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ATP-binding cassette transporter A1 (ABCA1) is required for the lipidation of apolipoprotein A-I (apoA-I), although molecular mechanisms supporting this process remain poorly defined. In this study, we focused on the role of cytosolic Ca2+ and its signaling and found that cytosolic Ca2+ was required for cholesterol efflux to apoA-I. Removing extracellular Ca2+ or chelating cytosolic Ca2+ were equally inhibitory for apoA-I lipidation. We provide evidence that apoA-I induced Ca2+ influx from the medium. We further demonstrate that calcineurin activity, the downstream target of Ca2+ influx, was essential; inhibition of calcineurin activity by cyclosporine A or FK506 completely abolished apoA-I lipidation. Furthermore, calcineurin inhibition abolished apoA-I binding and diminished JAK2 phosphorylation, an established signaling event for cholesterol efflux to apoA-I. Finally, we demonstrate that neither Ca2+ manipulation nor calcineurin inhibition influenced ABCA1's capacity to release microparticles or to remodel the plasma membrane. We conclude that this Ca2+-dependent calcineurin/JAK2 pathway is specifically responsible for apoA-I lipidation without directly modifying ABCA1 activity.

ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-poor apolipoprotein A-I (apoA-I) and generates HDL. Here, we demonstrate that ABCA1 also directly mediates the production of apoA-I free microparticles. In baby hamster kidney (BHK) cells and RAW macrophages, ABCA1 expression led to lipid efflux in the absence of apoA-I and released large microparticles devoid of apoB and apoE. We provide evidence that these microparticles are an integral component of the classical cholesterol efflux pathway when apoA-I is present and accounted for approximately 30% of the total cholesterol released to the medium. Furthermore, microparticle release required similar ABCA1 activities as was required for HDL production. For instance, a nucleotide binding domain mutation in ABCA1 (A937V) that impaired HDL generation also abolished microparticle release. Similarly, inhibition of protein kinase A (PKA) prevented the release of both types of particles. Interestingly, physical modulation of membrane dynamics affected HDL and microparticle production, rigidifying the plasma membrane with wheat germ agglutinin inhibited HDL and microparticle release, whereas increasing the fluidity promoted the production of these particles. Given the established role of ABCA1 in expending nonraft or more fluid-like membrane domains, our results suggest that both HDL and microparticle release is favored by a more fluid plasma membrane. We speculate that ABCA1 enhances the dynamic movement of the plasma membrane, which is required for apoA-I lipidation and microparticle formation.

Inflammatory processes play a central role in the development and complications of cardiovascular diseases (CVDs), profoundly affecting the severity and prognosis of these events. However, the current tools used to measure inflammation have some limitations. Blood biomarkers cannot pinpoint the location of inflammation and are vulnerable to various factors. Histological assessments ex vivo cannot accurately reflect the full dynamic picture of pathophysiology. The rapid development of positron emission tomography (PET) imaging not only enhances our understanding of biological processes in vivo but also contributes significantly to clinical management as a non-invasive biomarker. This review summarizes the PET imaging of key immune cell responses in CVDs, including immune cell metabolism, ligand/receptor interactions, and enzyme secretion, and discusses emerging opportunities and challenges in PET imaging-based inflammatory phenotyping and future perspectives.

Understanding the melting and sintering behavior of composite metal nanoparticles is of great significance to promote the synthesis and application of nanomaterials. In this work, molecular dynamics simulation method was employed to examine in detail the influence of sintering temperature, particle size and Fe content on the melting and sintering behavior of Cu-Fe mixed nanoparticles. The results show that the melting point of Cu-Fe mixed nanoparticles exhibits a strong size dependence and gradually increases with the increase in Fe content. High sintering temperatures significantly promotes the sintering process and the degree of atomic migration, and the diffusion behavior on the surface is enhanced, providing a significant driving force for sintering. Since smaller particle sizes have higher surface energy, the relationship between the neck parameters during the sintering process of different particle sizes is 4 nm > 6 nm > 8 nm, and the displacement of surface atoms is always greater than that of internal atoms. As the Fe content increases, the sintering of nanoparticles and the migration of atoms decrease, leading to a lower degree of sintering. This study further provides an atomic-scale theoretical basis for the melting and sintering behavior of Cu-Fe mixed nanoparticles.

The June 2013 extreme precipitation event in Alberta resulted in devastating flash floods that caused significant economic losses and societal disruption. In this study, two high-resolution experiments were conducted using the Weather Research and Forecasting (WRF) model to study the change of the 2013 Alberta extreme precipitation event in a warmer climate. The control experiment was forced with 6-hourly ERA-Interim reanalysis data, while the sensitivity experiment was forced with perturbed ERA-Interim reanalysis data with climate change signals derived from ten global climate models under the Representative Concentration Pathway 8.5 emission scenario. The results indicate that the 2013 Alberta extreme precipitation event is projected to exhibit two significant characteristics in a warming climate. First, precipitation is expected to increase over the Canadian Rocky Mountain region and eastern British Columbia. Second, the precipitation is expected to decrease over the Alberta and Saskatchewan Prairies. Future changes in the extreme precipitation event are associated with changes in the cyclone evolution, moisture transport, and atmospheric stability change caused by climate change. We also found that the increase in atmospheric stability due to the decrease of relative humidity in the lower atmosphere cause less precipitation to form over the plains and later enhance the orographic precipitation in the Canadian Rockies. In addition to the general increase of precipitable water under global warming, this mechanism causes the storm's precipitation to be more concentrated near the Canadian Rockies. The findings from this study could be beneficial for understanding future changes in extreme precipitation events that share similar characteristics.

ABSTRACT: Rising temperatures and intensified agricultural practices have heightened heat stress (HS)-related challenges in poultry farming, notably heat-induced sudden death in chickens. Wenchang chickens, recognized for their heat resistance, have emerged as the potential candidates for improving the economic efficiency of poultry farming. The adrenal gland plays a crucial role in preventing HS-induced heart failure sudden death by secreting hormones. However, little is known about the damage to and resilience of Wenchang chicken adrenal glands during HS. In this study, 34 healthy Wenchang chickens with similar weights were selected for formal experimentation, with 10 as the control group (Con). Following a single exposure to acute HS of 42 ± 1°C and 65% relative humidity for 5 h, 15 deceased individuals formed the HS death (HSD) group, and 9 survived comprised the HS survival (HSS) group. ELISA revealed significant higher (P < 0.05) levels of COR and NE in the HSS and the lowest levels of CORT and EPI in the HSD. Histopathological analysis indicated major degeneration in HSS cortical and chromaffin cells and extensive cell necrosis (nuclear pyknosis) in HSD. Proteomic analysis identified 572 DEPs in HSD vs. Con and 191 DEPs in HSS vs. Con. Bioinformatics highlighted ER protein processing, especially ERAD as a key pathway for heat stress resistance (HSR) in the adrenal gland, with HSPH1, DNAJA1, HSP90AA1, HSPA8 and HERPUD1 identified as regulating key molecules. Western blotting validated significantly higher (P < 0.01) protein levels in both HSS and HSD compared to the Con. Immunohistochemical staining showed increased cytoplasmic HSPH1-positive signal intensity under HS and enhanced HSP90AA1 nuclear signals, strongest in HSS. In summary, HS induces pathological damage in Wenchang chicken adrenal glands, affecting hormone secretion, and various heat shock proteins play crucial roles in cellular resistance. These results elucidate the biological basis of HSR in Wenchang chickens from the perspective of the adrenal gland and provide necessary research foundations for enhancing economic performance of various broilers in high-heat environments and screening drugs for HS treatment.

