Search

Achieving high surface quality is vital for improving the reflectivity of aluminum alloy optical components. However, aluminum alloy materials often have large-sized grain structures, and stress accumulates at the grain boundaries during ultraprecision machining processes, resulting in raised grain boundaries and a decrease in surface quality. In this work, we utilized a multiple high energy shot peening (SP) technique to refine the surface grain structure of Al–Mg–Si alloy. The results revealed that a gradient grain structure was formed within the depth range of 0∼150 μm, accompanied by the occurrence of various substructures such as dislocations, stack faults, and low-angle grain boundaries in the severely deformed layer. This led to a significant 30% increase in hardness. Furthermore, the shot peened sample exhibited remarkable ultraprecision machinability. A comparison with the sample that has not undergone SP treatment revealed a decrease in surface roughness from 2.5 nm to 1.4 nm. The improved surface quality can be attributed to the higher deformation uniformity and reduced grain rotation. Our study provided an innovative and cost-effective method for manufacturing large-sized metal optical components.

Abstract Introduction Social network strategies, in which social networks are utilized to influence individuals or communities, are increasingly being used to deliver human immunodeficiency virus (HIV) interventions to key populations. We summarized and critically assessed existing research on the effectiveness of social network strategies in promoting HIV self‐testing (HIVST). Methods Using search terms related to social network interventions and HIVST, we searched five databases for trials published between 1st January 2010 and 30th June 2023. Outcomes included uptake of HIV testing, HIV prevalence and linkage to antiretroviral therapy (ART) or HIV care. We used network meta‐analysis to assess the uptake of HIV testing through social network strategies compared with control methods. A pairwise meta‐analysis of studies with a comparison arm that reported outcomes was performed to assess relative risks (RR) and their corresponding 95% confidence intervals (CI). Results Among the 4496 manuscripts identified, 39 studies fulfilled the inclusion criteria, including one quasi‐experimental study, 22 randomized controlled trials and 16 observational studies. Networks HIVST testing was organized by peers (distributed to known peers, 15 studies), partners (distributed to their sexual partners, 16 studies) and peer educators (distributed to unknown peers, 8 studies). Among social networks, simulating the possibilities of ranking position, peer distribution had the highest uptake of HIV testing (84% probability), followed by partner distribution (80% probability) and peer educator distribution (74% probability). Pairwise meta‐analysis showed that peer distribution (RR 2.29, 95% CI 1.54−3.39, 5 studies) and partner distribution (RR 1.76, 95% CI 1.50−2.07, 10 studies) also increased the probability of detecting HIV reactivity during testing within the key population when compared to the control. Discussion All of the three social network distribution strategies enhanced the uptake of HIV testing compared to standard facility‐based testing. Linkage to ART or HIV care remained comparable to facility‐based testing across the three HIVST distribution strategies. Conclusions Network‐based HIVST distribution is considered effective in augmenting HIV testing rates and reaching marginalized populations compared to facility‐based testing. These strategies can be integrated with the existing HIV care services, to fill the testing gap among key populations globally. PROSPERO Number CRD42022361782

BackgroundThe rising prevalence of herpes simplex type 2 (HSV-2) infection poses a growing global public health challenge. A comprehensive understanding of its epidemiology and burden disparities in China is crucial for informing targeted and effective intervention strategies in the future.MethodsWe followed Cochrane and PRISMA guidelines for a systematic review and included publications published in Chinese and English bibliographic systems until March 31st, 2024. We synthesized HSV-2 seroprevalence data across different population types. We used random-effects models for meta-analyses and conducted meta-regression to assess the association between population characteristics and seroprevalence.ResultsOverall, 23,999 articles were identified, and 402 publications (1,203,362 participants) that reported the overall seroprevalence rates (858 stratified measures) were included. Pooled HSV-2 seroprevalence among the general population (lower risk) was 7.7% (95% CI: 6.8-8.7%). Compared to the general population, there is a higher risk of HSV-2 prevalence among intermediate-risk populations (14.8%, 95% CI: 11.0-19.1%), and key populations (31.7%, 95% CI: 27.4-36.1%). Female sexual workers (FSWs) have the highest HSV-2 risk (ARR:1.69, 95% CI: 1.61-1.78). We found northeastern regions had a higher HSV-2 seroprevalence than other regions (17.0%, 95% CI: 4.3-35.6%, ARR: 1.38, 95% CI: 1.26-1.50, Northern China as the reference group). This highlighted the disparity by population risk levels and regions. We also found lower HSV-2 prevalence estimates in publications in Chinese bibliographic databases than those in English databases among key populations (such as MSM and HIV-discordant populations).ConclusionThere is a gradient increase in HSV-2 prevalence risk stratification. We also identified region, population, and age disparities and heterogeneities by publication language in the HSV-2 burden. This study provides guidance for future HSV-2 prevention to eliminate disparities of HSV-2 infection and reduce overall HSV-2 burden.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=408108, identifier CRD42023408108.

Abstract Exosomes play a crucial role in intercellular communication and can be used as biomarkers for diagnostic and therapeutic clinical applications. However, systematic studies in cancer-associated exosomal nucleic acids remain a big challenge. Here, we developed ExMdb, a comprehensive database of exosomal nucleic acid biomarkers and disease-gene associations curated from published literature and high-throughput datasets. We performed a comprehensive curation of exosome properties including 4,586 experimentally supported gene-disease associations, 13,768 diagnostic and therapeutic biomarkers, and 312,049 nucleic acid subcellular locations. To characterize expression variation of exosomal molecules and identify causal factors of complex diseases, we have also collected 164 high-throughput datasets, including bulk and single-cell RNA sequencing (scRNA-seq) data. Based on these datasets, we performed various bioinformatics and statistical analyses to support our conclusions and advance our knowledge of exosome biology. Collectively, our dataset will serve as an essential resource for investigating the regulatory mechanisms of complex diseases and improving the development of diagnostic and therapeutic biomarkers.

