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Abstract Background Clear cell renal cell carcinoma (ccRCC) remains one of the most lethal urological malignancies even though a great number of improvements in diagnosis and management have achieved over the past few decades. Accumulated evidence revealed that histone deacetylases (HDACs) play vital role in cell proliferation, differentiation and apoptosis. Nevertheless, the biological functions of histone deacetylation modification related genes in ccRCC remains poorly understood. Method Bulk transcriptomic data and clinical information of ccRCC patients were obtained from the TCGA database and collected from the Chinese PLA General Hospital. A total of 36 histone deacetylation genes were selected and studied in our research. Univariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, random forest (RF) analysis, and protein-protein interaction (PPI) network analysis were applied to identify key genes affecting the prognosis of ccRCC. The ‘oncoPredict’ algorithm was utilized for drug-sensitive analysis. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the potential biological function. The ssGSEA algorithm was used for tumor immune microenvironment analysis. The expression levels of HDAC10 were validated by RT-PCR and immunohistochemistry (IHC). 5-ethynyl-2′-deoxyuridine (EdU assay), CCK-8 assay, cell transwell migration and invasion assay and colony formation assay were performed to detect the proliferation and invasion ability of ccRCC cells. A nomogram incorporating HDAC10 and clinicopathological characteristics was established to predict the prognosis of ccRCC patients. Result Two machine learning algorithms and PPI analysis identified four histone deacetylation genes that have a significant association with the prognosis of ccRCC, with HDAC10 being the key gene among them. HDAC10 is highly expressed in ccRCC and its high expression is associated with poor prognosis for ccRCC patients. Pathway enrichment and the experiments of EdU staining, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay demonstrated that HDAC10 mediated the proliferation and metastasis of ccRCC cells and involved in reshaping the tumor microenvironment (TME) of ccRCC. A clinically reliable prognostic predictive model was established by incorporating HDAC10 and other clinicopathological characteristics ( https://nomogramhdac10.shinyapps.io/HDAC10_Nomogram/ ). Conclusion Our study found the increased expression of HDAC10 was closely associated with poor prognosis of ccRCC patients. HDAC10 showed a pro-tumorigenic effect on ccRCC and promote the proliferation and metastasis of ccRCC, which may provide new light on targeted therapy for ccRCC.

Background and objective: Robot-assisted radical prostatectomy (RARP) is widely used because of the many advantages of a robotic approach. The da Vinci Si robot is one of the most commonly used surgical robot systems, but it may be associated with higher costs owing to the use of consumable surgical supplies. Our aim was to conduct a preliminary investigation of the capability of the MP1000 system for RARP. Methods: In this prospective, multicentre, single-blinded study, we randomly assigned 42 patients scheduled to undergo RARP between April and September 2021 to a da Vinci Si group (control) or an MP1000 group (intervention). Patients underwent RARP performed using the assigned robotic system and were followed up at 3-mo intervals. The primary outcome was the rate of conversion to open/laparoscopic surgery. Secondary outcomes were installation and operation times, intraoperative blood loss, postoperative surgical margin status, hospital stay, incontinence, complications, safety indicators, and surgeon ergonomics. Key findings and limitations: All procedures were successfully completed without conversion to open/laparascopic surgery or major complications. Secondary outcomes, including oncological and ergonomic indicators, did not differ significantly between the groups over the study period. One patient in the control group experienced dysuria (Clavien-Dindo grade 3). No patients had incontinence at 3 mo. A limitation of the study is the small sample size. Conclusions and clinical implications: RARP with the MP1000 system is feasible, safe, and effective in the management of localised prostate cancer. Patient summary: We assessed the effectiveness and safety of the new MP1000 robot system for robot-assisted removal of the prostate in comparison to the da Vinci Si robot. We found no difference in effectiveness or safety among 42 patients with prostate cancer who were assigned randomly to one of the two systems. We conclude that the MP1000 is a suitable robot for this surgery.

In this paper, the effects of hot isostatic pressing (HIP) and heat treatment (HT) on the stress rupture properties of nickel-based superalloy K417G were investigated. Scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM) were employed to analyze the microstructure, fracture morphology, determination of crack source and dislocation evolution after stress rupture fracture. The results indicate that, HIP specimens demonstrate a 19.5% reduction in stress rupture life compared to as-cast specimens, whereas HIP + HT specimens exhibit a 41% increase in stress rupture life, reaching a value of 63.04 h. The fracture mechanism of the samples under different heat treatment conditions is different. There are a large number of pores in the as-cast specimen, which leads to the initiation and propagation of cracks and eventually result in fracture. The pores in the HIP specimen are almost eliminated. However, the coarsening and uneven distribution of γ′ phase led to the weakening of the hindrance to dislocation movement. Additionally, the increase in elongated carbides at grain boundaries accelerates crack initiation and propagation. Under HIP and HT, the cubic γ′ phase is uniformly precipitated, which effectively hinders the movement of dislocation lines. Granular M23C6 carbides precipitate at grain boundaries, acting as pinning points to retard grain boundary sliding and crack propagation, thus improving the stress rupture life.

Abstract CO2 hydrogenation to chemicals and fuels is a significant approach for achieving carbon neutrality. It is essential to rationally design the chemical structure and catalytic active sites towards the development of efficient catalysts. Here we show a Ce-CuZn catalyst with enriched Cu/Zn-OV-Ce active sites fabricated through the atomic-level substitution of Cu and Zn into Ce-MOF precursor. The Ce-CuZn catalyst exhibits a high methanol selectivity of 71.1% and a space-time yield of methanol up to 400.3 g·kgcat −1·h−1 with excellent stability for 170 h at 260 °C, comparable to that of the state-of-the-art CuZnAl catalysts. Controlled experiments and DFT calculations confirm that the incorporation of Cu and Zn into CeO2 with abundant oxygen vacancies can facilitate H2 dissociation energetically and thus improve CO2 hydrogenation over the Ce-CuZn catalyst via formate intermediates. This work offers an atomic-level design strategy for constructing efficient multi-metal catalysts for methanol synthesis through precise control of active sites.

