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Limited healthcare capacity highlights the needs of integrated and simple sensing systems for personalized health monitoring. However, only a limited set of sensors can be employed for point-of-care applications, emphasizing the lack of a generalizable engineering strategy for sensor construction. Here, we report a de novo rational engineering strategy for the construction of an integrated electrochemical liquid biopsy (ELB) platform capable of direct profiling cancer exosomes from blood. Using a bottom-up approach for sensor design, a series of critical sensing functions is considered and encoded into the material interface by programming the electrode material with different chemical and structure features. We present that the rationally engineered electrochemical liquid biopsy platform is able to achieve one-step sensor fabrication, target isolation, non-fouling and high-sensitivity sensing, direct signal transduction and multiplexed detection. Integrating the multiplexed sensing with principal component analysis, we demonstrate the capability of the programmed sensing system on differentiating cancerous groups from healthy controls by analyzing clinical samples from lung cancer patients.

To realize the flow visualization of shock train structures by Schlieren measurements in a square-to-circular transition isolator, a high-precision conformal optical window was manufactured by fly-cutting technology. According to the light refraction principle, the window’s outer surface was iteratively optimized based on the super-elliptic curves of the internal flow channel. Through tolerance analysis and processing parameter optimization, the transmitted wavefront error (RMS value) of the finished window was 0.823 λ ( λ = 632.8 n m ). Based on a z -type Schlieren apparatus, the high-precision Schlieren measurements were conducted through the window and processed by an image filtering process method. The results promote high-precision Schlieren observation towards square-to-circular transition isolators.

Magnetorheological finishing (MRF) is a sub-aperture polishing process, which is often used to correct surface errors and remove sub-surface damage after grinding. A strong correlation exists between the material removal rate and surface roughness in MRF, but current theoretical models are incapable of predicting these two factors at the same time. In this paper, a theoretical model was developed to describe the material removal rate and surface quality after MRF in order to better understand the material removal mechanism of MRF and explain the relationship between surface roughness and material removal rate. Two modes of experiments (uniform polishing and fixed point polishing) were conducted on monocrystalline silicon to obtain the results of surface roughness and removal rate. The experimental results are highly consistent with the theoretical model calculated results. The theoretical model could be a reference for high-efficiency and ultra-smooth MRF process.

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 &lt, 10% in the full frequency range (0–1000 Hz).

We present uFS, a user-level filesystem semi-microkernel. uFS takes advantage of a high-performance storage development kit to realize a fully-functional, crash-consistent, highly-scalable filesystem, with relative developer ease. uFS delivers scalable high performance with a number of novel techniques: careful partitioning of in-memory and on-disk data structures to enable concurrent access without locking, inode migration for balancing load across filesystem threads, and a dynamic scaling algorithm for determining the number of filesystem threads to serve the current workload. Through measurements, we show that uFS has good base performance and excellent scalability; for example, uFS delivers nearly twice the throughput of ext4 for LevelDB on YCSB workloads.

Benefiting from high specific stiffness and high reflectance, aluminum optics with a complex surface profile are widely used in aerospace optical systems which have strict requirements for volume of the systems. Contact figuring polishing process provides highly deterministic technology for the fabrication of high precision aluminum optics. However, due to the high chemical activity of aluminum, the inevitable contamination layer will generate on the surface and bring difficulties for the subsequent processes, which greatly limit the fabrication precision. Ion beam figuring (IBF) is an effectively technology that can remove the contamination layer and improve surface quality. But, the surface profile may deteriorate during IBF. In this study, through experimental method, the nonuniformity of the contamination layer is found to be the inducer for deterioration and deviation of surface profile during IBF. The mapping between the characteristics of contamination layer and dwell time of contact polishing is studied. The thickness of the contamination layer will firstly increase with dwell time and stabilize to 120 nm when the dwell time exceeds a specific value. The variation of the IBF removal function with removal depth is also revealed through experimental and theoretical methods. Due to the dynamic variation of the composition in the contamination layer during IBF, the removal function increases with the removal depth and stabilizes when the depth exceeds 60 nm (the contamination layer is fully removed). Consequently, we propose two processing strategies to improve the aluminum optics fabrication process. Comparative experiments are performed on two off-axis aspherical surfaces. The results indicate that the surface profile can be stably maintained and improved during IBF processing based on the proposed strategies. Our research will significantly improve the fabrication precision of aluminum optics and promote the application of aluminum optics to the visible and even ultraviolet band.

