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Abstract UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.

Abstract Background TBK1 positively regulates the growth factor-mediated mTOR signaling pathway by phosphorylating mTOR. However, it remains unclear how the TBK1-mTOR signaling pathway is regulated. Considering that STING not only interacts with TBK1 but also with MARCH1, we speculated that MARCH1 might regulate the mTOR signaling pathway by targeting TBK1. The aim of this study was to determine whether MARCH1 regulates the mTOR signaling pathway by targeting TBK1. Methods The co-immunoprecipitation (Co-IP) assay was used to verify the interaction between MARCH1 with STING or TBK1. The ubiquitination of STING or TBK1 was analyzed using denatured co-immunoprecipitation. The level of proteins detected in the co-immunoprecipitation or denatured co-immunoprecipitation samples were determined by Western blotting. Stable knocked-down cells were constructed by infecting lentivirus bearing the related shRNA sequences. Scratch wound healing and clonogenic cell survival assays were used to detect the migration and proliferation of breast cancer cells. Results We showed that MARCH1 played an important role in growth factor-induced the TBK1- mTOR signaling pathway. MARCH1 overexpression attenuated the growth factor-induced activation of mTOR signaling pathway, whereas its deficiency resulted in the opposite effect. Mechanistically, MARCH1 interacted with and promoted the K63-linked ubiquitination of TBK1. This ubiquitination of TBK1 then attenuated its interaction with mTOR, thereby inhibiting the growth factor-induced mTOR signaling pathway. Importantly, faster proliferation induced by MARCH1 deficiency was weakened by mTOR, STING, or TBK1 inhibition. Conclusion MARCH1 suppressed growth factors mediated the mTOR signaling pathway by targeting the STING-TBK1-mTOR axis.

Abstract Objective Segmental bone defect animal studies require stable fixation which is a continuous experimental challenge. Large animal models are comparable to the human bone, but with obvious drawbacks of housing and costs. Our study aims to utilize CAD and 3D printing in the construction of a stable and reproducible segmental bone defect animal mode. Methods CAD-aided 3D printed surgical instruments were incorporated into the construction of the animal model through preoperative surgical emulation. 20 3D printed femurs were divided into either experimental group using 3D surgical instruments or control group. In Vitro surgical time and accuracy of fixation were analysed and compared between the two groups. A mature surgical plan using the surgical instruments was then utilized in the construction of 3 segmental bone defect Beagle models in vivo. The Beagles were postoperatively assessed through limb function and imaging at 1, 2 and 3 months postoperatively. Results In vitro experiments showed a significant reduction in surgical time from 40.6 ± 14.1 (23–68 min) to 26 ± 4.6 (19–36 min) (n = 10, p

Abstract Background Astragaloside IV (AST-IV), as an effective active ingredient of Astragalus membranaceus (Fisch.) Bunge. It has been found that AST-IV inhibits the replication of dengue virus, hepatitis B virus, adenovirus, and coxsackievirus B3. Enterovirus 71 (EV71) serves as the main pathogen in severe hand-foot-mouth disease (HFMD), but there are no specific drugs available. In this study, we focus on investigating whether AST-IV can inhibit EV71 replication and explore the potential underlying mechanisms. Methods The GES-1 or RD cells were infected with EV71, treated with AST-IV, or co-treated with both EV71 and AST-IV. The EV71 structural protein VP1 levels, the viral titers in the supernatant were measured using western blot and 50% tissue culture infective dose (TCID50), respectively. Network pharmacology was used to predict possible pathways and targets for AST-IV to inhibit EV71 replication. Additionally, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to investigate the potential targeted metabolites of AST-IV. Associations between metabolites and apparent indicators were performed via Spearman’s algorithm. Results This study illustrated that AST-IV effectively inhibited EV71 replication. Network pharmacology suggested that AST-IV inhibits EV71 replication by targeting PI3K-AKT. Metabolomics results showed that AST-IV achieved these effects by elevating the levels of hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-hydroxy-1 H-indole-3- acetamide, oxypurinol, while reducing the levels of PC (14:0/15:0). Furthermore, AST-IV also mitigated EV71-induced oxidative stress by reducing the levels of MDA, ROS, while increasing the activity of T-AOC, CAT, GSH-Px. The inhibition of EV71 replication was also observed when using the ROS inhibitor N-Acetylcysteine (NAC). Additionally, AST-IV exhibited the ability to activate the PI3K-AKT signaling pathway and suppress EV71-induced apoptosis. Conclusion This study suggests that AST-IV may activate the cAMP and the antioxidant stress response by targeting eight key metabolites, including hypoxanthine, 2-ketobutyric acid, adenine, nicotinic acid mononucleotide, prostaglandin H2, 6-Hydroxy-1 H-indole-3-acetamide, oxypurinol and PC (14:0/15:0). This activation can further stimulate the PI3K-AKT signaling to inhibit EV71-induced apoptosis and EV71 replication. Graphical Abstract

Chronic non-healing wounds induced by oxidative stress and inflammation can activate inflammatory cells and produce large amounts of inflammatory mediators, which fail to maintain homeostasis in the skin and delay the wound-healing process. To tackle this issue, heparin-loaded hierarchical composite scaffolds comprised of electrospun fibers and electrosprayed microspheres were prepared to act as an effective anti-inflammatory wound dressing. Microspheres with different electrosprayed densities were deposited into the surface of the electrospun fibers for the improvement of surface topographical cues and cellular activities. The results indicated that the electrospun fibers followed by electrosprayed for 3 ​min to fabricate the composite fiber/microsphere scaffolds contributed to the best performance in terms of promoting cellular activities, with no obvious cytotoxicity, good adhesion morphology, and the fastest cell migration rate. In addition, a suitable amount of heparin was added to the composite scaffolds to alleviate inflammation. The significant adsorption efficiency of heparin-loaded composite scaffolds on inflammatory mediator MCP-1 indicates a favorable anti-inflammation effect in vitro. Furthermore, the heparin-loaded hierarchical scaffolds accelerated the pace of inflammatory wound healing in vivo when compared to commercial 3 ​M Tegaderm and non-heparin-loaded scaffolds. Our work provided a facile strategy for fabricating heparin-loaded hierarchical fiber/microsphere scaffolds to modulate cellular activities via topographical cues and accelerating the inflammatory wound healing process by electrostatic interactions between heparin and MCP-1. These findings suggested that the heparin-loaded hierarchical scaffold was expected to be a promising dressing for inflammatory wound healing.

Abstract China’s extensive planted forests play a crucial role in carbon storage, vital for climate change mitigation. However, the complex spatiotemporal dynamics of China’s planted forest area and its carbon storage remain uncaptured. Here we reveal such changes in China’s planted forests from 1990 to 2020 using satellite and field data. Results show a doubling of planted forest area, a trend that intensified post-2000. These changes lead to China’s planted forest carbon storage increasing from 675.6 ± 12.5 Tg C in 1990 to 1,873.1 ± 16.2 Tg C in 2020, with an average rate of ~ 40 Tg C yr−1. The area expansion of planted forests contributed ~ 53% (637.2 ± 5.4 Tg C) of the total above increased carbon storage in planted forests compared with planted forest growth. This proactive policy-driven expansion of planted forests has catalyzed a swift increase in carbon storage, aligning with China’s Carbon Neutrality Target for 2060.

