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The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage.

Liver transplantation (LT) is a pivotal treatment for end-stage liver disease. However, bloodstream infections (BSI) in the post-operative period present a significant threat to patient survival. This study aims to identify risk factors for post-LT BSI and crucial prognostic indicators for mortality among affected patients.

Two sulfur-containing heterodimers of a cytochalasan and a macrolide, sucurchalasins A and B (1and 2), and four known cytochalasan monomers (3–6), as well as four known macrolide derivatives (7–10), were obtained from the endophytic fungus Aspergillus spelaeusGDGJ-286. Sucurchalasins A and B (1and 2) are the first cytochalasan heterodimers formed via a thioether bridge between cytochalasan and curvularin macrolide units. Their structures were elucidated by detailed analysis of NMR, LC-MS/MS, and X-ray crystallography. In bioassays, 1and 2exhibited cytotoxic effects on A2780 cells, with IC50values of 3.9 and 8.3 μM, respectively. They also showed antibacterial activities against E. faecalisand B. subtiliswith MIC values of 3.1 and 6.3 μg/mL, respectively.

With the increasing demand for clean energy sources, the need for large-scale energy storage systems to ensure the stable output of renewable energy sources, such as wind and solar, has also increased. Sodium-ion batteries have emerged as a potential solution for these storage systems owing to their high energy density, abundance in the Earth’s crust, and low cost. However, the larger atomic radius of sodium ions results in higher energy barriers for ion migration in cathode materials, which can affect the cycle life and rate performance of the battery. Therefore, developing a suitable structure that facilitates rapid sodiation and desodiation and maintains good cycling stability remains a significant challenge. This study aimed to reduce the content of trivalent manganese ions and minimize the impact of the Jahn–Teller effect to enhance the capacity retention of manganese-based layered oxides. Additionally, a series of P2-type Na0.78Li0.1ZnxNi0.15–xMn0.75O2compounds were successfully synthesized through doping with divalent zinc ions. Structural analyses of the doped material indicated that Zn doping did not alter the crystal structure but increased the interlayer distance of the transition metals. Electrochemical performance tests revealed that appropriate Zn2+doping promoted sodium-ion diffusion and improved the reversible capacity of the battery. This study provides a promising approach for developing sodium-ion batteries with rapid charging and discharging capabilities.

Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+‐M2BP) is a novel biomarker for evaluating hepatic fibrosis and hepatocellular carcinoma (HCC) development. However, no previous study has compared its diagnostic accuracy with that of FIB‐4 or APRI nor explored its clinical application for predicting esophageal varices bleeding in HCC patients. In this study, we explored these biomarkers and compared their clinical roles. Total 459 HCC patients who underwent curative operation were enrolled in this study. WFA+‐M2BP level was evaluated using stored blood samples that were collected during surgery, and liver fibrosis was diagnosed based on findings of surgical specimen analysis. Esophageal or gastric varices were evaluated in 207 patients who underwent esophagogastroduodenoscopy (EGD). The correlation between the markers was also determined. Our study showed WFA+‐M2BP level, FIB‐4, and APRI had a similar high accuracy of approximately 73% for liver cirrhosis diagnosis. Their levels were significantly correlated with the liver fibrosis stage (p< .0001). WFA+‐M2BP level, FIB‐4, and APRI also had high diagnostic accuracy for varices formation (accuracy, 76.8%–80.2%) and high predictive accuracy for variceal bleeding (accuracy, 73.9%–76.3%). The correlation between WFA+‐M2BP level and FIB‐4 or between WFA+‐M2BP level and APRI was weak (Pearson r< 0.5, p< .0001) but that between FIB‐4 and APRI was very strong (Pearson r> 0.9, p< .0001). Our study demonstrated WFA+‐M2BP level, FIB‐4, and APRI have all shown to be very useful noninvasive methods for evaluating liver fibrosis and predicting esophageal varices bleeding to avoid risky liver biopsy and EGD examination.