High-entropy alloys (HEA) are a unique class of engineering alloys with excellent properties, and the study of their weldability is one of the key steps in applying them in the engineering field. AC/DC mixed gas tungsten arc welding (MIX-GTAW) can achieve high-quality welding of metal components, but there are few reports on the use of MIX-GTAW for HEA welding. This study focused on the (FeCoNi)96Al4 HEA and investigated the weld formation, microstructure, and mechanical properties of the (FeCoNi)96Al4 HEA MIX-GTAW to explore the possibility of using MIX-GTAW for high-entropy alloys. The results showed that the MIX-GTAW weld seam produced fish scale patterns, and compared to those of the DC-GTAW weld seam, the surface oxidation phenomenon was improved. The microstructure of the MIX mode weld seam with 40% AC (MIX-2) is significantly improved, resulting in a smaller average grain size. The weld structure index J of MIX-2 (40% AC) is 3.27, and the maximum strength in the PF diagram decreases to 6.90. The minimum ultimate tensile strength after welding can reach 435 MPa, with an elongation after fracture of 61%, maintaining a tensile strength of 94.26% of the base material and an elongation of approximately 90%. The average hardness of the (FeCoNi)96Al4 HEA welded sample fluctuates between 167 and 180 HV, and the hardness of the center of the weld seam is higher than that of the base metal.

In this study, nano Ti/AZ31 composites were successfully prepared by powder metallurgy method, and the strength and plasticity of the composites were improved in both directions. The SEM shows that the Ti particles were evenly distributed at the grain boundary in the sintered composite, and the Ti particles pin the grain boundary to make the grain of the composite significantly refined. EBSD shows that the addition of nano Ti particles significantly reduces the texture strength of the composite and increases the starting probability of the slip system. TEM shows that nano Ti and AZ31 matrix formed stable Al3Ti and MgO phases at the interface, and shows a strong coherent relationship. The nanoindentation test shows that the Ti/AZ31 interface of the composite was stable, the interface bonding energy and interface fracture toughness were gradiently distributed, and the bonding energy and fracture toughness of the interface bonding area were better than those of the matrix. Tensile test shows that the 1.5 wt%Ti/AZ31 composite obtained the best comprehensive mechanical properties with yield strength, ultimate tensile strength and elongation of 143 MPa, 243 MPa and 11.5%, respectively, obviously higher than those of AZ31 alloys. The increased strength was mainly due to the grain refinement and strengthening at grain boundaries. The improved ductility was the result of weakened texture, increase of slip system start-up probability and strong interfacial bonding between Ti particles and AZ31 matrix.

Backgrounds: It is well known that epicardial adipose tissue (EAT) is associated with the development of atrial fibrillation (AF). The aim of this study was to investigate whether EAT density (EAT-d) is associated with the development of new-onset atrial fibrillation (POAF) after aortic valve replacement (AVR). Methods: We retrospectively studied 143 patients who underwent simple AVR at Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command between June 2020 to August 2023. All patients received cardiac coronary artery computed tomography (CT) before surgery. EAT-d, EAT volume and EAT volume index (EATVI) were quantitatively measured and analysed using EAT analysis software (TIMESlicePro). POAF was detected by 7-day Holter monitoring. Results: Of 143 patients undergoing AVR, 55 patients (38.46 %) developed POAF after surgery. Male patients and patients who had elder age or smoking history were more likely to develop POAF. On univariable analysis, patients developed POAF had significantly more EAT-d (−79.19(−83.91, −74.69) vs. −81.54(−87.16, −76.76); P = 0.043) and EATVI (4.14(3.32,5.03) vs. 3.90(2.70,4.51); P = 0.043) than patients without POAF. On multivariable analysis, EAT-d and age were independent risk factors for POAF (odds ratio (OR): 1.186, 95 % confidence interval (CI): 1.062–1.324, P = 0.002; OR: 1.119, 95 %CI: 1.055–1.187, P

In diabetic patients, compromised angiogenesis due to endothelial dysfunction leads to delayed intraoral wound healing. However, the moist and dynamic environment of the oral cavity impedes the use of normal wound dressings. Sulfated chitosan (SCS) is a promising biomaterial that promoting angiogenesis. Here, a light-responsive hydrogel combined with SCS explored intraoral wound healing. We designed a SCS-modified hydrogel combined with alginate Methacryloyl (AlgMA) and acrylamide (AM) and demonstrated efficient wet adhesion and mechanical properties suitable for the wet and dynamic oral environment. In vitro, the SAA hydrogel improved the tube formation of human umbilical vein endothelial cells (HUVECs) under high-glucose conditions. Further investigations revealed that the SAA hydrogel can regulate HUVEC-macrophage interactions, leading to a shift in macrophage polarization from M1 to M2, thereby fostering an environment conducive to angiogenesis under high-glucose condition. The results demonstrated the substantial therapeutic impact of the SAA hydrogel on diabetic oral defect repair by effectively enhancing the local blood supply and angiogenesis.

Anomalous behaviors in social networks can lead to privacy leaks and the spread of false information. In this paper, we propose an anomalous behavior detection method based on optimized graph embedding representation. Specifically, the user behavior logs are first extracted into a social network user behavior temporal knowledge graph, based on which the graph embedding representation method is used to transform the network topology and temporal information in the user behavior knowledge graph into structural embedding vectors and temporal information embedding vectors, and the hybrid attention mechanism is used to merge the two types of vectors to obtain the final entity embedding to complete the prediction and complementation of the temporal knowledge graph of user behavior. We use graph neural networks, which use the temporal information of user behaviors as a time constraint and capture both user behavioral and semantic information. It converts the two parts of information into vectors for concatenation and linear transformation to obtain a comprehensive representation vector of the whole subgraph, as well as joint deep learning models to evaluate abnormal behavior. Finally, we perform experiments on the Yelp dataset to validate that our method achieves a 9.56% improvement in the F1-score.

A novel magnesium-based multi-principal element alloy with the chemical formula Mg54Al22Li11Zn11Ti2 was prepared using the vacuum induction melting method and subsequently extruded at 350 °C. The phase composition of the alloy in its as-cast state and the microstructural changes after extrusion were investigated using various analytical techniques, including SEM, EBSD, EPMA, and TEM. The presented outcomes showed that the as-cast alloy exhibited lattice distortion and fine grain with segregation, while the average grain size decreased significantly and the second phase became more dispersed after extrusion. The mechanical properties of both the as-cast and extruded alloys, including microhardness, tensile strength, compressive strength, and wear characteristics, were evaluated. The extruded alloy demonstrated significant improvements in mechanical properties compared to the as-cast alloy, with a compressive strength of up to 460 MPa, which can be attributed to both fine grain and precipitation strengthening. Both the as-cast and extruded alloys exhibited high hardness due to the accumulation of local dislocations caused by the interlaced precipitation of sub-grains during the super-solid solution state in the as-cast condition. The hardness enhancement in the extruded state resulted from grain refinement induced by DRX. Furthermore, wear tests revealed that the extruded alloy, characterized by smaller second phase sizes, exhibited excellent wear resistance, with wear failure occurring in the form of abrasive and oxidative wear in both the cast and extruded alloys.