Abstract Background Patients with epithelial ovarian carcinoma (EOC) are usually diagnosed at an advanced stage with tumour cell invasion. However, identifying the underlying molecular mechanisms and biomarkers of EOC proliferation and invasion remains challenging. Results Herein, we explored the relationship between tumour microenvironment (TME) reprogramming and tissue invasion based on single-cell RNA sequencing (scRNA-seq) datasets. Interestingly, hypoxia, oxidative phosphorylation (OXPHOS) and glycolysis, which have biologically active trajectories during epithelial mesenchymal transition (EMT), were positively correlated. Moreover, energy metabolism and anti-apoptotic activity were found to be critical contributors to intratumor heterogeneity. In addition, HMGA1, EGR1 and RUNX1 were found to be critical drivers of the EMT process in EOC. Experimental validation revealed that suppressing EGR1 expression inhibited tumour cell invasion, significantly upregulated the expression of E-cadherin and decreased the expression of N-cadherin. In cell components analysis, cancer-associated fibroblasts (CAFs) were found to significantly contribute to immune infiltration and tumour invasion, and the accumulation of CAFs was associated with poorer patient survival. Conclusion We revealed the molecular mechanism and biomarkers of tumour invasion and TME reprogramming in EOC, which provides effective targets for the suppression of tumour invasion.

Phenylethanoid glycosides derived from Cistanche deserticola (PhGs) are plant-derived natural medicinal compounds that occur in many medicinal plants. This study aims to investigate whether PhGs treatment improves the stroke and its potential mechanisms. Adult male C57BL/6 J mice were administrated PhGs once daily for 7 days after MCAO surgery. The neurological score, and catwalk were evaluated on Day 1, 3 and 7 after ischemic stroke. Furthermore, triphenyl-2,3,5-tetrazoliumchloride (TTC) and hematoxylin-eosin (H&E) staining were used for evaluating the infarct volume and neuronal restoration. The effects of PhGs on NSCs proliferation were investigated in vitro and in vivo. Western blot was used to detect the proteins of Wnt/β-catenin signaling pathway. This study found that PhGs effectively improved the neurological functions in ischemic stroke mice. TTC and H&E staining demonstrated that PhGs not only reduced infarct volume, but also improved neuronal restoration. The immunohistochemistry and 5-Ethynyl-2-deoxyuridine (EdU) incorporation assays revealed that PhGs promoted the proliferation of neural stem cells (NSCs) in subventricular zone (SVZ). In addition, transcriptome analysis of NSCs showed that the Wnt/β-catenin signaling pathway was involved in the PhGs induced NSCs proliferation. Importantly, the related proteins in the Wnt/β-catenin signaling pathway were changed after PhGs treatment, including β-catenin, Wnt3a, GSK-3β, c-Myc. PhGs treatment improved the stroke through enhancing endogenous NSCs proliferation via activating Wnt/β-catenin signaling pathway. Due to its effect on the proliferation of NSCs, PhGs are a potential adjuvant therapeutic drug for post-stroke treatment.

As the upgrade of people’s requirements for automotive driving comfort, conventional passive suspensions for cars have fallen short of existing demands due to their nonadjustable damping and stiffness, so semiactive suspensions and active suspensions have gained growing acceptance. Compared with active suspensions, semiactive suspensions offer the advantages of a low manufacturing cost and reliable structure, and thus have become the preferred choice for most vehicles. To optimize the control effect of semiactive suspensions under different working conditions, this paper completed the modeling of magnetorheological semiactive suspension system dynamics and road inputs; then, the design of binocular camera sensing algorithms was performed to obtain the real-time distance of the target using the point cloud ranging function, and the parameters required for suspension control were also obtained. This was followed by the completion of the control-mode-switching rules and the design of the suspension controller. According to the different control objectives, the mode could be divided into the obstacle-road mode, straight-road mode, and curved-road mode. The suspension controller included the BP-PID (neural network PID controller) controller and the force distributor. Finally, the effectiveness of the mode-switching rules and the control method was verified through system simulation and the hardware-in-the-loop test.

As a flexible grinding method with high efficiency, abrasive belt grinding has been widely used in the machining of mechanical parts. However, abrasive belt grinding has not been well applied in the field of ultra-precision optical processing, due to the lack of a stable and controllable removal function. In this paper, based on the idea of deterministic machining, the time-controlled grinding (TCG) method based on the abrasive belt as a machining tool was applied to the deterministic machining of optical components. Firstly, based on the Preston equation, a theoretical model of the TCG removal function was established. Secondly, removal function experiments were carried out to verify the validity and robustness of the theoretical removal model. Further, theoretical and actual shaping experiments were carried out on 200 mm × 200 mm flat glass-ceramic. The results show that the surface shape error converged from 6.497 μm PV and 1.318 μm RMS to 5.397 μm PV and 1.115 μm RMS. The theoretical and experimental results are consistent. In addition, the surface roughness improved from 271 to 143 nm Ra. The results validate the concept that the removal function model established in this paper can guide the actual shaping experiments of TCG, which is expected to be applied to the deterministic machining of large-diameter optical components.

Introduction: Since xenografts offer a wide range of incomparable advantages, they can be a better option than allografts but only if the possibility of immunological rejection can be eliminated. In this study, we investigated the ability of α1,3-galactosyltransferase (α1,3-GT) gene knockout (GTKO) pig cancellous bone to promote the repair of a femoral condyle bone defect and its influence on heterologous immune rejection.Materials and methods: Cylindrical bone defects created in a rhesus monkey model were transplanted with GTKO bone, WT bone or left empty. For immunological evaluation, T lymphocyte subsets CD4+ and CD8+ in peripheral blood were assayed by flow cytometry, and the IL-2 and IFN-γ contents of peripheral blood serum were analyzed by ELISA at 2, 5, 7, 10, and 14 days post-surgery. Micro-CT scans and histological assessment were conducted at 4 and 8 weeks after implantation.Results: Compared with WT-pig bone, the heterologous immunogenicity of GTKO-pig bone was reduced. The defect filled with fresh GTKO-pig bone was tightly integrated with the graft. Histological analysis showed that GTKO-pig cancellous bone showed better osseointegration and an appropriate rate of resorption. Osteoblast phenotype progression in the GTKO group was not affected, which revealed that GTKO-pig bone could not only fill and maintain the bone defect, but also promote new bone formation.Conclusion: GTKO-pig cancellous bone decreased the ratio of CD4+ to CD8+ T cells and cytokines (IFN-γ and IL-2) to inhibit xenotransplant rejection. Moreover, GTKO group increased more bone formation by micro-CT analysis and osteoblastic markers (Runx2, OSX and OCN). Together, GTKO-pig cancellous bone showed better bone repair than WT-pig cancellous bone.