Intersection is one of the most complex and accident-prone urban traffic scenarios for autonomous driving wherein making safe and computationally efficient decisions with high-density traffic flow is usually non-trivial. Current rule-based methods decompose the decision-making task into several serial sub-modules, resulting in long computation time at complex scenarios for on-board computing devices. In this paper, we formulate the decision-making and control problem under intersections as a process of optimal path selection and tracking, where the former selects a path with the best safety measure from a set generated only considering static information, while the latter then considers dynamic obstacles and solve a tracking problem with safety constraints using the chosen path. To avoid the heavy computation introduced by that, we develop a reinforcement learning algorithm called generalized exterior point (GEP) to find a neural network (NN) solution offline. It first constructs a multi-task problem involving all the candidate paths and transforms it into an unconstrained problem with a penalty on safety violations. Afterward, the approximate feasible optimal control policy is obtained by alternatively performing gradient descent and enlarging the penalty. As an exterior point type method, GEP permits control policy to violate inequality constraints during the iterations. To verify the effectiveness of our method, we carried out experiments both in simulation and in a real road test. Results demonstrate that the learned policy can realize collision-free driving under different traffic conditions while reducing the computation time by a large margin.

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.

X ray mirrors are symmetrical workpieces along the length and width and are widely used in various optical systems. Unlike the center-symmetric circular mirror, it is more difficult to suppress the edge effect of the x ray mirror during the polishing process, which greatly limits the polishing accuracy and polishing efficiency. Based on this, the unique edge effect of x ray mirrors is investigated in depth in this paper. First, the causes and distribution laws of the edge effect of the x ray mirror were obtained by analyzing the inherent structure of the computer controlled optical surface (CCOS) and the motion trajectory of the polishing tool. Second, a mathematical model was established based on the material removal states of different regions on the x ray mirror. Finally, a combined polishing process based on the influence function of different shaped tools is proposed and experimentally verified. The results show that the edge effect on the x ray mirror is significantly weakened and its surface errors peak to valley (PV) and RMS are increased by 21.5 times and 47.9 times, respectively. This indicates that the combined polishing process has a good suppression effect on the edge effect of the x ray mirror.

Background Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear. Methods In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition. Results The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM. Conclusions Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.

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.

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.

Steering acid fracturing is a new way which can significantly increase oil and gas production. However, it is still unknown how to appropriately use steering acid in carbonate reservoir. Therefore, four true tri-axial acid fracturing experiments were carried out to study fracture initiation and propagation during steering acid fracturing. The experimental results reveal the following. 1. The results of the acid fracturing are easily affected by natural vugs, which can change the direction of the acid-etched fracture propagation. When there are few vugs in the reservoir, the steering acid etches the surface of the acid-etched fractures and forms crowds of acid-etched vugs. 2. When using high pumping rate, it is easy for the steering acid to plug the top of the acid-etched fracture and force the fracture to change its propagation direction. 3. The acid will etch the fracture surface, which results in a strong conductivity. The acid-etching phenomenon is obvious in the area near the wellbore and the turning area. The steering acid etches multiple channels with high conductivities rather than etching the entire area of the fracture surface. 4. Acid fatigue fracturing can effectively reduce the fracturing pressure. However, when using this method, there will be few acid-etched vugs in the area far from the wellbore. When acid is used as fracturing fluid, it would react with the carbonate, and form complex fracture networks.