Shield tunnels built in soft soil are prone to settlement, which is often accompanied by convergence deformation, further resulting in a series of damages to the tunnel structure and compromise its safety in service. This paper presents an engineering case on the settlement development and internal drilling grouting remediation of a tunnel section in Shaoxing Metro Line 1, where the inner diameter and thickness of the tunnel linings are increased to be 5.9 m and 400 mm simultaneously. The tunnel settlement arises from a comprehensive analysis of several contributing factors, encompassing ground disturbances such as pile driving, pile extraction, backfilling of pile holes, road structure construction, and road traffic. A grouting remediation plan is thoughtfully designed, including a careful assessment on the necessity for a temporary steel support system which is based on a full-scale three-ring test of the tunnel structure. The deformation of the tunnel during settlement and grouting processes is thoroughly analyzed to investigate the deformation resistance capacity exhibited by the thickened larger-diameter tunnel. The case study and experimental results demonstrate that tunnel structures with an increased diameter and thickness have better deformation resistance than conventional metro tunnels in soft soil layers. The analysis of this study can provide a reference for tunnel structures optimization and similar grouting remediation projects in shield tunnels.

Aim: Prior research has indicated a connection between CD4+ T cells and the development of anxiety, but the specific CD4+ T cell subsets linked to anxiety disorders remain uncertain. Our study seeks to investigate the relationship between distinct CD4+ T cell subsets and anxiety, as well as to explore whether CD4+ T cell subsets mediate the effect of chronic psychological stress on anxiety. Methods: 56 eligible matched participants were recruited in Peking Union Medical College Hospital. The diagnosis was made based on DSM-5 diagnostic criteria. The severity of anxiety and depression symptoms was assessed using the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale, respectively. The Life Events Scale (LES) evaluated the chronic stress level. CD4+ T cell subsets were characterized using multiparametric flow cytometry. To assess the impact of CD4+ T cells on the effect of chronic psychological stress on anxiety, Partial Least Squares Structural Equation Modeling (PLS-SEM) analysis was employed. Results: We discovered fifteen notably distinct CD4+ T-cell subsets in anxiety disorder patients compared to healthy controls. Multiple linear regression analysis unveiled an association between anxiety severity and CD27+CD45RA− Th cells, CD27+CD28+ Tregs, and the total Life Events Scale (LES) score. The PLS-SEM analysis demonstrated that CD4+ T cell subsets and LES could explain 80.2% of the variance in anxiety. Furthermore, it was observed that CD27+CD28+ Th/Treg cells acted as inverse mediators of the effects of LES on anxiety (P = 0.031). Conclusions: Drug naïve anxiety disorder patients exhibited significant alterations in numerous CD4+ T-cell subsets. Specifically, the memory subset of CD27+CD45RA− Th cells and the naïve subset of CD27+CD28+ Treg cells were found to be independent factors associated with the severity of anxiety. Additionally, the CD27+CD28+ Th and Treg cell subsets played a significant mediating role in the influence of long-term psychological stress on anxiety.

This work investigated the effects of the combined use of thermosonication-preconditioned lactic acid bacteria (LAB) with the addition of ultrasound-assisted pineapple peel extracts (UU group) on the post-acidification potential, physicochemical and functional qualities of yogurt products, aimed at achieving prolonged preservation and enhancing functional attributes. Accordingly, the physical–chemical features, adhesion properties, and sensory profiles, acidification kinetics, the contents of major organic acids, and antioxidant activities of the differentially processed yogurts during refrigeration were characterized. Following a 14-day chilled storage process, UU group exhibited acidity levels of 0.5–2 oT lower than the control group and a higher lactose content of 0.07 mg/ml as well as unmodified adhesion potential, indicating that the proposed combination method efficiently inhibited post-acidification and delayed lactose metabolism without leading to significant impairment of the probiotic properties. The results of physicochemical analysis showed no significant changes in viscosity, hardness, and color of yogurt. Furthermore, the total phenolic content of UU-treated samples was 98 μg/mL, 1.78 times higher than that of the control, corresponding with the significantly lower IC50 values of DPPH and ABTS radical scavenging activities of the UU group than those of the control group. Observations by fluorescence inverted microscopy demonstrated the obvious adhesion phenomenon with no significant difference found among differentially prepared yogurts. The results of targeted metabolomics indicated the proposed combination strategy significantly modified the microbial metabolism, leading to the delayed utilization of lactose and the inhibited conversion into glucose during post-fermentation, as well as the decreased lactic acid production and a notable shift towards the formation of relatively weak acids such as succinic acid and citric acid. This study confirmed the feasibility of thermosonication-preconditioned LAB inocula, in combination with the use of natural active components from fruit processing byproducts, to alleviate post-acidification in yogurt and to enhance its antioxidant activities as well as simultaneously maintaining sensory features.

Background and aims: Postoperative atrial fibrillation (POAF) is considered the most prevalent irregular heart rhythm after heart surgery. The cardiac autonomic nervous system significantly affects POAF, and neuropeptide Y (NPY), an abundant neuropeptide in the cardiovascular system, is involved in this autonomic regulation. The current work aimed to examine the potential association of NPY with POAF in individuals administered isolated off-pump coronary artery bypass grafting. Methods: From January 1 to May 31, 2020, we examined consecutive cases administered successful isolated off-pump coronary artery bypass grafting with no previously diagnosed atrial fibrillation (AF). Clinical characteristics and plasma samples were collected before surgery. NPY was quantified by enzyme-linked immunosorbent assay (ELISA) in peripheral blood, and POAF cases were identified through a 7-day Holter monitoring. Results: Among 120 cases with no previously diagnosed AF, 33 (27.5 %) developed POAF during hospitalization. Median NPY levels were markedly elevated in the POAF group in comparison with the sinus rhythm group (31.72 vs. 27.95, P = 0.014). Multivariable logistic regression analysis revealed age (OR = 1.135, 95%CI 1.054–1.223; P = 0.001), left atrial size (OR = 1.136, 95%CI 1.004–1.285; P = 0.043), and NPY levels in peripheral blood (OR = 1.055, 95%CI 1.002–1.111; p = 0.041) independently predicted POAF. Additionally, NPY levels were positively correlated with high-frequency (HF) (r = 0.2774, P = 0.0022) and low-frequency (LF) (r = 0.2095, P = 0.0217) components of heart rate variability. Conclusion: In summary, this study demonstrates an association between elevated NPY levels in peripheral blood before surgery and POAF occurrence.

Nowadays, 3D printing has become a popular method among surgeons due to its merits in orthopedic treatments. In this method, polymeric biomaterials are deposited in a layer-by-layer manner to fabricate 3D objects that can be used as orthopedic implants and plates; however, 3D-printed implants or plates may lack properties required to bond with host tissue. Coating surface of plates with nano-fibers is an appropriate way to modify plates to overcome this challenge. In this study, first, an orthopedic plate was 3D printed with Polylactic acid (PLA) and coated with polycaprolactone (PCL)/Akermanite (AKT) nano-fibers. The composition included 8 wt% of PCL and 3 wt% of nAKT, while diameter of the PCL/AKT nano-fibers was approximately 253 nm ± 33 nm. Thermomechanical properties such as pressure, three-point bending flexural, and thermal conductivity of coated and non-coated specimens were examined and compared. In the next step, the bioactivity of the coated samples was evaluated following a 28-day immersion in simulated body fluid (SBF). Further, scanning electron microscope (SEM) images were taken to assess morphology of nanofibers and apatite formation on samples. By adding PCL to PLA, the maximum pressure force is enhanced by 16.83%. Further by adding nAKT to PLA + PCL sample, the maximum pressure force is enhanced by 4.72%. Further, by adding PCL to PLA, the maximum bending flexural force is enhanced by 21.06%. Further by adding nAKT to PLA + PCL sample, the maximum bending flexural force is enhanced by 21.39%. The results of this study are used to improve modeling of the orthopedic plates.

