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Abstract Delta opioid receptor (δOR) plays a pivotal role in modulating human sensation and emotion. It is an attractive target for drug discovery since, unlike Mu opioid receptor, it is associated with low risk of drug dependence. Despite its potential applications, the pharmacological properties of δOR, including the mechanisms of activation by small-molecule agonists and the complex signaling pathways it engages, as well as their relation to the potential side effects, remain poorly understood. In this study, we use cryo-electron microscopy (cryo-EM) to determine the structure of the δOR-Gi complex when bound to a small-molecule agonist (ADL5859). Moreover, we design a series of probes to examine the key receptor-ligand interaction site and identify a region involved in signaling bias. Using ADL06 as a chemical tool, we elucidate the relationship between the β-arrestin pathway of the δOR and its biological functions, such as analgesic tolerance and convulsion activities. Notably, we discover that the β-arrestin recruitment of δOR might be linked to reduced gastrointestinal motility. These insights enhance our understanding of δOR’s structure, signaling pathways, and biological functions, paving the way for the structure-based drug discovery.

Abstract Background Simultaneous bilateral total hip arthroplasty (SI-THA) results in more blood loss and a greater need for postoperative allogeneic blood transfusion (ABT). Previous studies have reported that multimodal patient blood management (PBM) strategies were associated with a smaller effect of intraoperative cell salvage (ICS) in unilateral total hip arthroplasty. However, there are few studies on the role of ICS in SI-THA. This study aims to explore the effect of ICS with multimodal PBM strategies on SI-THA and to identify risk factors associated with ABT. Methods This retrospective matched cohort study included 72 patients in the ICS group and 72 patients in the control group who were matched according to age, sex, and year of hospitalization. Demographic data, hematological indicators, blood loss, and ABT were compared between the two groups. Logistic regression analysis was performed to identify independent risk factors for postoperative ABT. Postoperative outcomes were also recorded. Results In the cohort of 144 patients, 27 patients (37.5%) in the ICS group while 45 patients (62.5%) in the control group received postoperative ABT after SI-THA. Compared with the control group, the ICS group showed significant differences in terms of blood loss, postoperative hemoglobin and hematocrit. The transfused volume of allogeneic red blood cells per ABT patient was also lower in the ICS group. Multivariate logistic regression analysis indicated that sex, the utilization of ICS, and preoperative hematocrit level were identified as independent factors associated with postoperative ABT. The utilization of ICS significantly shortened off-bed time and length of hospital stay, but had no effect on early pain and functional outcomes. Conclusion The utilization of ICS can significantly affect postoperative ABT in SI-THA patients with multimodal PBM strategies. Sex, the utilization of ICS and preoperative hematocrit level were identified as independent factors associated with postoperative ABT. The utilization of ICS promoted weight-bearing functional exercises, but had no effect on early outcomes.

Aiming at the influence of hard and thick roof fracture and structural evolution on the impact of working face, taking the hard and thick roof condition of 63 upper 05 working face in Dongtan Coal Mine as the engineering background, the critical condition and structural evolution process of hard and thick roof fracture and instability are studied by theoretical analysis and numerical simulation, and the dangerous area of working face impact is divided. It is concluded that the thickness and strength of the roof are proportional to the vertical load at the end of the block breaking. The structure of immediate roof and main roof gradually evolved from “V” type to “U” type. The first and periodic steps of the double hard thick roof increase obviously compared with the conventional condition, and the evolution of the basic roof structure is more retarded than that of the direct roof. The vertical stress of the roof evolves in the form of stress arch, and many stress concentration phenomena are formed in the mined-out area during mining. Based on the above research results, the impact danger area of 63 upper 05 working face was divided and the accuracy was verified by microseismic monitoring technology.

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects. The primary challenge is to integrate diverse pharmacophores within a single-molecule framework. To address this, we introduced DeepSA, a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine, a well-known local anesthetic. DeepSA integrates deep neural networks into metaheuristics, effectively constraining molecular space during compound generation. This framework employs a sophisticated objective function that accounts for scaffold preservation, anti-inflammatory properties, and covalent constraints. Through a sequence of local editing to navigate the molecular space, DeepSA successfully identified AT-17, a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models. Mechanistic insights into AT-17 revealed its dual mode of action: selective inhibition of NaV1.7 and 1.8 channels, contributing to its prolonged local anesthetic effects, and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway. These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery, particularly within stringent chemical constraints.