Abstract Background Cisplatin (CDDP)-based chemotherapy is a standard first-line treatment for metastatic bladder cancer (BCa) patients, and chemoresistance remains a major challenge in clinical practice. Circular RNAs (circRNAs) have emerged as essential regulators in carcinogenesis and cancer progression. However, the role of circRNAs in mediating CDDP chemosensitivity has yet to be well elucidated in BCa. Methods CircSTX6 (hsa_circ_0007905) was identified by mining the public circRNA datasets and verified by Sanger sequencing, agarose gel electrophoresis, RNase R treatment and qRT-PCR assays. Then, function experiments were performed to evaluate the effects of circSTX6 on BCa metastasis. Luciferase reporter assay, RNA pull-down, RNA immunoprecipitation (RIP), RNA stability assay, Fluorescence in situ hybridization (FISH) and Immunofluorescence (IF) were conducted to evaluate the interaction among circSTX6, miR-515-3p, PABPC1 and SUZ12. Animal experiments were performed to explore the function of circSTX6 in tumor metastasis and CDDP sensitivity. Results We identified that circSTX6 was significantly upregulated in clinical samples and cells of BCa. Functionally, circSTX6 promoted cell migration and invasion both in vitro and in vivo. Mechanistically, circSTX6 could act as a miR-515-3p sponge and abolish its effect on SUZ12. Moreover, circSTX6 was confirmed to increase the stability of SUZ12 mRNA by interacting with a mRNA stabilizer PABPC1 and subsequently promote the expression of SUZ12. Importantly, silencing of circSTX6 improved the chemosensitivity of CDDP-resistant bladder cancer cells to CDDP. Furthermore, in vivo analysis supported that knockdown of circSTX6 attenuated CDDP resistance in BCa tumors. Conclusion These studies demonstrate that circSTX6 plays a pivotal role in BCa metastasis and chemoresistance, and has potential to serve as a therapeutic target for treatment of BCa.

Monitoring shear deformation of sliding zones is of great significance for understanding the landslide evolution mechanism, in which fiber optic strain sensing has shown great potential. However, the correlation between strain measurements of quasi-distributed fiber Bragg grating (FBG) sensing arrays and shear displacements of surrounding soil remains elusive. In this study, a direct shear model test was conducted to simulate the shear deformation of sliding zones, in which the soil internal deformation was captured using FBG strain sensors and the soil surface deformation was measured by particle image velocimetry (PIV). The test results show that there were two main slip surfaces and two secondary ones, developing a spindle-shaped shear band in the soil. The formation of the shear band was successfully captured by FBG sensors. A sinusoidal model was proposed to describe the fiber optic cable deformation behavior. On this basis, the shear displacements and shear band widths were calculated by using strain measurements. This work provides important insight into the deduction of soil shear deformation using soil-embedded FBG strain sensors.

The treatment of diabetic wounds is a major challenge faced by the medical system, and there is a growing interest in developing innovative therapies to accelerate wound healing. Regenerative medicine with cells has shown promising potential in skin repair, with the regenerative properties primarily attributed to the paracrine effects of secreted products, including exosomes. Compared to cell-based approaches, using exosomes as a cell-free therapy for chronic wounds has several advantages. Exosomes can regulate intercellular communication by releasing their contents, including mRNA, miRNA, lipids, and proteins, which further promote wound healing. Exosomes are well explored in biomedical application owing to their advantages such as their biocompatibility and low immunogenicity. However, the common method of exosome administration is through injection, but due to their rapid clearance rate in the body, maintaining the necessary therapeutic concentration around the wound is challenging. Therefore, it is necessary to develop a new biocompatible scaffold as a carrier for extracellular vesicles, allowing them to sustain the therapeutic concentration at chronic non-healing wound sites and continuously promote wound healing. Engineered exosomes are kinds of exosomes modified with internal treated molecules, surface decoration or delivered through engineered platform. In addition, some researchers have further processed and modified exosomes, known as engineered exosomes, with internal treated molecules, surface decoration, or delivery through engineered platforms. Compared to regular exosomes, engineered exosomes have greater advantages in promoting wound healing. In this review, we summarize the molecular mechanisms of exosomes from different sources with varying modifications in wound healing. Advantages and limitations of different engineered exosomes for chronic wound repair were also discussed. Finally, we highlight the challenges and future development directions for translating our knowledge of engineered exosomes into clinical practice.

Abstract As synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. Towards this mission, novel regulatory mechanisms and genetic circuits with unprecedented complexity have been implemented over the past decade. These regulatory mechanisms, such as transcription and translation control, could be integrated into hybrid circuits termed “multi-level circuits”. The multi-level circuit design will tremendously benefit the current genetic circuit design paradigm, from modifying basic circuit dynamics to facilitating real-world applications, unleashing our capabilities to customize cellular signal processing and address global challenges through synthetic biology.

Abstract Complex metal nanoparticles distributed uniformly on supports demonstrate distinctive physicochemical properties and thus attract a wide attention for applications. The commonly used wet chemistry methods display limitations to achieve the nanoparticle structure design and uniform dispersion simultaneously. Solid-phase synthesis serves as an interesting strategy which can achieve the fabrication of complex metal nanoparticles on supports. Herein, the solid-phase synthesis strategy is developed to precisely synthesize uniformly distributed CoFe@FeOx core@shell nanoparticles. Fe atoms are preferentially exsolved from CoFe alloy bulk to the surface and then be carburized into a FexC shell under thermal syngas atmosphere, subsequently the formed FexC shell is passivated by air, obtaining CoFe@FeOx with a CoFe alloy core and a FeOx shell. This strategy is universal for the synthesis of MFe@FeOx (M = Co, Ni, Mn). The CoFe@FeOx exhibits bifunctional effect on regulating polysulfides as the separator coating layer for Li-S and Na-S batteries. This method could be developed into solid-phase synthetic systems to construct well distributed complex metal nanoparticles.