TC4 titanium alloy wire arc additive manufacturing (WAAM) is easy to produce coarse columnar β grain structure which affects mechanical properties. So in this paper, an innovative process of interpass milling assisted TC4 titanium alloy gas tungsten arc welding (GTAW) WAAM is proposed. The controlling interpass milling depth is used to improve the microstructure and mechanical properties of TC4 titanium alloy parts during the GTAW-WAAM. The results showed that the coarse columnar β grains and fine α phase were observed in the non-interpass milling part. When the interpass milling assistance GTAW-WAAM was employed, the coarse columnar β grains transformed into short columnar and equiaxed grains. With the increased of interpass milling depth, the average size of α phase was gradually refined to 13.5 μm below. The highest average microhardness in the top, middle and bottom areas obtained by using the interpass milling depth of 300 μm were 369 HV0.2, 371 HV0.2 and 371 HV0.2 respectively, which was increased by 32 HV0.2, 28 HV0.2 and 26 HV0.2 compared with non-interpass milling respectively. The horizontal and vertical ultimate tensile strength first increases and then decreases with the increase of interpass milling depth, reaching its maximum at a milling depth of 300 μm. The highest tensile strength of the horizontal and vertical directions obtained by using the interpass milling depth of 300 μm were 1022 MPa and 1042 MPa. The level of the ultimate tensile strength is related to the combined proportion of total average β grain size and total average

Good surface forming accuracy is an important indicator for evaluating the quality of the additive components, especially for complex components that require high surface forming accuracy, and the regulation of microstructure and properties has a very important impact on metal processing and manufacturing. In this study, an experimental device for interpass milling hybrid direct energy deposition-arc was developed. Combined with the simulation method, the effect of interpass milling on the forming accuracy was deeply studied from the liquid metal's force and flow behavior. The changes in microstructure and properties were also studied in depth from the evolution mechanism of residual stress and the solidification of liquid metal, thereby enhancing the controllability of the forming and properties of stainless steel additive components. The results showed that the addition of interpass milling refined the grains, weakened the orientation texture of the crystal plane, and significantly improved the uniformity of the microstructure. Finally, the additive component with the best mechanical properties was obtained at a milling depth of 200 μm, with a 31.8 % increase in microhardness, 14.9 %, and 59.2 % increase in tensile strength and elongation, respectively. The anisotropy to isotropy of the deposited sample was transformed.

Additive manufacturing (AM) of metal usually forms columnar grains along the building direction due to the focused thermal energy directly heating the deposition layer to easily obtain an obvious temperature gradient. The columnar grains are not conducive to AM-sample application, which results in the property anisotropy of the AM-sample. In this work, a novel directed energy deposition-arc (DED-Arc) method for depositing layers without direct heating by focused thermal energy is proposed. The arc burns between the tungsten electrode and a water-cooled electrode, were only used to melt the wire during DED-Arc process. Using stainless steel wire as a model alloy, by studying droplet transfer, morphology of the deposition layer and microstructure evolution, the feasibility of the method was fully verified. Two kinds of droplet transfer modes were observed, and the difference between them was whether the droplet contacted the molten pool before falling off. The focused thermal energy is only used to melt the wire, and the droplet transfer cycle is mainly affected by gravity, greatly decreasing the heat accumulation compared with existing methods. The heat-affected zone (HAZ) was obviously inhibited. The grain morphology of the deposition layer mainly consists of equiaxed crystals (∼300 μm) without an obvious preferred orientation. The deposition layer without direct heating by focused thermal energy could reduce the heat accumulation, resulting in a decrease in the temperature gradient and the morphology of equiaxed grains. The microstructure of a cylindrical sample was produced and has the same characteristics as with the deposition layer. The average microhardness of 172.63 HV, 167.95 HV and 169.26 HV are obtained in the top, middle and bottom regions, respectively. In addition, the tensile strengths are 500 MPa and 490 MPa, respectively.

Summary: Directed self-assembly (DSA) lithography has demonstrated significant potential in fabricating integrated circuits. However, DSA encounters limited processing windows due to the requirement for precise matching between the period of block copolymers (BCPs) and graphoepitaxy templates. We propose a binary BCP/homopolymer blending strategy to manipulate the self-assembly behavior and the processing window of graphoepitaxy DSA in contact hole shrinking. By carefully tailoring the blending rates of poly(methyl methacrylate) (PMMA) with different molecular weights in cylindrical polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA), we manipulate the period and morphology of BCP/homopolymer self-assembly. Specifically, we employ BCP/homopolymer blending to fine-tune the critical dimension (CD) of contact holes with PS-affined topographical templates. Subsequent pattern transferring is achieved by selectively etching defect-free shrinkable cylinders as hard masks. Furthermore, self-consistent field theory (SCFT) simulation was employed to explore the self-assembly of BCP/homopolymer blending in confined cylindrical space and the results were in good consistency with the experimental results.

Summary: Tumor-derived small extracellular vesicles (TEVs) play a pivotal role in cancer progression by transferring functional biomolecules between the parental and recipient cells. Here, we present a protocol to isolate TEVs directly from murine primary mammary tumor using differential centrifugation. We describe steps for tissue dissociation, enzymatic digestion, and centrifugation. We then detail procedures for characterization of TEVs through transmission electron microscopy, immunoblotting, and nano-flow cytometry. This protocol can be used to extract EVs from other solid tumor types.For complete details on the use and execution of this protocol, please refer to Li, Mei-Xin et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The chemical recycling of polyolefin presents a considerable challenge, especially as upcycling methods struggle with the reality that plastic wastes typically consist of mixtures of polyethylene (PE), polystyrene (PS), and polypropylene (PP). We report a catalytic aerobic oxidative approach for polyolefins upcycling with the corresponding carboxylic acids as the product. This method encompasses three key innovations. First, it operates under atmospheric pressure and mild conditions, using O2 or air as the oxidant. Second, it is compatible with high-density polyethylene, low-density polyethylene, PS, PP, and their blends. Third, it uses an economical and recoverable metal catalyst. It has been demonstrated that this approach can efficiently degrade mixed wastes of plastic bags, bottles, masks, and foam boxes.

The recycling of key components in waste lithium-ion batteries (LIBs) is an important route to make up for the shortage of battery materials. Metal separation and purification is an important step. It is of great significance to propose an efficient and green separation technology. In this paper, an electrochemical precipitation method was applied to metal separation from spent LiNi0.5Mn1.5O4 cathode material. The Li and metal elements were effective separated and the precipitates were then used as precursor to synthesize high-performance R–O3-NaNFM cathode material for sodium-ion batteries. The R–O3-NaNFM exhibits excellent electrochemical cycling stability. The capacity retains 71.3 mAh g−1 after a long-term cycling of 200 times at 1 C. This method offers a referable strategy of the recycling for the waste cathode material in spent LIBs.

