal enhanced lifetimes of radical species in the presence of hydroquinone.

Osteosarcoma, one of the common malignant tumors in the skeletal system, originates in mesenchymal tissue, and the most susceptible area of occurrence is the metaphysis with its abundant blood supply. Tumors are characterized by highly malignant spindle stromal cells that can produce bone-like tissue. Most of the osteosarcoma are primary, and a few are secondary. Osteosarcoma occurs primarily in children and adolescents undergoing vigorous bone growth and development. Most cases involve rapid tumor development and early blood metastasis. In recent years, research has grown in the areas of molecular biology, imaging medicine, biological materials, applied anatomy, surgical techniques, biomechanics, and comprehensive treatment of tumors. With developments in molecular biology and tissue bioengineering, treatment methods have also made great progress, especially in comprehensive limb salvage treatment, which significantly enhances the quality of life after surgery and improves the 5-year survival rate of patients with malignant tumors. This article provides a review of limb salvage, immunotherapy, gene therapy, and targeted therapy from traditional amputation to neoadjuvant chemotherapy, providing a reference for current clinical treatments for osteosarcoma.

Capsular contracture is one of the most common complications of breast implants, which often leads to secondary surgery. Patients with unconspicuous breast contracture do not need treatment, while for those with severe symptoms, a capsule revision surgery is of great necessity, including a total periprosthetic capsulectomy and replacement with a new implant. However, if the capsular contracture happens in the submuscular space, it will be very difficult to release it completely, and it may lead to more complications such as damage to surrounding tissue. The new method of pouch can create a new subpectoral plane for the insertion of a new implant instead of a total capsulectomy, but this method is unsuitable for patients who have little breast tissue or thin skin. To solve this thorny clinical problem, we invented a double-headed separating instrument and came up with a novel operation method to release the capsular contracture, which opened from the nipple by the punctiform-incision approach and caused only a mild and undetectable trauma. This operation went off without a hitch, and the postoperative breast shape was good, and the breast felt and moved naturally. In addition, there were no significant complications throughout the one-year follow-up period. This case was an excellent demonstration of the novel breast capsular contracture release surgery using our optimized double-headed capsule contracture separator.

Background: TP53 protein is lost or mutated in about half of all types of human cancers and small molecules to regulate mutant p53 repair, or interrupt ubiquitination degradation of p53 induced by E3-ubiquitin ligase Mdm2 have a potential application in clinical application. Methods: To inhibit the deubiquitinase activity of 19S proteasome and restore the p53 protein level, in this study, we utilized p53 knockout mice to test the anti-cancer effect of a specific USP14 and UCH37 inhibitor b-AP15. Results: Our results show that UCHL5, USP14 and COPS5 are upregulated in p53-related tumors, and higher expression of these genes results in a shorter overall survival in patients with p53 deficiency. Treatment with b-AP15, a UCHL5 and USP14 deubiquitinating activity inhibitor in 19S regulatory subunit, induces tumor regression and prolong the survival period of tumor-loaded mice through down-regulation of COPS5 and its downstream AP-1 and E2F1, and up-regulation of the cell cycle-related proteins p27 and Cyclin E1. Conclusions: Thus, our results suggested that inhibition of UCHL5 and USP14 deubiquitinating activity in 19S proteasome may contribute an extensive approach to preventing tumor progress due to p53 deficiency.

