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Abstract In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p

Abstract Background Globally, breast cancer in women is the fifth leading cause of cancer death. There is an urgent need to explore the molecular mechanism of breast cancer proliferation and metastasis. Method TCGA database analysis was used to analyze genes expression in breast cancer and normal samples and the association between gene expression and prognosis. Immunohistochemical staining, qPCR and western blotting was sued to detected gene expression. The cell function tests were conducted to investigate the effects of TEX19 and CDK4 with abnormal expression on cell proliferation, migration, apoptosis, cell cycle, and colony formation. Bioinformatics analysis methods combined with CHX tracking experiment and Co-IP experiment were performed to screen and verify the downstream molecule and regulatory mechanism of TEX19. Besides, subcutaneous tumorigenesis model in nude mice was constructed. Results TEX19 was significantly upregulated in breast cancer, and the TEX19 level was related to tumor invasion and prognosis. TEX19 knockdown inhibited the proliferation and migration of breast cancer cells, increased cell apoptosis, and blocked the cell cycle in the G2 phase. Besides, TEX19 suppressed the growth of tumors in the body. Mechanically, TEX19 upregulated the level of CDK4 protein, which depended on the E3 ubiquitin ligase SKP2. Specifically, TEX19 knockdown and SKP2 protein overexpression destroyed the stability of CDK4 protein and enhanced the ubiquitination of CDK4 protein. Additionally, CDK4 knockdown inhibited the proliferation, migration, and colony formation of breast cancer cells, and alleviated the promotion of TEX19 overexpression on the proliferation and migration of breast cancer cell. Conclusion TEX19 and CDK4 were upregulated in breast cancer, and TEX19 increased the level of CDK4 protein by influencing SKP2-mediated ubiquitination of CDK4, thereby promoting the progression of breast cancer.

During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease.

The Ti2AlNb alloy, solution-treated at 1070 °C, underwent hot rolling at 960 °C with different thickness reductions to investigate the synergistic effects of the O phase and B2 phase and their impact on its properties. The results reveal that after solution treatment, the Ti2AlNb alloy consists of nearly spherical O, lath O, and B2 matrix at 30% and 50% thickness reductions during hot rolling. However, at a 70% thickness reduction, the alloy exhibits spherical O, worm-like O, and a continuously distributed B2 phase. The α2 phase formed during solution treatment decomposes during hot rolling. As the thickness reduction increases from 30% to 70%, the O phase content initially rises and then declines, accompanied by an increase in the average dimension of the O phase from 0.25 ± 0.16 μm to 0.36 ± 0.18 μm. Additionally, the B2 phase in the alloy undergoes dynamic recrystallization (DRX) during hot rolling, coinciding with the growth and spheroidization of the O phase. With an increase in the thickness reduction during hot rolling, the elongation of the alloy increases from 5.9% at 30% reduction to 12.47% at 70% reduction. Meanwhile, the ultimate tensile strength reaches its peak value of 1092.2 MPa at 30% reduction, decreases to 936 MPa at 50%, and then increases to 970 MPa at 70%. The tensile strength of the alloy improves due to the interaction and accumulation of dislocations at the phase interface. The continuous distribution of the B2 matrix, dislocation movement, rotation of the O phase, DRX of the B2 phase, and interface slip all contribute to enhanced ductility. Furthermore, the fracture behavior of the Ti2AlNb alloys under various hot rolling conditions was elucidated.

Steel cord core conveyor belt is a traction and carrying component of belt conveyor, and joint failure is the main cause of steel cord core conveyor belt failure. In order to improve the joint strength and vulcanization efficiency of the conveyor belt, this paper proposes a preformed core rubber laying technology based on the existing joint vulcanization process. Taking the ST1 600 steel cord core conveyor belt joint as the research object, the application of this technology is theoretically analyzed and experimentally studied. Firstly, the mechanical model of the conveyor belt joint is established and stress analysis is conducted. The influence of uneven horizontal and vertical spacing of steel cords on the joint strength is studied using ANSYS Workbench software. Then, a preformed core rubber laying method is proposed, and the effect of filling core rubber and triangular, trapezoidal, and semicircular core rubber grooves on limiting the offset of steel cords is compared through fluid-solid coupling analysis of core rubber. Finally, the influence of this technology on the adhesive strength of the conveyor belt, joint vulcanization efficiency, and joint strength is studied through joint preformed core rubber vulcanization experiments. The research shows that the stress of steel cords at the conveyor belt joint is related to their longitudinal displacement. Due to the inability to achieve uniform distribution of steel cords in traditional joint vulcanization operations, uneven stress of steel cords is caused, which affects the joint strength. The change of horizontal spacing of steel cords compared to vertical spacing has a more significant effect on the equivalent stress of steel cords, which is more likely to cause the failure of joint steel cords. The preformed core rubber laying technology can effectively reduce the offset of steel cords, among which the semicircular core rubber groove has the best effect, reducing by 70% in the horizontal direction and 86.9% in the vertical direction. Under the same vulcanization conditions, compared with filling core rubber, the adhesive strength after vulcanization of triangular, trapezoidal, and semicircular core rubber grooves increased by 1.91%, −3.51%, and 2.48%, respectively, with the best combination with semicircular core rubber. The preformed core rubber technology with semicircular core rubber groove laying can reduce the working time by 70% while concurrently boosting the joint strength of the vulcanized conveyor belt by 5.74%. The research findings can offer both theoretical and practical insights for streamlining joint enhancements.

Abstract Background Pulmonary large-cell neuroendocrine carcinoma (pLCNEC) represents a rare malignancy characterized by its aggressive behavior and a notably high recurrence rate. Remarkably, there is currently no established standard treatment protocol for this condition. Case description In this report, we present an intriguing case of pLCNEC diagnosed at clinical-stage IIB. This case involves a 64-year-old man with a smoking history spanning four decades. In our approach, we initiated a course of neoadjuvant chemotherapy in combination with pembrolizumab, administered for two cycles prior to surgical resection. This innovative treatment strategy resulted in a significant pathological response, culminating in a major pathological remission (MPR). As of the time of composing this report, the patient has been diligently monitored for 39 months post-surgery, exhibiting no indications of recurrence, and has demonstrated exceptional tolerance to the entire treatment regimen. Conclusions We have first reported a clinically successful case of neoadjuvant combination chemotherapy with pembrolizumab in the treatment of pLCNEC. This case offers promising clinical insights and suggests that this therapeutic approach could be a viable option for managing pLCNEC.

Highlights Covalent organic frameworks (COFs) were in situ homogeneously growing on the surface of metal–organic framework (MOF-808) by a covalent bond to construct a core–shell MOF@COF nanoparticle. MOF@COF optimized the crystallinity of perovskite to achieve 23.61% efficiency with superior open circuit voltage (1.20 V). MOF-assisted COFs to ‘trap’ leaked lead ions by in situ chemical fixation and adsorption. The amount of lead leakage (

In order to further improve the utilization value of Perilla resources, this study used Perilla seed shell extract (PSHE) as raw material, through single factor experiments, the effects of silver nitrate concentration, extract concentration, ultrasonic power, ultrasonic temperature and ultrasonic time on the silver ion reduction rate of Perilla seed shell extract silver nanoparticles (PSHE@AgNPs) were investigated, response surface methodology (RSM) was used to optimize the ultrasonic-assisted preparation of PSHE@AgNPs, the structure and properties of PSHE@AgNPs were characterized by X-ray diffraction, fourier transform infrared spectroscopy, thermogravimetric analysis and transmission electron microscope. The results showed that the optimal PSHE@AgNPs preparation process involved a silver nitrate concentration 15 mmol/L, extract concentration 0.4 g/mL, ultrasonic power 480 W, ultrasonic temperature 80 ℃, and ultrasonic time 7 hours. Under these conditions, the silver ion reduction rate of PSHE@AgNPs reached an impressive 92.37%. X-ray diffraction analysis confirmed the presence of a face-centered cubic structure in PSHE@AgNPs. Fourier-transform infrared spectroscopy showed that there were plant chemical substances on the surface of PSHE@AgNPs，and phenolic compounds were involved in the synthesis of nano-silver. Thermal gravimetric analysis demonstrated the exceptional thermal stability of PSHE@AgNPs，with a major mass loss of 46.74% in the range of 276.7~420.3 ℃. Transmission electron microscopy displayed PSHE@AgNPs as highly dispersed near-spherical particles with an average particle size of 27.97 nm. These research findings would provide valuable theoretical guidance for the ultrasound-assisted green synthesis of PSHE@AgNPs with small particle size, superior dispersion, and remarkable thermal stability in a face-centered cubic structure. Furthermore, these results contribute to advancing the application of PSHE@AgNPs in the fields of biomaterials and medicine.