BackgroundIn patients with tibial plateau bone cysts undergoing total knee arthroplasty (TKA), bone defects commonly occur following tibial plateau resection. Current strategies for addressing these defects include bone grafting, bone cement filling, and the cement-screw technique. However, there remains no consensus on the optimal approach to achieve the best surgical outcomes. This study aims to evaluate the most effective repair method for residual bone defects following tibial plateau bone cyst repair during TKA from a biomechanical perspective.MethodsThe treatment options for tibial plateau bone defects were classified into four categories: no treatment, cancellous bone filling, bone cement filling, and the cement-screw technique. Finite-element analysis (FEA) was employed to evaluate stress distribution and displacement across the models for each treatment group. In addition, static compression mechanical tests were used to assess the displacement of the models within each group.ResultsFEA results indicate that when employing the cement-screw technique to repair tibial plateau bone defects, the maximum stress on the prosthesis and the cement below the prosthesis is minimized, while the maximum stress on the cancellous bone is maximized. And the displacement of each component is minimized. Biomechanical tests results further demonstrate that the displacement of the model is minimized when utilizing the cement-screw technique for tibial plateau bone defects.ConclusionUsing cement-screw technique in treating residual tibial bone defects due to bone cysts in TKA offers optimal biomechanical advantages.

Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA.In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance.Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function.In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.

According to the World Health Organization's world report on hearing, nearly 2.5 billion people worldwide will suffer from hearing loss by 2050, which may contribute to a severe impact on individual life quality and national economies. Sensorineural hearing loss (SNHL) occurs commonly as a result of noise exposure, aging, and ototoxic drugs, and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear, which is mainly triggered by reactive oxygen species accumulation, inflammation, and mitochondrial dysfunction. Though recent advances have been made in understanding the ability of cochlear repair and regeneration, there are still no effective therapeutic drugs for SNHL. Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine. Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL, and elucidate their molecular mechanisms of action, to pave the way for further research and development of novel effective drugs in this field.

The storage time of rice determines its quality and nutritional value, and the longer the storage time, the greater the impact. In this study, different excitation wavelengths (405 nm, 365 nm, 310 nm) were used to detect the fluorescence spectrum of “Dongdao 12” brown rice. Support vector machine (SVM), K-nearest neighbor (KNN), and wide neural network (WNN) were used for modeling and analysis. Under the excitation of 310 nm, the accuracy of WNN classification is up to 99.2%. In order to reduce the scattering effect and other interference in the data, multiplicative scatter correction (MSC), standard normal variable (SNV), and Savitzky–Goray smoothing (SG) preprocessing methods were used. The results showed that SG + KNN classification achieved an accuracy of 99.3% under 310 nm excitation. In order to further improve the classification accuracy, the original spectrum and the preprocessed spectrum under different excitation light sources were fused. The classification accuracy of all methods was improved, and the original data fusion was combined with the WNN model to reach 100%. It shows that fluorescence spectroscopy has excellent potential in identifying rice storage years.

The origin of agricultural products significantly influences their quality and safety. Fluorescence spectroscopy was used to analyse Japonica rice 830, grown in different areas of Jilin Province, by examining rice seed, brown rice, and rice flour from 12 origins. Fluorescence spectra were pre-processed through normalisation and smoothing to remove noise. These processed spectra were input into decision trees, support vector machines (SVMs), K-nearest neighbour (KNN), and neural network models for classification. The analysis revealed that the combined four models achieved an average classification accuracy of 98.05% with a computation time of 180 s, while the reduced-scale models improved accuracy to 98.36% and reduced computation time to 11.25 s. Additionally, prediction models using standard rice starch content values across different states achieved R² values over 0.8. This method provides a rapid, precise approach for assessing rice quality and origin, demonstrating significant potential for application in rice analysis.