Objective To describe a surgical technique using suture tape for reconstruction of the medial patellofemoral ligament (MPFL). This technique restores the stability of the reconstructed ligament and has excellent postoperative outcomes. Method This is a retrospective analysis. From January 2016 to June 2018, 17 patients underwent MPFL reconstruction using high‐strength suture (FiberTape; Arthrex) augmentation, with at least 12 months of follow up. There were 11 female and 6 male patients. The mean age at the time of MPFL reconstruction was 22.1 years (range 13–34 years). Clinical outcomes included pain level, knee range of motion, passive patellar hypermobility, and maltracking at follow‐up. The lateral patellofemoral angles, congruence angles, and patellar tilt angles were measured in a skyline view by CT at 30° of knee flexion at 12 months. Functional outcomes were assessed using the Lysholm knee scoring scale, the SF‐12 score, the Tegner score, and the Crosby and Insall grading system at yearly follow‐up. Result No patients were lost at the last follow up. One patient had recurrence of patellar dislocation and none of the others had serious complications. The success rate of MPFL repair for preventing recurrent dislocations was 94.1% (16 of 17 knees). Fifteen knees had full range of motion of more than 130°. At follow‐up, 2 knees were judged to have mild hypermobility and none had severe hypermobility or maltracking. Using the Crosby and Insall grading system, 12 knees (70.6%) were graded as excellent, 4 knees (23.5%) as good, 1 knee (5.9%) as fair to poor, and none as worse at the last follow‐up assessment. In all patients, the Lysholm knee score (55.12 ± 13.52 vs 79.88 ± 7.50, P

BackgroundThe prevalence of diabetes mellitus remains high in China, and more cardiovascular and cerebrovascular adverse events due to diabetes mellitus are likely to occur in the future.ObjectiveTo analyze the gap between the current pharmacotherapy management and the guidelines for inpatients with type 2 diabetes mellitus from the perspective of pharmacists so as to provide a reference for optimal pharmacotherapy management methods and models for patients with type 2 diabetes mellitus.MethodsThe study was a cross-sectional observational study. The study was conducted by investigating and analyzing the use of glucose-lowering drugs, adjustment of blood pressure management strategy, lipid management, weight management, and application of antiplatelet drugs in type 2 diabetes inpatients.ResultsA total of 1086 patients with type 2 diabetes were included. Metformin, glycosidase inhibitors, and basal insulin were the most used among type 2 diabetes inpatients. The use of SGLT-2, GLP-1 RAs, DPP-4, and metformin all showed significant increase. SGLT-2 inhibitors (SGLT-2i) showed the fastest increase from 2020 to 2021 (14.5% vs. 39.6%); However, the application rate of SGLT-2i was low among patients with combined ASCVD, renal insufficiency, and diabetic nephropathy (46.4%, 40.9%, and 45.8% respectively). For patients with substandard blood pressure at admission, the average rate of intervention by endocrinologists for adjusting the antihypertensive regimen during hospitalization was 55.6%, and the application rate of ACEI/ARB drugs reached 64.4%. The application rate of statins among patients with type 2 diabetes was still relatively high, at 78.8%. However, the overall intervention rate for patients with suboptimal LDL-c was only 24.1%. The application rate of antiplatelet agents for patients with ASCVD was 77.6%, which was higher than that for patients without ASCVD.ConclusionThere is still a gap between the practice of medication treatment management of Chinese inpatients with type 2 diabetes and the guidelines, especially in the application of GLP-1RAs and SGLT-2i in patients with concomitant ASCVD, diabetic nephropathy, and renal insufficiency. Meanwhile, physicians and pharmacists should pay more attention on achieving blood pressure and LDL-c standards in type 2 diabetic patients and provide timely interventions.

Abstract Two-dimensional (2D) perovskites solar cells (PSCs) have attracted considerable attention owing to their excellent stability against humidity; however, some imperfectness of 2D perovskites, such as poor crystallinity, disordered orientation, and inferior charge transport still limit the power conversion efficiency (PCE) of 2D PSCs. In this work, 2D Ti3C2T x MXene nanosheets with high electrical conductivity and mobility were employed as a nanosized additive to prepare 2D Ruddlesden–Popper perovskite films. The PCE of solar cells was increased from 13.69 (without additive) to 15.71% after incorporating the Ti3C2T x nanosheets with an optimized concentration. This improved performance is attributed to the enhanced crystallinity, orientation, and passivated trap states in the 3D phase that result in accelerated charge transfer process in vertical direction. More importantly, the unencapsulated cells exhibited excellent stability under ambient conditions with 55 ± 5% relative humidity.