Nucleocapsid protein (N-protein) is required for multiple steps in betacoronaviruses replication. SARS-CoV-2-N-protein condenses with specific viral RNAs at particular temperatures making it a powerful model for deciphering RNA sequence specificity in condensates. We identify two separate and distinct double-stranded, RNA motifs (dsRNA stickers) that promote N-protein condensation. These dsRNA stickers are separately recognized by N-protein's two RNA binding domains (RBDs). RBD1 prefers structured RNA with sequences like the transcription-regulatory sequence (TRS). RBD2 prefers long stretches of dsRNA, independent of sequence. Thus, the two N-protein RBDs interact with distinct dsRNA stickers, and these interactions impart specific droplet physical properties that could support varied viral functions. Specifically, we find that addition of dsRNA lowers the condensation temperature dependent on RBD2 interactions and tunes translational repression. In contrast RBD1 sites are sequences critical for sub-genomic (sg) RNA generation and promote gRNA compression. The density of RBD1 binding motifs in proximity to TRS-L/B sequences is associated with levels of sub-genomic RNA generation. The switch to packaging is likely mediated by RBD1 interactions which generate particles that recapitulate the packaging unit of the virion. Thus, SARS-CoV-2 can achieve biochemical complexity, performing multiple functions in the same cytoplasm, with minimal protein components based on utilizing multiple distinct RNA motifs that control N-protein interactions.

An accurate, rapid, and cost-effective biosensing strategy for the quantification of disease biomarkers is vital for the development of early-diagnostic point-of-care systems, benefiting overall human health. The recent discovery of the trans-cleavage activity of CRISPR type V effectors makes CRISPR a potential high-accuracy sensing system. In this study, we report the first CRISPR Cas12a (cpf1) based electrochemical biosensor (E-CRISPR), which is more cost-effective and portable comparing with optical transduction based biosensing systems. The trans-cleavage activity of Cas12a endonuclease is investigated by ssDNA reporter linked with electrochemical tag on a three-electrode based disposable sensor. To optimize the on-chip trans-cleavage activity of CRISPR in order to boost the detection sensitivity, the activity of different Cas12a analogs (LbCas12a and AsCas12a), the surface density of ssDNA reporter, the length of the ssDNA reporter, the trans-cleavage period, the activated operation concentration of Cas12a-crRNA complex and the concentration of divalent cation were investigated, providing an endonuclease favored condition for enhanced in vitro cleavage activity. To demonstrate the versatility of the system, the developed E-CRIPSR was firstly applied for the detection of nucleic acids, including Human papillomavirus 16 (HPV-16) and Parvovirus B19 (PB-19). Owing to the optimized chemical environment for the in vitro trans-cleavage of Cas12a, without any enzymatic amplification, a detection limit at pico molar level was achieved. We further designed an aptamer based E-CRISPR cascade for the detection of protein target. Quantification of transforming growth factor beta 1 (TGF-β1) protein in clinical samples was demonstrated as an example for protein detection. Owing to the combination of electrochemistry and CRISPR, we believe that the E-CRISPR could be a powerful enabler for wide developments of portable, accurate, and cost-effective point-of-care diagnostic systems.

MnO2 with various structures, including three tunnel structures (α-, β-, γ-MnO2) and a layered structure (δ-MnO2), were synthesized and investigated for peroxymonosulfate (PMS) activation. The effects of different structured MnO2 on PMS activation in contaminant degradation, as quantified by the pseudo-first order rate constants of bisphenol A (BPA) oxidation, followed the order: α-MnO2 > γ-MnO2 > β-MnO2 > δ-MnO2. Results showed that under acidic conditions, BPA was degraded by both catalytic oxidation by PMS-MnO2 and direct oxidation by MnO2, and the relative importance of the two mechanisms differed for different MnO2. The direct oxidation accounted for 25.2, 7.4, 34.1, and 94.5% of the total reactivity of α-, β-, γ-, and δ-MnO2, respectively. Physicochemical properties of MnO2 including crystal structure, morphology, surface Mn oxidation states, surface area, oxygen species and conductivity were characterized and correlated with the catalytic reactivity. The results demonstrated that the crystallinity of MnO2 was the dominant factor in the catalytic reactivity, resulting in the lowest reactivity for the least crystalline δ-MnO2. For the crystalline MnO2, the catalytic reactivity linearly correlated with Mn average oxidation state, Mn(III) content, and conductivity. Electron spin resonance (ESR) and quenching experiments with ethanol and tert-butanol suggested that sulfate radicals (SO4 −) were the dominant radicals in the systems, while hydroxyl radicals ( OH) played a minor role. In addition, nonradical mechanisms such as singlet oxygen (1O2) also contributed to the BPA degradation, especially when δ-MnO2 was the catalyst. These findings offered new insights into the contaminant degradation mechanisms in PMS-MnO2 and provided guidance to develop cost-effective catalysts for water/wastewater treatment.