Abstract The brain consists of the left and right cerebral hemispheres and both are connected by callosal projections. Less is known about the basic mechanism of this cortical-cortical connection and its functional importance. Here we investigate the cortical-cortical connection between the bilateral anterior cingulate cortex (ACC) by using the classic electrophysiological and optogenetic approach. We find that there is a direct synaptic projection from one side ACC to the contralateral ACC. Glutamate is the major excitatory transmitter for bilateral ACC connection, including projections to pyramidal cells in superficial (II/III) and deep (V/VI) layers of the ACC. Both AMPA and kainate receptors contribute to synaptic transmission. Repetitive stimulation of the projection also evoked postsynaptic Ca2+ influx in contralateral ACC pyramidal neurons. Behaviorally, light activation of the ACC-ACC connection facilitated behavioral withdrawal responses to mechanical stimuli and noxious heat. In an animal model of neuropathic pain, light inhibitory of ACC-ACC connection reduces both primary and secondary hyperalgesia. Our findings provide strong direct evidence for the excitatory or facilitatory contribution of ACC-ACC connection to pain perception, and this mechanism may provide therapeutic targets for future treatment of chronic pain and related emotional disorders.

Abstract Rare earth element ore deposits associated with carbonatite derived from Earth’s mantle supply half of the world’s rare earth element. However, the formation of carbonatite and initial enrichment and transport of rare earth element in the mantle, is unclear. Here, we image the lithospheric architecture of a Cenozoic rare earth element ore belt in southwestern China by integrating seismic tomography with geochemical data. The subduction of the Indian continent caused vertical upwelling and lateral flow of the asthenosphere, which triggered the melting of the overlying subcontinental lithospheric mantle to generate carbonatites. Such a mantle source that previously metasomatized by fluids from recycled marine sediments is a precursor process critical for forming a giant rare earth element system. For the studied ore belt, three key factors are prerequisites to generating ore-forming carbonatites: thick lithosphere with a continental root; prior fertilization of the subcontinental lithospheric mantle; and trans-lithospheric weakness for magma ascent.

Background and objectiveStent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles.MethodsThis retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution.ResultsWe identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (−47.25 ± 3.88% vs. 42.85 ± 3.03%; p

In order to study the mechanical response and crack evolution law of different lithologic rock bodies under different stress environments in deep stress mines, based on the deviator stress theory, the actual triaxial disturbance unloading rock test system was used to simulate the stress occurrence environment of the original rock. The mechanical characteristics of different σ2 coal rock masses were studied, and the crack evolution law of coal and sandstone under different stress environments was analyzed. The results show that the increase of σ2 inhibits the deformation in the σ2 direction of coal and sandstone, promotes the expansion and deformation in the σ3 direction, and enhances its peak strength and elastic modulus. The development characteristics of internal cracks in rock mass are directly related to the stress environment, and the increase of σ2 promotes the increase of the proportion of coal RA value, weakens the proportion of sandstone RA value, aggravates the development of coal internal shear cracks, and inhibits the development of internal shear cracks in sandstone. The larger σ2, the greater the initial AE ringing count of coal and sandstone, and the greater the AE cumulative energy when the rock mass is finally damaged. At the same time, due to the self-organizing behavior in the process of crystal failure in sandstone, the cumulative energy curve of sandstone fluctuates in a step-like manner. The ringing count and cumulative energy increase suddenly, which can predict the imminent instability and failure of the rock, and the research results can provide an experimental basis for the sudden instability of deep high-stress roadways.

ABSTRACT: The comprehensive use and efficient management of straw are significant for agriculture's green and low-carbon transformation. This paper uses literature research and comparative analysis to systematically review the literature on comprehensive straw utilization and governance policy research in China over the past five years. The current literature has explored two major directions: regional and industrial policies and the main actors involved in the comprehensive use of straw. The research is complementary and fruitful concerning both micro and macro perspectives; however, the extant literature suffers from a lack of attention to straw intermediaries and enterprises and a lack of research across time. Therefore, this paper provides an outlook for future research. In the future, scholars should pay more attention to straw intermediaries and enterprises, conduct continuous observations of multiple regions over time to obtain panel data, and further test the heterogeneity of factors to obtain more scientific and valid results.

The AlGaN photocathode with a superlattice emission layer was grown by metal organic chemical vapor deposition. The existence of the superlattice structure was confirmed using a transmission electron microscope, and its optical and electrical properties were measured. The results showed that the introduction of a superlattice emission layer can reduce the transmittance and reflectance at 275 nm and improve the absorption of incident light. In particular, the Hall measurement results indicate that the introduction of a superlattice structure can significantly increase the concentration of holes in the AlGaN photocathode material. The activation experiment demonstrated that the photocurrent of the AlGaN photocathode subassembly with a superlattice structure increased significantly after Cs/O activation and that it showed better photoemission performance. The increase in the incident light absorption to produce more photoelectrons, the enhancement of photoelectron transport capacity by the polarized electric field generated by the superlattice structure, and the reduction in the surface barrier caused by the higher hole concentration were responsible for the significant improvement in photoemission performance.