Triple-negative breast cancer (TNBC) has become a thorny problem in the treatment of breast cancer because of its high invasiveness, metastasis and recurrence. Although immunotherapy has made important progress in TNBC, immune escape caused by many factors, especially metabolic reprogramming, is still the bottleneck of TNBC immunotherapy. Regrettably, the mechanisms responsible for immune escape remain poorly understood. Exploring the mechanism of TNBC immune escape at the metabolic level provides a target and direction for follow-up targeting or immunotherapy. In this review, we focus on the mechanism that TNBC affects immune cells and interstitial cells through hypoxia, glucose metabolism, lipid metabolism and amino acid metabolism, and changes tumor metabolism and tumor microenvironment. This will help to find new targets and strategies for TNBC immunotherapy.

Reconstructing critical-sized craniofacial bone defects is a global healthcare challenge. Current methods, like autologous bone transplantation, face limitations. Bone tissue engineering offers an alternative to autologous bone, with traditional approaches focusing on stimulating osteogenesis via the intramembranous ossification (IMO) pathway. However, IMO falls short in addressing larger defects, particularly in clinical scenarios where there is insufficient vascularisation. This review explores redirecting bone regeneration through endochondral ossification (ECO), a process observed in long bone healing stimulated by hypoxic conditions. Despite its promise, gaps exist in applying ECO to bone tissue engineering experiments, requiring the elucidation of key aspects such as cell sources, biomaterials and priming protocols. This review discusses various scaffold biomaterials and cellular sources for chondrogenesis and hypertrophic chondrocyte priming, mirroring the ECO pathway. The review highlights challenges in current endochondral priming and proposes alternative approaches. Emphasis is on segmental mandibular defect repair, offering insights for future research and clinical application. This concise review aims to advance bone tissue engineering by addressing critical gaps in ECO strategies.

BackgroundMore research is needed to solidify the basis for reasonable metronomic chemotherapy regimens due to the inconsistent clinical outcomes from studies on metronomic chemotherapy with antineoplastic agents, along with signs of a nonlinear dose–response relationship at low doses. The present study therefore explored the dose–response relationships of representative antineoplastic agents in low dose ranges and their underlying mechanisms.MethodsCyclophosphamide (CPA) and 5-fluorouracil (5-Fu) were employed to observe the effects of the frequent administration of low-dose antineoplastic agents on tumor growth, tumor angiogenesis, and bone-marrow-derived cell (BMDC) mobilization in mouse models. The effects of antineoplastic agents on tumor and endothelial cell functions with or without BMDCs were analyzed in vitro.ResultsTumor growth and metastasis were significantly promoted after the administration of CPA or 5-Fu at certain low dose ranges, and were accompanied by enhanced tumor angiogenesis and proangiogenic factor expression in tumor tissues, increased proangiogenic BMDC release in the circulating blood, and augmented proangiogenic BMDC retention in tumor tissues. Low concentrations of CPA or 5-Fu were found to significantly promote tumor cell migration and invasion, and enhance BMDC adhesion to endothelial cells in vitro.ConclusionThese results suggest that there are risks in empirical metronomic chemotherapy using low-dose antineoplastic agents and the optimal dosage and administration schedule of antineoplastic agents need to be determined through further research.

BackgroundHip replacement surgeries are increasing in demand, requiring rigorous improvements to a mature surgical protocol. Postoperative patient dissatisfaction mainly stems from postoperative complications resulting from the inappropriate selection of prostheses to meet the needs of each patient. This results in prosthesis loosening, hospital-related fractures, and postoperative complex pain, which can all be attributed to inappropriate sizing. In this study, we aimed to further explore the intraoperative and postoperative benefits of incorporating computer-aided design (CAD) in preoperative planning for total hip arthroplasty (THA).MethodsA total of 62 patients requiring total hip replacement surgery from January 2021 to December 2021 were collected and randomly divided into a preoperative computer-aided simulated group and a conventional x-ray interpretation group. The accuracy of implant size selection (femoral and acetabular implant) between the preoperative planning and surgical procedure of the two groups was compared. Patient parameters, perioperative Harris hip scores, operative time (skin-to-skin time), surgical blood loss, and postoperative hospital stay were recorded, and the differences between the two groups were statistically compared using a single sample t-test.ResultsAll patients in the study were successfully operated on and achieved good postoperative functional recovery. With CAD, the selection of the most suitable-sized prosthesis was significantly more accurate compared to the control group (accuracy of the acetabular component between the CAD/control: 80.6%/61.3%, and accuracy of the femoral component: 83.9%/67.7%). Intraoperative blood loss (177.4/231.0 ml, P = 0.002), operation time (84.2 ± 19.8 min/100.3 ± 25.9 min, P = 0.008), duration of hospital stay (6.5 ± 3/9.1 ± 3.9 days, P = 0.003), and postoperative Harris hip score (81.9 ± 6.5/74.7 ± 11.1, P = 0.003) were compared to the control group and showed statistical significance.ConclusionIncorporating CAD into the preoperative planning of total hip arthroplasty can effectively guide the selection of the most suitable-sized prosthesis, reduce intraoperative blood loss, and promote short-term functional recovery after THA.

To assess the energy saving and emission reduction effects of recycling technology, the quantitative analysis of energy consumption and carbon emission of recycled asphalt pavement is conducted of asphalt mixture production, transportation, paving and compaction. Firstly, the calculation model for energy consumption and carbon emissions of recycled asphalt pavement is established during the construction stage. In addition, the energy consumption and carbon emission of four recycling technologies, including the HCPR, HIR, CCPR and CIR, were compared. Finally, the FCE method is used to evaluate the actual effect of energy saving and emission reduction from the perspectives of the ecological benefit and the economic benefit. The research results indicate the most serious stage of energy consumption is the new material production stage, and the most serious stage of carbon emission is the asphalt mixture production stage of recycled asphalt pavement. Taking the HCPR technology as an example are calculated in detail. The energy consumption of the HCPR technology in the four stages of the construction stage was 17.59 MJ, 344.45 MJ, 228.51 MJ and 25.85 MJ, respectively, and the emissions in the four stages of the construction stage were 1307.89 g, 5971.28 g, 19,251.24 g and 1949.82 g, respectively. For different recycling technologies in the construction stage, the energy-saving ratios of HCPR, HIR and CCPR are 13.62%, 9.61% and 19.24% respectively when compared with the typical scheme, which have a certain energy-saving effect. However, the energy consumption of CIR reduced by 43.63%, which the energy saving effect is most significant. Moreover, the emission reduction ratios of HCPR, HIR and CCPR are 2.3%, 9.23% and 1.01% respectively when compared with the typical scheme, the emission of CIR reduced by 30.76%, so the emission reduction effect of CIR is most significant. Furthermore, the comprehensive evaluation score of the CIR technology with the most significant energy saving and emission reduction effect is 0.8021 in terms of ' ecological benefits ' and 0.8074 in terms of ' economic benefits '. In summary, it is recommended to adopt CIR technology in the engineering project, which can achieve the most significant energy-saving and emission reduction effects.