Nature's great repository provides nucleic acids and amino acids as the fundamental elements of life. Inspired by the programmability of nucleic acids, DNA nanotechnology has been extensively developed based on the strand displacement reaction of nucleic acids. In comparison with nucleic acids, amino acids possess higher programmability and more functionalities owing to the diversity of the amino acid unit. However, the design of the peptide-based bimolecular cascade is still limited. We herein describe a peptide-based strand displacement reaction, which was granted with a specific biological function by addition of a functional domain onto the coiled-coil peptide based displacement substrate. The displacement substrate was specifically designed to response to Tau protein based on a well-established Tau inhibition sequence. We demonstrated that the kinetics of the designed displacement reaction can be dynamically tuned through blocking the toehold region to prevent migration. A nanomolar Tau detection linear range was achieved through the designed displacement reaction within a rapid turnaround time of 30 min. We also presented the capability of the peptide strand displacement based sensing system operating in real human biological samples and its excellent orthogonality on response to irrelevant biological components. We envision that this will be of especially high utility for the development of next-generation biotechnology.

A number of very recently developed electrochemical biosensing strategies are promoting electrochemical biosensing systems into practical point-of-care applications. The focus of research endeavors has transferred from detection of a specific analyte to the development of general biosensing strategies that can be applied for a single category of analytes, such as nucleic acids, proteins, and cells. In this Minireview, recent cutting-edge research on electrochemical biosensing strategies are described. These developments resolved critical challenges regarding the application of electrochemical biosensors to practical point-of-care systems, such as rapid readout, simple biosensor fabrication method, ultra-high detection sensitivity, direct analysis in a complex biological matrix, and multiplexed target analysis. This Minireview provides general guidelines both for scientists in the biosensing research community and for the biosensor industry on development of point-of-care system, benefiting global healthcare.

The establishment of ungulate embryonic stem cells (ESCs) has been notoriously difficult via a conventional approach. We combined a traditional ESC culture method with reprogramming factors to assist the establishment of porcine naive-like ESCs (nESCs). Pig embryonic fibroblasts were transfected with a tetracycline-inducible vector carrying 4 classic mouse reprogramming factors, followed by somatic cell nuclear transfer and culturing to the blastocyst stage. Then, the inner cell mass was isolated and seeded in culture medium. The naive-like ESCs had characteristic verys similar to those of mouse ESCs and showed no signs of altered morphology or differentiation, even after 130 passages. They depended on leukemia inhibitory factor signals for maintenance of pluripotency, and the female cell lines had low expression of the X-inactive specific transcript gene and no histone H3 lysine 27 trimethylation spot. Notably, the ESCs differentiated into 3 germ layers in vitro and could be induced to undergo directional neural and kidney precursor differentiation under defined conditions, and the ESCs could keep proliferating after doxycycline was removed. nESCs can be established, and the well-characterized ESC lines will be useful for the research of transgenic pig models for human disease.-Zhang, M., Wang, C., Jiang, H., Liu, M., Yang, N., Zhao, L., Hou, D., Jin, Y., Chen, Q., Chen, Y., Wang, J., Dai, Y., Li, R. Derivation of novel naive-like porcine embryonic stem cells by a reprogramming factor-assisted strategy.

This work examined the effects of two second metal oxides (SiO2 and TiO2) on the reductive reactivity of Fe(II)/goethite, an important natural reductant. SiO2 significantly inhibited the reductive ...