ABSTRACT The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs.IMPORTANCEOur study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

BackgroundAttention deficit hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder in children, can be effectively alleviated by the herbal preparation Long Mu Qing Xin Mixture (LMQXM), but its mechanism has not been fully elucidated.ObjectiveTo scrutinize the potential pharmacological mechanisms by which LMQXM improves behavior in spontaneously hypertensive rats (SHR/NCrl).MethodsThe SHR/NCrl rats were randomly stratified into the model (SHR) group, the methylphenidate hydrochloride (MPH) group, and groups subjected to varying dosages of LMQXM into the medium dose (MD) group with a clinically effective dose, the low dose (LD) group with 0.5 times the clinically effective dose, and high dose (HD) group with 2 times the clinically effective dose. Furthermore, the WKY/NCrl rats constituted the control group. The evaluation of behavior involved the open field test and the Morris water maze test. HPLC, LC-MS, ELISA, immunohistochemistry, Western blot, and RT-qPCR were utilized to scrutinize the catecholamine neurotransmitter content and the expression of proteins and genes associated with the dopamine receptor D1 (DRD1)/cAMP/protein kinase A (PKA)-cAMP response element-binding (CREB) pathway in prefrontal cortex (PFC) and striatum.ResultsMPH and LMQXM ameliorated hyperactivity and learning and memory deficits of SHR/NCrl rats. Among them, LMQXM-MD and MPH also upregulated dopamine (DA), norepinephrine (NE), adenylate cyclase (AC) and cAMP levels, and the expression of proteins and genes associated with the DRD1/cAMP/PKA-CREB pathway in PFC and striatum of SHR/NCrl rats. PFC and striatum DA levels were also upregulated in the LMQXM-LD group as well as the striatum DA levels in the LMQXM-HD group, but there were no statistically significant differences in their NE levels compared to the SHR group. LMQXM-LD and LMQXM-HD also upregulated some DRD1/cAMP/PKA-CREB pathway-related proteins and gene expression, but the effects were discernibly disparate in PFC and striatum. Upon comprehensive analysis, LMQXM-MD appeared to be the most effective dose.ConclusionOur study tentatively suggests that LMQXM may rectify hyperactivity and learning and memory deficits of SHR/NCrl rats by elevating catecholamine neurotransmitters in the PFC and striatum. This effect may be attributed to the potential activation of the DRD1/cAMP/PKA-CREB signaling pathway, which appears to achieve an optimal response at moderate doses.

IntroductionOxidative stress plays a pivotal role in modulating the balance of intestinal flora and the gut-liver axis, while also serving as a key determinant of the growth potential of weaned piglets. However, few studies have subdivided and compared acute and chronic oxidative stress.MethodsIn this study, an intestinal model of acute oxidative stress in weaned piglets using paraquat (PQ) and a chronic oxidative stress model using D-galactosa in weaned piglets were conducted. And we further systematically compare their effects.ResultsBoth acute and chronic oxidative stress models impaired intestinal barrier function and liver function. Chronic stress caused by D-galactose can result in severe redox dysregulation, while acute stress caused by paraquat can lead to inflammation and liver damage. Additionally, the components involved in the CAR pathway were expressed differently. Chronic or acute oxidative stress can reduce the diversity and composition of intestinal flora. In the PQ group, the richness of Mogibacterium and Denitratisoma improved, but in the D-gal group, the richness of Catenisphaera and Syntrophococcus increased.DiscussionNot only does this research deepen our understanding of the effects of acute and chronic oxidative stress on intestinal functions, but it also characterizes characteristic changes in the gut flora, potentially identifying novel therapeutic targets and opening new avenues for future research.

Abstract Purpose Medical insurance fraud has caused huge losses to countries around the world, and public reporting has become an important means to combat medical insurance fraud. The attitude of medical insurance fraud whistleblowers affects people’s reporting behavior, and understanding people’s attitude toward medical insurance fraud whistleblowers provides a basis for further improving the system and policy of public participation in medical insurance fund supervision. Methods We adopted the questionnaire method to conduct a national cross-sectional survey of the Chinese public and analyzed the data using Chi-square tests, Fisher’s exact tests, and binary logistic regression models. Results A total of 837 respondents were included, and 81.8% of the population had a supportive attitude toward medical insurance fraud whistleblowers, with gender, whether they had used medical insurance reimbursement, and present life satisfaction being statistically significant (P

Abstract Introduction Young and middle-aged people are important participants in the fight against health insurance fraud. The study aims to investigate the differences in their willingness to report health insurance fraud and the factors influencing it when it occurs in familiar or unfamiliar healthcare settings. Methods Data were obtained from a validated questionnaire from 828 young and middle-aged people. McNemar’s test was used to compare the public’s willingness to report under the two scenarios. Chi-square tests and multiple logistic regression analysis were used to analyze the determinants of individuals’ willingness to report health insurance fraud in different scenarios. Results Young and middle-aged people were more likely to report health insurance fraud in a familiar healthcare setting than in an unfamiliar one (McNemar’s χ²=26.51, P

SLAM (Simultaneous Localization and Mapping) is the core technology enabling autonomous exploration by mobile robots in unknown environments. While there have been numerous impressive SLAM systems developed, many of them are primarily based on the assumption of static environments, limiting their applicability in real-world settings. In order to enhance the robustness and accuracy of systems in dynamic real-world scenarios, we have introduced a parallelized real-time SLAM system called PR-SLAM, building upon the foundation of ORB-SLAM3. This algorithm introduces a dynamic probability update strategy within the semantic segmentation thread, completely decoupling the semantic segmentation thread from the tracking thread. Theoretically, the processing time per frame is solely dependent on the runtime of the tracking thread. Furthermore, we employ a geometric approach based on reprojection error to compensate for semantic gaps generated during semantic segmentation model inference. We have also designed a semantic optimization thread based on the dynamic probability of map points to optimize camera poses during semantic gaps. Finally, to reduce semantic gaps, we have performed lightweight modifications to SOLOV2. Comparative experiments were conducted against the state-of-the-art SLAM systems using the TUM dataset. The results indicate significant improvements in both accuracy and real-time performance for PR-SLAM. When compared to ORB-SLAM3, PR-SLAM achieved a remarkable 97.83% improvement in absolute trajectory accuracy and demonstrated an impressive 86.71% increase in runtime speed compared to DynaSLAM.

Abstract As a new data management paradigm, knowledge graphs can integrate multiple data sources and achieve quick responses, reasoning and better predictions in drug discovery. Characterized by powerful contagion and a high rate of morbidity and mortality, porcine reproductive and respiratory syndrome (PRRS) is a common infectious disease in the global swine industry that causes economically great losses. Traditional Chinese medicine (TCM) has advantages in low adverse effects and a relatively affordable cost of application, and TCM is therefore conceived as a possibility to treat PRRS under the current circumstance that there is a lack of safe and effective approaches. Here, we constructed a knowledge graph containing common biomedical data from humans and Sus Scrofa as well as information from thousands of TCMs. Subsequently, we validated the effectiveness of the Sus Scrofa knowledge graph by the t-SNE algorithm and selected the optimal model (i.e., transR) from six typical models, namely, transE, transR, DistMult, ComplEx, RESCAL and RotatE, according to five indicators, namely, MRR, MR, HITS@1, HITS@3 and HITS@10. Based on embedding vectors trained by the optimal model, anti-PRRSV TCMs were predicted by two paths, namely, VHC-Herb and VHPC-Herb, and potential anti-PRRSV TCMs were identified by retrieving the HERB database according to the pharmacological properties corresponding to symptoms of PRRS. Ultimately, Dan Shen's (Salvia miltiorrhiza Bunge) capacity to resist PRRSV infection was validated by a cell experiment in which the inhibition rate of PRRSV exceeded 90% when the concentrations of Dan Shen extract were 0.004, 0.008, 0.016 and 0.032 mg/mL. In summary, this is the first report on the Sus Scrofa knowledge graph including TCM information, and our study reflects the important application values of deep learning on graphs in the swine industry as well as providing accessible TCM resources for PRRS.