Traditional enhancement techniques can improve the contrast of low-light and low-resolution images, but they fail to recover their resolution. Conversely, traditional super-resolution (SR) algorithms can enhance resolution but not restore contrast. To address this issue, a novel progressive joint enhancement and SR tactic, named PESiT, is proposed to synchronously improve contrast and resolution in low-light and low-resolution images. PESiT comprises an enhanced multi-scale Retinex module followed by a blind SR module with regularization optimization. In the first module, the common logarithm is replaced with an S-function to expand the intensity distribution of images and prevent color inversion. In the latter module, those merits of reconstruction- and learning-based tactics are combined to tackle various unknown degradations by imposing consistency constraints on high- and low-resolution image pairs. Extensive experiments on public datasets demonstrate the robustness and superiority of PESiT in processing low-light and low-resolution images under various scenarios. Compared with state-of-the-art techniques, PESiT achieves superior performance, e.g., the highest peak signal-to-noise ratio, structural similarity index, feature similarity index, and the lowest learned perceptual image patch similarity, highlighting its validity in achieving optimal image quality improvements.

Over the last decade, a number of techniques for individual tree segmentation has been developed for terrestrial laser scanning data. The superpoint segmentation algorithm based on point cloud has been widely used in individual tree segmentation because of its high efficiency and numerous geometric features. However, this algorithm is generally developed for specific tree species and forest types, limiting its universality and performance for different forest types. To handle this problem, a new method based on the topology of tree branches for individual tree segmentation was proposed. Focusing on the general topological structure of trees, the proposed method iteratively assigns each branch based on its directivity to its upper branch at the superpoint level. The proposed method was tested compared with the original superpoint method and an ecological method in six sample plots with different forest conditions. In such plots, the proposed method achieved anticipated performance with an average accuracy of 40% improvements compared with the other two methods, especially in complicated forest conditions. Experimental results also showed an improved average accuracy of 70% compared with the original superpoint method at the point level. This proposed method can effectively expand the universality of the superpoint method to further advance ecological and forest research.

Abstract Customizable and number‐tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4‐Lox‐DNA‐Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H2O2 is generated through the Lox catalytic reaction, amplifying the H2O2 supply for dextran iron‐based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO‐Keap1 plasmid (DNA) with tumor hypoxia‐activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio‐intelligent plasmids, presenting a promising approach for tumor therapy.

To address the issues of superconducting and charge properties in hydrated sodium cobalt, we investigate an extended ionic Hubbard model on the triangular lattice, which includes off-site attractions between sites with minor charges. Our quantum Monte Carlo simulations show that close to quarter filling, the off-site attractions induce a significant enhancement of d-wave and extended s-wave pairing correlations. Simultaneously, they render an increase of the charge structure factor at most of wave vectors. A combination with charge correlations in real space indicates the development of short-range finite-q charge density waves on the sites with minor charges. Our findings provide a new perspective on the superconducting mechanism in hydrated sodium cobalt based on the electronic structure which explicitly takes the effect of sodium atoms into account.

Out-of-hospital cardiac arrest is a major public health problem worldwide due to its high burden and poor outcomes. Despite progress in treatment, patient outcomes remain unsatisfactory, particularly in low-resource settings. The establishment of a registry is the first step towards gaining a comprehensive understanding of prevailing local conditions and identifying potential opportunities for improving patient survival. Here, we provide a narrative review of the BASeline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA), the first national OHCA registry in China, to introduce its development history, current state, challenges and future directions. We aim to enhance cross-cultural understanding by providing insights from China, while also serving as a reference for the implementation of large-scale registries in low-resource settings.

Recently, the existing unmanned systems of combine harvesters mostly adopts satellite navigation scheme, lacking real-time observation of harvesting adjustment. To improve the operational efficiency of combine harvester assisted navigation operation, this paper designs a combine harvester navigation control system based on vision simultaneous localization and mapping (SLAM)-inertial guidance fusion. The system acquires field image information and extracts the crop boundary line as the navigation datum by binocular camera. First, the system acquires field image information through binocular camera and extracts the crop boundary line as the navigation datum. Second, fusing camera and inertial guidance information to obtain the real-time relative position of a combine harvester. Third, constrained optimization of image and inertial guidance information is achieved through a sliding window optimization method based on tightly coupled nonlinear optimization. Finally, obtain the position of the combine harvester relative to the navigation datum line, and output a signal to the steering mechanism to realize the combine harvester in the field intelligent positioning navigation control. The system consists of binocular camera, inertial measurement unit, motorized steering wheel, monitor display, angle sensor and microcontroller. During field testing, the system underwent repetitive harvesting trials over a distance of 25 m.. The testing machine performs field operations at a speed of 0.9-1.5 m/s, with an average lateral deviation range of 2.21-8.62 cm, a standard deviation range of 0.13-4.21 cm and an average cutting rate range of 92.2%-96.0%, achieving the expected harvesting effect.

Existing methods for classifying image emotions often overlook the subjective impact emotions evoke in observers, focusing primarily on emotion categories. However, this approach falls short in meeting practical needs as it neglects the nuanced emotional responses captured within an image. This study proposes a novel approach employing the weighted closest neighbor algorithm to predict the discrete distribution of emotion in abstract paintings. Initially, emotional features are extracted from the images and assigned varying K-values. Subsequently, an encoder-decoder architecture is utilized to derive sentiment features from abstract paintings, augmented by a pre-trained model to enhance classification model generalization and convergence speed. By incorporating a blank attention mechanism into the decoder and integrating it with the encoder's output sequence, the semantics of abstract painting images are learned, facilitating precise and sensible emotional understanding. Experimental results demonstrate that the classification algorithm, utilizing the attention mechanism, achieves a higher accuracy of 80.7% compared to current methods. This innovative approach successfully addresses the intricate challenge of discerning emotions in abstract paintings, underscoring the significance of considering subjective emotional responses in image classification. The integration of advanced techniques such as weighted closest neighbor algorithm and attention mechanisms holds promise for enhancing the comprehension and classification of emotional content in visual art.

Abstract The organic thin-film transistor is advantageous for monolithic three-dimensional integration attributed to low temperature and facile solution processing. However, the electrical properties of solution deposited organic semiconductor channels are very sensitive to the substrate surface and processing conditions. An organic-last integration technology is developed for wafer-scale heterogeneous integration of a multi-layer organic material stack from solution onto the non-even substrate surface of a III-V micro light emitting diode plane. A via process is proposed to make the via interconnection after fabrication of the organic thin-film transistor. Low-defect uniform organic semiconductor and dielectric layers can then be formed on top to achieve high-quality interfaces. The resulting organic thin-film transistors exhibit superior performance for driving micro light emitting diode displays, in terms of milliampere driving current, and large ON/OFF current ratio approaching 1010 with excellent uniformity and reliability. Active-matrix micro light emitting diode displays are demonstrated with highest brightness of 150,000 nits and highest resolution of 254 pixels-per-inch.