Three MnO2 nanoparticles with different tunnel structures, α-, β-, and γ-MnO2, were synthesized and characterized. We demonstrated and compared their capabilities on the electrochemical oxidation of nitrite, providing a new perspective for MnO2 or MnO2 based materials on sensing application. α-MnO2 exhibited higher electrochemical reactivity than β- or γ-MnO2, which was ascribed to its higher conductivity, more exposure to MnO6 edges, longer average Mn O bond length, and lower Mn average oxidation state(AOS). We hereby reported the first α-MnO2 nanoparticle-based electrochemical sensor for nitrite sensing. A highly controlled micro-plotter was used to deposit the MnO2 nanoparticles for the sensor fabrication, providing a micro-pattern of the sensing surface area of MnO2 and ensuring the reproducibility and sensitivity of this MnO2 based sensor. Using differential pulse voltammetry, a detection range of 10–800 μM of nitrite was accomplished along with a sensitivity of 17.1 μA μM−1 and a detection limit of 0.5 μM.

In order to perform the flow visualization of a shock train structure by the schlieren imaging method in the cylindrical isolator, to the best of our knowledge, a novel integrative design and processing scheme of an aluminum alloy pipe with an acrylic conformal optical window pair are proposed. The optical ray tracing and wavefront correction methods were applied to design the inner cylindrical surfaces and outer aspherical cylindrical surfaces of the optical window pair for parallel light correction based on the conjoint analysis with the processing capability. Under the tolerance analysis and the optimization of the machining path, the integrative model was fabricated on a three-axis computer numerical control machine using two-axis turning and fast tool servo machining. The wavefront aberration (peak-to-valley value) and wavefront aberration (RMS) of the optical window pair were corrected within 12.189 and 2.658 λ ( λ = 632.8 n m ) in the observation area which met the requirements of high-precision schlieren observation.

In this paper, we take a game called “Desert Crossing” into research. With the game strategy of avoiding failure and maximizing the revenue, we proposed a topological model for removing redundant paths in maps with Dijkstra. For the simple case of known daily weather in the game, we established a goal programming model with the constraint of game rules. A method based on Tree DP is proposed to solve the complex mathematical model. For the complex case of random weather, a probability model of weather is established by Markov Chain, and a multi-goal programming model is proposed.

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.

Integrated knowledge regarding pre-exposure prophylaxis (PrEP) awareness and willingness to use PrEP can be useful for HIV prevention in high incidence groups. This review summarizes the awareness of PrEP and willingness to use PrEP among men who have sex with men (MSM).Online electronic databases were searched before 31 August 2021. A meta-analysis was conducted to pool studies analysing PrEP awareness and willingness to use PrEP. LOESS regression and linear regression were applied to fit the trends over time for the proportion of MSM aware of PrEP and willing to use PrEP. Dose-response meta-analysis (DRMA) was conducted by a restricted cubic spline model to explore the relationship between willingness to use PrEP and selected factors.A total of 156 articles involving 228,403 MSM were included. The pooled proportions of MSM aware of PrEP and willing to use PrEP were 50.0 (95% CI: 44.8-55.2) and 58.6% (95% CI: 54.8-62.4), respectively. PrEP awareness varied among countries with different economic status and different WHO regions, among different publication and research years, PrEP types and support policies. PrEP willingness differed among countries with different economic status and groups with different risks of HIV. The awareness of PrEP increased from 2007 to 2019 with a slope of 0.040260 (p0.0001), while the proportion of MSM willing to use PrEP decreased from 2007 to 2014 (slope = -0.03647, p = 0.00390) but increased after 2014 (slope = 0.04187, p = 0.03895). The main facilitators of willingness to use PrEP were PrEP awareness, condomless sexual behaviours, high perceived risk of HIV infection and influence of social network. The main barriers were doubts about the efficacy and side effects of PrEP. DRMA results indicated that MSM with more sexual partners and lower level of education were more willing to use PrEP. No publication bias was observed.The proportions of PrEP awareness and willingness to use PrEP among MSM have increased since 2014, although the awareness was low and the willingness was moderate. Improving awareness of PrEP through increasing access to PrEP-related health education and enhancing risk perceptions of HIV infection could have positive effects on the willingness to use PrEP among MSM.