Abstract Chlorophyll degradation is an important physiological process and is essential for plant growth and development. However, how chlorophyll degradation is controlled at the cellular and molecular level remains largely elusive. Pectin is a main component of the primary cell wall, and polygalacturonases (PGs) is a group of pectin-hydrolases that cleaves the pectin backbone and release oligogalacturonide. Whether and how PGs affect chlorophyll degradation metabolism and its association with ethylene (ETH) have not been reported before. Here, we report a novel function of PG in a mutant ‘high chlorophyll content1’ hcc1, which displayed a decrease in growth and yield. Our morphological, biochemical and genetic analyses of hcc1, knockout lines and complementation lines confirm the function of HCC1 in chlorophyll degradation. In hcc1, the PG activity, ETH content and D-galacturonic acid (D-GA) was significantly decreased and showed an increase in the thickness of the cell wall. Exogenous application of ETH and D-GA can increase ETH content and induce the expression of HCC1, which further can successfully induce the chlorophyll degradation in hcc1. Together, our data demonstrated a novel function of HCC1 in chlorophyll degradation via the ETH pathway.

In female animals, metabolic homoeostasis and reproductive fitness are critical to population expansion. The trade-off between lipid storage and reproduction inevitably occurs. However, most studies have focused on the complex network of relationships between reproductive and metabolic physiology at the transcriptional level. In this study, we identified a microRNA, miR-2b-2-5p, in a highly invasive quarantine pest, Bactrocera dorsalis. Knockdown of miR-2b-2-5p by antagomiR microinjection impaired ovarian development, reduced fecundity, and decreased triglyceride (TAG) storage in the fat body, whereas overexpression of miR-2b-2-5p by injection of its mimic caused reproductive defects similar to knockdown but increased TAG. Bioinformatics analysis and dual luciferase assay indicated that cyclic AMP response element (CRE)-binding protein (CREB) was the target gene of miR-2b-2-5p. RNAi-mediated knockdown of CREB led to excessive lipid storage and reproductive defects. Further starvation treatment revealed that miR-2b-2-5p functions by fine-tuning CREB expression in response to dietary stimuli. These results suggest that miR-2b-2-5p acts as a monitor to regulate CREB mRNA levels in the fat body, maintaining lipid homoeostasis and keeping the reproductive system on track. Thus, our study not only provides new insights into the interaction between metabolism and reproduction at the posttranscriptional level in B. dorsalis, but also providing a potential eco-friendly control strategy (RNAi-based biopesticides targeting essential miRNAs) for this notorious agricultural pest.

Abstract Background Osteosarcoma (OS) is a refractory malignancy. This study aimed to explore the roles and mechanisms of Inhibin subunit beta A (INHBA) in OS. Methods INHBA expression levels in OS tissues and cells were assessed using RT-qPCR and western blotting. The impact of INHBA silencing on OS development was then explored by transfecting the OS cell lines U2OS and MG63 with INHBA-small interfering RNA (siRNA). The influence of INHBA silencing on U2OS and MG63 cell proliferation, migration, and invasion was examined using MTT and Transwell assays. Epithelial–mesenchymal transition (EMT) markers (E-cadherin and N-cadherin) were analyzed by RT-qPCR. The expression of genes involved in cell proliferation, migration, invasion, and the TGF-β signaling pathway was evaluated by western blotting and RT-qPCR. Results INHBA levels were elevated in the OS tissues and cells. Furthermore, the transforming growth factor-β (TGF-β) signaling pathway of OS cells was suppressed in response to INHBA-siRNA, whereas proliferation, migration, and invasion of OS cells were inhibited. Besides, INHBA-siRNA significantly inhibited OS cell EMT, evidenced by enhanced E-cadherin mRNA expression and reduced N-cadherin mRNA expression. Further mechanistic studies revealed that the TGF-β1 agonist SRI-011381 hydrochloride increased OS cell proliferation, migration, and invasion after INHBA downregulation. Conclusion We found that INHBA silencing could play a vital role in OS via TGF-β1-regulated proliferation, migration, and invasion.

Abstract A new type of parallel operation unit for excavating and supporting anchors is proposed to address the issue of imbalanced excavation anchor ratio in coal mines. By equipping a straddle type anchoring drilling rig group, the synchronous parallel and fast operation mode for excavating and supporting anchors is achieved; Consider the problem of poor drilling stability of drill pipes in coal mines due to the coupling vibration between surrounding rock and anchoring equipment. Firstly, taking the multi drilling rig anchoring system as the research object, considering the influence of the equipment itself as an influencing factor on the vibration of the drill pipe, a dynamic model of the system is constructed using Lagrangian equations, and analytical solutions for the vibration displacement of each mass block are obtained; In order to more intuitively represent the vibration process of the drill pipe, Ansys is used to conduct modal analysis on the key components of the anchoring drilling rig system, and obtain the natural frequencies and vibration modes of each order of the key components; Using Adams to solve the rigid flexible coupling dynamic model of the anchoring drilling rig system, the vibration response laws of the drill pipe under different operating states were obtained. Secondly, Abaqus was used to simulate the drilling process of the drill pipe and obtain the vibration response law generated by the interaction between the drill pipe and the surrounding rock; The results indicate that the anchoring equipment has a greater impact on the vibration of the drill pipe, and the surrounding rock has a more stable impact on the vibration of the drill pipe. Due to the short body and large span structure of the anchoring system crossbeam expansion frame, the vibration response of the drill pipe is significantly greater than that of the retracted state of the drilling rig due to being in an unstable cantilever state when the drilling rig is extended. The theoretical reliability of the vibration response law of the drill pipe under different states has been further verified through drilling experiments of the anchoring system prototype. The relevant theories can provide a theoretical basis for the implementation of automatic anchoring technology in the anchoring system.

Abstract Background Reduced supplies of oxygen and nutrients caused by vascular injury lead to difficult-to-heal pressure ulcers (PU) in clinical practice. Rapid vascular repair in the skin wound is the key to the resolution of this challenge, but clinical measures are still limited. We described the beneficial effects of extracellular vesicle-derived silk fibroin nanoparticles (NPs) loaded with milk fat globule EGF factor 8 (MFGE8) on accelerating skin blood vessel and PU healing by targeting CD13 in the vascular endothelial cells (VECs). Methods CD13, the specific targeting protein of NGR, and MFGE8, an inhibitor of ferroptosis, were detected in VECs and PU tissues. Then, NPs were synthesized via silk fibroin, and MFGE8-coated NPs (NPs@MFGE8) were assembled via loading purified protein MFGE8 produced by Chinese hamster ovary cells. Lentivirus was used to over-express MFGE8 in VECs and obtained MFGE8-engineered extracellular vesicles (EVs-MFGE8) secreted by these VECs. The inhibitory effect of EVs-MFGE8 or NPs@MFGE8 on ferroptosis was detected in vitro. The NGR peptide cross-linked with NPs@MFGE8 was assembled into NGR-NPs@MFGE8. Collagen and silk fibroin were used to synthesize the silk fibroin/collagen hydrogel. After being loaded with NGR-NPs@MFGE8, silk fibroin/collagen hydrogel sustained-release carrier was synthesized to investigate the repair effect on PU in vivo. Results MFGE8 was decreased, and CD13 was increased in PU tissues. Similar to the effect of EVs-MFGE8 on inhibiting ferroptosis, NPs@MFGE8 could inhibit the mitochondrial autophagy-induced ferroptosis of VECs. Compared with the hydrogels loaded with NPs or NPs@MFGE8, the hydrogels loaded with NGR-NPs@MFGE8 consistently released NGR-NPs@MFGE8 targeting CD13 in VECs, thereby inhibiting mitochondrial autophagy and ferroptosis caused by hypoxia and accelerating wound healing effectively in rats. Conclusions The silk fibroin/collagen hydrogel sustained-release carrier loaded with NGR-NPs@MFGE8 was of great significance to use as a wound dressing to inhibit the ferroptosis of VECs by targeting CD13 in PU tissues, preventing PU formation and promoting wound healing. Graphical Abstract