Abstract Background Major adverse cardiovascular events (MACE) are critical complications responsible for the morbidity and mortality of elderly hip fracture patients. There was an urgent need to explore an effect biomarker for predicting MACE in elderly patients receiving hip fracture surgery. Objective This study focused on an age-related miRNA, miR-409-3p, and assessed its significance in elderly hip fracture patients. Methods A total of 267 hip fracture patients were enrolled in this study including 104 elderly patients (age ≥ 60 years). All patients were followed up for 1 year to monitor the occurrence of MACE. The risk factors for the occurrence of MACE were evaluated by the logistic regression analysis. Results Elderly age and reduced cardiac and renal function were identified as risk factors for MACE in hip fracture patients. Elderly patients also showed a high incidence of MACE. In elderly hip fracture patients, significant upregulation of miR-409-3p was observed, which was associated with patients’ elderly age, higher level of revised cardiac risk index (RCRI), lower left ventricular ejection fraction (LVEF), and higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), and high sensitivity troponin I (hsTnI). Additionally, miR-409-3p was identified as an independent factor for the MACE in elderly patients received hip fracture surgery. Conclusion Upregulated miR-409-3p was an age-related miRNA and could predict the occurrence of MACE in elderly hip fracture patients.

Background: The trochanter of the femur is a common site for bone tumors. However, locating the specific boundary of bone tumor infiltration and determining the surgical method can be challenging. The objective of this study was to review the diagnosis, treatment, and surgical outcomes of patients with tumors or tumor-like changes in the femoral trochanter after computer-assisted precise tumor resection and hip-preserving reconstruction of the trochanter. Methods: From January 2005 to September 2020, 11 patients with trochanteric tumors (aged: 18–53 years; six males and five females) were treated in Guangzhou First People's Hospital. The cases included aneurysmal bone cyst (n = 1), giant cell tumor of bone (n = 2), fibrous histiocytoma of bone (n = 1), endochondroma (n = 1), and fibrous dysplasia of bone (n = 6). For patients with trochanteric tumors, computed tomography and magnetic resonance imaging scanning were performed before operation to obtain two-dimensional image data of the lesion. A three-dimensional digital model of bilateral lower limbs was reconstructed by computer technology, the boundary of tumor growth was determined by computer simulation, the process of tumor resection and reconstruction was simulated, and the personalized guide template was designed. During the operation, the personalized guide plate guided the precise resection of the tumor, and the allogeneic bone was trimmed to match the shape of the bone defect. Results: All 11 patients underwent accurate resection of the tumor or tumor-like lesion and reconstruction of the hip. In eight cases, the lesion was confined to the trochanter, which was fixed with large segment allogeneic bone, autologous iliac bone, and proximal femoral anatomic plate. In three cases, allogeneic bone, autologous iliac bone, and femoral reconstruction nail were used to fix the tumor under the trochanter. Postoperative X-ray examination showed that the repair and reconstruction of the bone defect was effective, and callus bridging between the allogenic bone and autogenous bone was observed 6 months after operation. All patients recovered their walking function 3–6 months after operation. The duration of the follow-up period ranged from 6 months to 6 years. A patient experienced recurrence of endochondroma; pathological examination revealed chondrocytic sarcoma. The remaining 10 patients were treated with segmental resection and reconstruction. The operation time ranged 2.5–4.5 h (average: 3.2 h). Intraoperative blood loss ranged from 300 to 500 ml (average: 368 ml). The local recurrence rate was 9.1%, and the overall survival rate was 100%. The average Musculoskeletal Tumor Society score was 27 (excellent and good for eight and three patients, respectively). Conclusions: Three-dimensional computer skeleton modeling and simulation-assisted resection and reconstruction of femoral trochanteric tumor is a new surgical technique, which might markedly improve the surgical effect, shorten the surgical time, increase the overall survival rate of patients with tumors, reduce the local recurrence rate, assist in the digitization and programming of femoral trochanteric tumor surgery, and improve surgical accuracy.

Breast cancer remains a significant public health issue, being a leading cause of cancer-related mortality among women globally. Timely diagnosis and efficient treatment are crucial for enhancing patient outcomes, reducing healthcare burdens and advancing community health. This systematic review, following the PRISMA guidelines, aims to comprehensively synthesize the recent advancements in computer-aided diagnosis and treatment for breast cancer. The study covers the latest developments in image analysis and processing, machine learning and deep learning algorithms, multimodal fusion techniques and radiation therapy planning and simulation. The results of the review suggest that machine learning, augmented and virtual reality and data mining are the three major research hotspots in breast cancer management. Moreover, this paper discusses the challenges and opportunities for future research in this field. The conclusion highlights the importance of computer-aided techniques in the management of breast cancer and summarizes the key findings of the review.

The hypervapotron structure was considered to be a feasible configuration to meet the high heat-dissipating requirement of divertors in nuclear fusion devices. In this work, symmetric CuCrZr-based transverse microchannels (TMHC) and longitudinal microchannels (LMHC) with an integrated hypervapotron channel were proposed and manufactured, and subcooled flow boiling experiments were conducted using deionized water at an inlet temperature of 20 °C with a traditional flat-type hypervapotron channel (FHC) for comparison. The LMHC and TMHC obtained lower wall temperatures than the FHC for all conditions, and the TMHC yielded the lowest temperatures. The heat transfer coefficients of the LMHC and TMHC outperformed the FHC due to the enlarged heat transfer area, and the TMHC had the greatest heat transfer coefficient (maximumly increased by 132% compared to the FHC) because the transverse-arranged microchannels were conductive, promoting the convection and liquid replenishment ability by introducing branch flow between fins; however, the microchannels of the LMHC were insensible to flow velocities due to the block effect of longitudinal microchannels. The LMHC obtained the largest pressure drop, and the pressure drop for the FHC and TMHC were comparable since the transverse-placed microchannels had little effect on frictional pressure loss. The TMHC attained the greatest comprehensive thermohydraulic performance which might bring significant insight to the structural design of hypervapotron devices.

Abstract Concrete pumping, integral to building construction, governs pipeline durability and overall construction efficiency. This study advances the traditional methods by employing the CFD-DEM coupling technique, a pioneering approach that integrates the irregular shape of coarse aggregates, capturing the intricacies of concrete pumping in pipelines. Beyond identifying primary wear areas and quantifying wear magnitudes, this research unveils a quadratic progression in average wear over time. The most pronounced wear appears in the pipeline’s bent sections. Notably, pumping speed, more influential than aggregate volume fraction, is pivotal to pipeline wear. Minimized speeds increase blockage risks, notably at elbows, while augmented speeds intensify wear. An optimal speed range between 2 and 3 m/s is deduced. Additionally, as the aggregate volume fraction surges, wear amplifies and blockages frequent. Hence, an aggregate volume fraction between 15 and 20% emerges as the recommendation.

Abstract Based on the emergency rescue, the subsequent disposal, and the development and utilization projects of the Hongshiyan Landside Dam in Ludian, Yunnan, China, research has been conducted on key technical issues facing the development and utilization of landside dams, including the possibilty evaluation of development and utilization, structure analysis of wide gradation material, performance evaluation, investigation and design, dam seepage control, construction technology and equipment, and safe operation assessment. And innovative results has made in all seven aspects mentioned above, writing the history in this field. The achievements were directly applied to the development planning, investigation and design, construction, and operation and maintenance of the Hongshiyan Landside Dam, a comprehensive water conservancy project that integrates flood control, water supply, irrigation, and power generation, with significant comprehensive benefits.