Aluminum optics are widely used in modern optical systems because of high specific stiffness and high reflectance. Magnetorheological finishing (MRF) provides a highly deterministic technology for high precision aluminum optics fabrication. However, the contamination layer will generate on the surface and bring difficulties for the subsequent processes, which highly limit the fabrication efficiency and precision. In this study, characteristics of the contamination layer and its formation process are firstly revealed through experimental and theoretical methods. Impurities such as abrasives are embedded into the aluminum substrate causing increasing surface hardness. The influence of the contaminant layer on machining accuracy and machining efficiency is analyzed in this study. Based on the analysis, ion beam sputtering (IBS) is induced as a contamination layer modification method. Impurities will be preferential sputtered during the process. Surface hardness and brightness will restore to the state before MRF. Moreover, the thickness of the contamination layer reduces dynamically during IBS because of the bombardment-induced Gibbsian segregation and sputter yield amplification mechanism. Consequently, we proposed a combined technique that includes MRF, IBS and smoothing polishing. Comparative experiments are performed on an elliptical shape plane surface. The results indicate that the efficiency has been increased sevenfold and surface precision is also highly improved. Our research will promote the application of aluminum optics to the visible and even ultraviolet band.

Single point diamond turning (SPDT) is highly versatile in fabricating axially symmetric form, non-axially-symmetric form and free form surfaces. However, inevitable microstructure known as turning marks left on the surface have limited the mirror’s optical performance. Based on chemical mechanical polishing (CMP) mechanism, smoothing polishing (SP) process is believed to be an effective method to remove turning marks. However, the removal efficiency is relatively low. In this paper, based on Greenwood-Williamson (GW) theory, the factors that limit removal efficiency of SP are discussed in details. Influences of process parameters (work pressure and rotational speed) are firstly discussed. With further analysis, surface spectral characteristics are identified as the inherent factor affecting further efficiency improvement. According to theoretical analysis, the removal efficiency of isotropic surface is nearly 1.8 times higher than anisotropy surface like surface with turning marks. A high efficiency turning marks removal process combining ion beam sputtering (IBS) and SP is proposed in our research. With removal depth exceeding 100 nm, the isotropic aluminum surface can be constructed by IBS so that the efficiency of SP process can be greatly improved. Though deteriorated by IBS, the surface roughness will be rapidly reduced by SP process. Finally, experiments are conducted to verify our analysis. A 3.7 nm roughness surface without turning marks is achieved by new method while direct SP can only reach roughness of 4.3 nm with evident turning marks. Experimental results show that removal efficiency nearly doubled which matches well with the theoretical analysis. Our research not only can be used as a high efficiency turning marks removal and surface quality improvement method but also can be a new method for high precision aluminum optics fabrication.

The surface quality and subsurface damage (SSD) distribution achieved with a fine-grained grinding wheel under different depth-of-cut and cutting speed is experimentally studied. The ground surface roughness (SR) is investigated via white light interferometry and expressed in terms of four typical roughness values (PV, RMS, Rz, and Ra). The SSD is characterized by the magnetorheological finishing (MRF) spot method and transmission electron microscopy. The results show that brittle-ductile surfaces and ductile-like surfaces are generated during ultra-precision grinding. Largely due to plastic flow removal, fracture defects such as fractured pits and grinding streaks on the ground surface can be mitigated. Instead, a ductile-like surface covered with grinding streaks is found. When the depth-of-cut decreases from 4 to 1 μm, the SR and SSD depth decreases from PV 1.34 μm, Ra 15.23 nm, Rz 0.94 μm, RMS 22.24 nm, and SSD 6.1 μm to PV 0.51 μm, Ra 5.07 nm, Rz 0.24 μm, RMS 6.70 nm, and SSD 1.2 μm. In addition, when the cutting speed increases from 3.9 to 23.4 m/s, the SR and SSD depth decreases from PV 1.03 μm, Ra 15.01 nm, Rz 0.82 μm, RMS 21.43 nm, and SSD 5.6 μm to PV 0.12 μm, Ra 3.17 nm, Rz 0.07 μm, RMS 4.65 nm, and SSD 0.003 μm. Moreover, the material removal mechanism under different grinding parameters is revealed by calculating undeformed chip thickness, and the mechanism of surface morphology and subsurface crack produced in brittle-ductile mode is analyzed. A linear relationship between the SR and SSD depth is in accord with the formula SSD = 0.41Ra−0.68 for brittle-ductile surfaces.