Breast cancer is the most prevalent malignancy among women. Doxorubicin (Dox) resistance was one of the major obstacles to improving the clinical outcome of breast cancer patients. The purpose of this study was to investigate the relationship between the FABP signaling pathway and Dox resistance in breast cancer. The resistance property of MCF-7/ADR cells was evaluated employing CCK-8, Western blot (WB), and confocal microscopy techniques. The glycolipid metabolic properties of MCF-7 and MCF-7/ADR cells were identified using transmission electron microscopy, PAS, and Oil Red O staining. FABP5 and CaMKII expression levels were assessed through GEO and WB approaches. The intracellular calcium level was determined by flow cytometry. Clinical breast cancer patient’s tumor tissues were evaluated by immunohistochemistry to determine FABP5 and p-CaMKII protein expression. In the presence or absence of FABP5 siRNA or the FABP5-specific inhibitor SBFI-26, Dox resistance was investigated utilizing CCK-8, WB, and colony formation methods, and intracellular calcium level was examined. The binding ability of Dox was explored by molecular docking analysis. The results indicated that the MCF-7/ADR cells we employed were Dox-resistant MCF-7 cells. FABP5 expression was considerably elevated in MCF-7/ADR cells compared to parent MCF-7 cells. FABP5 and p-CaMKII expression were increased in resistant patients than in sensitive individuals. Inhibition of the protein expression of FABP5 by siRNA or inhibitor increased Dox sensitivity in MCF-7/ADR cells and lowered intracellular calcium, PPARγ, and autophagy. Molecular docking results showed that FABP5 binds more powerfully to Dox than the known drug resistance-associated protein P-GP. In summary, the PPARγ and CaMKII axis mediated by FABP5 plays a crucial role in breast cancer chemoresistance. FABP5 is a potentially targetable protein and therapeutic biomarker for the treatment of Dox resistance in breast cancer.

Titanite is a widespread accessory mineral in igneous, metamorphic, and hydrothermal rocks, but few comply with gem-grade requirements. Previous studies on Moroccan titanite focused on elementary composition and U-Pb dating. In this study, two gem-grade titanites (MA-1 and MA-2) from the Moroccan Central High Atlas were investigated through gemological and chemical studies, including infrared spectrum, Raman spectrum, SEM-EDS, and LA-ICP-MS. Two titanite samples are yellow, transparent–translucent with a greasy luster, 3.5 and 2.5 mm long. MA-1 and MA-2 have similar gemological properties, the refractive index (RI) is beyond the range of the refractometer (>1.78), the specific gravity (SG) values fall in the range of 3.52~3.54 and both are inert to short-wave and long-wave UV radiation. The spectral characteristics have high consistency with the RRUFF database. The major elements’ composition shows a negative correlation between Al, Fe, V, and Ti, suggesting the titanites underwent substitutions such as (Al, Fe3+) + (F, OH) ↔ Ti + O. The titanite samples, characterized by a low abundance of REE (802~4088 ppm) and enriched in LREE, exhibit positive Eu (δEu: 1.53~7.79) and Ce (δCe: 1.08~1.33) anomalies, indicating their formation in a hydrothermal environment with low oxygen fugacity. The 238U/206Pb and 207Pb/206Pb ratios of the titanites yield lower intercept ages of 152.6 ± 2.2 and 151.4 ± 5.3 Ma (1s), consistent with their weighted average 206Pb/238U ages of 152.3 ± 2.0 and 150.7 ± 3.2 Ma (1s) respectively. The results of U-Pb dating are matched with the second main magmatic activities in the High Atlas intracontinental belt of Morocco during the Mesozoic to Cenozoic period. Moreover, the two titanite samples have almost no radiational damage. All the results show that the titanite from High Atlas, Morocco, has the potential to be a reference material for LA-ICP-MS U–Pb dating, but further experiments are needed to be sure.