Abstract Phototropism is a classic adaptive growth response that helps plants to enhance light capture for photosynthesis. It was shown that hydrogen peroxide (H2O2) participates in the regulation of blue light-induced hypocotyl phototropism; however, the underlying mechanism is unclear. In this study, we demonstrate that the unilateral high-intensity blue light (HBL) could induce asymmetric distribution of H2O2 in cotton hypocotyls. Disruption of the HBL-induced asymmetric distribution of H2O2 by applying either H2O2 itself evenly on the hypocotyls or H2O2 scavengers on the lit side of hypocotyls could efficiently inhibit hypocotyl phototropic growth. Consistently, application of H2O2 on the shaded and lit sides of the hypocotyls led to reduced and enhanced hypocotyl phototropism, respectively. Further, we show that H2O2 inhibits hypocotyl elongation of cotton seedlings, thus supporting the repressive role of H2O2 in HBL-induced hypocotyl phototropism. Moreover, our results show that H2O2 interferes with HBL-induced asymmetric distribution of auxin in the cotton hypocotyls. Taken together, our study uncovers that H2O2 changes the asymmetric accumulation of auxin and inhibits hypocotyl cell elongation, thus mediating HBL-induced hypocotyl phototropism.

Dry and hot Foehn wind weather often occurs in Urumqi, China, due to its canyon terrain. This directly impacts the lives and health of local people. Using surface meteorological variables (including the hourly wind, temperature, humidity, and pressure) measured in situ at the Urumqi Meteorological Station and ERA5 reanalysis from the European Centre for Medium-Range Weather Forecasts in the past 15 years (2008–2022), the characteristics of Foehn wind and their relationship with EI Niño and extreme high-temperature events in Urumqi are analyzed. The results show that the annual distributions of Foehn wind present a fluctuating pattern, and the highest frequency occurred in 2015. Compared to the summer (July) and winter (February) seasons, Foehn wind occurs most frequently in spring (March, April, May) and autumn (September, October, and November). Daily variations in Foehn wind occur most frequently from 9:00 a.m. to 14:00 p.m. In particular, high levels are found at 10:00 a.m. and 11:00 a.m. in April and May. In 2011, 2012, and 2014, the average wind speed of FW exceeded 6 m/s, and the lowest average wind speed was 3.8 m/s in 2021. The temperature and relative humidity changes (ΔT and ΔRH) caused by Foehn wind are the most significant in winter and when Foehn wind begins to occur. The high-temperature hours related to Foehn wind weather in Urumqi represented 25% of the total in the past 15 years. During the EI Niño period, the amount of Foehn wind in Urumqi significantly increased; The correlation coefficient beteewn slide anomaly of Foehn days and the Oceanic Niño Index is as high as 0.71. Specifically, Foehn wind activity aggravates extreme high-temperature events. This study provides indications for Foehn wind weather forecasting in Urumqi.

Background: For almost a decade, virtual reality (VR) has been employed in otology simulation. The realism and accuracy of traditional three-dimensional (3D) mesh models of the middle ear from clinical CT have suffered because of their low resolution. Although micro-computed tomography (micro-CT) imaging overcomes resolution issues, its usage in virtual reality platforms has been limited due to the high computational requirements. The aim of this study was to optimize a high-resolution 3D human middle ear mesh model suitable for viewing and manipulation in an immersive VR environment using an HTC VIVE VR headset (HTC and Valve Corporation, USA) to enable a seamless middle ear anatomical visualisation viewing experience in VR while preserving anatomical accuracy. Methods: A high-resolution 3D mesh model of the human middle ear was reconstructed using micro-CT data with 28 μm voxel resolution. The models were optimised by tailoring the surface model polygon counts, file size, loading time, and frame rate. Results: The optimized middle ear model and its surrounding structures (polygon counts reduced from 21 million polygons to 2.5 million) could be uploaded and visualised in immersive VR at 82 frames per second with no VR-related motion sickness reported. Conclusion: High-resolution micro-CT data can be visualized in an immersive VR environment after optimisation. To our knowledge, this is the first report on overcoming the translational hurdle in middle ear applications of VR.

Abstract Background Immunotherapy is currently applied in the first-line treatment regimens for numerous advanced cancers, especially advanced lung cancer. Immune-related adverse events (irAEs) resulting from immunotherapy can vary in severity and cause a substantial symptom burden to patients. However, there are limited data on symptom burden in patients with advanced lung cancer following immunotherapy. To address this deficit, this study aims to provide insight into the symptom burden and severity through patient-reported outcome measurements and conduct an analysis of temporal trends and clinical consequences of symptom burden in patients with advanced lung cancer receiving combination immunotherapy. Methods We will prospectively recruit 168 eligible patients from 14 hospitals in China. Eligible patients will be aged ≥ 18 years, pathologically diagnosed with locally advanced or stage IV primary lung cancer without surgical indications, and agreed to receive immunotherapy in combination with other therapies. The primary outcome of this study is the symptom burden of patients during the immunotherapy course. Longitudinal symptom data will be collected using the MD Anderson Symptom Inventory–Lung Cancer module (MDASI-LC) and the symptomatic irAEs scale at baseline (once before treatment) and weekly after treatment, until 1 month after the last treatment cycle has been completed. The trajectory of symptom burden following combination immunotherapy will be depicted, and by linking it to clinical outcomes (the secondary outcome and exploratory outcome of this study), the consequence of symptom burden in patients with advanced lung cancer receiving combination immunotherapy will be examined further. Discussion This study intends to establish longitudinal symptom trajectories in patients with lung cancer receiving immunotherapy, and explore its association with clinical outcomes. These findings may serve as an important reference for clinicians in the symptomatic management of patients with lung cancer receiving immunotherapy. Trial registration number ChiCTR2200061540. Registered on June 28, 2022.

Abstract High-intensity interval training (HIIT) is a physical therapy that may benefit patients with osteoarthritis (OA). Cacna2d1 is a calcium channel subunit protein that plays an important role in the activity of nerve cells. However, there is currently no evidence on HIIT relieving OA-associate hyperalgesia by decreased Cacna2d1. Our study established the OA rat models with intra-articular injection of monosodium iodoacetate (MIA). This experiment was divided into two stages. The first stage comprised three groups: the control, OA, and OA-HIIT groups. The second stage comprised two groups, including the AAV-C and AAV-shRNA-Cacna2d1 groups. OA rats were positioned at the L5–L6 segments, and 20 µl of AAV virus was injected intrathecally. The pain threshold, cartilage analysis, Cacna2d1, and pain neurotransmitters were measured and compared. The pain threshold was significantly lower in OA rats than in control rats from the first to the tenth week. Starting from the sixth week, OA-HIIT rats exhibited significantly increased pain thresholds. The expression of Cacna2d1 increased in OA rats. Moreover, the knockdown of Cacna2d1 significantly down-regulated the expression of c-Fos, SP, and Vglut2 in the posterior horn of the spinal cord. In conclusion, HIIT attenuates OA-associated hyperalgesia, which may be related to the down-regulation of Cacna2d1.