Abstract Cannulated screw fixation is essential in treating femoral neck fractures, and the widely used freehand technique has several limitations. Therefore, we designed a new laser-positioning and navigation system and compared its efficacy with that of the traditional freehand technique in the cannulated screw fixation of femoral neck fractures. This randomized controlled single-blind trial recruited patients with femoral neck fracture, who were treated using either the newly designed laser-navigation device or the freehand technique. In in-vitro experiments, using the femoral neck model, the laser group was better than the freehand group in terms of operation time (P = 0.0153) and radiation exposure time (P

The operating environment of large mechanical equipment on ships is extremely harsh. Under such harsh conditions, it is necessary to effectively monitor and assess the health status of machinery and equipment and to take appropriate maintenance measures to ensure the normal operation of the ship and the safety of the lives and property of the crew. However, currently used methods are less effective in detecting non-ferromagnetic abrasive particles and non-metallic contaminants and may not be able to respond to certain emergencies promptly. Therefore, in this paper, a quad-solenoid coil multi-contaminant oil detection sensor is proposed to detect metallic abrasive particles and non-metallic contaminants using the voltage–capacitance dual mode. We provide an analytical expression for the magnetic field strength of the present sensor and develop a corresponding mathematical model. In order to verify its accuracy, we compared the model results with finite element analysis and verified them experimentally. Analysis of the experimental results shows that by switching the detection mode of the sensor, ferromagnetic metal particles, non-ferromagnetic metal particles, and non-metallic contaminants in the oil can be identified according to the different experimental signal curves. The sensor recognizes ferromagnetic particles over 70 μm in diameter, non-ferromagnetic particles over 220 μm in diameter, water droplets over 100–110 μm in diameter, and air bubbles over 180–190 μm in diameter. By comparing the sensor with existing sensors, the sensor can provide accurate information about various pollutants, help maintenance personnel to develop a reasonable maintenance program, and reduce the maintenance cost of ship machinery.

This research was to examine the impacts of long-term integrated rice–crayfish farming on soil nutrients, carbon pools, and rice yields in paddy fields. The aim was to establish a scientific basis for the sustainable development of RS in the northern region of Zhejiang. The results showed that the change from rice monoculture (CK) to rice–crayfish coculture systems (RS) led to a 24.99% increase in the 5-year average of soil ammonium nitrogen (AN), while the soil nitrate nitrogen (NN), available potassium (AK), and available phosphorus content (AP) decreased by 28.02%, 16.05%, and 28.76%, respectively. Moreover, the total organic carbon (TOC), easily oxidizable organic carbon (EOC), dissolved organic carbon (DOC), and microbial biomass carbon (MBC) exhibited a reduction of 2.45%, 8.82%, 35.31%, and 65.84%, respectively. Correlation analysis revealed a significant positive correlation between NN, EOC, and MBC in the RS mode. In terms of rice yield, the 5-year average of rice yield in RS decreased by 8.40% compared to CK. The mean yield of early-maturing rice varieties was reduced by 13.16%, while that of late-maturing rice varieties was reduced by 6.00%. These results shed light on the annual variation in soil nutrients, carbon pools, and rice yield in the RS mode, providing insights for the sustainable development of RS in northern Zhejiang.

In the conversion process of syngas-to-C2 species, the OH species are inevitably produced accompanying the production of key intermediates CHx (x = 1–3), traditionally, the function of surface OH species is generally accepted as the hydrogenating reactive species. This work for the first time proposed and confirmed the assisted catalytic mechanism of surface OH species that performed as the promoter for syngas-to-C2 species on Cu-based catalysts. DFT and microkinetic modeling results reveal that the produced OH species accompanying the intermediates CHx production on the MCu (M = Co, Fe, Rh) catalysts can stably exist to form OH/MCu catalysts, on which the presence of surface OH species as the promoter not only presented better activity and selectivity toward CHx (x = 1–3) compared to MCu catalysts, but also significantly suppressed CH3OH production, providing enough CHx sources to favor the production of C2 hydrocarbons and oxygenates. Correspondingly, the electronic properties analysis revealed the essential relationship between the electronic feature of OH/MCu catalysts and catalytic performance, attributing to the unique electronic micro−environment of the catalysts under the interaction of surface OH species. This new mechanism is called as OH-assisted catalytic mechanism, which may be applied in the reaction systems related to the generation of OH species.

IntroductionPlatelet indices (PIs) are hematological parameters that indicate the number, morphology, and activation of platelets. Although some clinical trials suggest an association between PIs and the risk of stroke, the lack of robust evidence is attributed to confounding effects and reverse causation.ObjectiveThis study aimed to evaluate the association between PIs and stroke risk through Mendelian randomization (MR) while exploring the mediating effect of blood pressure in this association.MethodsWe identified genetic variants associated with PIs, including platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet crit (PCT), in the UK Biobank (n = 350,474). Relevant genome-wide association studies were utilized to gather summary statistics pertaining to the traits of interest. We primarily used the inverse-variance weighted analysis to obtain estimates for individual causal power.ResultWe observed a positive correlation between genetically predicted increases in PCT levels with the stroke onset [PCT: OR (95%CI) = 1.113(1.047, 1.183), p

ABSTRACTBackground Non-responsiveness is a major barrier in current cancer immune checkpoint blockade therapies, and the mechanism has not been elucidated yet. Therefore, it is necessary to discover the mechanism and biomarkers of tumor immunotherapeutic resistance.Methods Bioinformatics analysis was performed based on CD8+ T cell infiltration in multiple tumor databases to screen out genes related to anti-tumor immunity. Associations between Regulator of G-protein signaling 1 (RGS1) and IFNγ-STAT1 signaling, and MHCI antigen presentation pathway were examined by RT-qPCR, western blotting, and flow cytometry. The modulatory mechanisms of RGS1 were investigated via CHIP-qPCR and dual-luciferase assay. The clinical and therapeutic implications of RGS1 were comprehensively investigated using tumor cell lines, mouse models, and clinical samples receiving immunotherapy.Results RGS1 was identified as the highest gene positively correlated with immunogenicity among RGS family. Inhibition of RGS1 in neoplastic cells dampened anti-tumor immune response and elicited resistance to immunotherapy in both renal and lung murine subcutaneous tumors. Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Clinically, lower expression level of RGS1 was associated with resistance of PD1 inhibition therapy and shortened progression-free survival among 21 NSCLC patients receiving immunotherapy.Conclusions Together, these findings uncover a novel mechanism that elicits immunotherapy resistance and highlight the function of tumor-intrinsic RGS1, which brings new insights for future strategies to sensitize anti-PD1 immunotherapy.