Abstract Woven architectures are prepared by physical entanglement of fibrous components to expand one-dimensional material into two-dimensional sheets with enhanced strength and resilience to wear. Here, we capitalize on the elastic properties of long organic crystals with a high aspect ratio to prepare an array of centimeter-size woven network structures. While being robust to mechanical impact, the woven patches are also elastic due to effective stress dissipation by the elasticity of the individual warp and weft crystals. The thermal stability of component crystals translates into favorable thermoelastic properties of the porous woven structures, where the network remains elastic over a range of 300 K. By providing means for physical entanglement of organic crystals, the weaving circumvents the natural limitation of the small size of slender organic crystals that is determined by their natural growth, thereby expanding the prospects for applications of organic crystals from one-dimensional entities to expandable, two-dimensional robust structures.

Gastric carcinoma (GC) progression is mainly caused by local aggression and lymph node metastasis. However, some patients with early T-stage disease have lymph node metastasis, whereas some patients with late T-stage disease do not have lymph node metastasis, which indicates that invasion and metastasis are not always sequential in some GC patients. In the present study, the data of 101 GC cases were acquired from TCGA and divided into T-late-N-negative and T-early-N-positive groups according to pathological stages. A total of 338 genes were identified as differential genes between the T-late-N-negative and T-early-N-positive groups. GSEA showed that epithelial cell signaling in the Helicobacter pylori (HP) infection pathway was enriched in the T-early-N-positive group. MB staining indicated that the HP infection rate was 63% (39/62) in N-positive patients compared to 42% (16/38) in N-negative patients. To investigate the potential mechanism, we focused on the gene chemokine (C-X-C motif) receptor 2 (CXCR2), which was not only clustered in the gene set of epithelial cells signaling in the HP infection pathway but also significantly upregulated in T-early-N-positive GC by the analysis of the different genes based on the TCGA dataset. A meta-analysis showed that CXCR2 expression was positively correlated with N-stage but not with T-stage in GC. This study indicated that invasion and metastasis could be independent processes driven by different molecular mechanisms in some GC patients. HP infection was a potential factor that promoted lymph node metastasis by upregulating CXCR2 expression.

Summary: The gut must perform a dual role of protecting the host against toxins and pathogens while harboring mutualistic microbiota. Previous studies suggested that the NADPH oxidase Duox contributes to intestinal homeostasis in Drosophila by producing reactive oxygen species (ROS) in the gut that stimulate epithelial renewal. We find instead that the ROS generated by Duox in the Malpighian tubules leads to the production of Upd3, which enters the gut and stimulates stem cell proliferation. We describe in Drosophila the existence of a countercurrent flow system, which pushes tubule-derived Upd3 to the anterior part of the gut and stimulates epithelial renewal at a distance. Thus, our paper clarifies the role of Duox in gut homeostasis and describes the existence of retrograde fluid flow in the gut, collectively revealing a fascinating example of inter-organ communication.

IntroductionMacrophage-mediated inflammatory response may have crucial roles in the pathogenesis of a variety of human diseases. Growth differentiation factor 15 (GDF15) is a cytokine of the transforming growth factor-β superfamily, with potential anti-inflammatory activities. Previous studies observed in human lungs some macrophages which expressed a high level of GDF15.MethodsIn the present study, we employed multiple techniques, including immunofluorescence, flow cytometry, and single-cell RNA sequencing, in order to further clarify the identity of such GDF15high macrophages.ResultsWe demonstrated that macrophages derived from human peripheral blood mononuclear cells and rat bone marrow mononuclear cells by in vitro differentiation with granulocyte-macrophage colony stimulating factor contained a minor population (~1%) of GDF15high cells. GDF15high macrophages did not exhibit a typical M1 or M2 phenotype, but had a unique molecular signature as revealed by single-cell RNA sequencing. Functionally, the in vitro derived GDF15high macrophages were associated with reduced responsiveness to pro-inflammatory activation; furthermore, these GDF15high macrophages could inhibit the pro-inflammatory functions of other macrophages via a paracrine mechanism. We further confirmed that GDF15 per se was a key mediator of the anti-inflammatory effects of GDF15high macrophage. Also, we provided evidence showing that GDF15high macrophages were present in other macrophage-residing human tissues in addition to the lungs. Further scRNA-seq analysis in rat lung macrophages confirmed the presence of a GDF15high sub-population. However, these data indicated that GDF15high macrophages in the body were not a uniform population based on their molecular signatures. More importantly, as compared to the in vitro derived GDF15high macrophage, whether the tissue resident GDF15high counterpart is also associated with anti-inflammatory functions remains to be determined. We cannot exclude the possibility that the in vitro priming/induction protocol used in our study has a determinant role in inducing the anti-inflammatory phenotype in the resulting GDF15high macrophage cells.ConclusionIn summary, our results suggest that the GDF15high macrophage cells obtained by in vitro induction may represent a distinct cluster with intrinsic anti-inflammatory functions. The (patho)physiological importance of these cells in vivo warrants further investigation.

Abstract The multifaceted switches are part of our everyday life from the macroscopic to the molecular world. A molecular switch operating in the solution and in the crystalline state is very different. In this review, we summarize the state‐of‐the‐art of smart molecular crystal switches based on molecular martensites. These crystal switches respond to external stimuli and reversibly change between states, retaining their macroscopic integrity. The operation of the switches predominantly relies on temperature alterations or mechanical stress, with emerging methods based on photothermal effects, photoisomerization, and host‐guest chemistry. The capability of changing the molecular orientation and interaction in smart molecular crystal switches offers opportunities in several applications, including actuators, reversibly shaping structural materials, optoelectronic and magnetic materials, as well as switchable porous materials. Smart molecular crystal switches have vast potential in modern scientific and technological progress. The ongoing research shapes a rich landscape for innovation and future scientific exploration across diverse disciplines.

In recent years, a substantial body of research has demonstrated the close relationship between the built environment and urban nighttime vitality. While scholars have established slightly varied evaluation systems for the built environment, most have utilized the open-source nighttime light (NTL) data (2012 ∼ ) from the Visible Infrared Imaging Radiometer Suite (VIIRS) sensor on the Suomi National Polar-orbiting Partnership (NPP) Satellite to characterize nighttime vitality. However, with the release of the high spatial resolution NTL data from Glimmer Imager for Urbanization (GIU) sensor on the Sustainable Development Goals Satellite 1 (SDGSAT-1) by the Chinese Academy of Sciences (CAS), more options are now available for indicating nighttime vitality. Yet, no studies have so far measured the representational capability of this new NTL data. In this study, we selected Shanghai, one of the most urbanized cities in Asia, as our research area. We utilized both GIU NTL data and VIIRS NTL data to represent nighttime vitality and collected multidimensional geospatial big data as indicators of the built environment. Various regression models were employed to explore the differences in explanatory power when using different NTL data. To obtain more reliable conclusions, we have also divided the study area according to urban functional zone categories and conducted experiments on both the overall scale (entire study area) and local scale (different urban functional zones). The results showed that regression models using GIU NTL data had higher R2 values both at overall scale(0.529 > 0.268) and local scale (0.704 > 0.641, 0.701 > 0.408, 0.537 > 0.512, 0.674 > 0.589), indicating stronger explanatory power of GIU NTL data. Furthermore, we found that the use of GIU NTL data revealed an amplification effect, where the impact of certain representative built environment factors (such as road density, building height, and vegetation coverage) on nighttime vitality was magnified, demonstrating more pronounced spatial heterogeneity. Our study investigated the performance of the new open-source SDGSAT1/GIU NTL data in representing nighttime vitality and shows its potential application in research on the relationship between the built environment and nighttime vitality. Additionally, our study also reveals the differences in the impact of the built environment on nighttime vitality across different urban functional zones. All these results will provide more valuable references for city managers aspiring to enhance the nighttime vitality and help them to make more rational planning plans.