Double-stranded DNA-specific cytidine deaminase (DddA) base editors hold great promise for applications in bio-medical research, medicine, and biotechnology. Strict sequence preference on spacing region presents a challenge for DddA editors to reach their full potential. To overcome this sequence-context constraint, we analyzed a protein dataset and identified a novel DddAtox homolog from Ruminococcus sp. AF17-6 (RsDddA). We engineered RsDddA for mitochondrial base editing in a mammalian cell line and demonstrated RsDddA-derived cytosine base editors (RsDdCBE) offered a broadened NC sequence compatibility and exhibited robust editing efficiency. Moreover, our results suggest the average frequencies of mitochondrial genome-wide off-target editing arising from RsDdCBE are comparable to canonical DdCBE and its variants.

Abstract Electrocatalytic urea synthesis via coupling of nitrate with CO2 is considered as a promising alternative to the industrial urea synthetic process. However, the requirement of sub‐reaction (NO3RR and CO2RR) activities for efficient urea synthesis is not clear and the related reaction mechanisms remain obscure. Here, the construction, breaking, and rebuilding of the sub‐reaction activity balance would be accompanied by the corresponding regulation in urea synthesis, and the balance of sub‐reaction activities was proven to play a vital role in efficient urea synthesis. With rational design, a urea yield rate of 610.6 mg h−1 gcat.−1 was realized on the N‐doped carbon electrocatalyst, superior to that of noble‐metal electrocatalysts. Based on the operando SR‐FTIR measurements, we proposed that urea synthesis arises from the coupling of *NO and *CO to generate the key intermediate of *OCNO. This work provides new insights and guidelines into urea synthesis from the aspect of activity balance.

Early detection of cracks enables timely mitigation and maintenance actions, ensuring the safety of personnel and equipment within the open-pit coal mine. Monitoring open-pit coal mines and cracks is essential for the safety of workers and for saving national assets. Digital twins (DTs) can be crucial in open-pit coal mine crack detection. DTs enable continuous real-time monitoring of the open-pit mine, including its structures and surrounding environment. Various sensors and internet-of-things devices can be deployed to collect data on factors such as ground movement and strain. Integrating this data into the DT makes it possible to identify and analyze anomalous behavior or changes that may indicate crack formation or propagation. Deep learning-based networks are a crucial factor in detecting open-pit coal mine cracks. In this work, we propose a deep learning-based densely connected lightweight network incorporated into the DT-based framework for detecting cracks and taking predictive maintenance-based decisions by combining historical data, real-time sensor data, and predictive models. The proposed DT-based framework provides insights into the potential crack formation, allowing for proactive maintenance and mitigation measures. We compare the performance of our proposed network on different evaluation measures such as precision, recall, overall accuracy, mean average precision, F1-score, and kappa coefficient, where our proposed lightweight multiscale feature fusion-based network outperformed all other state-of-the-art deep neural networks. We also achieved the best performance on mean average precision by surpassing all other models. Additionally, we also compared the performance of our proposed network with U-Net and recurrent neural network on model training and prediction time benchmarks by outperforming those cutting-edge models.

Percutaneous puncture is a common medical procedure that involves accessing an internal organ or tissue through the skin. Image guidance and surgical robots have been increasingly used to assist with percutaneous procedures, but the challenges and benefits of these technologies have not been thoroughly explored. The aims of this systematic review are to furnish an overview of the challenges and benefits of image-guided, surgical robot-assisted percutaneous puncture and to provide evidence on this approach. We searched several electronic databases for studies on image-guided, surgical robot-assisted percutaneous punctures published between January 2018 and December 2022. The final analysis refers to 53 studies in total. The results of this review suggest that image guidance and surgical robots can improve the accuracy and precision of percutaneous procedures, decrease radiation exposure to patients and medical personnel and lower the risk of complications. However, there are many challenges related to the use of these technologies, such as the integration of the robot and operating room, immature robotic perception, and deviation of needle insertion. In conclusion, image-guided, surgical robot-assisted percutaneous puncture offers many potential benefits, but further research is needed to fully understand the challenges and optimize the utilization of these technologies in clinical practice.

Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide. Receptor tyrosine kinases (RTKs) have long been sought as therapeutic targets for EOC, as they are frequently hyperactivated in primary tumors and drive disease relapse, progression, and metastasis. More recently, these oncogenic drivers have been implicated in EOC response to poly(ADP-ribose) polymerase (PARP) inhibitors and epigenome-interfering agents. This evidence revives RTKs as promising targets for therapeutic intervention of EOC. This review summarizes recent studies on the role of RTKs in EOC malignancy and the use of their inhibitors for clinical treatment. Our focus is on the ERBB family, c-Met, and VEGFR, as they are linked to drug resistance and targetable using commercially available drugs. The importance of these RTKs and their inhibitors is highlighted by their impact on signal transduction and intratumoral heterogeneity in EOC and successful use as maintenance therapy in the clinic through suppression of the VEGF/VEGFR axis. Finally, the therapeutic potential of RTK inhibitors is discussed in the context of combinatorial targeting via co-inhibiting proliferative and anti-apoptotic pathways, epigenomic/transcriptional programs, and harnessing the efficacy of PARP inhibitors and programmed cell death 1/ligand 1 immune checkpoint therapies.

Abstract Background The evolutionarily conserved Polycomb Repressive Complex 2 (PRC2) plays a vital role in epigenetic gene repression by depositing tri-methylation on lysine residue K27 of histone H3 (H3K27me3) at the target loci, thus participating in diverse biological processes. However, few reports about PRC2 are available in plant species with large and complicated genomes, like cotton. Results Here, we performed a genome-wide identification and comprehensive analysis of cotton PRC2 core components, especially in upland cotton (Gossypium hirsutum). Firstly, a total of 8 and 16 PRC2 core components were identified in diploid and tetraploid cotton species, respectively. These components were classified into four groups, E(z), Su(z)12, ESC and p55, and the members in the same group displayed good collinearity, similar gene structure and domain organization. Next, we cloned G. hirsutum PRC2 (GhPRC2) core components, and found that most of GhPRC2 proteins were localized in the nucleus, and interacted with each other to form multi-subunit complexes. Moreover, we analyzed the expression profile of GhPRC2 genes. The transcriptome data and quantitative real-time PCR (qRT-PCR) assays indicated that GhPRC2 genes were ubiquitously but differentially expressed in various tissues, with high expression levels in reproductive organs like petals, stamens and pistils. And the expressions of several GhPRC2 genes, especially E(z) group genes, were responsive to various abiotic and biotic stresses, including drought, salinity, extreme temperature, and Verticillium dahliae (Vd) infection. Conclusion We identified PRC2 core components in upland cotton, and systematically investigated their classifications, phylogenetic and synteny relationships, gene structures, domain organizations, subcellular localizations, protein interactions, tissue-specific and stresses-responsive expression patterns. Our results will provide insights into the evolution and composition of cotton PRC2, and lay the foundation for further investigation of their biological functions and regulatory mechanisms.