The specific mechanism of clear cell renal cell carcinoma (ccRCC) progression, a pathological type that accounts for the highest proportion of RCC, remains unclear. In this study, bioinformatics analysis of scRNA-seq dataset in ccRCC revealed that MIOX was a gene specifically down-regulated in tumor epithelial cells of ccRCC. Analysis of the TCGA database further validated the association between decreased MIOX mRNA levels and ccRCC malignant phenotype and poor prognosis. Immunohistochemistry indicated the down-regulation of MIOX in ccRCC tissues compared to paired adjacent renal tissues, with further down-regulation of MIOX in the primary tumors of patients with primary metastasis compared to those without metastasis. Also, patients with low expression of MIOX showed shorter metastasis-free survival (MFS) compared to those with high MIOX expression. In vitro results showed that overexpression of MIOX in ccRCC cells inhibited the proliferation, migration and invasion and promoted apoptosis. Mechanistically, up-regulation of MIOX inhibited autophagy to elevate the levels of ROS, and thus suppressed STAT3/c-Myc-mediated epithelial-mesenchymal transition in ccRCC cells. In vivo data further confirmed that increased MIOX expression suppressed the growth and proliferation of RCC cells and reduced the ability of RCC cells to form metastases in the lung. This study demonstrates that MIOX is an important regulatory molecule of ccRCC, which is conducive to understanding the potential molecular mechanism of ccRCC progression.

InP, which exhibits attractive physical characteristics, such as high electron mobility, high conductivity, and high bandgap width, has always been fanatically pursued in high frequency and high speed devices in recent years. However, the inherent high density defects hinder the quality of the epitaxial layer and, even worse, impede the device’s life. Here, we found a kind of defect in the distributed feedback laser layers on an InP based substrate. A focused ion beam was employed in order to dissect the defect. The formation process was characterized using a transmission electron microscope and a high-resolution transmission electron microscope. Closer analysis reveals that defects form a subsurface damage layer between the substrate and the epitaxial layer. The subsurface damage layer already has a potentially destructive lattice, including lots of dislocations and lattice distortions, which leads to anisotropy in the interface layer. As the epitaxial film thickness increases, so does this strain relax, and dislocations form.

Abstract The Warburg effect‐related metabolic dysfunction of the tricarboxylic acid (TCA) cycle has emerged as a hallmark of various solid tumors, particularly renal cell carcinoma (RCC). RCC is characterized by high immune infiltration and thus recommended for immunotherapeutic interventions at an advanced stage in clinical guidelines. Nevertheless, limited benefits of immunotherapy have prompted investigations into underlying mechanisms, leading to the proposal of metabolic dysregulation‐induced immunoevasion as a crucial contributor. In this study, a significant decrease is found in the abundance of alpha‐ketoglutarate (αKG), a crucial intermediate metabolite in the TCA cycle, which is correlated with higher grades and a worse prognosis in clinical RCC samples. Elevated levels of αKG promote major histocompatibility complex‐I (MHC‐I) antigen processing and presentation, as well as the expression of β2‐microglobulin (B2M). While αKG modulates broad‐spectrum demethylation activities of histone, the transcriptional upregulation of B2M is dependent on the demethylation of H3K4me1 in its promoter region. Furthermore, the combination of αKG supplementation and PD‐1 blockade leads to improved therapeutic efficacy and prolongs survival in murine models when compared to monotherapy. Overall, the findings elucidate the mechanisms of immune evasion in anti‐tumor immunotherapies and suggest a potential combinatorial treatment strategy in RCC.

Abstract Background This study aimed to explore the appropriate location of renal tumors for retroperitoneal approach. Materials and Methods We retrospectively analyzed 1040 patients with renal tumor who were treated at our institution from Janurary 2015 to June 2020 and had underwent retroperitoneal robotic assisted-laparoscopic partial nephrectomy (rRAPN). Clinical features and postoperative outcomes were evaluated. Results Patients with incomplete data were excluded, and we included 896 patients in total. The median tumor size was 3.0 (range: 0.8–10.0) cm. The median RENAL Nephrometry Score was 7 (range: 4–11), and the median PADUA Nephrometry Score was 8 (range: 6–14). The median surgical time was 120 min, and the median warm ischemia time was 18 min. The median estimated blood loss was 50 ml. The follow-up time was 20.2 (range: 12–69) months. The mean change of eGFR 1 year after operation was 14.6% ± 19.0% compared with preoperative estimated glomerular filtration rate (eGFR). When compared the tumor at different locations, as superior or inferior pole, anterior of posterior face of kidney, there were no significant differences of intra- and post-operative outcomes such as surgical time, warm ischemia time, estimated blood loss, removal time of drainage tube and catheter, postoperative feeding time and hospital stay, and changes of eGFR one year after surgery. We also compared tumors at special locations as endophytic or exophytic, anterior of posterior hilus of kidney, there were no significant differences in surgical time, warm ischemia time, estimated blood loss and changes of eGFR. There was no significant difference in intraoperative features and postoperative outcomes when tumor larger than 4 cm was located at different positions of kidney. Though the surgical time was longer when BMI ≥ 28 (132.6 min vs. 122.5 min, p = 0.004), no significant differences were observed in warm ischemia time, estimated blood loss, changes in eGFR. Twenty-seven patients (3.0%) had tumor progression, including 8 (0.9%) recurrence, 19 (2.1%) metastasis, and 9 (1.0%) death. Conclusion Retroperitoneal approach for RAPN has confirmed acceptable intra- and postoperative outcomes and suits for renal tumors of all different locations. Large tumor size and obesity are not contraindications for rRAPN.