Introduction:Zeugodacus tau (Walker) is an invasive pest. An effective method to control this pest is the sterile insect technique (SIT). To better apply this technique, it is necessary to understand testis development progression.Methods: Differentially expressed genes (DEGs) during testis development were analyzed by PacBio Iso-Seq and RNA-seq.Results: RNA-Seq library of Z. tau testes on day 1, 6, and 11 post eclosion were constructed. We identified 755 and 865 differentially expressed genes in the comparisons of T6 (testes on day 6) vs. T1 and T11 vs. T1, respectively. The KEGG pathway analysis showed that the DEGs were significantly enriched in retinol metabolism, vitamin B6 metabolism, and ascorbate and aldarate metabolism pathways. Knockdown of retinol dehydrogenase 12-like (rdh12-like), pyridoxal kinase (pdxk) and regucalcin (rgn), the representative gene in each of the above 3 pathways, reduced the hatching rate of Z. tau offspring. In addition, we identified 107 Drosophila spermatogenesis-related orthologous genes in Z. tau, of which innexin 2 (inx2) exhibited significantly up-regulated expression throughout testis development, and the knockdown of this gene reduced offspring hatching rate. Discussion: Our data indicated that rdh12-like, pdxk, rgn, and inx2 genes were related to testis development, and they were conserved in tephritid species. These results suggested that this gene might have the same function in tephritid. The findings provide an insight into testis development and spermatogenesis in tephritid species.

A novel nanocomposite hydrogel with photothermal therapeutic properties, which could enhance the healing of surgical wounds, was developed. The composite comprises functionalized silica nanoparticles (FSNs) loaded with desferoxamine (DFO) as the core and a dexamethasone (Dex) filled hyaluronic acid–chitosan hydrogel (HA-CS) as the shell. Dex can effectively control inflammation at the wound site, and DFO is beneficial in proliferating the skin cells. The two drugs effectively promote wound healing at the surgical site. The aim of this approach is to demonstrate the hierarchical and continuous release of Dex and DFO from the FSNs@DFO-H@Dex system to reduce wound inflammation and promote healing. Furthermore, the controlled release of DFO can be achieved by controlling the near-infrared illumination. The composite nano hydrogel has a photothermal response, which accelerates wound healing by effectively reducing inflammation through the controlled release of drugs and regulating the immunological response of damaged skin tissue.

Summary: Background: Neoadjuvant chemoimmunotherapy has offered novel therapeutic options for patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Depicting the landscape of genomic and immune profiles is critical in predicting therapeutic responses. Methods: We integrated whole-exome sequencing, single-cell RNA sequencing, and immunofluorescence data of ESCC samples from 24 patients who received neoadjuvant treatment with PD-1 inhibitors plus paclitaxel and platinum-based chemotherapy to identify correlations with therapeutic responses. Findings: An elevation of small insertions and deletions was observed in responders. DNA mismatch repair (MMR) pathway alternations were highly frequent in patients with optimal responses and correlated with tumour infiltrating lymphocytes (TILs). Among the TILs in ESCC, dichotomous developing trajectories of B cells were identified, with one lineage differentiating towards LMO2+ germinal centre B cells and another lineage differentiating towards CD55+ memory B cells. While LMO2+ germinal centre B cells were enriched in responding tumours, CD55+ memory B cells were found to correlate with inferior responses to combination therapy, exhibiting immune-regulating features and impeding the cytotoxicity of CD8+ T cells. The comprehensive evaluation of transcriptomic B cell lineage features was validated to predict responses to immunotherapy in patients with cancer. Interpretation: This comprehensive evaluation of tumour MMR pathway alternations and intra-tumoural B cell features will help to improve the selection and management of patients with ESCC to receive neoadjuvant chemoimmunotherapy. Funding: National Science Foundation of China (82373371, 82330053), Eastern Scholar Program at Shanghai Institutions of Higher Learning, National Science and Technology Major Project of China (2023YFA1800204, 2020YFC2008402), and Science and Technology Commission of Shanghai Municipality (22ZR1410700, 20ZR1410800).

With the development and advancements of modern industry, the application of enhanced tubes is becoming more and more extensive in various engineering domains and technological applications. When water is used as the working fluid for thermal energy utilization, there is a large chance of accumulating a large amount of fouling on the surface of the enhanced tubes. This paper establishes a mathematical model of the local fouling deposition of calcium carbonate in enhanced tubes. The model is used to simulate and compare the local fouling characteristics of CaCO3 in different tubes. In addition, a study is conducted on the effects of different inlet flow rates, water temperature, and calcium carbonate concentrations on the local fouling resistance of bellows tubes. The results showed that the local fouling resistance (average) and local fouling resistance of enhanced tubes is smaller than that of circular tubes. Additionally, the bellows tubes yielded the best scale inhibition effect. The obtained local fouling resistance is also found to change periodically along the length of the tube. The local fouling resistance decrease with an increase in the inlet flow rate and wall temperature, and increases with an increase in the calcium carbonate solution concentration.

A new type of parallel operation unit for excavation, support and anchor is proposed to address the imbalance of excavation and anchor ratio in coal mines. It has high adaptability to the shape of tunnel sections, coal rock properties, and unevenness of roof and floor under complex geological conditions. By equipped with a multi posture new anchoring drilling rig system, the synchronous parallel and fast operation mode of excavation and anchor is achieved; Considering factors such as the spatial position relationship of anchor excavation operation, the shape and size of anchor section, and the influence of coupling vibration of anchor operation, a drilling vibration suppression device for anchor drilling rig system is proposed, which adopts a “sky to earth” stable support form to reduce the coupling vibration influence of adjacent systems during synchronous operation of anchor drilling rig group system; Considering that the anchor drilling rig group is composed of multi mass and multi degree of freedom systems, a vibration Transitive model diagram of the unit’s attitude changing operation state under complex terrain conditions is proposed. The finite element analysis software Abaqus is used to simulate the drilling conditions with different rock properties, and the analysis can obtain the change law of the drill pipe’s propulsion resistance under different coal seam conditions; In order to find out the variation law of the stiffness value of the key components of the anchoring drill system under the action of the vibration suppression device, the variation range of the stiffness value of the beam stretching out of different lengths and the cylinder outrigger stretching out/retracting state is solved based on the deformation coordination method in Strength of materials; Through the List of numerical-analysis software Matlab, the dynamic model of the above anchoring rig system is solved, and the vibration parameters of the rig group under different working conditions such as the extension of the left and right crossbeams and the extension and retraction of the outriggers are obtained. The analysis shows that the drilling rig outriggers have a very significant effect on reducing the lateral rolling vibration of the anchoring unit. By conducting prototype testing and analysis of the anchoring system, it is verified that the vibration suppression effect of the support legs of the anchoring drilling rig system meets the requirements. By improving the stability of the anchoring system, a certain theoretical basis can be provided for research on automatic anchoring positioning, drilling and hole forming quality, and other aspects.

To obtain healthy, low-sodium cured pork with good flavor, the processing optimization of the liquid smoke and baking was carried out through single factor experiment and orthogonal experiment in the present study. The effect of different amounts of smoking liquid, liquid smoking time, baking time and baking temperature on the yield, water activity, pH and color of low-sodium cured pork was investigated. Results showed that, the order affecting sensory quality of low-sodium cured pork was as follows: Baking temperature>baking time>smoking liquid amount>liquid smoking time. The optimized technological conditions of smoking and baking were as follows: The amount of smoking liquid was 4%, the time of liquid smoking was 150 min, the baking time was 28 h, the baking temperature was 50 ℃, and the sensory score of low-sodium cured pork under this processing technology was 37 points. The electronic tongue test was conducted to compare the taste of low-sodium cured pork with that of commercial cured pork. Results showed that the saltiness of low-sodium cured pork was significantly lower than that of commercial cured pork, and the bitterness and astringency were not significantly different from those of commercial cured pork.