Metaproteomics has increasingly been applied to study functional changes in the human gut microbiome. Peptide identification is an important step in metaproteomics research, with sequence database search (SDS) and spectral library search (SLS) as the two main methods to identify peptides. However, the large search space in metaproteomics studies causes significant challenges for both identification methods. Moreover, with the development of mass spectrometry, it is now feasible to perform metaproteomic projects involving 100–1000 individual microbiomes. These large-scale projects create a conundrum for searching large databases. In this study, we constructed MetaPep, a core peptide database (including both collections of peptide sequences and tandem MS spectra) greatly accelerating the peptide identifications. Raw files from fifteen metaproteomics projects were re-analyzed and the identified peptide-spectrum matches (PSMs) were used to construct the MetaPep database. The constructed MetaPep database achieved rapid and accurate identification of peptides for human gut metaproteomics. MetaPep has a large collection of peptides and spectra that have been identified in published human gut metaproteomics datasets. MetaPep database can be used as an important resource in the current stage of human gut metaproteomics research. This study showed the possibility of applying a core peptide database as a generic metaproteomics workflow. MetaPep could also be an important resource for future human gut metaproteomics research, such as DIA (data-independent acquisition) analysis.

Abstract Background Inflammatory bowel disease (IBD) is a chronic nonspecific disease with unknown etiology. Currently, the anti-inflammatory therapeutic approaches have achieved a certain extent of effects in terms of inflammation alleviation. Still, the final pathological outcome of intestinal fibrosis has not been effectively improved yet. Results In this study, dextran-coated cerium oxide (D-CeO2) nanozyme with superoxide dismutase (SOD) and catalase (CAT) activities was synthesized by chemical precipitation. Our results showed that D-CeO2 could efficiently scavenge reactive oxide species (ROS) as well as downregulate the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and iNOS) to protect cells from H2O2-induced oxidative damage. Moreover, D-CeO2 could suppress the expression of fibrosis-related gene levels, such as α-SMA, and Collagen 1/3, demonstrating the anti-fibrotic effect. In both TBNS- and DSS-induced colitis models, oral administration of D-CeO2 in chitosan/alginate hydrogel alleviated intestinal inflammation, reduced colonic damage by scavenging ROS, and decreased inflammatory factor levels. Notably, our findings also suggested that D-CeO2 reduced fibrosis-related cytokine levels, predicting a contribution to alleviating colonic fibrosis. Meanwhile, D-CeO2 could also be employed as a CT contrast agent for noninvasive gastrointestinal tract (GIT) imaging. Conclusion We introduced cerium oxide nanozyme as a novel therapeutic approach with computed tomography (CT)-guided anti-inflammatory and anti-fibrotic therapy for the management of IBD. Collectively, without appreciable systemic toxicity, D-CeO2 held the promise of integrated applications for diagnosis and therapy, pioneering the exploration of nanozymes with ROS scavenging capacity in the anti-fibrotic treatment of IBD.

Accurate identification and analysis of traffic conflicts through surrogate safety measures (SSMs) are crucial for safety evaluation in road systems. Existing SSMs for conflict identification and analysis mostly consider the temporal–spatial proximity of conflicts without taking into account the severity of potential collisions. This makes SSMs unsuitable for traffic safety evaluation in complex road environments. In order to address the shortcomings above, this study first introduces a new SSM called the Potential Conflict Risk Index (PCRI). To validate the effectiveness of PCRI, the inD dataset is adopted for conflict identification comparison between time-to-collision (TTC) and PCRI. Using PCRI, this study conducts a conflict analysis in the freeway merging areas based on the data from the Outer Ring Expressway Dataset (ORED), accounting for differences between cars and trucks. The comparative results between TTC and PCRI show that PCRI can provide a more comprehensive identification of conflicts and a more accurate identification of the moment with the highest conflict risk. The results of conflict analysis suggest that conflicts occur more frequently in situations involving trucks, and these conflicts commonly occur in closer proximity to the on-ramp at freeway merging areas. The findings from this study can improve the accuracy of conflict identification under different conflict patterns, enhancing the specificity of traffic safety measures and ultimately ensuring the safety of road systems.

In this research, fully degradable elastomeric sealing materials were developed to enhance the environmental sustainability of oil and gas extraction. The modification of millable polyurethane rubber (MPU) with polyglycolic acid/hydrogenated nitrile butadiene rubber (PGA/HNBR) led to the synthesis of PGA@MPU/HNBR composite materials. The impact of varying monomer quantities on the mechanical properties, degradation behavior, degradation mechanisms, and thermal stability of these materials was investigated. Our findings illustrate that an increasing proportion of HNBR in the PGA@MPU/HNBR composite materials resulted in a decreased degradation rate. Simultaneously, higher HNBR content improved the thermal stability of the materials, while the inclusion of PGA reduced material hardness, rendering the composites more susceptible to swelling. At an HNBR content of 40 phr, MPU at 60 phr, and PGA at 6 phr, the composite material demonstrated the highest retention of mechanical properties at 31.3% following 168 h of hydrolysis at 100 °C. The degradation of the composite materials in 100 °C water primarily resulted from the hydrolysis of MPU’s ester groups, with HNBR remaining unaffected.

Within the framework of isotropic materials, this paper introduces an efficient topology optimization method that incorporates fail-safe design considerations using a penalty function approach. Existing methods are either computationally expensive or overlook fail-safe requirements during optimization. This approach not only achieves optimized structures with fail-safe characteristics, but also significantly enhances the computational efficiency of fail-safe topology optimization. In this method, the minimization of worst-case compliance serves as the optimization objective, employing the Kreisselmeier–stein Hauser function to approximate the non-differentiable maximum operator. A sensitivity analysis, derived through the adjoint method, is utilized, and a universal fail-safe optimization criterion is developed to update the design variables. During the optimization process for fail-safe strategies, a density-based filtering method is applied, effectively reducing damage scenarios. Finally, the effectiveness and computational efficiency of this method are validated through several numerical examples.

Introduction Mechanical neck pain (MNP) is defined as pain in the area of the neck and/or neck-shoulder provoked by body mechanics and which adversely affects physical, psychological and social function. The treatments for MNP are limited. Previous studies and clinical experience have indicated that myofascial acupuncture might be a better treatment option for MNP, but the efficacy is controversial. Therefore, our aim is to compare the efficacy of myofascial acupuncture and routine acupuncture for MNP.Methods and analysis The study is a multicentre, prospective randomised clinical trial. Patients will be recruited from four tertiary hospitals in China. A total of 438 participants with MNP will be randomly assigned into two groups, namely the ‘Sancai-Tianbu’ myofascial acupuncture group and the routine acupuncture group, at a ratio of 1:1. Each group will receive the acupuncture treatment twice a week for 21 days, totalling six sessions. The primary outcome will be the Visual Analogue Scale score. The secondary outcomes will be the Neck Disability Index, the cervical range of motion and the MOS 36-Item Short Form Health Survey. The assessments will be performed at baseline (immediately after allocation), pretreatment (5 min before every treatment), post-treatment (within 10 min after every treatment), postcourse (within 1 day after the course), and at 1, 3 and 6 months after the course. All patients will be included in the intent-to-treat analysis. Repeated-measure analysis of covariance will be used to determine the effects of the intervention on the outcome measures.Ethics and dissemination Ethics approval was obtained from China Aerospace Science & Industry Corporation 731 Hospital, with permission number 2022-0204-01. Written informed consent will be obtained from the enrolled patients. Trial results will be disseminated in peer-reviewed publications.Trial registration number ChiCTR2200061453.