The healing process of diabetic wounds is typically disordered and prolonged and requires both angiogenesis and epithelialization. Disruptions of the endogenous electric fields (EFs) may lead to disordered cell migration. Electrical stimulation (ES) that mimics endogenous EFs is a promising method in treating diabetic wounds; however, a microenvironment that facilitates cell migration and a convenient means that can be used to apply ES are also required. Chitosan-Vaseline® gauze (CVG) has been identified to facilitate wound healing; it also promotes moisture retention and immune regulation and has antibacterial activity. For this study, we created a wound dressing using CVG together with a flexible ES device and further evaluated its potential as a treatment for diabetic wounds. We found that high voltage monophasic pulsed current (HVMPC) promoted healing of diabetic wounds in vivo. In studies carried out in vitro, we found that HVMPC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) by activating PI3K/Akt and ERK1/2 signaling. Overall, we determined that the flexible ES-chitosan dressing may promoted healing of diabetic wounds by accelerating angiogenesis, enhancing epithelialization, and inhibiting scar formation. These findings provide support for the ongoing development of this multidisciplinary product for the care and treatment of diabetic wounds.

The combination of 5,5′-bistetrazole-1,1′-diolate (TKX-50) and ammonium perchlorate (AP) can make greater use of the chemical energy of TKX-50 based energetic materials. The research on the interaction mechanism between TKX-50 and AP is very important for designing TKX-50-AP compounds and judging the formation feasibility of composite particles, which can lay a theoretical foundation for the preparation of TKX-50-AP mixed crystals and the application of TKX-50 in propellant, propellant and explosive. Herein, in order to research the interaction mechanism between TKX-50 and AP, density-functional theory calculation was applied to optimize three configurations of TKX-50-AP compounds. The geometry structure, electrostatic potential and binding energy of the compounds were predicted, and the electronic density topological analysis was also carried out. Then TKX-50-AP mixed crystals structures were constructed, and the radial distribution function of H–O and H–N in mixed crystals was calculated. Finally, solvent/non-solvent method was applied to prepare TKX-50-AP composites, and the infrared spectroscopy and the non-isothermal decomposition performance of the composites were characterized. Results show that the superposition of positive charges in TKX-50 molecule and negative charges in AP makes the electrostatic potential distributions of TKX-50-AP compounds different from that of TKX-50 and AP. The interaction energies of TKX-50-AP 1, TKX-50-AP 2 and TKX-50-AP 3 are 39.743 kJ/mol, 61.206 kJ/mol and 27.702 kJ/mol, respectively. The interaction between TKX-50 molecules and AP molecules in TKX-50-AP mixed crystals both depends on hydrogen bonds and van der Waals force, and the number and strength of hydrogen bonds are significantly greater than that of van der Waals force. The composition of AP and TKX-50 makes the absorption peak of the five-membered rings and NH3OH+ of TKX-50 shift to low wavenumber in the infrared spectroscopy. In general, TKX-50 interacts with AP via hydrogen bonds and van der Waals force, and the calculated results are in good agreement with the experimental results. The composition of TKX-50 and AP can also prolong the decomposition process.