Abstract High-efficiency rock breaking technology is an important problem to be solved urgently in deep mining. The existing auxiliary rock breaking technology for coal mine excavation has problems such as polluting coal, high requirements for tool materials, and difficulty in subsequent washing. In this paper, an active excitation cutting system for rotary cylinder of cantilever roadheader based on alternating valve is proposed. According to the classical calculation formula of cutting load of roadheader, considering the stiffness-damping characteristics of cutting part and cutting cylinder, the simulation algorithm of cutting load is compiled based on MATLAB simulation analysis software. The excitation cutting experiments of different cutting depths are carried out on the cutting test bench, and compared with the simulation algorithm of cutting load. Taking the cutting load as the discriminant index, the influence of oil supply pressure and excitation frequency of rotary cylinder on the cutting load is analyzed based on the simulation algorithm of cutting load. The results show that the error between the simulation results and the experimental results of the active excitation state is less than 12%, and the two are in good agreement. Under the condition of 30 HZ, when the excitation amplitude is 8 Mpa, 10 Mpa, 12 Mpa, 14 Mpa, when the rotary cylinder excitation amplitude is 10 Mpa, the minimum is 131.42 KN. Compared with the rotary cylinder excitation amplitude under the condition of 10 Mpa, when the excitation frequency is 30 HZ, 35 HZ, 40 HZ, 45 HZ, when the excitation frequency is 40 HZ, the minimum is 83.08 KN, indicating that changing the excitation amplitude or oil supply pressure of the rotary cylinder is helpful to adjust the cutting performance.

Visual SLAM technology is one of the important technologies for mobile robots. Existing feature-based visual SLAM techniques suffer from tracking and loop closure performance degradation in complex environments. We propose the DFD-SLAM system to ensure outstanding accuracy and robustness across diverse environments. Initially, building on the ORB-SLAM3 system, we replace the original feature extraction component with the HFNet network and introduce a frame rotation estimation method. This method determines the rotation angles between consecutive frames to select superior local descriptors. Furthermore, we utilize CNN-extracted global descriptors to replace the bag-of-words approach. Subsequently, we develop a precise removal strategy, combining semantic information from YOLOv8 to accurately eliminate dynamic feature points. In the TUM-VI dataset, DFD-SLAM shows an improvement over ORB-SLAM3 of 29.24% in the corridor sequences, 40.07% in the magistrale sequences, 28.75% in the room sequences, and 35.26% in the slides sequences. In the TUM-RGBD dataset, DFD-SLAM demonstrates a 91.57% improvement over ORB-SLAM3 in highly dynamic scenarios. This demonstrates the effectiveness of our approach.

Background: Cytokines modulate the glioma tumor microenvironment, influencing occurrence, progression, and treatment response. Strategic cytokine application may improve glioma immunotherapy outcomes. Gliomas remain refractory to standard therapeutic modalities, but immunotherapy shows promise given the integral immunomodulatory roles of cytokines. However, systematic evaluation of cytokine glioma immunotherapy research is absent. Bibliometric mapping of the research landscape, recognition of impactful contributions, and elucidation of evolutive trajectories and hot topics has yet to occur, potentially guiding future efforts. Here, we analyzed the structure, evolution, trends, and hotspots of the cytokine glioma immunotherapy research field, subsequently focusing on avenues for future investigation.Methods: This investigation conducted comprehensive bibliometric analyses on a corpus of 1529 English-language publications, from 1 January 2000, to 4 October 2023, extracted from the Web of Science database. The study employed tools including Microsoft Excel, Origin, VOSviewer, CiteSpace, and the Bibliometrix R package, to systematically assess trends in publication, contributions from various countries, institutions, authors, and journals, as well as to examine literature co-citation and keyword distributions within the domain of cytokines for glioma immunotherapy. The application of these methodologies facilitated a detailed exploration of the hotspots, the underlying knowledge structure, and the developments in the field of cytokines for glioma immunotherapy.Results: This bibliometric analysis revealed an exponential growth in annual publications, with the United States, China, and Germany as top contributors. Reviews constituted 17% and research articles 83% of total publications. Analysis of keywords like “interleukin-13,” “TGF-beta,” and “dendritic cells” indicated progression from foundational cytokine therapies to sophisticated understanding of the tumor microenvironment and immune dynamics. Key research avenues encompassed the tumor microenvironment, epidermal growth factor receptor, clinical trials, and interleukin pathways. This comprehensive quantitative mapping of the glioma immunotherapy cytokine literature provides valuable insights to advance future research and therapeutic development.Conclusion: This study has identified remaining knowledge gaps regarding the role of cytokines in glioma immunotherapy. Future research will likely focus on the tumor microenvironment, cancer vaccines, epidermal growth factor receptor, and interleukin-13 receptor alpha 2. Glioma immunotherapy development will continue through investigations into resistance mechanisms, microglia and macrophage biology, and interactions within the complex tumor microenvironment.

Abstract Natural articular cartilage is a typical self‐healing and superlubrication system capable of maintaining extremely low friction under physiological loadings. Cartilage wear and accidental trauma can cause irreversible defects to cartilage and subchondral bone with a significant decrease in intra‐articular lubrication, leading to the development of severe osteoarthritis and osteochondral defect. To address the important clinical problem of osteochondral defect, a bioinspired hard–soft (PEEK‐lubrication hydrogel) composite scaffold is designed and developed. The polymerization of polyethylene glycol diacrylamide (PEGDAA) and 2‐methacryloyloxyethyl phosphorylcholine (MPC) on polyetheretherketone (PEEK) substrate is achieved by UV initiation to form a strong interfacial bonding, and nano‐hydroxyapatite is deposited on porous PEEK substrate via polydopamine coating to improve osteogenic capability. Accordingly, the composite scaffold is successfully developed with lubrication and osteogenic activity. The tribological tests show that the lubrication performance of the composite scaffold is based on the hydration lubrication mechanism of the upper hydrogel layer, and the in vitro and in vivo experiments demonstrate that the composite scaffold is endowed with excellent biocompatibility and bioactivity. In conclusion, the bioinspired strategy for preparing a hard–soft composite scaffold shows a promising way in the treatment of osteochondral defect and provided a guideline for designing functional PEEK‐based biomaterials in tissue engineering scaffolds.

Ischemic stroke, the most prevalent and serious manifestation of cerebrovascular disease, is the main cause of neurological problems that require hospitalization, resulting in disability and death worldwide. Currently, clinical practice focuses on the effective management of blood lipids as a crucial approach to preventing and treating ischemic stroke. In recent years, a great breakthrough in ischemic stroke treatment has been witnessed with the emergence and use of a novel lipid-lowering medication, Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor. And its remarkable potential for reducing the occurrence of ischemic stroke is being acknowledged. This article aims to provide a comprehensive review, encompassing the association between PCSK9 and the heightened risk of ischemic stroke, the mechanisms, and the extensive evidence supporting the proven efficacy of PCSK9 inhibitors in clinical practice. Through this present study, we can gain deeper insights into the utilization and impact of PCSK9 inhibitors in treating ischemic stroke.