The node upset may occur in the memory cell if the charged particle from cosmos rays or packaging materials strikes the integrated circuit. Radiation-hardened-by-design (RHBD) techniques introduce redundant transistors in the SRAM cell to improve its ability of recovering from the undesired node upset. However, the extra redundant transistors may increase the number of sensitive nodes in the SRAM cell, which decreases its capability of node-upset tolerance in turn. This work proposes an RHBD 14T SRAM cell and an RHBD 16T SRAM cell. Both the proposed SRAM cells only have two sensitive nodes. The proposed SRAM cells are able to recover from all the SNU cases. The layout harden technique is used to protect the proposed cells from SEMNU, and the blank of the hardened layout is reused so the proposed 14T and 16T SRAM cells consume the same area. Although the proposed cells have more transistors, the hardened layout areas of NS-10T/ PS-10T/ RHD-12T/ RHBD-10T/ RHBD-10T[VLSI]/ QUCCE-12T are respectively $1.78\times $ / $1.78\times $ / $1.83\times $ / $1.78\times $ / $1.78\times $ / $1.99\times $ larger than that of the proposed cells. The reason is that the layout harden technique is easier to be applied to the proposed cells because they only have two sensitive nodes.

In this brief, two differential absorptive bandpass filters (ABPFs) with additional resistively terminated absorptive stubs (RTASs) are presented. The proposed RTAS is constructed of a $\lambda $ /4 microstrip line and a grounded resistor, improving the complementarity between bandpass and bandstop responses effectively. A single-ended ABPF is designed using a coupled-line resonator, two RTASs, and T-shaped bandstop sections. Higher return loss at passband edges is realized with additional RTASs. By employing two microstrip-slotline transition structures, the differential ABPF I is proposed with high common-mode (CM) suppression levels. Differential ABPF II is designed based on two coupled lines loaded by a microstrip stub, two additional RTASs, and lossy bandstop sections. For the differential-mode signals, the out-of-band noise is absorbed and the return loss at two passband edges is improved by additional RTASs. All-stop CM suppression is also realized. The theoretical analysis and explicit equations of two differential ABPFs are detailed and illustrated. For experimental validation, two prototypes are fabricated and measured. The simulated and measured results are in good agreement.

This study aimed to examine the spatial distribution of immune cells by application of Gcross function in 170 patients with stage I to IIIA lung adenocarcinoma (LUAD) and explore its prognostic value. A total of 170 stage I to IIIA LUAD patients who underwent radical surgery were enrolled. Paraffinized tumor sections were collected for 2 panels of multicolor immunofluorescence staining (panel 1: CD4, CD8, FOXP3, CD69, CD39, CD73, and DAPI; panel 2: CD68, CD163, CD20, CD11c, PDL1, IDO, and DAPI). The immune cells were categorized as CD8+, CD4+T helper cell (CD4Th), regulatory T cell, macrophage type 1 (M1), M2, dendritic cell (DC), and B cell. The immune cell numbers were enumerated, and the immune cell proximity score was calculated employing the Gcross function. The correlation between immune cell variables and disease-free survival (DFS) was explored through univariate Cox regression analyses. Factors with P< 0.05 were subjected to multivariate analyses. According to univariate Cox regression analyses, total PDL1+and PDL1+DC counts were negative factors (P =0.003 and 0.031, respectively). CD4Th and IDO−DC counts were positive factors (P =0.022 and 0.024, respectively). The proximity score (M1 to M2) was a positive factor for DFS (P= 0.032), and the proximity score (PDL1 +DC to M1) was a negative factor (P= 0.009) according to univariate Cox analyses. In multivariate analyses, stage (IIIA vs I + II) (hazard ratio [HR]: 1.77 [95% confidence interval (CI): 1.18–2.64], P= 0.006) and proximity score (PDL1 +DC to M1) (HR: 1.60 [95% CI: 1.07–2.37], P= 0.021) were independent negative factors and CD4Th counts (HR: 0.60 [95% CI: 0.40–0.90], P= 0.013) was an independent positive factor. Our study indicated that a higher level of tumor-infiltrating CD4Th cells predicted longer DFS, and a closer proximity of PDL1+DCs to M1 cells was associated with dismal DFS in stage I to IIIA LUAD patients.A closer proximity of PDL1+dendritic cells to macrophage type 1 cells was associated with a dismal disease-free survival in stage I to IIIA lung adenocarcinoma patients.