ABSTRACT: Heat stress (HS) can result in sudden death and is one of the most stressful and costly events in chicken. Currently, biomarkers used clinically to detect heat stress state in chickens are not optimal, especially for living ones. Analysis of changes in serum proteins of heat-stressed chickens can help to identify some novel convenient biomarkers for this. Twenty-four chickens were exposed to HS at 42°C ± 1°C with a relative humidity of 65% for continuous 5 h in a single day, and 10 birds were used as controls (Con). During HS, 15 dead chickens were categorized as heat stress death group (HSD), and 9 surviving ones served as heat stress survivor group (HSS). Label-free quantitative proteomics (LFQP) was used to analyze differentially expressed proteins (DEPs) in serum of tested animals. Candidate proteins associated with HS were validated by enzyme-linked immunosorbent assay (ELISA). Diagnostic value of candidate biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Source of the selected proteins was analyzed in liver tissues with immunohistochemistry and in cell culture supernatant of primary chicken hepatocytes (PCH) using ELISA. In this study, compared to Con, LFQP identified 123 and 53 significantly different serum proteins in HSD and HSS, respectively. Bioinformatics analysis showed that XDH, POSTN, and HSP90 were potential HS biomarkers in tested chickens, which was similar with results from serum ELISAs and immunohistochemistry in liver tissues. The ROC values of 0.793, 0.752, and 0.779 for XDH, POSTN, and HSP90, respectively, permitted the distinction of heat-stressed chickens from the control. Levels of 3 proteins above in the cell culture supernatant of PCH showed an increasing trend as HS time increased. Therefore, considering that mean concentration of POSTN in serum was higher than that of HSP90, XDH, and POSTN may be optimal biomarkers in serum for detecting HS level in chickens, and mainly secreted from hepatocytes. The former indicates that heat-stressed chickens are in a damaged state, and the latter implies that chickens can repair heat stress damage.

Summary: Deep brain stimulation (DBS) in the basal lateral amygdala (BLA) has been established to correct symptoms of refractory post-traumatic stress disorder (PTSD). However, how BLA DBS operates in correcting PTSD symptoms and how the BLA elicits pathological fear and anxiety in PTSD remain unclear. Here, we discover that excitatory synaptic transmission from the BLA projection neurons (PNs) to the adBNST, and lateral central amygdala (CeL) is greatly suppressed in a mouse PTSD model induced by foot shock (FS). BLA DBS revises the weakened inputs from the BLA to these two areas to improve fear and anxiety. Optogenetic manipulation of the BLA-adBNST and BLA-CeL circuits shows that both circuits are responsible for anxiety but the BLA-CeL for fear in FS mice. Our results reveal that synaptic transmission dysregulation of the BLA-adBNST or BLA-CeL circuits is reversed by BLA DBS, which improves anxiety and fear in the FS mouse model.

The novel AZ31B/SiCps composite was prepared by wire-arc directed energy deposition (DED-Arc) method. The effects of SiCps content in the range of 1.0–3.0 wt% on grain orientation, average grain size, grain boundary angle distribution, and mechanical properties of AZ31B magnesium alloy were studied. The results showed that SiCps, as a reinforcing phase uniformly dispersed in the matrix, could effectively reduce the free energy of the α-Mg matrix, and promoted non-uniform nucleation as a heterogeneous nucleation point. At the same time, SiCps was also pushed to the grain boundary by the solid-liquid interface, hindering the columnar grain of epitaxial growth, which helped to reduce the subcooling of components at the grain growth front (ΔTcs = ΔTn-min). With the increase of SiCps mass fraction, the transformation of columnar crystals to equiaxed crystals was realized. The average grain size of the deposited specimen and the texture strength of the crystal face of the α-Mg matrix (0001) gradually decreased. Finally, the AZ31B magnesium alloy with a mass fraction of 2.0 wt% SiCps exhibited excellent mechanical properties with a tensile strength of 233.35 MPa and an elongation of 24.04%. The anisotropy of the deposited sample was converted to isotropy.

A new method of Ultrasonic-Magnetic field coaxial hybrid GTAW (U-M-GTAW) was proposed in this paper to improve the joints properties by coaxially coupling ultrasonic vibration and magnetic field to the welding arc. The microstructure and mechanical properties of 304 stainless steel in the welded joints of GTAW, Ultrasonic-GTAW (U-GTAW), Magnetic field-GTAW (M-GTAW), and U-M-GTAW were compared and analyzed to clarify the mechanism of microstructure evolution and mechanical properties changes under the combined action of the ultrasonic and magnetic field. The results showed that the U-GTAW arc energy was increased and the grain size in the joint center was reduced by 25.7% compared to GTAW. The heat affected zone (HAZ) of the M-GTAW joint almost disappeared and the columnar crystals gradually transformed into equiaxed crystals, exhibiting the lowest texture strength. When ultrasonic and magnetic field were applied to GTAW together, the grain size of the U-M-GTAW joint center was reduced by 12.4% compared to GTAW, and the joint center was almost completely transformed into equiaxed crystals. The external energy fields all improved the mechanical properties of the joints, with the most significant improvement in U-M-GTAW.

The high expression of programmed death 1 (PD-1) is a hallmark of T cell exhaustion, consequently inhibiting the anti-tumor immunity, tumor-associated macrophages (TAMs) aggravate Osteosarcoma (OS) progression. However, PD-1 expression on TAMs in OS metastasis remains unclear. Here, we used scRNA-Seq of 15500 individual cells from human OS lung metastatic lesion, identified thirteen major cell clusters. Our data revealed that tumor-infiltrating lymphocytes (TILs) OS lung metastatic accompanied by accumulation of exhausted T cells and regulatory T cells (Tregs). CD3+ T cells from human OS lung metastatic exhibited lower proliferation than in primary tissue. Importantly, TAMs mainly comprise immunosuppressive M2 phenotype in OS metastasis. Mechanistically, we found that PD-1 of TAMs inhibits the phagocytic potency, further promoting the progression of OS metastasis. Therefore, the study provides a strong technical support for OS immunotherapy based on PD-1 inhibitors.

Block copolymer (BCP) self-assembly has tremendous potential applications in next-generation nanolithography. It offers significant advantages, including high resolution and cost-effectiveness, effectively overcoming the limitations associated with conventional optical lithography. In this work, we demonstrate a focused solar annealing (FSA) technique that is facile, eco-friendly, and energy-efficient for fast self-assembly of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) thin films. The FSA principle involves utilizing a common biconvex lens to converge incident solar radiation into a high-temperature spot, which is directly used to drive the microphase separation of PS-b-PMMA thin films. As a result, PS-b-PMMA undergoes self-assembly, forming ordered nanostructures in a vertical orientation at seconds timescales on silicon substrates with a neutral layer. In addition, the FSA technique can be employed for grafting neutral polymer brushes onto the silicon substrate. Furthermore, the FSA's compatibility with graphoepitaxy-directed self-assembly (DSA) of BCP is also demonstrated in the patterning of contact holes. The results of contact hole shrinking show that contact hole prepatterns of ∼60.4 nm could be uniformly shrunk to ∼20.5 nm DSA hole patterns with a hole open yield (HOY) of 100 %. For contact hole multiplication, doublet DSA holes were successfully generated on elliptical templates, revealing an average DSA hole size of ∼21.3 nm. Most importantly, due to the direct use of solar energy, the FSA technique provides many significant advantages such as simplicity, environmental friendliness, solvent-free, low cost, and net-zero carbon emissions, and will open up a new direction for BCP lithography that is sustainable, pollution-free, and carbon-neutral.