The essential properties of a biosensor are its sensitivity and selectivity to detect, monitor and quantify the biomarker(s) for the interests of medicine [...]

The technology of in situ measurement of cylindrical shapes is an important means of improving the surface machining accuracy of cylindrical workpieces. As a method of cylindricity measurement, the principle of the three-point method has not been fully studied and applied, so it is seldom used in the field of high-precision cylindrical topography measurement. Since the three-point method has the advantages of a simpler measurement structure and smaller system error compared with other multi-point methods, the research on it is still of great significance. Based on the existing research results of the three-point method, this paper proposes the in situ measurement and reconstruction technology of the cylindrical shape of a high-precision mandrel by means of a three-point method. The principle of the technology is deduced in detail and an in situ measurement and reconstruction system is built to carry out the experiments. Experiment results are verified using a commercial roundness meter and the deviation of cylindricity measurement results is 10 nm, which is 2.56% of the measurement results of commercial roundness meters. This paper also discusses the advantages and application prospects of the proposed technology.

The radial error is an important parameter to evaluate the performance of ultra-precision spindles. The three-point method has not yet been well applied in nanometer-scale measurement due to its disadvantages of harmonic suppression and the complicated error separation process. In order to verify that the three-point method can realize the nanometer-scale measurement of the radial error in the machining environment, an in situ measurement and evaluation system is established. Experiments are performed using the system, and a comparative experiment is conducted to verify the accuracy of the system. The average value and standard deviation of the measurement results are 23.096 nm and 0.556 nm, respectively. The in situ measurement result was in good agreement with the Donaldson reversal method using a commercially available spindle analyzer.

To improve the material removal efficiency and surface quality of single-crystal silicon after magnetorheological finishing, a novel green chemical-mechanical magnetorheological finishing (CMMRF) fluid was developed. The main components of the CMMRF fluid are nano-Fe3O4, H2O2, CH3COOH, nanodiamond, carbonyl iron powder, and deionized water. The novel CMMRF fluid can simultaneously achieve Ra 0.32 nm (0.47 mm × 0.35 mm measurement area), Ra 0.22 nm (5 μm × 5 μm measurement area), and 1.91 × 10−2 mm3/min material removal efficiency. Comprehensive studies utilizing a scanning electron microscope and a magnetic rheometer show that the CMMRF fluid has a high mechanical removal effect due to the well-dispersed nanodiamond and nano-Fe3O4 particles. The results of Fourier transform infrared spectra and Young’s modulus test reveal the mechanism of the chemical reaction and the mechanical characteristics deterioration of the modified layer. Under co-enhanced chemical and mechanical effects, an ultra-smooth and highly efficient MRF technology for single-crystal silicon is realized.

About one-fifth of the population suffers from liver diseases in China, meaning that liver disorders are prominent causative factors relating to the Chinese mortality rate. For patients with end-stage liver diseases such as hepatocellular carcinoma or acute liver diseases with life-threatening liver dysfunction, allogeneic liver transplantation is the only life-saving treatment. Hepatocyte transplantation is a promising alternative for patients with acute liver failure or those considered high risk for major surgery, particularly for the bridge-to-transplant period. However, the lack of donors has become a serious global problem. The clinical application of porcine xenogeneic livers and hepatocytes remains a potential solution to alleviate the donor shortage. Pig grafts of xenotransplantation play roles in providing liver support in recipients, together with the occurrence of rejection, thrombocytopenia, and blood coagulation dysfunction. In this review, we present an overview of the development, potential therapeutic impact, and remaining barriers in the clinical application of pig liver and hepatocyte xenotransplantation to humans and non-human primates. Donor pigs with optimized genetic modification combinations and highly effective immunosuppressive regimens should be further explored to improve the outcomes of xenogeneic liver and hepatocyte transplantation.

Pig to human xenotransplantation is considered to be a possible approach to alleviate the shortage of human allografts. Porcine endogenous retrovirus (PERV) is the most significant pathogen in xenotransplantation. We screened for pigs that consistently did not transmit human-tropic replication competent PERVs (HTRC PERVs), namely, non-transmitting pigs. Then, we conducted whole-genome resequencing and full-length transcriptome sequencing to further investigate the sequence characteristics of one non-transmitting pig. Using in vitro transmission assays, we found 5 (out of 105) pigs of the Chinese Wuzhishan minipig inbred line that did not transmit PERV to human cells, i.e., non-transmitting pigs. Whole-genome resequencing and full-length transcriptome sequencing of one non-transmitting pig showed that all of the pol genes were defective at both the genome and transcript levels. We speculate that the defective PERV pol genes in this pig might be attributable to the long-term inbreeding process. This discovery is promising for the development of a strain of highly homozygous and genetically stable pigs with defective PERV pol genes as a source animal species for xenotransplantation.

Abstract Background Pirfenidone (PFD) is effective for pulmonary fibrosis (PF), but its action mechanism has not been fully explained. This study explored the signaling pathways involved in anti-fibrosis role of PFD, thus laying a foundation for clinical application. Methods Pulmonary fibrosis mice models were constructed by bleomycin (BLM), and TGF-β1 was used to treat human fetal lung fibroblasts (HLFs). Then, PFD was added into treated mice and cells alone or in combination with β-catenin vector. The pathological changes, inflammatory factors levels, and Collagen I levels in mice lung tissues were assessed, as well as the activity of HLFs was measured. Levels of indices related to extracellular matrix, epithelial-mesenchymal transition (EMT), Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways were determined in tissues or cells. Results After treatment with BLM, the inflammatory reaction and extracellular matrix deposition in mice lung tissues were serious, which were alleviated by PFD and aggravated by the addition of β-catenin. In HLFs, PFD reduced the activity of HLFs induced by TGF-β1, inhibited levels of vimentin and N-cadherin and promoted levels of E-cadherin, whereas β-catenin produced the opposite effects to PFD. In both tissues and cells, Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways were activated, which could be suppressed by PFD. Conclusions PFD alleviated pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β1/Smad2/3 signaling pathways, which might further improve the action mechanism of anti-fibrosis effect of PFD.