Developing highly efficient catalysts for selective oxidation of benzene to phenol with low H2O2 consumption remains challenging. Here the authors report a highly active and selective non-noble metal catalyst for selective oxidation of benzene to phenol with low H2O2 addition via regulating the electron configuration of single-atom Cu catalyst.

Abstract Vibration compensation in track displacement monitoring is explored by using rail image feature points. The key point is to compare the image of the rail to be tested with the image of the standard rail. A downstream section of Metro Line A is selected for real time analysis of image. The sampling frequency of the detection system is 0.5m/point, and the driving speed of the detection vehicle is about 40km/h, take the distance of 100m between K23+000‐K22+900 of kilometer mark, total 200 points, and analyze the image data by grey scale conversion concept. In order to verify the accuracy of the vibration compensation data, one point is taken at an interval of 5m, and a total of 20 points are measured, and compare and analyze with dynamic real‐time detection data. After vibration compensation, the geometric parameters of the contact rail are closer to the expected value, and the maximum error can be controlled within ±3mm. Using biomedical image‐based processing concept to realize the track displacement monitoring method, which meets the requirements of non‐contact measurement, and the degree of automation is high, it can be monitored and alarmed in real time, and it has a good application prospect.

Abstract Background Intramedullary nail (IMN) is one of the key essential minimally invasive “weapons” in orthopaedic trauma, while the distal locking is still challenging for surgeons. Although there are various inventions and technologies to improve the locking procedure, there are still problems such as inaccurate positioning, excessive radiation exposure, low first success rate and long learning curve. Therefore, a new laser guiding navigation device was designed and compared with the traditional freehand (FH) technique in the distal locking of femoral IMN. Methods This randomized controlled single-blind trial recruited patients with femoral diaphyseal fracture. The self-designed laser navigation device (laser group) and freehand technique (FH group) were used in the distal locking of the IMNs. The patients enrolled were randomized into FH group and laser group, all operations were performed by two surgeons of the same level. The differences between the two groups were compared in terms of radiation exposure time, operative time, first success rate, blood loss, visual analogue score (VAS), Harris score and healing time. Results 32 patients ended the study period and 16 patients in each group. The results showed that the laser group was better than the FH group in terms of distal locking time (10(9/11) vs 19.5 (17.25/21) min, Z = 4.83, P

Abstract Background Open reduction and internal fixation have been frequently applied for displaced midshaft clavicular fracture. Plate and screw fixation of clavicular fractures could provide rigid fixation and rotational control. Proper implant positioning in surgical fixation is critical to prevent iatrogenic complications. Fluoroscopy plays an important role in the intraoperative evaluation of implants. This study aimed to introduce a new fluoroscopic projection to evaluate the positioning of plates and screws. Methods Adult patients with a diagnosis of acute displaced midshaft clavicular fracture were included in this study. The slope angle of the midshaft clavicle was measured on sagittal reconstructions of preoperative computed tomography (CT) scans. The incidence of screw revision based on intraoperative standard posteroanterior (PA) and PA 25° cephalic skyline projections was compared. The interobserver agreement for the two projections was calculated. Results Twenty-nine patients with midshaft clavicular fractures were enrolled from January 2020 to June 2021. The PA 25° skyline projection could clearly display the tangential line of the plate and inferior border of the clavicle. The slope angle on the superior surface of the midshaft clavicle was 26.0 ± 5.8° (range: 18.5–38.3°). The incidence of screw revision using the PA projection (72.4%) was significantly different from that using the PA 25° skyline projection (34.5%) (P

Biosensors are analytical devices that utilize biological sensing elements, such as enzymes, antibodies, nucleic acids, or cells, to detect a given analyte [...]

C2H2 semi-hydrogenation has been widely applied in industry to eliminate trace C2H2 from C2H4 feed. C2H2 semi-hydrogenation to C2H4 on a series of the newly designed catalysts, graphdiyne (GDY) as a new carbon allotrope supported different sizes of PdxMy clusters (PdxMy/GDY, M = Cu, Ag, Au, Ni; x+y = 1–3), were studied using DFT calculations. The results found that C2H2 semi-hydrogenation to C2H4 on PdxMy/GDY catalysts exhibits that both the activity and selectivity greatly depend on the composition and size of PdxMy/GDY catalysts. Surprisingly, our results for the first time discovered the Pd1/GDY catalyst with GDY supported the single atom Pd that presents the best selectivity and activity toward C2H4 formation compared to the previously reported catalysts so far in C2H2 semi-hydrogenation. This study would provide a theoretical clue for designing and screening out the potential catalysts with GDY supported small sizes of PdxMy and other metal clusters in C2H2 hydrogenation.

In type II CRISPR systems, the guide RNA (gRNA) comprises a CRISPR RNA (crRNA) and a hybridized trans-acting CRISPR RNA (tracrRNA), both being essential in guided DNA targeting functions. Here the authors investigate the programmability of crRNA-tracrRNA hybridization for Cas9 and apply this to biosensing.

Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

The lytic replication of bacteriophage P1 requires RepL expression and the lytic stage origin, oriL, which is postulated to be located within repL gene sequence. The exact sequence of P1 oriL and the mechanism(s) of RepL-mediated DNA replication, however, are not fully understood. By using repL gene expression to induce DNA replication of a gfp and a rfp reporter plasmids, we demonstrated that synonymous base substitution in an adenine/thymidine-rich region of repL gene sequence, termed AT2, significantly inhibited the RepL-mediated signal amplification. Contrastingly, mutations in an IHF and two DnaA binding sites did not affect the RepL-mediated signal amplification significantly. A truncated repL sequence with the AT2 region allowed RepL-mediated signal amplification in trans therefore verifying a significant role of the AT2 region in RepL-mediated DNA replication. A combination of repL gene expression and a non-protein-coding copy of repL gene sequence (termed nc-repL) was able to amplify the output of an arsenic biosensor. Furthermore, mutation(s) at single or multiple positions within the AT2 region produced varying levels of RepL-mediated signal amplification. Overall, our results provide novel insights into the identity and location of P1 oriL as well as demonstrating the potential of using repL constructs to amplify and modulate the output of genetic biosensors.

Summary Synthetic biology offers new tools and capabilities of engineering cells with desired functions for example as new biosensing platforms leveraging engineered microbes. In the last two decades, bacterial cells have been programmed to sense and respond to various input cues for versatile purposes including environmental monitoring, disease diagnosis and adaptive biomanufacturing. Despite demonstrated proof‐of‐concept success in the laboratory, the real‐world applications of microbial sensors have been restricted due to certain technical and societal limitations. Yet, most limitations can be addressed by new technological developments in synthetic biology such as circuit design, biocontainment and machine learning. Here, we summarize the latest advances in synthetic biology and discuss how they could accelerate the development, enhance the performance and address the present limitations of microbial sensors to facilitate their use in the field. We view that programmable living sensors are promising sensing platforms to achieve sustainable, affordable and easy‐to‐use on‐site detection in diverse settings.

Abstract Higher magnetic fields are always favoured in the magnetoplasmadynamic thruster (MPDT) due to its superior control of the plasma profile and acceleration process. This paper introduces the world's first integrated study on the 150 kW level AF-MPDT equipped with a superconductive coil. A completely new way of using superconducting magnet technology to confine plasma with high energy and extremely high temperatures is proposed. Using the PIC method of microscopic particle simulation, the plasma magnetic nozzle effect and performance of the MPDT under different magnetic-field conditions were studied. The integrated experiment used demonstrated that, in conjunction with the superconducting coil, greater homogeneity and a stronger magnetic field not only caused more even cathode ablation and improved its lifespan but also improved the performance of the MPDT (maximum thrust was 4 N at 150 kW, 0.56 T). Maximum thrust efficiency reached 76.6% and the specific impulse reached 5714 s.

Recent studies have revealed that chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) promotes tumor progression and modulates tumor immunity by regulating programmed death-ligand 1 stability; however, its intrinsic functions and regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain poorly understood. Here, we show that CMTM6 is upregulated in ccRCC tissues and is strongly associated with advanced tumor grades, early metastases, and a worse prognosis. CMTM6 depletion significantly impaired the proliferation, migration, and invasion of ccRCC cells in vitro and in xenograft mouse models in vivo. In addition, targeting CMTM6 promotes anti-tumor immunity, represented by increased infiltration of CD4+ and CD8+ T cells in syngeneic graft mouse models. Further research revealed that loss of CMTM6 triggered aberrant activation of DNA damage response, resulting in micronucleus formation and G2/M checkpoint arrest, finally leading to cellular senescence with robust upregulation of numerous chemokines and cytokines. Our findings show for the first time the novel role of CMTM6 in maintaining cancer genome stability and facilitating tumor-mediated immunosuppression, linking DNA damage signaling to the secretion of inflammatory factors. Targeting CMTM6 may improve the treatment of patients with advanced ccRCC.

In this work, we investigate the effect of hot isostatic pressing on the intermediate temperature tensile property of nickel-base single crystal superalloy. The experimental results indicate that the hot isostatic pressing improves the intermediate temperature plasticity of single crystal superalloy from 6.4% to 9.3%, but the yield strength remains unchanged. In addition, the fracture surface is changed by hot isostatic pressing, the microporosities disappear in the fracture surface under hot isostatic pressing, and an initial crack is formed from the region of plenty of stacked slip planar instead of microcracks by microporosities. The mechanism of the improvement of plasticity and the change of fracture behavior is explored in detail. The application of hot isostatic pressing reduces the size and volume faction of microporosities, which makes it difficult for the crack initiation and propagation, and further leads to the improvement of plasticity.

Ferredoxin 1 (FDX1), an iron-sulphur protein, is responsible for electron transfer in a range of metabolic redox reactions. Clear cell renal cell carcinoma (ccRCC) is an aggressive cancer characterised by metabolic reprogramming, and FDX1 is a critical regulator of cuproptosis. However, the expression profile and prognostic value of FDX1 associated with clinicopathological features in ccRCC remain largely unelucidated. In this study, we integrated a series of public bioinformatic analysis to explore the mRNA and protein profiles of FDX1 across human cancers and cell lines and validated its expression and prognostic value, especially in ccRCC. In this study, FDX1 mRNA and protein expression were aberrantly downregulated and associated with ccRCC grade, stage, and nodal metastasis, whereas in adjacent non-tumour kidney tissue, it was abundantly expressed and cytoplasmically localised in renal tubular epithelial cells. Multivariate analysis indicated that low FDX1 expression contributed to unfavourable overall and disease-free survival. The functional enrichment of FDX1 co-expressed genes in ccRCC involved mainly mitochondrial dysfunction in various metabolic processes and biological oxidation, besides iron-sulphur cluster biogenesis. Furthermore, FDX1 modulates immunological infiltration to affect prognosis. Thus, FDX1 downregulation is mechanistically because of ccRCC tumourigenesis and is a promising prognostic biomarker to stratify patients with ccRCC.