Functional elimination of p53 is a common feature of a large percentage of human malignancies. Here, we report the development of a pharmacological strategy aimed at restoring p53 function and its use for targeted therapy in p53-deficient mice. Specific inhibition of deubiquitinases ubiquitin-specific peptidase 14 (USP14) resulted in durable tumor regressions of autochthonous lymphomas and sarcomas in p53-deficient mice without affecting normal tissues, and therapeutic response was correlated with an increase in the ubiquitination of constitutive photomorphogenesis 9 (COP9) signalosome subunit 5 (COPS5), a key negative regulatory effector for p53. Inhibition of USP14 resulted in durable tumor regression through COPS5 deubiquitilation and a p53-dependent and -independent regulation mechanism by USP14. This series highlights the utility of proteasome deubiquitinating activity inhibition as a novel treatment paradigm for p53-deficient cancers. In addition, it provides preliminary evidence that inhibition of USP14 resulted in durable tumor regression through COPS5 deubiquitilation and p53-dependent and -independent regulation mechanism by USP14. These findings suggest that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target for patients with p53 deficiency. Keywords: p53, COPS5, USP14, DUB, ubiquitination

Small ubiquitin-related modifiers (SUMO) represent a class of ubiquitin-like proteins that are conjugated, like ubiquitin, by a set of enzymes to form cellular regulatory proteins, and play key roles in the control of cell proliferation, differentiation, and apoptosis. We found that ginkgolic acid (GA) can significantly reduce cell vitality in a dose- and time-dependent manner and can also accelerate cyto-apoptosis in both Tca8113 and Cal-27 cells. Migration and wound-healing assays were executed to determine the anti-migration effect of GA in oral squamous cell carcinoma (OSCC) cell lines. GA represses transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) markers in OSCC cell lines. This investigation is the first evidence that GA suppresses TGF-β1-induced SUMOylation of SMAD4. We show that GA affects the phosphorylation of SMAD2/3 protein and the release of SMAD4. In the xenograft mouse model, the OSCC progression was reduced by GA, effectively suppressing the growth of tumors. In addition, siSMAD4 improved cell migration and viability, which was inhibited by GA in Tca8113 cells. GA suppresses tumorigenicity and tumor progression of OSCC through inhibition of TGF-β1-induced enhancement of SUMOylation of SMAD4. Thus, GA could be a promising therapeutic for OSCC. Keywords: small ubiquitin-like modifiers, oral squamous cell carcinoma, ginkgolic acid, proliferation, migration

Abstract Background Previous studies suggest that poor sleep quality or abnormal sleep duration may be associated with frailty. Here we test the associations of sleep disturbances with both frailty and pre-frailty in an elderly population. Methods Participants included 1726 community-dwelling elders aged 70–87 years. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep disturbances. Frailty was defined using phenotype criteria. Logistic regression models were used to estimate odds ratio of the associations. Results The average PSQI score was 5.4 (SD, 3.1). Overall 43.6% of the participants had poor sleep quality (PSQI> 5), 8.2% had night sleep time ≤ 5 h, and 27.8% had night sleep time ≥ 9 h. The prevalence of frailty and pre-frailty was 9.2 and 52.8%, respectively. The proportions of PSQI> 5 increased with the severity of frailty status (robust: pre-frail: frail, 34.5%: 48%: 56.1%, P 5) was associated with higher odds of frailty (OR = 1.78, 95% CI 1.19–2.66) and pre-frailty (OR = 1.51, 95% CI 1.20–1.90). Sleep latency, sleep disturbance, and daytime dysfunction components of PSQI measurements were also associated with frailty and pre-frailty. In addition, sleep time 9 h/night was associated with higher odds of frailty and pre-frailty. Conclusions We provided preliminary evidences that poor sleep quality and prolonged sleep duration were associated with being frailty and pre-frailty in an elderly population aged 70–87 years. The associations need to be validated in other elderly populations.

Although type Ia supernovae (SNe Ia) are very important in many astrophysical fields, such as cosmology, their explosion mechanisms and progenitor systems still remain unclear. In physics, the relative equivalent width (REW) of the Si ii 635.5 nm absorption feature reflects the velocity interval of the silicon in the SN ejecta, which may then provide constraints on the explosion mechanisms of SNe Ia. In this paper, we divide the SNe Ia into broad-line (BL) and normal-line (NL) subsamples, based on the REW of the Si ii 635.5 nm absorption lines around their maximum lights, and we find that the BL SNe Ia have a dimmer mean brightness than the NL ones, which is possibly a result of their different metallicities. However, based on a pixel statistics study of the environments of the two subsamples, we do not find any significant potential differences in the environments of the BL and NL SNe Ia, which implies that the explosion mechanisms of SNe Ia could be independent of their progenitor populations.