Abstract Backgrounds Streptozotocin (STZ)‐ induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs. There are serious side effects of this method, including nausea, emesis, weight loss, liver damage, renal failure, and metabolic acidosis. In order to reduce the side effects, diabetic monkeys were induced using clinical‐grade STZ. However, clinical‐grade STZ is not available in China. Here, we establised a method by using 100 mg/kg analytical‐grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and renal. Methods Three cynomolgus monkeys were used in this study. 100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular vein. After the STZ administration, blood glucose levels were examined every 1 or 2 hours in the first 48 hours. Then, blood glucose levels were examined twice per day during the first week after the STZ injection. Insulin and C‐peptide levels were measured by ELISA. Blood chemistry of hepatic and renal function tests were performed. Insulin and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry assays. Results The stimulated C‐peptide level (Intravenous glucose tolerance test) which is less than 0.5 ng/mL, the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes model. No apparent adverse effects were observed including no signs of vomiting and toxicity after STZ injection. Conclusion In summary, we established a safe and reproducible STZ‐induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes.

Recently, more and more research has been conducted to develop Connected Autonomous Vehicles (CAVs) applications that ensures the safety driving of CAVs under some extreme situations. This brief presents a robust control strategy for CAVs to preserve a precise tracking performance and maintain the stability of lateral dynamics when passing a sharp curve with uncertain road friction coefficient changes. In the proposed robust lateral dynamics control, robust optimization-based lateral dynamics controller is designed to achieve the stability of the lateral dynamics with the consideration of the road friction coefficient uncertainty. Simulation validations are carried out to evaluate the proposed control strategy. The results show that the robust optimization-based lateral dynamics can improve the robustness even with the uncertainty of the road friction coefficient.

Extreme ultraviolet lithography objective lenses require surface figure accuracy of approximately sub-nanometer root mean square (RMS). As the key equipment for sub-nanometer accuracy figuring, the dynamic and static performance of ion beam figuring (IBF) machine tools are critical. However, the related research is not sufficient and comprehensive. To this end, a general model of dynamic and static performance requirements on three-axis IBF machine tools was established. The requirements on dynamic and static performance under different figuring process for different surface shape were comprehensively analyzed. Analysis results revealed that the three-axis IBF machine tools require typical motion accuracy better than 100 μm and certain dynamic performance for achieving sub-nanometer accuracy. According to the theoretical and simulation results, a process optimization based on analysis of dynamic and static performance requirements of IBF machine tools for sub-nanometer figuring is proposed. To verify the proposed method, a Φ90 mm mirror with 2.594 nm RMS was figured to 0.251 nm RMS by optimizing the processing parameters to ensure that the IBF machine tool with measured performance (positioning error of 52.74 μm, 53.04 μm, 37.71 μm, and maximum acceleration of 1.0 m/s2, 1.3 m/s2, and 1.5 m/s2 for axes x, y, and z, respectively) meets the performance requirements. The proposed method can promote the application of three-axis IBF machine tools in sub-nanometer accuracy figuring.

The profile and concentricity of hemispherical shells affect the frequency split and quality factor of hemispherical resonators. To compensate for machining errors caused by tool wear and tool setting, an on-machine measurement (OMM) method for the profile and concentricity of hemispherical shells in ultra-precision grinding was developed without the removal of workpieces from the machine tool. The OMM utilizes an inductive lever probe to test the inner and outer surfaces of the shell. A standard sphere is utilized to calibrate the relative position of the inductive lever probe at the two different work positions. To enhance the test accuracy of the OMM, a zero-position trigger-sampling method for the inductive lever probe was developed. It was verified to achieve a stable repeatability accuracy of 0.04 μm when using the OMM to realize a single-point sampling. Hemispherical shells were tested using the proposed OMM method. The concentricity test’s accuracy was verified to achieve accuracy better than 1 μm using a coordinate measuring machine and a standard sphere. The accuracy was 0.26 μm for testing the profiles of the hemispherical shell. The proposed OMM system was integrated with an ultra-precision machine tool. It is hoped that this method can help realize the integration function of machining-measurement-compensation.

The geometric accuracy of a hemispherical shell resonator (HSR) affects the assembly accuracy and final performance of a hemispherical resonant gyroscope in many ways. During the precision grinding of a resonator, the tool-setting error and wear error affect the form and positional accuracy of the inner and outer spherical surfaces. In this study, a compensation method for generating grinding of the HSR is proposed to address this problem. The geometric errors of the inner and outer spherical surfaces are systemically analyzed and a geometric model of the tool setting and wheel wear is established for generating grinding of the HSR. According to this model, a mapping relationship between the wheel pose and size, form, and positional error of the HSR was proposed. Experiments regarding machining, on-machine measurements, and error compensation were performed using the mapping relationship. The results demonstrate that the proposed method can reduce the radius error of the inner and outer spherical surfaces from 10 μm to 1 μm, sphericity from 5 μm to 1.5 μm, and concentricity from 15 μm to 3 μm following grinding. The form and positional errors are simultaneously improved, verifying the effectiveness of the proposed method.

Liquid state machine (LSM) is a type of recurrent spiking network with a strong relationship to neurophysiology and has achieved great success in time series processing. However, the computational cost of simulations and complex dynamics with time dependency limit the size and functionality of LSMs. This paper presents a large-scale bioinspired LSM with modular topology. We integrate the findings on the visual cortex that specifically designed input synapses can fit the activation of the real cortex and perform the Hough transform, a feature extraction algorithm used in digital image processing, without additional cost. We experimentally verify that such a combination can significantly improve the network functionality. The network performance is evaluated using the MNIST dataset where the image data are encoded into spiking series by Poisson coding. We show that the proposed structure can not only significantly reduce the computational complexity but also achieve higher performance compared to the structure of previous reported networks of a similar size. We also show that the proposed structure has better robustness against system damage than the small-world and random structures. We believe that the proposed computationally efficient method can greatly contribute to future applications of reservoir computing.