Recent studies have shown that B cells and the associated tertiary lymphoid structures (TLS) correlate with the response of patients to immune checkpoint inhibitors (ICIs) and predict overall survival (OS) in cancer patients. We screened 145 B cell marker genes (BCMG) by a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of head and neck squamous cell carcinoma (HNSC) from the Gene Expression Omnibus (GEO) database. The BCMG signature (BCMGS) was established using The Cancer Genome Atlas (TCGA) dataset of HNSC and verified in four independent datasets. The multivariate Cox regression analysis identified the signature as an independent prognostic factor. A prognostic nomogram was constructed with independent prognostic factors using the TCGA dataset. GO and KEGG analysis revealed the underlying signaling pathways related to this signature. Study of immune profiles showed that patients in the low-risk group presented discriminative immune-cell infiltrations. Furthermore, the low-risk group was featured by higher TCR and BCR diversity, which suggested that low-risk patients may be more sensitive to ICIs. Immunohistochemistry was performed, and we found that high expression of FTH1 was significantly correlated with poor OS (P = 0.025). The expression of TIM-3, LAG-3 and PD-1 was positively correlated and associated with better OS in HNSC. However, there was no statistically significant difference between PD-L1, PD-L2, CTLA-4, TIGIT and prognosis. The BCMGS was a promising prognostic biomarker in HNSC, which may help to interpret the responses to immunotherapy and provide a new perspective for future research on the treatment in HNSC.

In this work, a new current waveform, the AC/DC mix current waveform was employed to improve the microstructure and mechanical properties of 307Si stainless steel component during the TIG based wire arc additive manufacturing (TIG-WAAM). The results showed that the morphology of γ-austenite is changed from the columnar dendrites (with DC mode) to the equiaxed dendrites (with AC/DC mix mode). The grain size was refined due to the reduction of the temperature gradient in the AC/DC mix mode. The degree of refinement grain is increased with the increase of AC ratio. The tensile strength of the 70%DC+30%AC-sample in the traveling and building directions are respectively increased by about 60 MPa and 41 MPa compared with that of the 100%DC-sample. The grain refinement is the mainly reason of the improvement of mechanical properties of the TIG-WAAM component with the AC/DC mix mode.

Introduction: Triterpenoids and saponins have a broad range of pharmacological activities. Unlike most legumes which contain mainly oleanane-type scaffold, Astragalus membranaceus contains not only oleanane-type but also cycloartane-type saponins, for which the biosynthetic pathways are unknown. Objectives: This work aims to study the function and catalytic mechanism of oxidosqualene cyclases (OSCs), one of the most important enzymes in triterpenoid biosynthesis, in A. membranaceus. Methods: Two OSC genes, AmOSC2 and AmOSC3, were cloned from A. membranaceus. Their functions were studied by heterologous expression in tobacco and yeast, together with in vivo transient expression and virus-induced gene silencing. Site-directed mutagenesis and molecular docking were used to explain the catalytic mechanism for the conserved motif. Results: AmOSC2 is a β-amyrin synthase which showed higher expression levels in underground parts. It is associated with the production of β-amyrin and soyasaponins (oleanane-type) in vivo. AmOSC3 is a cycloartenol synthase expressed in both aerial and underground parts. It is related to the synthesis of astragalosides (cycloartane-type) in the roots, and to the synthesis of cycloartenol as a plant sterol precursor. From AmOSC2/3, conserved triad motifs VFM/VFN were discovered for β-amyrin/cycloartenol synthases, respectively. The motif is a critical determinant of yield as proved by 10 variants from different OSCs, where the variant containing the conserved motif increased the yield by up to 12.8-fold. Molecular docking and mutagenesis revealed that Val, Phe and Met residues acted together to stabilize the substrate, and the cation-π interactions from Phe played the major role. Conclusion: The study provides insights into the biogenic origin of oleanane-type and cycloartane-type triterpenoids in Astragalus membranaceus. The conserved motif offers new opportunities for OSC engineering.

Ni interlayer was applied in the lap welding of Ti6Al4V titanium (Ti) alloy and 301 stainless steel (SS). By adjusting the welding parameters, the SS irradiated by the laser was not completely penetrated. The SS/Ni and Ni/Ti interfaces were metallurgically bonded due to indirect heating. Two bonding interfaces formed based on solid phase diffusion bonding and eutectic reaction. As the laser power increased, the thickness of the remaining Ni interlayer gradually decreased. A Ni transition layer, as barrier to mixing of the two base materials can prevent the formation of Ti–Fe IMCs. The shear test results showed that the shear strength of the joint increased first and then decreased with the increase of laser power, and the maximum shear strength of joint was 269.8 MPa.

By laser cladding, FeCoNi2CrMnV0.5Nbx high-entropy alloy (HEA) coatings with different content of Nb were fabricated on the ZG25MnNi cast steel in the current study. The microstructure evolution, microhardness, corrosion resistance and wear resistance of FeCoNi2CrMnV0.5Nbx HEA coatings were studied systematically. The results indicated that the HEA alloy coatings transformed into dendrite (DR) structure after adding the Nb element. The dendrite was FCC phase and the interdendritic (IR) eutectic structure was composed of the FCC phase and Laves phase. The wear resistance and microhardness of the HEA coatings increased gradually with the increase of Nb content. When the Nb content x was 1.2, the microhardness of the upper part of the coatings reached 631.1 HV, which was 4 times higher than that of the base metal, and the wear resistance was improved to about 14.2 times the substrate. With the increase of Nb content, the corrosion resistance of coatings first increased and then weakened. When the Nb content x was 0.8, FeCoNi2CrMnV0.5Nbx HEA coatings had the best corrosion resistance.

Timely monitoring of the sandy desert and sandy land (SDSL) dynamics and their driving factors is vital for ecological restoration policy-making to combat the expansion of the SDSL. Northern China, being the principal implementation area of ecological restoration projects, is ecologically fragile and encompasses almost all of the SDSL regions in China. To explore and compare the dominant driving factors for SDSL changes by extracting both aeolian activity information and vegetation indices, the SDSL datasets in northern China from 2010 to 2020 were first constructed in this study by the human–computer interactive interpretation method based on the series Landsat image data. The spatiotemporal dynamic characteristics of SDSL were subsequently analyzed, and the dominant driving factors of SDSL changes were further explored via the geodetector model by the fractional vegetation cover trend and the difference of aeolian activity index. The results showed a net decrease of 3,780.25 km2 in the total SDSL area between 2010 and 2020, and the decrease rate was 2.44 times higher in the shorter period of 2015–2020 compared to 2010–2015. The spatial differentiation between the western and eastern parts of the Helan Mountains was prominently exhibited by the relatively higher changed SDSL area in the eastern part (62.74% for aeolian activity weakened and 83.32% for aeolian activity intensified) and the increasingly changed SDSL area in the western part (from 33.09% to 39.60% in aeolian activity weakened and from 13.02% to 19.60% in aeolian activity intensified). Especially, the increased aeolian activity intensified SDSL area has happened on the southern edge of the Gurbantunggut Desert and along both sides of the Tarim River from 2015 to 2020 deserve attention. The co-driving of the multiple driving factors dominated the change of SDSL from 2010 to 2020, with the county mean value of the difference in aeolian activity index (MDAAI) and the county mean value of the trend in fractional vegetation cover (MFVCT) as dependent variables, respectively. Climatic factors of the mean annual average temperature, the mean annual cumulative precipitation, and the mean annual aridity index have a relatively larger explanatory power for the change of SDSL in both MDAAI and MFVCT. Anthropogenic factors of the mean annual afforestation area and the mean annual number of large livestock and sheep and goats (year-end) have a greater explanatory power in MDAAI, while the mean annual number of large livestock and sheep and goats (year-end) and the mean annual population density in MFVCT. In particular, the dependent variable MDAAI is better at identifing the dominant drivers of aeolian activity intensified SDSL area compared to MFVCT, with anthropogenic factors playing a stronger dominant role.