To optimize the energy output and improve the energy utilization efficiency of an aluminized explosive, an explosion device was developed and used to investigate the detonation pressure and temperature of R1 (Al6) aluminum powder and the aluminum powder particle gradation of R2 (Al6+Al13), R3 (Al6+Al24) and R4 (Al6+Al flake) in a confined space. By using gas chromatography, quantitative analysis and calculations were carried out to analyze the gaseous detonation products. Finally, the reaction ratios of the aluminum powder and the explosion reaction equations were calculated. The results show that in a confined space, the quasi-static pressures and equilibrium temperature of the aluminum powder in air are higher than in vacuum. In vacuum, the quasi-static pressures and equilibrium temperatures of the samples in descending order are R1>R3>R4>R2 and R3>R4>R1>R2, respectively. In air, the quasi-static pressures and equilibrium temperatures of the samples in descending order are R1>R2>R4>R3 and R1>R4>R2>R3, respectively. R4 (Al6+Al flake) and R3 (Al6+Al24) have relatively higher temperatures after detonation, which shows that the particle gradation method can enhance the reaction energy output of aluminum during the initial reaction stage of the explosion and increase the reaction ratio by 10.6% and 8.0%, respectively. In air, the reaction ratio of Al6 aluminum powder can reach as high as 78.16%, and the reaction ratio is slightly reduced after particle gradation. Finally, the reaction equations of the explosives in vacuum and in air were calculated by quantitative analysis of the explosion products, which provides a powerful basis for the study of RDX-based explosive reactions. Keywords: Particle gradation, Quasi-static pressure, Equilibrium temperature, Reaction ratio

A non-enzymatic electrochemical sensor for glucose detection is executed by using a conductive metal–organic framework (MOF) Cu-MOF, which is built from the 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) ligand and copper acetate by hydrothermal reaction. The Cu-MOF demonstrates superior electrocatalytic activity for glucose oxidation under alkaline pH conditions. As an excellent non-enzymatic sensor, the Cu-MOF grown on Cu foam (Cu-MOF/CF) displays an ultra-low detection limit of 0.076 μM through a wide concentration range (0.001–0.95 mM) and a strong sensitivity of 30,030 mA μM−1 cm−2. Overall, the Cu-MOF/CF exhibits a low detection limit, high selectivity, excellent stability, fast response time, and good practical application feasibility for glucose detection and can promote the development of MOF materials in the field of electrochemical sensors.

The oxygen evolution reaction (OER) is kinetically sluggish due to the limitation of the four-electron transfer pathway, so it is imperative to explore advanced catalysts with a superior structure and catalytic output under facile synthetic conditions. In the present work, an easily accessible strategy was proposed to implement the plant-polyphenol-involved coordination assembly on Co(OH)2 nanosheets. A TA-Fe (TA = tannic acid) coordination assembly growing on Co(OH)2 resulted in the heterostructure of Co(OH)2@TA-Fe as an electrocatalyst for OER. It could significantly decrease the overpotential to 297 mV at a current density of 10 mA cm−2. The heterostructure Co(OH)2@TA-Fe also possessed favorable reaction kinetics with a low Tafel slope of 64.8 mV dec−1 and facilitated a charge-transfer ability. The enhanced electrocatalytic performance was further unraveled to be related to the confined growth of the coordination assembly on Co(OH)2 to expose more active sites, the modulated surface properties and their synergistic effect. This study demonstrated a simple and feasible strategy to utilize inexpensive biomass-derived substances as novel modifiers to enhance the performance of energy-conversion electrocatalysis.