Steering acid fracturing is a technique that improves the conductivity of carbonate reservoir. It is widely used in a carbonate reservoir. However, due to the lack of comparative experiments, the application of steering acid to improve the fracturing results is still unknown. Therefore, a series of true triaxial acid fracturing experiments were conducted to study steering acid fracturing in carbonate reservoir. The carbonate specimens used in the experiment were from the Qixia group and Dengsi Member in Sichuan, China. In this study, slick water, cross-linked gel, and self-generating acid were used as ahead fluid to cooperate with steering acid. Experimental results show that (1) the low-viscosity ahead fluid with steering acid can result in more complex fractures; (2) the complexity of fractures is influenced by natural fracture and the viscosity of the ahead fluid; and (3) based on the 3D scanning results of the fracture surface, different ahead fluids will lead to different corrosion results. This study provides useful suggestions on steering acid fracturing design and physical simulation experiments.

Various items of roll molds are popularly used to fabricate different kinds of optical films for optoelectronic information and other new and high-tech fields, while the fabrication and evaluation of optical microstructures on a cylindrical roller surface is more difficult than ecumenically manufactured products. In this study, the machinability of microstructures on the roll based on a fast tool servo (FTS) system is investigated. First, the flexible hinge holder for a FTS is designed and its structural parameters are optimized with finite-element analysis and fatigue reliability theory. The tool radius compensation algorithm for complicated microstructures is then deduced based on the surface fitting and bilinear interpolation algorithm of discrete data. Meanwhile, the evaluation index and method are proposed by the medium section method. Finally, a machining test of aspheric arrays on a cylindrical aluminum surface is carried out, and the high quality of the microstructure indicates that the proposed method is able to be used to fabricate optical microstructures.

With the development of optoelectronic information technology, high-performance optical systems require an increasingly higher surface accuracy of optical mirrors. The fast tool servo (FTS) based on the piezoelectric actuator is widely used in the compensation machining of high-precision optical mirrors. However, with the low natural frequency of mechanical structures, hysteresis of the piezoelectric actuators, and phase delay of the control systems, conventional FTS systems face problems such as a low working frequency and a large tracking error. This study presents a method for the design of a high-performance FTS system. First, a flexure hinge servo turret with a high natural frequency was designed through multi-objective optimization and finite element simulations. Subsequently, a composite control algorithm was proposed, targeting the problems of hysteresis and phase delay. The modified Prandtl–Ishlinskii inverse hysteresis model was used to overcome the hysteresis effect and a zero-phase error tracker was designed to reduce the phase error. The experimental results reveal that the tracking error of the designed FTS system was

The computer-controlled optical surface (CCOS) can process good optical surfaces, but its edge effect greatly affects its development and application range. In this paper, based on the two fundamental causes of the CCOS’s edge effect—namely the nonlinear variation of edge pressure and the unreachable edge removal—a combined polishing method of double-rotor polishing and spin-polishing is proposed. The model of the combined polishing method is established and theoretically analyzed. Combined with the advantages of double-rotor polishing and spin-polishing, the combined polishing process can achieve full-aperture machining without pressure change. Finally, the single-crystal silicon sample with a diameter of 100 mm is polished by the combined polishing process. The results show that, compared with the traditional CCOS polishing, the residual error of the sample after the combined polishing process is more convergent, and the edge effect is effectively controlled.

Currently, meter-long guideways rarely achieve an accuracy of dozens of nanometers due to processing difficulties such as the material and the edge effect. In this paper, we focus on this problem and propose a set of optimization processing methods to cope with it. In the grinding stage, a grinding tool is designed to improve the reciprocating processing and address the problem of warping; in the polishing stage, three different processes are compared, and the combination of magnetorheological finishing technology and the polyurethane disc technology process is purposed to reduce the polishing cycle and improve the surface figure accuracy. Moreover, through the combined process of magnetorheological finishing and smoothing, the edge effect and medium- and high-frequency error are essentially suppressed. The meter-long guideway is achieved with an accuracy of dozens of nanometers. Although the sizes of surface A/C and B/D are 1000 mm × 240 mm and 1000 mm × 160 mm, the surface figures are 20.33 nm, 22.78 nm, 39.23 nm and 26.58 nm RMS (Root Mean Square), respectively. The nanometer accuracy guideway is critical to an ultra-precision machine tool. Finally, the X-axis straightness of the profile measurement system formed by the guideway reaches 200 nm/600 mm.

Aluminum optics are widely used in modern optical systems because of their high specific stiffness and high reflectance. With the applied optical frequency band moving to visible, traditional processing technology cannot meet the processing precision. Ion beam sputtering (IBS) provides a highly deterministic technology for high-precision aluminum optics fabrication. However, the surface quality is deteriorated after IBS. The interaction between the bombard atoms and the surface morphology evolution mechanism are not clear, and systematic research is needed. Thus, in this paper, the IBS process for single crystal aluminum with different crystallographic orientations are studied by the molecular dynamics method. The ion beam sputter process is firstly demonstrated. Then, the variation of sputter yield of the three crystal faces is analyzed. The sputter yield difference of different crystal surfaces causes the appearance of the relief structure. Then, the gravel structure generates on the single crystal surfaces and dominates the morphology evolution. The state of the atom diffusion of the specific crystal surfaces will determine the form of the gravel structure. Furthermore, the form and distribution of subsurface damage and stress distribution of three different crystal surfaces are analyzed. Although there are great differences in defect distribution, no stress concentration was found in three workpieces, which verifies that the ion beam sputter is a stress-free machining method. The process of IBS and the mechanism of morphology evolution of aluminum are revealed. The regularity and mechanism will provide a guidance for the application of IBS in aluminum optics manufacture fields.