Background: A minimal decrease in renal function in partial nephrectomy is an important clinical and experimental research objective. We compared the effect of intermittent hilar occlusion (IHO) and continuous hilar occlusion (CHO) on kidney injury and oxidative damage. Method: Using CHO or IHO for 24, 30, and 45 min, intraoperative ischaemia, as well as a sham group, were set up in an ischaemia-reperfusion long-term survival mouse model. Renal function, pathological injury, subcellular structure injury, and cell apoptosis were evaluated at 1, 30, and 90 d postoperatively to study the protective effect of IHO. To do so, oxidative damage analysis, antioxidant activities, and ischaemia time dose-response curves on relative acute renal function injury were analysed. Results: All parameters indicated that kidney injury was dramatically attenuated in the IHO groups compared to those in the corresponding CHO groups. Particularly, mice in the IHO 24-min group incurred no tubular injury or renal functional injury; mice in the CHO 30-min group incurred severe acute and chronic kidney injury, but mice in the IHO 30-min group only experienced transient mild renal functional injury. IHO prolonged tolerable ischaemia duration. Conclusions: IHO can prolong the duration of tolerable ischaemia, at least partly through protecting the kidney from oxidative stress, consequently attenuating or preventing renal ischaemia-reperfusion injury. Reduced kidney injury after ischaemia-reperfusion is linked to a greater maintenance of antioxidant activity and less oxidative damage. The protective effect of IHO can be extremely efficient if properly applied; IHO may avoid renal ischaemia-reperfusion injury during partial nephrectomy.

PurposeTo evaluate the impact of histological subtype on the survival of patients with renal cell carcinoma (RCC) and tumor thrombus (TT).Patients and methodsWe retrospectively analyzed 350 patients with RCC and TT admitted to Chinese People’s Liberation Army General Hospital between January 2006 and June 2021. The patients underwent radical nephrectomy and thrombectomy using robot-assisted laparoscopic, laparoscopic, or open surgery. The clinical and pathological parameters of the patients were taken from their medical records. Survival was calculated with the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic significance of variables on overall survival (OS) and progression-free survival (PFS).ResultsTT levels 0–IV were observed in 132 (37.71%), 43 (12.29%), 134 (38.29%), 20 (5.71) and 21 (6.00%) patients, respectively. Papillary (pRCC), clear cell, and other histological subtypes of RCC were detected in 28 (8.00%), 286 (81.71%), and 36 (10.29%) patients, respectively. Compared to the clear cell cohort, collecting systemic invasion (46.43 vs. 25.17%; p = 0.030) and lymph node metastasis (39.29 vs. 11.54%; p < 0.01) were more common in the pRCC cohort. Kaplan–Meier analyses showed that patients with pRCC and other subtypes had significantly worse OS and PFS compared to patients with the clear cell subtype (p < 0.05). Multivariate analyses revealed that histology was independently associated with reduced OS and PFS, including among patients without lymph node and distant metastasis (N0M0).ConclusionPapillary or other subtypes have a considerably shorter OS and PFS compared to clear cell subtype in RCC patients with TT. Strict follow-up and surveillance should be performed for papillary or other subtypes RCC with TT.

ObjectiveBoth bone forearm fractures are common in children and rare in adults. The main surgical treatment is open reduction and internal fixation (ORIF) with plate, while the hybrid fixation of elastic-stable intramedullary nailing (ESIN) and the plate has been rarely reported before.Case reportWe report a case of a 29-year-old male patient with both bone forearm fractures. Temporarily closed reduction and plaster external fixation were performed in the emergency room, and the patient was admitted to the orthopedic trauma ward for surgery. The patient underwent open reduction and plate fixation of the ulna and closed reduction and ESIN fixation of the radius. The fractures healing was satisfactory and the internal fixation was removed 12 months postoperatively.ConclusionThe hybrid fixation of ESIN and plate is an effective option for both bone forearm fractures in adults.

L-3-n-butylphthalide (NBP), which is used for treatment of mild and moderate acute ischemic stroke, exerts its effects by modulating the Nrf2 pathway. However, it has not been established whether NBP exerts its preventive effects in high-risk ischemic stroke patients through the Nrf2 pathway. We investigated whether NBP exerts its preventive effects through the Nrf2 pathway in long-term NBP pretreated dMCAO mice models. Nrf2+/+ wild-type and Nrf2−/− knockout mice were randomized into the vehicle group (equal volume vegetable oil), NBP-low-dose group (20 mg/kg) and NBP-high-dose group (60 mg/kg). The drug was administered once daily by gavage for a month. Then, a permanent distal middle cerebral artery occlusion model (dMCAO) was established after pretreatment with NBP. Neurological deficits, cerebral infarct volumes, brain water contents, activities of SOD, GSH-Px and MDA levels were determined. Further, axonal injury and demyelination, expression levels of Nrf2, HO-1 and NQO1 in ischemic brains were determined. Long-term NBP pretreatment significantly improved neurological functions, reduced cerebral infarction volumes, reduced brain water contents, increased SOD, GSH-Px activities, decreased MDA contents, reduced neurological injuries, axonal damage as well as demyelination, while increasing Nrf2, HO-1 and NQO1 mRNA as well as protein expressions in dMCAO mice models.

Split inteins are powerful tools for designing synthetic split proteins. Here the authors use a mini-Mu transposon screen to map split sites, enabling the development of protein-based logic gates and fine control of protein activity.