Background In China, on more than 100 weekends or holidays, only on-duty cardiologists are available during admissions. This study aimed to analyze the impact of admission time on major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI). Methods This prospective observational study enrolled patients with AMI between October 2018 and July 2019. The patients were assorted into off-hour (admitted on weekends or national holidays) and on-hour groups. The outcome was MACEs at admission and 1 year after discharge. Results A total of 485 patients with AMI were enrolled in this study. The occurrence of MACEs was significantly higher in the off-hour group compared with the on-hour group (P

This article describes the process of multidisciplinary team (MDT) discussion and comprehensive treatment of a case of advanced gastric cancer that tested positive for programmed death ligand 1 (PD-L1). During diagnosis, the patient presented with advanced gastric cancer and numerous unresectable metastases in the lesser omental lymph nodes, both lungs, liver, and left parietal occipital lobe. A meeting was arranged for the departments of oncology, gastrointestinal surgery, radiotherapy, imaging, and pathology to discuss the case. Initially, the patient had a partial response to the first-line treatment, which was a combination of pembrolizumab and chemotherapy. However, after nineteen months, the patient presented with a metachronous isolated lesion in the left frontal lobe. After mutual agreement among the oncology, brain surgery, gastrointestinal surgery, radiotherapy, imaging, and pathology departments, the intracranial lesion underwent resection. Following this, the operation was supplemented by stereotactic radiation therapy (SRT) and whole-brain radiation therapy (WBRT). The patient showed excellent signs of recovery after the operation, and her general condition remained favorable after 16 months of follow-up. Nonetheless, the outlook for patients facing advanced-stage gastric cancer remains distressing. Through multidisciplinary team (MDT) discussions, patients diagnosed with advanced gastric cancer can receive standardized diagnostic and treatment approaches to develop reasonable and personalized comprehensive treatment plans. Such plans help to improve the quality of life of patients and effectively prolong their survival time.

BackgroundElderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict overall survival (OS) and cancer-specific survival (CSS), assisting clinical decision-making.MethodsWe scrutinized data from the SEER database on 5,245 elderly patients diagnosed with high-grade glioma between 2000-2020, segmenting them into training (3,672) and validation (1,573) subsets. An additional external validation cohort was obtained from our institution. Prognostic determinants were pinpointed using Cox regression analyses, which facilitated the construction of the nomogram. The nomogram’s predictive precision for OS and CSS was gauged using calibration and ROC curves, the C-index, and decision curve analysis (DCA). Based on risk scores, patients were stratified into high or low-risk categories, and survival disparities were explored.ResultsUsing multivariate Cox regression, we identified several prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with high-grade gliomas, including age, tumor location, size, surgical technique, and therapies. Two digital nomograms were formulated anchored on these determinants. For OS, the C-index values in the training, internal, and external validation cohorts were 0.734, 0.729, and 0.701, respectively. We also derived AUC values for 3-, 6-, and 12-month periods. For CSS, the C-index values for the training and validation groups were 0.733 and 0.727, with analogous AUC metrics. The efficacy and clinical relevance of the nomograms were corroborated via ROC curves, calibration plots, and DCA for both cohorts.ConclusionOur investigation pinpointed pivotal risk factors in elderly glioma patients, leading to the development of an instrumental prognostic nomogram for OS and CSS. This instrument offers invaluable insights to optimize treatment strategies.

Background: The high incidence and severe clinical manifestations of phlebitis pose a complex and urgent clinical challenge. The rapid and simple establishment of animal phlebitis models and the development of preventive strategies are crucial to resolving this problem. Methods: In this study, we established such models by mixing vinorelbine ditartrate (VNR) and carbomer to form a sustained-release gel carrier, and then injected it around the veins rather than inside the vessels. Furthermore, we analyzed the efficacy of the carbomer/VNR gel in inducing phlebitis by monitoring the morphology of the veins using HE staining, immunohistochemical and immunofluorescence staining, and western blotting. Reactive oxygen species (ROS) and lipid peroxidation levels were determined using flow cytometry. Finally, we evaluated the inhibitory effect of N-acetylcysteine (NAC) on VNR-induced phlebitis in rabbits and rats. Results: Our findings suggested that the carbomer/VNR gel rapidly and easily induced phlebitis due to by retention of the gel in situ, wrapping the veins, and the prolonged release of VNR. NAC alleviated the VNR-induced oxidative stress response and expression of inflammatory cytokines by attenuating mitochondrial damage in venous endothelial cells, thereby preventing the occurrence of phlebitis in rabbits and rats. Conclusion: The in situ carbomer/VNR gel provides a rapid and simple method for establishing an animal model to study the pathogenesis of phlebitis. Furthermore, the observed therapeutic effect of NAC highlights its novel and efficacious role in preventing and treating phlebitis.

Abstract Background Pennisetum giganteum (AABB, 2n = 4x = 28) is a C4 plant in the genus Pennisetum with origin in Africa but currently also grown in Asia and America. It is a crucial forage and potential energy grass with significant advantages in yield, stress resistance, and environmental adaptation. However, the mechanisms underlying these advantageous traits remain largely unexplored. Here, we present a high-quality genome assembly of the allotetraploid P. giganteum aiming at providing insights into biomass accumulation. Results Our assembly has a genome size 2.03 Gb and contig N50 of 88.47 Mb that was further divided into A and B subgenomes. Genome evolution analysis revealed the evolutionary relationships across the Panicoideae subfamily lineages and identified numerous genome rearrangements that had occurred in P. giganteum. Comparative genomic analysis showed functional differentiation between the subgenomes. Transcriptome analysis found no subgenome dominance at the overall gene expression level; however, differentially expressed homoeologous genes and homoeolog-specific expressed genes between the two subgenomes were identified, suggesting that complementary effects between the A and B subgenomes contributed to biomass accumulation of P. giganteum. Besides, C4 photosynthesis-related genes were significantly expanded in P. giganteum and their sequences and expression patterns were highly conserved between the two subgenomes, implying that both subgenomes contributed greatly and almost equally to the highly efficient C4 photosynthesis in P. giganteum. We also identified key candidate genes in the C4 photosynthesis pathway that showed sustained high expression across all developmental stages of P. giganteum. Conclusions Our study provides important genomic resources for elucidating the genetic basis of advantageous traits in polyploid species, and facilitates further functional genomics research and genetic improvement of P. giganteum.

Abstract The performance of any engineering material is naturally limited by its structure, and while each material suffers from one or multiple shortcomings when considered for a particular application, these can be potentially circumvented by hybridization with other materials. By combining organic crystals with MXenes as thermal absorbers and charged polymers as adhesive counter-ionic components, we propose a simple access to flexible hybrid organic crystal materials that have the ability to mechanically respond to infrared light. The ensuing hybrid organic crystals are durable, respond fast, and can be cycled between straight and deformed state repeatedly without fatigue. The point of flexure and the curvature of the crystals can be precisely controlled by modulating the position, duration, and power of thermal excitation, and this control can be extended from individual hybrid crystals to motion of ordered two-dimensional arrays of such crystals. We also demonstrate that excitation can be achieved over very long distances (>3 m). The ability to control the shape with infrared light adds to the versatility in the anticipated applications of organic crystals, most immediately in their application as thermally controllable flexible optical waveguides for signal transmission in flexible organic electronics.

Abstract Background Stroke represents the second most prevalent contributor to global mortality. The Chinese Visceral Adiposity Index (CVAI) serves as an established metric for assessing visceral adiposity in the Chinese population, exhibiting prognostic capabilities. This investigation aimed to explore the association of CVAI and new-onset stroke among middle-aged and older Chinese populations. Methods The study employed data from the 2011 and 2018 China Health and Retirement Longitudinal Study (CHARLS) to assess the association of CVAI and the incidence of new-onset stroke. Utilizing a directed acyclic graph (DAG), 10 potential confounders were identified. Moreover, to explore the association between CVAI and new-onset stroke, three multifactor logistic regression models were constructed, accounting for the identified confounders and mitigating their influence on the findings. Results The study comprised 7070 participants, among whom 417 (5.9%) experienced new-onset strokes. After controlling for confounding variables, regression analysis suggested that the new-onset stroke’s highest risk was linked to the fourth quartile (Q4) of the CVAI, with an odds ratio (OR) of 2.33 and a 95% confidence interval (CI) of 1.67–3.28. The decision tree analysis demonstrated a heightened probability of new-onset stroke among hypertensive individuals with a CVAI equal to or greater than 83, coupled with a C-reactive protein level no less than 1.1 mg/l. Age seemed to have a moderating influence on the CVAI and new-onset stroke association, exhibiting a more prominent interaction effect in participants under 60 years. Conclusions In middle-aged and older Chinese populations, a linear relationship was discerned between CVAI and the probability of new-onset stroke. CVAI provides a predictive framework for stroke incidence in this demographic, laying the groundwork for more sophisticated risk prediction models that improve the precision and specificity of stroke risk evaluations.