Weak-stiffness mirrors are widely used in various fields such as aerospace and optoelectronic information. However, it is difficult to achieve micron-level precision machining because weak-stiffness mirrors are hard to clamp and are prone to deformation. The machining errors of these mirrors are randomly distributed and non-rotationally symmetric, which is difficult to overcome by common machining methods. Based on the fast tool servo system, this paper proposes a high-precision machining method for weak-stiffness mirrors. Firstly, the clamping error and cutting error compensation strategy is obtained by analyzing the changing process of the mirror surface morphology. Then, by combining real-time monitoring and theoretical simulation, the elastic deformation of the weak-stiffness mirror is accurately extracted to achieve the compensation of the clamping error, and the compensation of the cutting error is achieved by iterative machining. Finally, a weak-stiffness mirror with a thickness of 2.5 mm was machined twice, and the experimental process produced a clamping error with a peak to valley (PV) value of 5.2 µm and a cutting error with a PV value of 1.6 µm. The final machined surface after compensation had a PV value of 0.7 µm. The experimental results showed that the compensation strategy proposed in this paper overcomes the clamping error of the weak-stiffness mirror and significantly reduces cutting errors during the machining process, achieving the high precision machining of a weak-stiffness mirror.

Abstract Complement protein C3 is the pivotal component of the complement system. Previous studies have demonstrated that C3 has implications in various human diseases and exerts profound functions under certain conditions. However, the delineation of pathological and physiological roles of C3 has been hampered by the insufficiency of suitable animal models. In the present study, we applied the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system to target the C3 gene in porcine fetal fibroblasts. Our results indicated that CRISPR/Cas9 targeting efficiency was as high as 84.7%, and the biallelic mutation efficiency reached at 45.7%. The biallelic modified colonies were used as donor for somatic cell nuclear transfer (SCNT) technology to generate C3 targeted piglets. A total of 19 C3 knockout (KO) piglets were produced and their plasma C3 protein was undetectable by western blot analysis and ELISA. The hemolytic complement activity and complement-dependent cytotoxicity assay further confirmed that C3 was disrupted in these piglets. These C3 KO pigs could be utilized as a valuable large animal model for the elucidation of the roles of C3.

Miniature pigs have advantages over rodents in modeling atherosclerosis because their cardiovascular system and physiology are similar to that of humans. Apolipoprotein E (ApoE) deficiency has long been implicated in cardiovascular disease in humans. To establish an improved large animal model of familial hypercholesterolemia and atherosclerosis, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 system (CRISPR/Cas9) was used to disrupt the ApoE gene in Bama miniature pigs. Biallelic-modified ApoE pigs with in-frame mutations (ApoEm/m) and frameshift mutations (ApoE−/−) were simultaneously produced. ApoE−/− pigs exhibited moderately increased plasma cholesterol levels when fed with a regular chow diet, but displayed severe hypercholesterolemia and spontaneously developed human-like atherosclerotic lesions in the aorta and coronary arteries after feeding on a high-fat and high-cholesterol (HFHC) diet for 6 months. Thus, these ApoE−/− pigs could be valuable large animal models for providing further insight into translational studies of atherosclerosis.

An aerostatic spindle is a core component in ultra-precision machine tools. The rotor of the spindle has extremely high manufacturing accuracy, which cannot be directly achieved via traditional machining, but always via manual grinding. The deterministic figuring theory is introduced into the machining of shaft parts, which overcomes many shortcomings of manual grinding. The manufacturing error of the shaft’s surface contains different frequency components, which have different effects on its working performance and the figuring process. Because the deterministic figuring method can only correct the error within a limited frequency range, in order to ensure high efficiency and high precision of the figuring process, we need to use reasonable filtering parameters to filter out the error with unnecessary frequencies. In this paper, the influence of contour error with different frequencies and amplitudes on the air film are analyzed using computational fluid dynamics (CFD) software, and the amplitude–frequency analysis as a function of the power spectral density (PSD) characteristic curve is used to study the filtering parameters of the measured data. After the figuring experiment using the filtering parameters obtained from the analysis, the average roundness of the shaft converged from 0.419 μm to 0.101 μm, and the cylindricity converged from 0.76 μm to 0.35 μm. The precision reached the level of manual grinding, which proves the rationality of the analysis using filtering parameters in a shaft’s deterministic figuring.

The application of ultra-precision shaft parts is widely used, such as the spindle core of the air bearing spindle in ultra-precision machine tools. The precision of the spindle core is extremely high, and it is very difficult to obtain directly by traditional Computer Numerical Control (CNC) machine tools but is mostly obtained by manual grinding, whose machining efficiency is greatly limited. Based on the deterministic figuring theory, this paper focuses on the ultra-precision roundness, optimizing the filtering parameters of the measurement error data and studying the generation mechanism of the removal function morphology; the shape of the removal function is adjusted by combining the analysis of the figuring ability and positioning error. Finally, the optimized removal function is used on an experimental steel shaft, the average roundness convergence ratio is 72% higher than that of the original removal function, and the roundness reaches a 0.1 μm level. The result shows that a reasonable filtering of measured data and the removal function adjusted for the surface feature can improve the efficiency and precision of deterministic figuring on shaft parts.

Nanoscale laser damage precursors generated from fabrication have emerged as a new bottleneck that limits the laser damage resistance improvement of fused silica optics. In this paper, ion beam etching (IBE) technology is performed to investigate the evolutions of some nanoscale damage precursors (such as contamination and chemical structural defects) in different ion beam etched depths. Surface material structure analyses and laser damage resistance measurements are conducted. The results reveal that IBE has an evident cleaning effect on surfaces. Impurity contamination beneath the polishing redeposition layer can be mitigated through IBE. Chemical structural defects can be significantly reduced, and surface densification is weakened after IBE without damaging the precision of the fused silica surface. The photothermal absorption on the fused silica surface can be decreased by 41.2%, and the laser-induced damage threshold can be raised by 15.2% after IBE at 250 nm. This work serves as an important reference for characterizing nanoscale damage precursors and using IBE technology to increase the laser damage resistance of fused silica optics.