Abstract Introduction Drug development has been challenged by the dual drawbacks involving unpredictable disease outcomes and drug resistance, which has placed greater demands on pharmacology education. Molecular pharmacology, as a frontier crossover field of pharmacology, focuses on the research of new drugs and targets. However, due to the lack of a systematic experimental training system, molecular pharmacology has not made a corresponding contribution in promoting the training of innovative talent in pharmacology. We aim to establish an experimental training program suitable for molecular pharmacology to improve students' ability to engage in drug development in future. Methods Based on the feasibility of drug–target projects, a comprehensive training program containing molecular docking, target stability experiment, and fluorescent probe detection of protein expression in living cells and mice was conducted among 20 pharmacy graduate students. The experimental training was assessed by the experimental training report and the student recognition questionnaires. Results All 20 students mastered the experimental principles and operations required for the training program. The experimental reports proved that the students were in good command of the experimental principles, operations and applications. The results of the Likert questionnaire indicated that the training program promoted the understanding of the drug research process and increased motivation to learn. Conclusion The designed experimental training program has a positive effect on the training of pharmacology talents, and can be implemented as a part of molecular pharmacology education.

Background: Anlotinib is a multi-target anti-angiogenic agent. The retrospective study was conducted to evaluate the safety and effectiveness of anlotinib as monotherapy or combination therapy for the treatment of recurrent high-grade gliomas. Methods: In this retrospective study, patients with recurrent high-grade glioma (according to the 2021 World Health Organization classification as levels III-IV) at Sichuan Cancer Hospital from June 2019 to June 2022 were included. The patients were divided into an anlotinib-monotherapy group and an anlotinib-combination group, and received oral anlotinib 8 to 12 mg once a day, with 2 weeks on/1 week off. The primary endpoint was progression-free survival (PFS). The Secondary endpoints included overall survival (OS), 6-month PFS rate, objective response rate (ORR), and disease control rate (DCR). Also, adverse events were evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE version 5.0). Results: A total of 29 patients (including 20 glioblastomas, 1 diffuse midline glioma, 5 anaplastic astrocytoma, and 3 anaplastic oligodendroglioma) were included in this study. Of these, 34.48% of the patients were treated with anlotinib alone and 65.52% with anlotinib combination therapy. The median follow-up time was 11.6 months (95% confidence interval [CI]: 9.4-15.7). The median PFS was 9.4 months (95% CI: 6.5-12.3), and the 6-month PFS rate was 62.1%. The median OS was 12.7 months (95% CI: 9.7-15.7), and the 12-month OS rate was 48.3%. Evaluation of treatment response was performed according to RANO (response assessment in neuro-oncology, RANO) criteria, including 21 partial response, 6 stable disease, and 2 PFS events. The ORR and DCR were 72.4%, and 93.1%, respectively. Grade III AEs occurred in 2 patients, and the others were less than grade III. The most common AE was thrombocytopenia, with an incidence rate of 31.0%. All AEs were alleviated and controlled by symptomatic treatment. No treatment-related deaths occurred. Conclusion: Anlotinib had a low incidence of AEs and good safety in the treatment of recurrent high-grade glioma. Moreover, it showed good short-term effectiveness and significantly prolonged the PFS of patients, which may become a promising therapeutic option for recurrent high-grade glioma and lay a foundation for further clinical studies.

Many concrete columns exhibit a decline in structural performance due to construction inaccuracy, increased load demand and corrosive environment. It is urgent to adopt necessary strengthening methods to improve the mechanical behavior of pre-damaged columns. This paper presents a numerical investigation on the compressive behavior of pre-damaged concrete columns strengthened with a composite jacket of basalt fiber textile and engineered cementitious composites (ECC). After verification of the developed FE model, the failure mechanism of the pre-damaged concrete columns strengthened with TRE (textile-reinforced ECC) under axial compression was evaluated. Furthermore, a parameter analysis was performed to address the effects of thickness of ECC layer, spacing of fiber textile and concrete core strength on the axial behaviour of the pre-damaged columns strengthened with TRE. The results showed that the reinforced columns with different pre-damage levels showed ductile failure characteristics, which was due to a good binding force provided by the textile-ECC composite reinforcement layer. The axial stiffness, ultimate compressive load, and deformation capacity of the strengthened pre-damaged columns decreased with the increasing pre-damage level. The compressive behaviour of confined pre-damaged columns could be improved by increasing thickness of ECC, reducing the spacing of textile, and decreasing strength of the core concrete, especially for the major pre-damaged column.

Abstract Background A safe and effective technique for anterolateral portal placement in elbow arthroscopy is significant. We compared the outcomes of patients who underwent elbow arthroscopy using different ultrasound-assisted techniques. Methods From May 2016 to June 2021 a retrospective analysis on all patients who underwent elbow arthroscopy in our department was performed. Patients were separated into three groups: non-ultrasound; preoperative ultrasound; and intraoperative ultrasound. The minimum follow-up period was 1 year. Nerve injuries, visual analog scale (VAS), Mayo elbow-performance score (MEPS), Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH), and range of motion (ROM) of the elbow were evaluated for comparison among the three groups pre- and post-operatively. Results All 55 patients completed a 1-year follow-up: non-ultrasound (n = 20); preoperative ultrasound (n = 17); and intraoperative ultrasound (n = 18). There were 3 cases (15.0%) of transient radial nerve palsy in the non-ultrasound group. No nerve complications occurred in preoperative ultrasound and intraoperative ultrasound groups. The probability of postoperative radial nerve injury in the three groups was statistically different (P 0.05). Conclusion Performing anterolateral portal placement during elbow arthroscopy with ultrasound-assisted techniques successfully avoided radial nerve injury.

AbstractIn the present work, the fermentation of molasses using Saccharomyces cerevisiae was optimized in terms of denitrification efficiency, using the relative total nitrogen (TN) removal ratio and the C/N consumption ratio as the indicators. The denitrification efficiency in different wastewater was also measured in the presence of different carbon sources for denitrification, that is, fermentation broth, unfermented molasses, sodium acetate, ethanol and methanol. The results indicated that the optimal fermentation conditions were as follows: pH = 4.0; temperature, 33 °C; dilution rate, 0.15 h−1; sugar concentration, 13%; ammonium chloride concentration, 0.5 g/L; and air-flow rate in the reactor, 0.1 vvm for 30 min every 12 h. The relative TN removal ratio with the fermentation broth was 39% higher than that with unfermented molasses. However, the denitrification efficiency of the fermentation broth varied between landfill leachate, herbicide wastewater and brewing wastewater. The relative TN removal ratio was significantly higher only in the brewing wastewater, and the C/N consumption ratio was also significantly lower than that with methanol, ethanol and molasses. These results showed that the use of molasses fermentation broth as the carbon source for denitrification has advantages for specific sewage regarding effectiveness. The raw material cost of the fermentation broth was ca. 30% lower than sodium acetate. The results also suggested that the bacterial community structure had a significant impact on the denitrification efficiency of the fermentation broth.