Islet transplantation is poised to play an important role in the treatment of type 1 diabetes mellitus (T1DM). However, there are several challenges limiting its widespread use, including the instant blood-mediated inflammatory reaction, hypoxic/ischemic injury, and the immune response. Mesenchymal stem/stromal cells (MSCs) are known to exert regenerative, immunoregulatory, angiogenic, and metabolic properties. Here, we review recent reports on the application of MSCs in islet allo- and xenotransplantation. We also document the clinical trials that have been undertaken or are currently underway, relating to the co-transplantation of islets and MSCs. Increasing evidence indicates that co-transplantation of MSCs prolongs islet graft survival by locally secreted protective factors that reduce immune reactivity and promote vascularization, cell survival, and regeneration. MSC therapy may be a promising option for islet transplantation in patients with T1DM.

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.

A three-step quasi-absolute testing method for optical cylinders is proposed in this Letter. Three measurements are taken at the so-called cat's eye position and confocal null testing positions with a computer-generated hologram (CGH) rotated around the axis parallel to that of the cylinder. The quasi-absolute surface error of the cylinder is obtained by simple operations including addition/subtraction and flip of the datasets. The uncertainty is traceable to an optical flat. Two different CGHs are used for a convex cylinder and give consistent quasi-absolute testing results of the surface error, which experimentally validates the method.

With the application spectrum moving from infrared to visible light, aluminum optics with complex forms are difficult to fabricate by the majority of existing processing methods. Possessing the highest machining precision and low processing contamination, ion beam figuring (IBF) is a better method for fabrication of aluminum optics. However, the surface roughness deteriorates with the removal depth during IBF. In this study, the extra material removal during the IBF process is studied systematically. Extra material removal consists of two parts, determined by the convolution process and the limitation of the dynamic performance of machining tools. Extra material removal can be reduced by filtering out the surface residual error with a spatial frequency higher than the cut-off frequency and reducing the iterations of the machining process. Then, the executability of the dwell time matrix and the figuring ability of the removal function are analyzed. Adjusting the working parameters (volume removal rate) reduces the requirements for dynamic performance of machining tools. Finally, a minimal material removal processing strategy for aluminum optics based on power spectral density analysis and a spatial frequency filtering method is proposed. A simulation is conducted to verify the feasibility of the proposed strategy. With the same final precision (59.8 nm PV and 4.4 nm RMS), the maximum material removal decreases nearly 36 nm by applying the strategy, which reduces roughness nearly 10 nm. This study promotes the application of IBF in the field of aluminum optics fabrication as well as improves the machining precision of aluminum optics.

Ion beam figuring (IBF) provides a deterministic figuring method for fabricating ultra-high precision optical components such as lithographic objective lenses. But in the previous IBF process, the convergence of surface accuracy is often uncertain. Therefore, the iterative processing methods are mostly adopted. In the iterative process, the convergence ratio (the ratio of root mean square before and after figuring) of single figuring is relatively low. With the improvement of machining accuracy, the convergence ratio continues to decrease. The study analyzes the factors that limit the convergence ratio of single processing and the influence form and degree of each element on the convergence ratio. Furthermore, we present an IBF strategy with a high convergence ratio based on an optimized removal function. Based on this strategy, we complete the figuring experiment. The convergence ratio is much higher than the previous level. Compared with the surface of iterative figuring, the surface is simple and more favorable to figuring to sub-nanometer precision. The experimental results show that we can optimize the removal function to achieve rapid optical surface fabrication with nanometer precision.