Liver-resident macrophages (Kupffer cells, KCs) and autophagy play critical roles in the pathogenesis of toxin-induced liver injury. Recent evidence indicates that autophagy can regulate macrophage M1/M2 polarization under different inflammatory conditions. Polyamines, including putrescine, spermidine, and spermine (SPM), are polycations with anti-oxidative, anti-aging, and cell autophagy induction properties. This study aimed to determine the mechanisms by which SPM protects against thioacetamide (TAA)-induced acute liver injury in a mouse model. Pretreatment with SPM significantly alleviated liver injury and reduced intrahepatic inflammation in TAA-induced liver injury compared to controls. SPM markedly inhibited M1 polarization, but promoted M2 polarization of KCs obtained from TAA-exposed livers, as evidenced by decreased IL-1β and iNOS gene induction but increased Arg-1 and Mrc-1 gene induction accompanied by decreased STAT1 activation and increased STAT6 activation. Furthermore, pretreatment with SPM enhanced autophagy, as revealed by increased LC3B-II levels, decreased p62 protein expression, and increased ATG5 protein expression in TAA-treated KCs. Knockdown of ATG5 in SPM-pretreated KCs by siRNA resulted in a significant increase in pro-inflammatory TNF-α and IL-6 secretion and decreased anti-inflammatory IL-10 secretion after TAA treatment, while no significant changes were observed in cytokine production in the TAA treatment alone. Additionally, the effect of SPM on regulation of KC M1/M2 polarization was abolished by ATG5 knockdown in TAA-exposed KCs. Finally, in vivo ATG5 knockdown in KCs abrogated the protective effect of SPM against TAA-induced acute liver injury. Our results indicate that SPM-mediated autophagy inhibits M1 polarization, while promoting M2 polarization of KCs in TAA-treated livers via upregulation of ATG5 expression, leading to attenuated liver injury. This study provides a novel target for the prevention of acute liver injury.

Clinical organ allotransplantation is limited by the availability of deceased human donors. However, the transplantation of human organs produced in other species would provide an unlimited number of organs. The pig has been identified as the most suitable source of organs for humans as organs of any size would be available. Genome editing by RNA-guided endonucleases, also known as clustered regularly interspaced short palindromic repeat (CRISPR/Cas9), in combination with induced pluripotent stem cells (iPSC), may have the potential to enable the creation of human organs from genetically-modified chimaeric pigs. These could potentially provide an unlimited supply of organs that would not be rejected by the recipient’s immune system. However, substantial research is needed to prove that this approach will work. Genetic modification of chimaeric pigs could also provide useful models for developing therapies for various human diseases, especially in relation to drug development.

Islet allotransplantation results in increasing success in treating type 1 diabetes, but the shortage of deceased human donor pancreata limits progress. Islet xenotransplantation, using pigs as a source of islets, is a promising approach to overcome this limitation. The greatest obstacle is the primate immune/inflammatory response to the porcine (pig) islets, which may take the form of rapid early graft rejection (the instant blood-mediated inflammatory reaction) or T-cell-mediated rejection. These problems are being resolved by the genetic engineering of the source pigs combined with improved immunosuppressive therapy. The results of pig-to-diabetic nonhuman primate islet xenotransplantation are steadily improving, with insulin independence being achieved for periods >1 year. An alternative approach is to isolate islets within a micro- or macroencapsulation device aimed at protecting them from the human recipient's immune response. Clinical trials using this approach are currently underway. This review focuses on the major aspects of pig-to-primate islet xenotransplantation and its potential for treatment of type 1 diabetes.

A deterministic figuring method for cylindrical surface based on abrasive belt polishing is proposed in this study in order to improve the geometric accuracy of metal shaft parts. The principal motion of material removal is performed through the axial oscillation of the abrasive belt, and the different material removal at different positions can be obtained through servo control of the machine tool spindle by removing high error spots on the cylindrical surface and finally deterministically corrects the roundness error. An abrasive belt-based deterministic figuring device was built, and the figuring experiments were performed on the surface of steel workpieces 100 mm in diameter and 130 mm in effective length. The roundness errors of the entire workpiece after twice figuring iterations decreased nearly from the initial 3 μm to 1 μm, which preliminary verified the feasibility of this method. This deterministic figuring method is expected to break the machining accuracy limit and improve the rotation precision of the precision shaft parts such as the aerostatic spindle.

Metallic elements can contaminate single crystal silicon mirror during ion beam etching (IBE) and other postprocessing methods, which can affect the performance of components in an infrared laser system. In this work, scanning electron microscope (SEM) and atomic force microscope (AFM) were used to characterize the distribution of contaminant represented by aluminum (Al). After characterizing contaminated area, elastic jet polishing (EJP), EJP, and static alkaline etching (SAE) combined technique were used to process the mirror. The morphology and laser-induced absorption were measured. Results show that metallic elements can mix with silicon and generate bulges due to the sputtering effect. In addition, SAE and EJP combined technique can remove metallic contaminant and stabilize the surface quality. Research results can be a reference on conducting postprocessing technologies to improve laser damage resistance property of single crystal silicon mirror in infrared laser system.

A cuprous oxide (Cu2O) thin layer served as the base for a non-enzymatic glucose sensor in an alkaline medium, 0.1 NaOH solution, with a linear range of 50–200 mg/dL using differential pulse voltammetry (DPV) measurement. An X-ray photoelectron spectroscopy (XPS) study confirmed the formation of the cuprous oxide layer on the thin gold film sensor prototype. Quantitative detection of glucose in both phosphate-buffered saline (PBS) and undiluted human serum was carried out. Neither ascorbic acid nor uric acid, even at a relatively high concentration level (100 mg/dL in serum), interfered with the glucose detection, demonstrating the excellent selectivity of this non-enzymatic cuprous oxide thin layer-based glucose sensor. Chronoamperometry and single potential amperometric voltammetry were used to verify the measurements obtained by DPV, and the positive results validated that the detection of glucose in a 0.1 M NaOH alkaline medium by DPV measurement was effective. Nickel, platinum, and copper are commonly used metals for non-enzymatic glucose detection. The performance of these metal-based sensors for glucose detection using DPV were also evaluated. The cuprous oxide (Cu2O) thin layer-based sensor showed the best sensitivity for glucose detection among the sensors evaluated.