The effects of laser shock peening (LSP) on the microstructural evolution and mechanical properties of the Ti6242 alloy, including the residual stress, surface roughness, Vickers microhardness, tensile mechanical response, and high-cycle fatigue properties, were studied. The results showed that the LSP induced residual compressive stresses on the surface and near surface of the material. The maximum surface residual compressive stress was −661 MPa, and the compressive-stress-affected depth was greater than 1000 μm. The roughness and Vickers micro-hardness increased with the number of shocks, and the maximum hardness-affected depth was about 700 μm after three LSP treatments. LSP enhanced the fraction of low-angle grain boundaries, changed the grain preferred orientations, and notably increased the pole density of αphase on the near surface from 2.41 to 3.46. The surface hardness values of the LSP samples increased with the increase of the number of shocks due to work hardening, while the LSP had a limited effect on the tensile properties. The high-cycle fatigue life of the LSP-treated sample was significantly enhanced by more than 20% compared with that of the untreated sample, which was caused by the suppression of the initiation and propagation of fatigue cracks.

An in-array Build-In Self-Test (BIST) scheme is proposed for the embedded SRAM array. The linear feedback shift register (LFSR) is used to implement the pattern generator, and the single/multiple-input signature register (SISR/MISR) is used to implement the response compactor. The proposed BIST scheme only consumes half the number of transistors and area compared with the conventional LFSR/MISR BIST, and it is testable. The conventional BIST circuit outside the SRAM array is unnecessary if the proposed BIST scheme is applied. The proposed BIST scheme is able to implement various March sequences to test the other part of the memory array.

Palladium-catalyzed intermolecular [3 + 2] annulation reactions via C–H activation represent a powerful and charming tool for assembling cyclopentanes. Herein, we have developed a strategy for the palladium-catalyzed intermolecular alkene-relayed annulation reaction of aryl iodides and maleimides via C(sp3)–H activation for the construction of polycyclic structures. In contrast to directed-group-enabled intermolecular maleimide-relayed [3 + 2] annulation reactions, this protocol stands out for its utilization of aryl iodides as substrates. Notably, monoprotected amino acids played a crucial role as ligands in this reaction, which is rarely observed in C–H activation reactions initiated with organohalides.

2(3H)-Furanones are tremendously important not only because of their wide occurrence in bioactive compounds but also due to their versatility in organic synthesis. Here, a straightforward approach to 2(3H)-furanones from readily available tertiary propargylic alcohols with arylboronic acids in the presence of CO using rhodium as a catalyst has been established. The method exhibits a broad substrate scope tolerating useful functional groups with a moderate to high stereoselectivity.

Organic–inorganic hybrid perovskite solar cells (PSCs) have recently been demonstrated to be promising renewable harvesters because of their prominent photovoltaic power conversion efficiency (PCE), although their stability and efficiency still have not reached commercial criteria. Trouble-oriented analyses showcase that defect reduction among the grain boundaries and interfaces in the prepared perovskite polycrystalline films is a practical strategy, which has prompted researchers to develop functional molecules for interface passivation. Herein, the pyridine-based bifunctional molecule dimethylpyridine-3,5-dicarboxylate (DPDC) was employed as the interface between the electron-transport layer and perovskite layer, which achieved a champion PCE of 21.37% for an inverted MAPbI3-based PSC, which was greater than 18.64% for the control device. The mechanistic studies indicated that the significantly improved performance was mainly attributed to the remarkably enhanced fill factor with a value greater than 83%, which was primarily due to the nonradiative recombination suppression offered by the passivation effect of DPDC. Moreover, the promoted carrier mobility together with the enlarged crystal size contributed to a higher short-circuit current density. In addition, an increase in the open-circuit voltage was also observed in the DPDC-treated PSC, which benefited from the improved work function for reducing the energy loss during carrier transport. Furthermore, the DPDC-treated PSC showed substantially enhanced stability, with an over 80% retention rate of its initial PCE value over 300 h even at a 60% relative humidity level, which was attributed to the hydrophobic nature of the DPDC molecule and effective defect passivation. This work is expected not only to serve as an effective strategy for using a pyridine-based bifunctional molecule to passivate perovskite interfaces to enhance photovoltaic performance but also to shed light on the interface passivation mechanism.