Based on adopting the global super-efficiency slacks-based measure (GSSBM) model to calculate green innovation efficiency (GIE), this paper systematically investigates GIE’s overall difference, distribution dynamics and convergence trends in eight national urban agglomerations (UAs) of China from 2004 to2018 by combining the methods of Dagum Gini Coefficient (DGC), Kernel Density Estimation (KDE), Variation Coefficient (VC), fixed-effect model (FEM) and spatial Durbin model (SDM). The results show that: (1) the average GIE of eight UAs was 0.632 during 2004–2018, which is generally low and has substantial potential for improvement, and seven of them achieved positive growth with an annual average growth rate of 2.70%. (2) The overall difference of GIE within eight UAs was significant with the inter-UA difference as the main contributor. (3) The distribution curves of GIE in eight UAs were distinct in terms of location, form, ductility and polarization trend. (4) Besides five UAs presenting significant σ convergence characteristics, all eight UAs displayed significant absolute or conditional β convergence trends with different speeds and cycles. The findings of this paper can provide important insights on the promotion of green innovation-driven development for UAs in China.

Ultrasound cycloplasty(UCP)procedure using high intensity focused ultrasound(HIFU)is a new non-invasive glaucoma treatment based on miniaturized transducers. In recent years, the safety and efficacy of UCP on various types of glaucoma have been well verified, and it has shown broad application prospects in the treatment of glaucoma. This article collects and reviews the relevant literature on glaucoma treatment by UCP, and summarizes the information on the development of equipment, composition and operation, treatment mechanisms, indications, efficacy and safety, with the purpose to provide relevant basis for clinical applications and future research.

Abstract The pharmacological interventions aimed at activating pathways inducing chondrocyte autophagy or reversing extracellular matrix degradation may be promising approaches for the management of osteoarthritis (OA). Evidence exists suggesting that sirtuin 1 (SIRT1) is involved in the pathogenesis of OA. The present study aimed to explore the regulatory role and downstream mechanisms of SIRT1 in OA. Bioinformatics predictions identified downstream factors phosphatase and tensin homolog (PTEN) and epidermal growth factor receptor (EGFR) in OA. We validated poorly expressed SIRT1 and EGFR and highly expressed PTEN in cartilage tissues of OA patients. OA was induced in vitro by exposing human primary chondrocytes to IL-1β and in vivo by destabilization of the medial meniscus (DMM) in a mouse model. SIRT1 knockdown was found to augment IL-1β-stimulated inflammation and chondrocyte metabolic imbalance. Knockdown of SIRT1 diminished PTEN acetylation and then enhanced PTEN expression. PTEN inactivation decreased EGFR ubiquitination and promoted EGFR expression by destabilizing the EGFR-Cbl complex, which in turn inhibited extracellular matrix degradation in cartilage tissues and activated chondrocyte autophagy. In the DMM mouse model, knockdown of SIRT1 inhibited chondrocyte autophagy, promoted metabolic imbalance, thus accelerating osteoarthritic process. In conclusion, SIRT1 represses the ubiquitination of EGFR by down-regulating PTEN, inhibits extracellular matrix degradation and activates chondrocyte autophagy, thereby performing an OA-alleviating role.

New aquamarine deposits have been found around the world in recent years, and how to compare and distinguish aquamarines of different origin has become a significant problem. Aquamarines from Koktokay, Minas Gerais, and Namaqualand were collected for standard gemology tests, spectroscopy, and chemical analysis in this paper. The spectroscopy experiment included infrared spectroscopy and Raman spectroscopy. Chemical composition analysis comprises electron microprobe and laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS). The results show that infrared absorption peaks related to [Fe2(OH)4] and NaH are found in Koktokay and Minas Gerais aquamarines, respectively. Compared with other two origins, Namaqualand aquamarine have strongest type II water Raman peak related to alkali metal content. Compared with aquamarines from other sources, aquamarines from Xinjiang and Minas Gerais are characterized by relatively high aluminum and low alkali contents in chemical composition, while Namaqualand aquamarine have a high scandium content.