A simple in vitro biosensor for the detection of β-amyloid 42 in phosphate-buffered saline (PBS) and undiluted human serum was fabricated and tested based on our platform sensor technology. The bio-recognition mechanism of this biosensor was based on the effect of the interaction between antibody and antigen of β-amyloid 42 to the redox couple probe of K4Fe(CN)6 and K3Fe(CN)6. Differential pulse voltammetry (DPV) served as the transduction mechanism measuring the current output derived from the redox coupling reaction. The biosensor was a three-electrode electrochemical system, and the working and counter electrodes were 50 nm thin gold film deposited by a sputtering technique. The reference electrode was a thick-film printed Ag/AgCl electrode. Laser ablation technique was used to define the size and structure of the biosensor. Cost-effective roll-to-roll manufacturing process was employed in the fabrication of the biosensor, making it simple and relatively inexpensive. Self-assembled monolayers (SAM) of 3-Mercaptopropionic acid (MPA) was employed to covalently immobilize the thiol group on the gold working electrode. A carbodiimide conjugation approach using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and N–hydroxysuccinimide (NHS) was undertaken for cross-linking antibody of β-amyloid 42 to the carboxylic groups on one end of the MPA. The antibody concentration of β-amyloid 42 used was 18.75 µg/mL. The concentration range of β-amyloid 42 in this study was from 0.0675 µg/mL to 0.5 µg/mL for both PBS and undiluted human serum. DPV measurements showed excellent response in this antigen concentration range. Interference study of this biosensor was carried out in the presence of Tau protein antigen. Excellent specificity of this β-amyloid 42 biosensor was demonstrated without interference from other species, such as T-tau protein.

This research has developed a simple to use, cost effective sensor system for the detection of lead ions in tap water. An under-potential deposited bismuth sub-layer on a thin gold film based electrochemical sensor was designed, manufactured, and evaluated. Differential pulse voltammetry (DPV) measurement technique was employed in this detection. Tap water from the Cleveland, OH, USA regional water district was the test medium. Concentrations of lead ion in the range of 8 × 10−7 M to 5 × 10−4 M were evaluated, showing a good sensitivity over this concentration range. The calibration curve for the DPV measurements of lead ions in tap water showed excellent reproducibility with R2 value of 0.970. This DPV detection system required 3–6 min to complete the detection measurement. A longer measurement time of 6 min was used for the lower lead ion concentration. The selectivity of this lead ion sensor was very good, and Fe III, Cu II, Ni II, and Mg II at a concentration level of 5 × 10−4 M did not interfere with the lead ion measurement.

A single-use, in vitro biosensor for the detection of T-Tau protein in phosphate-buffer saline (PBS) and undiluted human serum was designed, manufactured, and tested. Differential pulse voltammetry (DPV) served as the transduction mechanism. This biosensor consisted of three electrodes: working, counter, and reference electrodes fabricated on a PET sheet. Both working and counter electrodes were thin gold film, 10 nm in thickness. Laser ablation technique was used to define the size and structure of the biosensor. The biosensor was produced using cost-effective roll-to-roll process. Self-assembled monolayers (SAM) of 3-mercaptopropionic acid (MPA) were employed to covalently immobilize the anti-T-Tau (T-Tau antibody) on the gold working electrode. A carbodiimide conjugation approach using N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) and N–hydroxysuccinimide (NHS) cross-linked anti-T-Tau to the carboxylic groups on one end of the MPA. A T-Tau protein ladder with six isoforms was used in this study. The anti-T-Tau concentration used was 500,000 pg/mL. The T-Tau protein concentration ranged from 1000 pg/mL to 100,000 pg/mL. DPV measurements showed excellent responses, with a good calibration curve. Thus, a practical tool for simple detection of T-Tau protein, a biomarker of neuro-degenerative disorders, has been successfully developed. This tool could also be extended to detect other biomarkers for neuro-degenerative disorders, such as P-Tau protein and β-amyloid 42.

BACKGROUND:Although liver transplantation is one of the most efficient curative therapies of end stage liver diseases, recipients may suffer liver graft loss opst-operation. IRF-5, a member of Interferon Regulatory Factors, functions as a key regulator in TLR4 cascade, and is capable of inducing inflammatory cytokines. Although TLR4 has been proved to contribute to acute allograft rejection, including after liver transplantation, the correlation between IRF5 gene and acute rejection has not been elucidated yet. METHODS:The study enrolled a total of 289 recipients, including 39 females and 250 males, and 39 recipients developed acute allograft rejection within 6 months post-transplantation. The allograft rejections were diagnosed by liver biopsies. Genome DNA of recipients was extracted from pre-operative peripheral blood. Genotyping of IRF-5, including rs3757385, rs752637 and rs11761199, was performed, followed by SNP frequency and Hardy-Weinberg equilibrium analysis. RESULTS:The genetic polymorphism of rs3757385 was found associated with acute rejection. G/G homozygous individuals were at higher risk of acute rejection, with a P value of 0.042 (OR = 2.34 (1.07-5.10)). CONCLUSIONS:IRF5, which transcriptionally activates inflammatory cytokines, is genetically associated with acute rejection and might function as a risk factor for acute rejection of liver transplantations.

Preserving and enhancing the primary function of transplanted islets is not only crucial for improving the outcome of the islet transplantation, but is also important for reducing the islet mass required to achieve insulin independence. Uncoupling protein 2 (UCP2) is a member of the uncoupling protein family, which is localized to the inner mitochondrial membrane and negatively regulates insulin secretion in the pancreatic β-cells. In this study, we assessed the importance of UCP2 in improving islet graft primary function by using UCP2 gene-knockout (UCP2-KO) mice in a syngeneic islet transplantation model. Islets were isolated from UCP2-KO or wild-type (WT) C57BL/6J mice. The effects of deficiency of UCP2 on islet transplantation and islet function were determined. Two hundred islets from UCP2-KO, but not from WT, donors were capable of completely restoring normoglycemia in 1 week in all syngeneic diabetic recipients. Islets harvested from UCP2-KO mice secreted onefold more insulin in GSIS assay than that from WT mice, and maintained normal GSIS after 72-h exposure to high glucose challenge. In addition, UCP2-KO islets expressed twohold higher Bcl-2 mRNA than that from WT islets, and were resistant to high glucose and proinflammatory cytokine induced death. Our study explored a potential mechanism that may explain the benefit of UCP2-KO islets in islet transplantation. Targeting UCP2 may provide a novel strategy to improve primary function of transplanted islets and reduce the number of islets required in transplantation.