Although sex‐related disparities in hepatocellular carcinoma (HCC) incidence have been well‐reported, whether any such disparities exist in HCC prognosis remains controversial. We aim to characterize sex‐related differences in HCC presentation and prognosis. Consecutive patients who were newly diagnosed with HCC between 2011 and 2020 at our institution were enrolled in this retrospective study. Of the 3977 identified patients diagnosed with HCC between January 2011 and December 2020, 72.2% were men (n= 2871) and 27.8% were women (n= 1106). The age at HCC diagnosis was higher (p< .001), the proportion positive for hepatitis B surface antigen was lower (p< .001), the proportion positive for anti‐hepatitis C virus antibody was higher (p< .001), the proportion of alcoholics was lower (p< .001), the proportion with early stage tumor (i.e., Barcelona Clinic Liver Cancer [BCLC] stages 0 and A) was higher (p< .001), the proportion with alpha‐fetoprotein (AFP) >20 ng/mL was higher (p= .02), the proportion with cirrhosis was higher (p< .001), the proportion in receipt of liver resection was lower, and the proportion in receipt of ablation was higher (p< .001) among women than among men. Multivariate analysis showed that an age of >65 years (hazard ratio [HR] = 1.162; 95% confidence interval [CI] = 1.051–1.285; p= .003), BCLC stages B–D (HR = 2.660; 95% CI = 2.372–2.983; p< .001), AFP >20 ng/mL (HR = 1.776; 95% CI = 1.599–1.971; p< .001), and non‐curative treatment (HR = 3.248; 95% CI = 2.910–3.624; p< .001) were associated with mortality, whereas sex was not. Sex was not an independent predictor of mortality of patients with HCC.

To reduce excessive vibration of a turboprop engine with qualified balanced compressor and turbine rotor, the finite element model of the rotor system was established. The magnitude, axial distribution and especially the phase combinations of the residual unbalances were considered and optimized. Based on the numerical results, the whole engine tests were conducted for verification. The numerical and experimental results show that the vibration level of the rotor system can be significantly reduced by only changing the phase combination of the residual unbalances. The magnitude, axial distribution of residual unbalance and rotational speed of the rotor play a very important role in determining the optimal phase combination. The optimal phase combination under different rotational speeds might be conflicting, and reasonably designed optimization would be a feasible solution. The findings of the research can provide important reference for the design and troubleshooting for similar industrial turbine engines.

Two metal borate–carbonates, M6[Cd2(CO3)2(B12O18)(OH)6] [M = K (1), Rb (2)], were obtained under surfactant-thermal conditions. In 1and 2, each cyclic [(B12O18)(OH)6]6–anion captures two CdCO3in two sides of the rings and finally forms the unusual (CdCO3)2@[(B12O18)(OH)6] cluster. Both 1and 2show moderate birefringence. Density functional theory calculations indicate that carbonate groups have a major contribution to electron-related optical transition.

7-Xylosyl-10-deacetyl paclitaxel is a crucial semisynthetic precursor of paclitaxel, which could prevent cancer cells from dividing and growing. In this study, twin-column recycling chromatography with a step solvent gradient was applied to the isolation and purification of 7-xylosyl-10-deacetyl paclitaxel. By introduction of a weak solvent between the two columns, band broadening was counteracted to facilitate the separation process. Also the effects of various variables including the magnitude of solvent gradient, feeding volume, switch number, and interval were comprehensively investigated, and the operating conditions were systematically optimized. In the results, 7-xylosyl-10-deacetyl paclitaxel was successfully refined from 23.90% to almost 100%, with a remarkable yield of over 95%. This study demonstrates the distinct advantage of utilizing a new chromatography system in the separation of natural products.

Annular air nozzles with different geometrical properties are used to investigate their influence on the primary breakup of discontinuous shear-thickening suspensions. By the use of a high-speed camera, the primary breakup process is visualized. Contrary to conventional fluids, no improvement in the atomization performance of discontinuous shear-thickening suspensions is achieved by using convergent annular air nozzles. Compared to a uniform sectional nozzle, the suspension jet exhibits shattering breakup at a higher critical Weber number when using convergent nozzles. In the shattering breakup mode, the breakup occurs close to the exit, while the cross-section is flat, which may be due to being stretched. Based on the discussion of the experimental results, this phenomenon is found to be connected to the anisotropic microstructure of the discontinuous shear-thickening suspension and the geometrical properties of the convergent nozzle.