Abstract Aims To investigate the mechanism of exosomes' role in the transformation of MDS to AML. Methods Exosomes in culture supernatants of MDS and AML cell lines, were extracted by ultrafiltration and identified in three ways: morphology, size, and exosome protein surface markers. Exosomes from AML cell lines were then co-cultured with MDS cell lines and their impacts on MDS cell microenvironment, proliferation, differentiation, cell cycle, and apoptosis were analyzed by CCK-8 assay and flow cytometry. Furthermore, exosomes from MSC were extracted for further authentication. Results The transmission electron microscopy, nanoparticle tracking analysis, Western blotting, and flow cytometry methods all verify that ultrafiltration is a reliable method to extract exosomes in the culture medium. Exosomes from AML cell lines inhibit the proliferation of MDS cell lines, block cell cycle progression, and promote apoptosis and cell differentiation. It also leads to increased secretion of tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) in MDS cell lines. In addition, MSC-derived exosomes were found to inhibit the proliferation of MDS cell lines, arrest cell cycle progression, promote apoptosis, and inhibit differentiation. Conclusion Ultrafiltration is a proper methodology in extracting exosomes. The exosomes of AML origin and MSC origin may play a role in MDS leukemia transformation via targeting TNF-α/ROS-Caspase3 pathway.

Abstract Background To assess the effectiveness of China's medicine and health care reform in promoting equity in health care utilization among rural residents, it is necessary to analyze temporal trends in equity in health care utilization among rural residents in China. This study is the first to assess horizontal inequity trends in health care utilization among rural Chinese residents from 2010 to 2018 and provides evidence for improving government health policies. Methods Longitudinal data obtained from China Family Panel Studies from 2010 to 2018 were used to determine trends in outpatient and inpatient utilization. Concentration index, concentration curve, and horizontal inequity index were calculated to measure inequalities. Decomposition analysis was applied to measure the contribution of need and non-need factors to the unfairness. Results From 2010 to 2018, outpatient utilization among rural residents increased by 35.10%, while inpatient utilization increased by 80.68%. Concentration indices for health care utilization were negative in all years. In 2012, there was an increase in the concentration index for outpatient utilization (CI = -0.0219). The concentration index for inpatient utilization decreased from -0.0478 in 2010 to -0.0888 in 2018. Except for outpatient utilization in 2012 (HI = 0.0214), horizontal inequity indices for outpatient utilization were negative in all years. The horizontal inequity index for inpatient utilization was highest in 2010 (HI = -0.0068) and lowest in 2018 (HI = -0.0303). The contribution of need factors to the inequity exceeded 50% in all years. Conclusions Between 2010 and 2018, low-income groups in rural China used more health services. This seemingly pro-poor income-related inequality was due in large part to the greater health care need among low-income groups. Government policies aimed at increasing access to health services, particularly primary health care had helped to make health care utilization in rural China more equitable. It is necessary to design better health policies for disadvantaged groups to reduce future inequities in the use of health services by rural populations.

Abstract YOLOv5 is one of the most popular object detection algorithms, which is divided into multiple series according to the control of network depth and width. To realize the deployment of mobile devices or embedded devices, the paper proposes a lightweight aerial image object detection algorithm (LAI-YOLOv5s) based on the improvement of YOLOv5s with a relatively small amount of calculation and parameter and relatively fast reasoning speed. Firstly, to better detect small objects, the paper replaces the minimum detection head with the maximum detection head and proposes a new feature fusion method, DFM-CPFN(Deep Feature Map Cross Path Fusion Network), to enrich the semantic information of deep features. Secondly, the paper designs a new module based on VoVNet to improve the feature extraction ability of the backbone network. Finally, based on the idea of ShuffleNetV2, the paper makes the network more lightweight without affecting detection accuracy. Based on the VisDrone2019 dataset, the detection accuracy of LAI-YOLOv5s on the mAP@0.5 index is 8.3% higher than that of the original algorithm. Compared with other series of YOLOv5 and YOLOv3 algorithms, LAI-YOLOv5s has the advantages of low computational cost and high detection accuracy.

Abstract We aimed to compare the relationship between hypertension and obesity-related anthropometric indices (waist circumference [WC], waist-height ratio, waist-hip ratio [WHR], and body mass index; unconventional: new body shape index [ABSI] and body roundness index [BRI]) to identify best predictors of new-onset hypertension. The study included 4123 adult participants (2377 women). Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using a Cox regression model to estimate the risk of new-onset hypertension with respect to each obesity index. In addition, we assessed the predictive value of each obesity index for new-onset hypertension using area under the receiver operating characteristic curve (AUC) after adjusting for common risk factors. During the median follow-up of 2.59 years, 818 (19.8%) new hypertension cases were diagnosed. The non-traditional obesity indices BRI and ABSI had predictive value for new-onset hypertension; however, they were not better than the traditional indexes. WHR was the best predictor of new-onset hypertension in women aged ≤ 60 and > 60 years, with HRs of 2.38 and 2.51 and AUCs of 0.793 and 0.716. However, WHR (HR 2.28, AUC = 0.759) and WC (HR 3.24, AUC = 0.788) were the best indexes for predicting new-onset hypertension in men aged ≤ 60 and > 60 years, respectively.

Gold-plated substrate is widely used in sintering with silver paste because of its high conductivity, stability, and corrosion resistance. However, due to massive interdiffusion between Ag and Au atoms, it is challenging for sintered Ag-Au joints to maintain high reliability. In order to study the effect of grain structure of gold plating layer on the environmental reliability of sintered Ag-Au joints, we prepared four substrates with different gold structures. In addition to the original gold structure (Au substrate), other gold structures were obtained by heat treatment at temperatures of 150 °C (Au-150 substrate), 250 °C (Au-250 substrate), and 350 °C (Au-350 substrate) for 1 h. Compared with the other three gold substrates, the sinter jointed on the Au-350 substrate obtained the highest shear strength. By analyzing the grain structure of the gold plating layer, it is found that the average grain size of the Au-350 substrate is the largest, and the proportion of low-angle grain boundaries is less. Few grain boundaries have a positive impact on inhibiting the excessive diffusion of Ag atoms and improving the bonding performance of the joint. Based on the above study, we further evaluated the environmental reliability of sintered joints. In 150 °C high-thermal storage, the interdiffusion of Ag and Au in the sintered joint on the Au-350 substrate was restricted, retaining stronger bonding until 200 h. In a hygrothermal environment of 85 °C/85% RH, the shear strength of the sintered Ag-Au joint with the Au-350 substrate maintained above 40.2 MPa during 100 h aging. The results indicated that the sintered Ag-Au joint on the Au-350 substrate with the largest grain size has superior high thermal reliability and hygrothermal reliability.

The development of high-performance rubber composites has always been a research hotspot in the field of conveyor belt manufacturing. In this work, a rubber cover joint composite made of reduced graphene oxide (rGO) was prepared using latex mixing and mechanical blending methods, with a steel wire rope conveyor belt as the research object, and the influence of the rGO content on the properties of the rubber composite is discussed. The structure and morphology characterization of the rGO/NR rubber show that the addition of rGO does not change its crystal structure, and 1.2 phr rGO is uniformly dispersed throughout the rubber composite. As more rGO is added, the mechanical properties of the rGO rubber cover joint first improve and then worsen. With the addition of 1.2 phr, the cross-linking density increases by 80.6%, the tensile strength of the rubber composites increases by 49.7%, the elongation at break increases by 23.6%, and the adhesion strength increases by 12.4%. The tensile strength of the rGO rubber cover joint can still maintain 72.5% of its pre-thermal aging value. The wear resistance and thermal conductivity increase as more phr is added. When 3.0 phr is added, the wear resistance of the rubber composites increases by 32.9%, the thermal conductivity increases by 118.8%, and the temperature difference at the completion of vulcanization decreases from 4.5 °C to 1.8 °C. The results show that when 1.2 phr of rGO is added, the rubber conveyor belt joint obtains the best comprehensive performance. These enhanced comprehensive properties allow for the practical application of rGO nanomaterials to conveyor belt rubber.