The Chengdu–Chongqing urban agglomeration (CCUA), as the only national-level city cluster in southwestern China, serves as a strategic support for the Yangtze River Economic Belt and an important demonstration area for promoting new urbanization in the country. The study of the networked characteristics of the CCUA contributes to a systematic understanding of its spatial connectivity patterns, optimization of spatial structure and layout, and promotion of high-quality regional development. In this study, we constructed models for traffic flow, information flow, migration flow, and composite flow to calculate the strength of connections between cities and the total flow of various elements in the CCUA. ArcGIS spatial visualization tools were used to depict the spatial connectivity patterns of the element flows within the CCUA. Additionally, social network analysis methods, including network density, centrality, and cohesive subgroups analysis, were employed to reveal the spatial network structure characteristics of the CCUA. The findings are as follows: (1) The overall structure of the cities within the CCUA is relatively loose, with significant differences in connectivity strength. It exhibits a west-strong and east-weak pattern, with Chengdu-Chongqing, Chengdu-Deyang, Chengdu-Mianyang, and Chengdu-Meishan occupying the top tier, while Zigong and Ya'an have relatively weak connections with other cities. Chengdu and Chongqing have prominent positions in the CCUA, with Chengdu having a more prominent core position compared to Chongqing, resulting in an overall hierarchical distribution of “1 + 1+7 + 7”. (2) The network density of the element flows in the CCUA is relatively low, indicating a generally weak element connectivity. The centrality of cities other than Chengdu and Chongqing is at a moderate to lower level, suggesting a weak overall resource connectivity capacity in the CCUA. (3) Most cities tend to form cohesive subgroups based on geographic proximity, while the cohesive subgroup in Chongqing is still in its early stages of development due to administrative boundaries. The research results quantitatively depict the spatial network structure characteristics of the CCUA, providing theoretical references for its development.

Biological organisms are exposed to low-dose arsenic or N-nitro compounds (NOCs) alone or in combination worldwide, especially in areas with high cancer prevalence through drinking water or food exposure; however, information on their combined exposure effects is limited. Here, we conducted an in-depth study of the effects on the gut microbiota, metabolomics, and signaling pathways using rat models exposed to arsenic or N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), one of the most active carcinogenic NOCs, separately or in combination with metabolomics and high-throughput sequencing. Compared to exposure alone, combined exposure to arsenic and MNNG exacerbated damage to gastric tissue morphology, interfered with intestinal microflora and substance metabolism, and exerted a stronger carcinogenic effect. This may be related to intestinal microbiota disorders, including Dyella, Oscillibacter, Myroides, and metabolic pathways such as glycine, serine, and threonine metabolism, arginine biosynthesis, central carbon metabolism in cancer, and purine and pyrimidine metabolism, thereby enhancing the cancer-causing effects of gonadotrophin-releasing hormone (GnRH), P53, and Wnt signaling pathways.

Summary: Background: The ability to accurately identify the absolute risk of neurosyphilis diagnosis for patients with syphilis would allow preventative and therapeutic interventions to be delivered to patients at high-risk, sparing patients at low-risk from unnecessary care. We aimed to develop, validate, and evaluate the clinical utility of simplified clinical diagnostic models for neurosyphilis diagnosis in HIV-negative patients with syphilis. Methods: We searched PubMed, China National Knowledge Infrastructure and UpToDate for publications about neurosyphilis diagnostic guidelines in English or Chinese from database inception until March 15, 2023. We developed and validated machine learning models with a uniform set of predictors based on six authoritative diagnostic guidelines across four continents to predict neurosyphilis using routinely collected data from real-world clinical practice in China and the United States (through the Dermatology Hospital of Southern Medical University in Guangzhou [659 recruited between August 2012 and March 2022, treated as Development cohort], the Beijing Youan Hospital of Capital Medical University in Beijng [480 recruited between December 2013 and April 2021, treated as External cohort 1], the Zhongshan Hospital of Xiamen University in Xiamen [493 recruited between November 2005 and November 2021, treated as External cohort 2] from China, and University of Washington School of Medicine in Seattle [16 recruited between September 2002 and April 2014, treated as External cohort 3] from United States). We included all these patients with syphilis into our analysis, and no patients were further excluded. We trained eXtreme gradient boosting (XGBoost) models to predict the diagnostic outcome of neurosyphilis according to each diagnostic guideline in two scenarios, respectively. Model performance was measured through both internal and external validation in terms of discrimination and calibration, and clinical utility was evaluated using decision curve analysis. Findings: The final simplified clinical diagnostic models included neurological symptoms, cerebrospinal fluid (CSF) protein, CSF white blood cell, and CSF venereal disease research laboratory test/rapid plasma reagin. The models showed good calibration with rescaled Brier score of 0.99 (95% CI 0.98–1.00) and excellent discrimination (the minimum value of area under the receiver operating characteristic curve, 0.84; 95% CI 0.81–0.88) when externally validated. Decision curve analysis demonstrated that the models were useful across a range of neurosyphilis probability thresholds between 0.33 and 0.66 compared to the alternatives of managing all patients with syphilis as if they do or do not have neurosyphilis. Interpretation: The simplified clinical diagnostic models comprised of readily available data show good performance, are generalisable across clinical settings, and have clinical utility over a broad range of probability thresholds. The models with a uniform set of predictors can simplify the sophisticated clinical diagnosis of neurosyphilis, and guide decisions on delivery of neurosyphilis health-care, ultimately, support accurate diagnosis and necessary treatment. Funding: The Natural Science Foundation of China General Program, Health Appropriate Technology Promotion Project of Guangdong Medical Research Foundation, Department of Science and technology of Guangdong Province Xinjiang Rural Science and Technology（Special Commissioner）Project, Southern Medical University Clinical Research Nursery Garden Project, Beijing Municipal Administration of Hospitals Incubating Program.

Biallelic variants in the USH2A gene cause Usher syndrome type 2 (USH2), in which patients’ symptoms are progressive night blindness, reduced visual field, decreased central vision and sensorineural hearing impairment. There is currently no effective drug for USH2. In this study, we isolated peripheral blood mononuclear cells from a patient with USH2. The pluripotency of induced cells was verified by the presence of cell surface markers, the expression of pluripotent genes, and the formation of teratomas. The generation of this induced pluripotent stem cell line provides an effective way to study USH2, such as disease modeling and drug screening.Usher syndrome type 2 (USH2) is a genetic disease mainly caused by biallelic variants in the USH2A gene. Patients usually present with progressive night blindness, reduced visual field, and then reduced central vision. Patients with USH2 also have sensorineural hearing impairment. There is currently no effective treatment for USH2, and the pathogenesis is still unclear. Therefore, it is of great significance to study the pathogenic mechanism of USH2A gene variants for the study of therapeutic targets. In this study, we obtained induced pluripotent stem cell (iPSC) line containing USH2A gene variants. We isolated mononuclear cells from the peripheral blood of patient and established iPSCs by reprogramming with nonintegrating vectors. We then confirmed the pluripotency of our generated iPSCs through the detection of multiple cell surface markers, the expression of pluripotency-related genes, and the ability to form teratomas with three germ layer structures in vivo. The generation of this cell line will facilitate research on USH2 disease and will play a role that cannot be underestimated in future organoid generation, drug screening, and research on drug targets as well as mechanisms.

Since 2007, the Yellow Sea has undergone a large-scale outbreak of green tide for 15 years. The large biomass of green tide has caused great economic losses to Shandong and Jiangsu Province. The monitoring data in the recent years indicated that the dominant algae in the Southern Yellow Sea (SYS) was a special ecological type of Ulva species (Ulva prolifera). In order to make rational use of green tide algae and avoid the waste of biological resources, the achievements in the research and technical development on the resource utilization of green tide algae were systematically introduced. Moreover, the utilization and development of U. prolifera, such as food, beauty products, feed or feed additives, fertilizer, energy and papermaking engineering, were summarized. In addition, solutions to reduce the losses caused by the outbreak of green tide algae were also proposed.