The direct functionalization of methylene C(sp3)–H bonds is one of the greatest challenges in transition metal-catalyzed C–H activation. Although Pd(0)-catalyzed intramolecular cyclization reactions of methylene C(sp3)–H bonds have been reported, intermolecular functionalization remains to be discovered. Herein, we report the first example of a Pd(0)-catalyzed intermolecular methylene C(sp3)–H functionalization reaction. By use of a N-heterocyclic carbene ligand, the methylene C(sp3)–H bonds of 1-(benzyloxy)-2-iodobenzenes are activated and disilylated with hexamethyldisilane, affording disilylated products.

Background: Venous thromboembolism (VTE) in critically ill patients has been well-studied in Western countries. Many studies have developed risk assessments and established pharmacological protocols to prevent deep venous thrombosis (DVT). However, the DVT rate and need for pharmacologic VTE prophylaxis in critically ill Taiwanese patients are limited. This study aimed to prospectively determine the DVT incidence, risk factors, and outcomes in critically ill Taiwanese patients who do not receive pharmacologic VTE prophylaxis.Methods: We conducted a prospective study in a surgical intensive care unit (SICU) of a tertiary academic medical center in Taiwan. Adult patients admitted to SICU from March 2021 to June 2022 received proximal lower extremities DVT surveillance with venous duplex ultrasound. No patient received pharmacologic VTE prophylaxis. The outcomes were the incidence and risk factors of DVT.Results: Among 501 enrolled SICU patients, 21 patients (4.2%) were diagnosed with proximal lower extremities DVT. In a multivariate regression analysis, hypoalbuminemia (odd ratio (OR) = 6.061, 95% confidence interval (CI): 1.067–34.421), femoral central venous catheter (OR = 4.515, 95% CI: 1.547–13.174), ICU stays more than 10 days (OR = 4.017, 95% CI: 1.270–12.707), and swollen leg (OR = 3.427, 95% CI: 1.075–10.930) were independent risk factors for DVT. In addition, patients with proximal lower extremities DVT have more extended ventilator days (p= 0.045) and ICU stays (p= 0.044).Conclusion: Our findings indicate critically ill Taiwanese patients have a higher incidence of DVT than results from prior retrospective studies in the Asian population. Physicians who care for this population should consider the specific risk factors for DVT and prescribe pharmacologic prophylaxis in high-risk groups.

Byline: Yin. Xu, Xiao-yan. Fei, You-hua. Xue, Xue-mei. Wang, Xiao-yan. Wang, Yu-ting. Zheng, Ke. Chen, Jing-jing. He, Xiu-hong. Ren, Lei. Pan, Ling. Wang, Duo. Qian, Wei-feng. Li, Yan. Liang, Yan. [...]

Here, we describe a strategy for the copper-catalyzed asymmetric heteroarylation of yne-thiophene carbonates with indoles viaremote substitution. The key to the success of this strategy lies in the design of the alkynyl group at the ortho-position of the heterocycle thiophene, enabling the formation of a triarylmethane moiety viavery remote substitution. Thus, the concept of remote copper-catalyzed asymmetric transformation extends not only to yne-allylic esters but also to yne-aryl esters. The reaction readily provides a diverse array of chiral triarylmethanes with high efficiency, enantioselectivity, and excellent functional group compatibility. Moreover, facile follow-up transformations underscore their potential utility in the synthesis of various enantioenriched building blocks. Preliminary mechanistic studies support the plausibility of the remote substitution pathway.

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%–77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivoand in vitro. Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACCGlu) projecting to the VTA indirectly inhibit dopaminergic neurons (VTADA) by activating local GABAergic interneurons (VTAGABA), and this effect is reinforced after nerve injury. VTADAneurons in turn project to the ACC and synapse to the initial ACCGluneurons to convey feedback information from emotional changes. Thus, an ACCGlu–VTAGABA–VTADA–ACCGlupositive-feedback loop mediates the progression to and maintenance of persistent pain and comorbid anxiodepressive-like behavior. Disruption of this feedback loop relieves hyperalgesia and anxiodepressive-like behavior in a mouse model of neuropathic pain, both acutely and in the long term.