Objective To determine the effect of overworking on vascular smooth muscle cells (VSMC) in rats. Methods Clean SD rats were randomly divided into control group (CON), overworking group (OW) and overworking and sleep deficiency group (OW+SD). The rat model of overworking was established by exhaustive swimming in the latter 2 groups, and the rats of the last group was subjected to sleep deprivation with an underwater platform. In 15 d later, the abdominal aorta of rats was collected for pathological observation by HE staining, and the thickness of media was measured with aid of Image J software. The intracellular ultrastructure was observed by transmission electron microscopy. The apoptotic rate of VSMC was detected by TUNEL, the mRNA expression of Caspsae-3, Bax, Bcl-2 and Ki67 in the VSMC were detected by RT-qPCR, and the content of apoptotic protein Caspase-3 was measured by immunohistochemical assay. Results ① The results of HE staining showed that VSMC were in disordered arrangment and formed vacuole-like cells in the OW and OW+SD groups, and the vascular intima-media thickness was significantly thicker in the OW and OW+SD groups than the CON group (P < 0.05). ② Electron microscopy displayed the apoptotic bodies in the VSMC of the OW and OW+SD groups. ③TUNEL results showed that the apoptotic rate of VSMC was significantly higher in the OW and OW+SD groups than the CON group (P < 0.05). ④RT-qPCR showed that the expression levels of Bax and Ki67 were significantly increased (P < 0.05), while those of Caspase-3 and Bcl-2 were not obviously changed in OW and OW+SD groups (P>0.05) when compared with the CON group. ⑤ Immunohistochemical results showed that the protein content of Caspase-3 in vascular middle membrane of the OW and OW+SD groups was increased significantly than that in the CON group (P < 0.05). Conclusion Overworking aggravates the apoptosis of VSMC and induces the proliferation and repair of VSMC, which form the pathological basis of early arterial lesions. During the experimental time, sleep could not alleviate the injury of VSMC caused by overworking.

Abstract Objective High tibial osteotomy (HTO) has been used for the treatment of patients with knee osteoarthritis. However, the successful implementation of HTO requires precise intraoperative positioning, which places greater requirements on the surgeon. In this study, we aimed to design a new kind of 3D-printed patient-specific instrument (PSI) for HTO, including a positioning device and an angle bracing spacer, and verify its effectiveness using cadaveric specimens. Methods This study included ten fresh human lower-limb cadaveric specimens. Computed tomography (CT) and X-ray examinations were performed to make preoperative plans. PSI was designed and 3D-printed according to the preoperative plan. Then, the PSI was used to guide HTO. Finally, we performed X-ray and CT after the operation to verify its validity and accuracy. Results The PSI using process was adjusted according to the pre-experimental procedure in 1 case. Hinge fracture occurred in 1 case. According to X-rays of the remaining eight cadaveric specimens, no statistically significant difference was noted between the preoperative planning medial proximal tibial angle (MPTA) and postoperative MPTA (P > 0.05) or the preoperative and postoperative posterior slope angle (PSA) (P > 0.05). According to the CT of 10 cadaveric specimens, no statistically significant difference was noted between the design angle and actual angle, which was measured according to the angle between the osteotomized line and the cross section (P > 0.05). The gap between the designed osteotomy line and the actual osteotomy line was 2.09 (0.8 ~ 3.44) mm in the coronal plane and 1.58 (0.7 ~ 2.85) mm in the sagittal plane. Conclusion This 3D-printed PSI of HTO accurately achieves the angle and position of the preoperative plan without increasing the stripping area. However, its use still requires a certain degree of proficiency to avoid complications, such as hinge fracture.

Based on employing the global super efficiency epsilon-based measure (GSE-EBM) model to evaluation the green innovation efficiency (GIE) of 285 prefecture-level or above cities in China during the period 2004–2018, this paper combines the approaches of kernel density estimation, cold hot spot analysis and standard deviation ellipse to intuitively describe GIE’s spatiotemporal pattern evolution features, and then utilizes the geographical weighted regression (GWR) model to explore the spatial heterogeneity of GIE’s affecting factors. The results show that: (1) China’s urban GIE displayed a fluctuating increasing trend, revealing clearly regional disparities, and gradually decreased from the Eastern coastal region to the Central, the Western and the Northeast region. (2) The spatial difference of China’s urban GIE exhibited the characteristics of expansion, polarization, and spatial agglomeration with the center of gravity gradually shifting to the Southeast region. (3) In the analysis of socio-economic factors of China’s urban GIE, the GWR model effectively identified the spatial heterogeneity, and improved the explanatory ability compared to ordinary least squares (OLS) model. (4) The GWR model analysis indicate that population density, economic development, transportation infrastructure, openness and industrial structure played significant impacts on China’s urban GIE, and there exists significant spatial heterogeneity in the impact of each influencing factor. The findings of this study can provide valuable references for urban green transformation and high-quality development in China.