Abstract The relationship between air temperature and the hospital admission of adult patients with community-acquired pneumonia (CAP) was analyzed. The hospitalization data pertaining to adult CAP patients (age ≥ 18 years) in two tertiary comprehensive hospitals in Baotou, Inner Mongolia Autonomous Region, China from 2014 to 2018 and meteorological data there in the corresponding period were collected. The exposure–response relationship between the daily average temperature and the hospital admission of adult CAP patients was quantified by using a distributed lag non-linear model. A total of 4466 cases of adult patients with CAP were admitted. After eliminating some confounding factors such as relative humidity, wind speed, air pressure, long-term trend, and seasonal trend, a lower temperature was found to be associated with a higher risk of adult CAP. Compared to 21 °C, lower temperature range of 4 to –12 °C was associated with a greater number of CAP hospitalizations among those aged ≥ 65 years, and the highest relative risk (RR) was 2.80 (95% CI 1.15–6.80) at a temperature of − 10 °C. For those

Herpes simplex virus type 1 (HSV-1) is a ubiquitous and important human pathogen capable of causing significant clinical diseases ranging from skin damage to encephalitis, particularly in immunocompromised and neonatal hosts. Currently, widely used nucleoside analogs, including acyclovir and penciclovir, have some limitations in their use due to side effects and drug resistance. Herein, we report sophoridine's (SRI) dramatic inhibition of HSV-1 replication in vitro. SRI exhibited a remarkable inhibitory influence on HSV-1 virus-induced cytopathic effect and plaque formation, as well as on progeny viruses in Vero and HeLa cells, with selection indexes (SI) of 38.96 and 22.62, respectively. Moreover, SRI also considerably suppressed HSV-1 replication by hindering the expression of viral immediate-early (ICP0 and ICP22), early (ICP8 and TK), and late (gB and gD) genes and the expression of viral proteins ICP0, gB, and gD. We suggest that SRI can directly inactivate viral particles and block some stages in the life cycle of HSV-1 after adsorption. Further experiments showed that SRI downregulated the cellular PI3K/Akt signaling pathway and obstructed HSV-1 replication even more. Most importantly, SRI markedly repressed HSV-1-induced p38 MAPK pathway activation. Collectively, this natural bioactive alkaloid could be a promising therapeutic candidate against HSV-1 via the modulation of cellular PI3K/Akt and p38 MAPK pathways.

The randomized controlled study investigated the impacts of immediate peri-operative Intermittent pneumatic compression (IPC) on hemodynamic indicators in patients undergoing laparoscopic gynecologic surgery. Patients scheduled for elective laparoscopic gynecologic surgery were randomized to control (IPC not used), pre-operative IPC, post-operative IPC, and peri-operative IPC (performed both before and after surgery) groups. Systolic blood pressure (SBP), mean blood pressure (MBP) cardiac output (CO), heart rate (HR) and systemic vascular resistance (SVR) were measured at different time points. The results showed that SBP changes not obviously over time in the control and peri-operative IPC group. Compared with values before surgery, the pre-operative IPC group had a lower SBP (P

Here, we screened the COL4A1 variants in Chinese intracerebral hemorrhage (ICH) patients to summarize the relationship between the variants and clinical characteristics. Targeted sequencing of a 65-gene panel including COL4A1 was performed to detect all the coding regions and ±10-bp splicing sites. In total, 568 patients were included. Regarding rare nonsynonymous variants with a minor allele frequency (MAF) 5%, we did not find a significant association between the allele or genotype distribution of the SNP loci and the risk of ICH. Rs3742207 was nominally associated with death at 1-year follow-up (p = 0.02027, OR 1.857, 95% CI 1.101-3.133) after adjusted by age, hypertension history, hematoma volume and recurrent ICH history. Nevertheless, after the Bonferroni correction, the association was no longer significant. In conclusion, rare nonsynonymous variants in COL4A1 were identified in 1.94% (11/568) of Chinese ICH patients, while rs3742207 maybe indicate a worse prognosis of ICH.

Background Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI.Methods We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography.Results Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p

This paper presents a novel approach to microbubble technology for the treatment of aquatic invasive organisms in ship ballast water. The microbubbles are produced by hydrodynamic cavitation with a sudden and dramatic water pressure drop. The air and ozone microbubbles, respectively, verified the bioavailability of ship ballast water treatment using marine microalgae as an indicator. Besides the effects of an ozone injection dose, the morphological changes of cells and the effluent toxicity were investigated. Compared with the ozone microbubble treatment, the inactivation of marine microalgae by air microbubbles required a long treatment time. In the storage experiment, it was found that air microbubbles did not inhibit the growth of microalgae cells, and that the injection of active matter such as ozone was still necessary to ensure the validity of biological invasion. However, even with very low doses of ozone, the inactivation effect of ozone microbubbles was still very evident. Overall, it helps to minimize the use of active matter to reduce the toxicity of treated water, and this has the capability to develop into an environmentally acceptable and practical ballast water treatment technology.

(1) Background: For completely lower pole renal tumors, we compared the perioperative outcomes of robotic partial nephrectomy via transperitoneal and retroperitoneal approaches. (2) Methods: Complete lower pole renal tumors were defined as tumors that received 1 point for the “L” element of the R.E.N.A.L. and located at the lower pole of kidney. After confirming consistency in baseline characteristics, oncological and functional benefits were compared. Pentafecta achievement was used to represent the perioperative optimal outcome, followed by multivariate analysis of factors associated with the lack of pentafecta achievement. (3) Results: Among 151 patients identified, 116 (77%) underwent robotic partial nephrectomy via a transperitoneal approach and 35 (23%) via a retroperitoneal approach. Patients undergoing transperitoneal robotic partial nephrectomy experienced more blood loss than those undergoing retroperitoneal robotic partial nephrectomy (50 mL vs. 40 mL, p = 0.015). No significant differences were identified for operative time (120 min vs. 120 min), ischemia time (19 min vs. 20 min), positive surgical margins (0.0% vs. 2.86%), postoperative rate of complication (12.07% vs. 5.71%). No significant differences were identified in pathologic variables, eGFR decline in postoperative 12-month (3.9% vs. 5.4%) functional follow-up. Multivariate cox analysis showed that tumor size (OR: 0.523; 95% CI: 0.371–0.736; p < 0.001) alone was independently correlated to the achievement of pentafecta. (4) Conclusions: For completely lower pole renal tumors, transperitoneal and retroperitoneal robotic partial nephrectomy provide similar outcomes. These two surgical approaches remain feasible options for these cases.

Decoy binding sites are natural regulators of gene expression. Here the authors design synthetic DNA sponges that fine tune the performance of synthetic gene circuits in a simple yet systematic manner, expanding the synthetic biology toolkit for gene regulation.