The positioning accuracy of medical bone drilling has a great impact on the success rate of orthopedic surgery. Due to the need for high accuracy of medical bone drilling, with use of any 6-DoF-type robotic arm to assist in drilling, a novel six-degree-of-freedom compensation positioning algorithm of robotic arm-assisted medical bone drilling is proposed, in which only position but also orientation errors of robotic end are considered, increasing positioning capability of drilling instrument end effector with position and orientation correction for medical drilling motion accurate controlling. For the different position and orientation characteristics of the robot arm controlling and measurement point/zone, position and orientation transformation from measurement to controlling point/zone is established through position and angle calibration experiments, realizing position and orientation error measured by optical tracking system from measurement point/zone to controlling point/zone. Based on 6-DoF parameter and principle of robotic arm, a positioning compensation model based on the 6-DoF position and orientation errors of robotic arm end is proposed, and iteration cycle is used for higher accuracy, realizing double correction of position and orientation of robotic arm end. The accuracy verification experiments measured by the optical tracking system shows that the average position error before and after the 6-DoF compensation positioning algorithm reduces from 1.42 mm (before compensation with DH-based inverse kinematic model) to 0.20 mm (after compensation model) and the average angle error from 0.470° to 0.046°. A bovine spine drilling experiment is carried out based on the 6-DoF compensation algorithm, and the average position error of the hole in the specific direction measured by the contour projector is 0.221 mm, achieving high positioning accuracy of bone drilling, demonstrating reliability and practical application value of medical bone drilling with the compensation of positioning algorithm.

Background: Transcolonic endoscopic appendectomy (TEA) is rapidly evolving and has been reported as a minimally invasive alternative to appendectomy. We aimed to characterize the feasibility and safety of a novel unassisted single-channel TEA. Method: We retrospectively investigated 23 patients with appendicitis or appendiceal lesions who underwent TEA from February 2016 to December 2022. We collected clinicopathological characteristics, procedure‑related parameters, and follow‑up data and analyzed the impact of previous abdominal surgery and traction technique. Results: The mean age was 56.0 years. Of the 23 patients with appendiceal lesions, fourteen patients underwent TEA and nine underwent traction-assisted TEA (T-TEA). Eight patients (34.8%) had previous abdominal surgery. The En bloc resection rate was 95.7%. The mean procedure duration was 91.1 ± 45.5 min, and the mean wound closure time was 29.4 ± 18.6 min. The wounds after endoscopic appendectomy were closed with clips (21.7%) or a combination of clip closure and endoloop reinforcement (78.3%), and the median number of clips was 7 (range, 3–15). Three patients (13.0%) experienced major adverse events, including two delayed perforations (laparoscopic surgery) and one infection (salvage endoscopic suture). During a median follow-up of 23 months, no residual or recurrent lesions were observed, and no recurrence of abdominal pain occurred. There were no significant differences between TEA and T-TEA groups and between patients with and without abdominal surgery groups in each factor. Conclusion: Unassisted single-channel TEA for patients with appendiceal lesions has favorable short- and long-term outcomes. TEA can safely and effectively treat appendiceal disease in appropriately selected cases.

Evolutionary algorithms (EAs), such as the genetic algorithm (GA), offer an elegant way to handle combinatorial optimization problems (COPs). However, limited by expertise and resources, most users lack the capability to implement EAs for solving COPs. An intuitive and promising solution is to outsource evolutionary operations to a cloud server, however, it poses privacy concerns. To this end, this article proposes a novel computing paradigm called evolutionary computation as a service (ECaaS), where a cloud server renders evolutionary computation services for users while ensuring their privacy. Following the concept of ECaaS, this article presents privacy-preserving genetic algorithm (PEGA), a privacy-preserving GA designed specifically for COPs. PEGA enables users, regardless of their domain expertise or resource availability, to outsource COPs to the cloud server that holds a competitive GA and approximates the optimal solution while safeguarding privacy. Notably, PEGA features the following characteristics. First, PEGA empowers users without domain expertise or sufficient resources to solve COPs effectively. Second, PEGA protects the privacy of users by preventing the leakage of optimization problem details. Third, PEGA performs comparably to the conventional GA when approximating the optimal solution. To realize its functionality, we implement PEGA falling in a twin-server architecture and evaluate it on two widely known COPs: 1) the traveling Salesman problem (TSP) and 2) the 0/1 knapsack problem (KP). Particularly, we utilize encryption cryptography to protect users’ privacy and carefully design a suite of secure computing protocols to support evolutionary operators of GA on encrypted chromosomes. Privacy analysis demonstrates that PEGA successfully preserves the confidentiality of COP contents. Experimental evaluation results on several TSP datasets and KP datasets reveal that PEGA performs equivalently to the conventional GA in approximating the optimal solution.