Background: Breast cancer is the most common malignancy in women. Clinical models such as Oncotype DX recurrence score (RS) and Clinical Treatment Score post–5 years (CTS5) model for survival prediction are crucial for clinical practice. However, it remains unclear whether CTS5 or RS would be a more powerful clinical model for recurrence risk evaluation. Therefore, we conducted the present study to compare the performance of CTS5 risk model and RS on different recurrence evaluation. And we further integrated the two models into a novel nomogram to improve the power for prognosis prediction. Methods: Female patients with invasive hormone receptor positive breast cancer in the Surveillance, Epidemiology, and End Results Program (SEER) database with RS data available were included. The clinicopathological data were directly extracted from SEER database. Participants were divided into three subsets according to recurrence timing (60 months) for model evaluation. Survival receiver operating characteristic curve and C-index were calculated to evaluate discrimination. Calibration curve were used to visual inspection for calibration. Model comparison was assessed by net reclassification index (NRI) method. Nomogram prognostic model was developed with the combination of CTS5 score and RS and also included other critical clinicopathological parameters. Results: In total, 64044 breast cancer patients were enrolled for analysis. The number of patients with survival 60 months (late recurrence subset) were 64044, 36878 and 15926, respectively. For model discrimination, CTS5 model was superior to RS for overall survival (OS) prediction (likelihood ratio test P

Perfluorooctane sulfonate (PFOS) is a synthetic chemical and an environmental pollutant widely recognized for its industrial use, given its thermal and chemical stability. Growing evidence suggests that PFOS exposure is linked with epigenomic alteration and disease progression. Whether PFOS toxicity could lead to a phenotypical epigenetic state is of interest in toxicology research. Given the limited studies on kidney cancer and disease, the molecular mechanisms underlying the epigenetic modulated state upon PFOS exposure remains unclear. This study explores epigenetic indicators associated with PFOS exposure in A498 kidney cancer cells. We demonstrate a data-driven approach to identify critical features by classifying the epigenetic states upon PFOS exposure. By combining single-cell super-resolution imaging and machine learning analysis, we show that the repressive epigenetic markers are distinctively different upon PFOS exposure. Further we note that, PFOS exposure altered the spatial distribution of H3K9me3 and H3K27me3 with nanoscale imaging. Quantification of gene expression related to tumorigenesis indicates altered expression levels upon PFOS exposure. Our results suggest that the epigenetic changes partake in establishing PFOS-induced toxicity development. Furthermore, the distribution of H3K9me3/H3K27me3 alteration could act as one of the drivers for PFOS-induced phenotype development in disease progression.

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment.

Background & Aims: Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV), existing as a stable minichromosome in the hepatocyte, is responsible for persistent HBV infection. Maintenance and sustained replication of cccDNA require its interaction with both viral and host proteins. However, the cccDNA-interacting host factors that limit HBV replication remain elusive. Methods: Minicircle HBV (MC-HBV), a recombinant cccDNA, was constructed based on chimeric intron and minicircle DNA technology. By mass spectrometry based on pull-down with biotinylated MC-HBV, the cccDNA-hepatocyte interaction profile was mapped. HBV replication was assessed in different cell models that support cccDNA formation. Results: MC-HBV supports persistent HBV replication and mimics the cccDNA minichromosome. The MC-HBV–based screen identified cohesin complex as a cccDNA binding host factor, leading to reduced HBV replication. Mechanistically, with the help of CCCTC-binding factor (CTCF), which has specific binding sites on cccDNA, cohesin loads on cccDNA and reshapes cccDNA confirmation to prevent RNA polymerase II enrichment. Interestingly, HBV X protein transcriptionally reduces structural maintenance of chromosomes complex expression to partially relieve the inhibitory role of the cohesin complex on HBV replication. Conclusions: Our data not only provide a feasible approach to explore cccDNA-binding factors, but also identify cohesin/CTCF complex as a critical host restriction factor for cccDNA-driven HBV replication. These findings provide a novel insight into cccDNA–host interaction and targeted therapeutic intervention for HBV infection.

The copper/graphene (Cu/Gr) composites made of Gr/Cu/Gr foils with a thickness of 25 μm were prepared using spark plasma sintering diffusion bonding (SPS) and hot press diffusion bonding (HP) in an Ar atmosphere at 900 °C for 20 min under a pressure of 50 MPa. The electrical conductivity of the prepared Cu/Gr composites was measured by the van der Pauw method, the microstructure was characterized using Raman spectroscopy, scanning electron microscope and transmission electron microscope, and the corresponding mechanism was analyzed by employing the first-principles calculations. The result indicates that, SPS process reduces the interfacial impurities of Cu/Gr composites, rendering a much higher electrical conductivity (108.6% IACS) than that prepared by using HP (98.8% IACS). This finding is correlated to the reduced oxygen (O) impurities on Gr/Gr interface, which is attributed to the high temperature plasma sputtering effect of SPS. In the prepared Cu/Gr composites, the impurity-free Gr/Gr interface has an ideal spacing of ∼3.3 Å wherein carbon (C) across the interface do not bond. Despite the generated C–C covalent bonding within the same Gr layer bounds some of the electrons, the remaining electrons of the p orbital on each C atom are free electrons, leading to the excellent electrical conductivity. In contrast, absorption of O impurities on the Gr/Gr interface increases the spacing between the Gr layers to ∼3.8 Å, and generates covalent C–O–C bonding across the interface due to p orbital hybridization. This reduces the free electron concentration and the corresponding electrical conductivity.

Summary: Placental hormones orchestrate maternal metabolic adaptations to support pregnancy. We hypothesized that placental ER stress, which characterizes early-onset pre-eclampsia (ePE), compromises glycosylation, reducing hormone bioactivity and these maladaptations predispose the mother to metabolic disease in later life. We demonstrate ER stress reduces the complexity and sialylation of trophoblast protein N-glycosylation, while aberrant glycosylation of vascular endothelial growth factor reduced its bioactivity. ER stress alters the expression of 66 of the 146 genes annotated with “protein glycosylation” and reduces the expression of sialyltransferases. Using mouse placental explants, we show ER stress promotes the secretion of mis-glycosylated glycoproteins. Pregnant mice carrying placentas with junctional zone-specific ER stress have reduced blood glucose, anomalous hepatic glucose metabolism, increased cellular stress and elevated DNA methyltransferase 3A. Using pregnancy-specific glycoproteins as a readout, we also demonstrate aberrant glycosylation of placental proteins in women with ePE, thus providing a mechanistic link between ePE and subsequent maternal metabolic disorders.

Laser wakefield acceleration, a highly nonlinear process, can provide high-quality electron beams and betatron radiation. However, it has always been a challenge to optimize the photon number of betatron radiation because X-ray production is the secondary process followed by electron generation and many influential parameters are highly coupled with each other. To balance these parameters and optimize target value, we use a machine-learning algorithm called Bayesian optimization that ignores the complicated middle process and so is suitable to solve this kind of problems. Without designed initialization, we optimize betatron radiation in experiments by changing plasma density and laser focal position. The X-ray photon number doubles compared with initial condition within 10 iterations, which shows the rapidity of this algorithm. PIC simulation also illustrates the complexity of the optimization and reveals the reason why X-ray photon number increases.