Ultra-smooth surfaces with low contamination and little damage are a great challenge for aluminum optical fabrication. Ion beam sputtering (IBS) has obvious advantages of low contamination and non-contact that make it a perfect method for processing aluminum optics. However, the evolution laws of aluminum surface morphology are quite different from conventional amorphous materials, which affects the roughness change and needs systematic research. Thus, in this paper, the roughness evolution of an aluminum optical surface (i.e., aluminum mirror) subjected to IBS has been studied with experimental and theoretical methods. The surface morphology evolution mechanisms of turning marks and second phase during IBS are revealed. The newly emerging relief morphology and its evolution mechanism are studied in depth. The experimental results find that IBS causes the coarsening of optical surfaces and the appearance of microstructures, leading to the surface quality deterioration. Turning marks have been through the process of deepening and vanish, while second phase generates microstructures on the original surface. The corresponding mechanism is discussed exhaustively. Preferential sputtering, curvature-dependent sputtering and material properties play important roles on surface quality deterioration. A modified roughness evolution mechanism and an improved binary sputtering theory are proposed to describe the polycrystalline sputtering phenomena. The current research can provide a guidance for the application of IBS in aluminum optics manufacture fields.

In recent years, requirements such as over-the-horizon, high resolution, large field of view, wide spectrum and dexterity have pointed out new directions for the development of optical imaging systems. Common optical surfaces such as planes and spherical surfaces have been difficult to meet the requirements of optical indicators. It is often necessary to use multiple high-precision complex optical surfaces such as high-order aspherical surfaces, off-axis aspherical surfaces, non-rotational symmetric curved surfaces, microstructured optical array surfaces and freeform surfaces. This brings processing, testing and adjustment in terms of problems, the monolithic multisurface optics as a new type of optical element are increasingly attracting researchers' attention.

BackgroundAcute hypoxic-ischemic brain damage (HIBD) occurs not only in newborns but also in adults. It is associated with series of cellular and biochemical pathways that lead to neuronal injury. N-3 polyunsaturated fatty acids (PUFAs) have been reported to improve neuron functions via G protein-coupled receptor 120 signal pathway in cells or with exogenous supplementation. Possible protective targets and underlying mechanisms of high proportion of n-3/n-6 PUFAs contained in the brains of mfat-1 transgenic mice on HIBD-induced adult brain damage needed to be further investigated.MethodsThe adult C57BL/6J (WT) and mfat-1 transgenic mice adopted HIBD model. A gas chromatograph was used to determine the composition of PUFAs. Neurological deficit scores test, TTC staining and Nissl staining were employed to evaluate the neuroprotective effects. Cleaved-caspase3 and TUNEL experiment were used to detect apoptosis after injury. Inflammatory factors were detected by ELISA assay. RNA-sequencing analysis was processed and the differential expressed genes were verified by real-time quantitative PCR. Key factors related to inflammation were detected by immunofluorescence and western blot.ResultsThe mfat-1 transgenic mice with high ratio of n-3/n-6 PUFAs in brain tissues were showed to have protective effects on HIBD-induced brain damage by reduced infarct range and greatly improved neurobehavioral defects. Further analysis revealed that the level of neuronal necrosis, apoptosis and inflammation induced by brain injury were relatively low. RNA-seq analysis showed multiple pathways and targets involved in this process. Significant activation of GPR120, reduction of phosphorylation of TAK1 and NF-κB P65 in the downstream of the pro-inflammatory pathway were found in the brains of mfat-1 mice on HIBD. ConclusionsThe study showed that mfat-1 transgenic mice had protective effects on HIBD-induced brain injury by multiple pathways. Activation of GPR120 and reduction of related pro-inflammatory pathway involved in this process, which may improve or prevent dangerous perioperative and postoperative complications, innovate clinical intervention strategy and potentially benefit more patients.

Xenotransplantation is a feasible method to treat organ failure. However, how to effectively monitor the immune rejection of xenotransplantation is a problem for physicians and researchers. This manuscript describes a simple and effective method to monitor immune rejection in pig-to-mouse cell transplantation models and pig-to-monkey artery patch transplantation models. Circulating DNA is a potentially non-invasive biomarker for organ damage. In this study, circulating pig-specific DNA (cpsDNA) was monitored during xenograft rejection by quantitative real-time PCR (qPCR). In this protocol, porcine specific primers were designed, plasmids-containing porcine specific DNA fragments were constructed, and standard curves for quantitation were established. Species-specific primers were then used to quantify cpsDNA by qPCR in pig-to-mouse cell transplantation models and pig-to-monkey artery patch transplantation models. The value of this method suggests that it can be used as a simple, convenient, low cost, and less invasive method to monitor the immune rejection of xenotransplantation.