The in-memory computing (IMC) architecture eliminates the frequent data transfers between the memory banks and the processor cores. Researchers have utilized different SRAM cells to implement the in-memory logic operations. However, most of the previous works implement the column-wise logic/CAM operations, which require the column-wise stored operands. These column-wise logic/CAM operations are incompatible with the traditional row-wise SRAM mode. This brief proposes an SRAM cell with 11 transistors, which can work in four operation modes: the SRAM mode, the logic mode, and the BCAM/TCAM modes. All the operations in these four modes can be performed both in the column-wise and the row-wise style. The incompatibility between different modes is eliminated. In the logic mode, the proposed SRAM achieves frequency of 595MHz and energy consumption of 17.94fJ/bit at 1.2V with TSMC 65nm technology file. In the BCAM/TCAM modes, it can work with 407MHz, and it consumes 0.62fJ/bit and 1.38fJ/bit at 1.2V

Parkin (PARK2) deficiency is frequently observed in various cancers and potentially promotes tumor progression. Here, we showed that Parkin expression is downregulated in liver cancer tissues, which correlates with poor patient survival. Parkin deficiency in liver cancer cells promotes migration and metastasis as well as changes in EMT and metastasis markers. A negative correlation exists between TMEFF1 and Parkin expression in liver cancer cells and tumor tissues. Parkin deficiency leads to upregulation of TMEFF1 which promotes migration and metastasis. TMEFF1transcription is activated by Parkin-induced endogenous TGF-β production and subsequent phosphorylation of Smad2/3 and its binding to TMEFF1promotor. TGF-β inhibitor and TMEFF1 knockdown can reverse shParkin-induced cell migration and changes of EMT markers. Parkin interacts with and promotes the ubiquitin-dependent degradation of HIF-1α/HIF-1β and p53, which accounts for the suppression of TGF-β production. Our data have revealed that Parkin deficiency in cancer leads to the activation of the TGF-β/Smad2/3 pathway, resulting in the expression of TMEFF1 which promotes cell migration, EMT, and metastasis in liver cancer cells.

Background and Aim: The incidence of rectal neuroendocrine tumors (R-NETs) has increased in recent years. However, the predictors of lymph node (LN) metastasis and clinical outcomes, particularly following endoscopic treatment, remain unclear. Our study aims to elucidate the potential risk factors for LN metastasis and the clinical outcomes of patients undergoing endoscopic resection in R-NETs. Methods: A total of 128 patients with R-NETs were retrospectively identified from a single center between June 2012 and December 2021. Risk factors for LN metastasis in R-NETs were analyzed using multivariate analysis. Additionally, the clinical outcomes of endoscopic resections in patients with R-NETs were assessed. Results: In our study, 128 patients with R-NETs were retrospectively analyzed. The risk factors for LN metastasis determined by multivariate analysis were tumor size and patient age at diagnosis. Among the 111 patients treated with endoscopic resection and with tumor margin records available, 92 underwent endoscopic submucosal dissection (ESD) and 19 underwent conventional endoscopic mucosal resection (EMR). There was no significant difference between the two groups regarding the positive rates of basal tumor margin and lateral tumor margin. Furthermore, 64 patients who underwent endoscopic resection for R-NETs were successfully followed up (range, 1.64–76.71 months), during which only one patient developed local recurrence. Conclusion: Tumor size and age at diagnosis were predictors for LN metastasis of R-NETs. Both ESD and EMR are alternative techniques with a favorable prognosis for R-NETs, even in cases with positive resection margins. However, due to the relatively small number of patients undergoing EMR and missing data in follow-up protocols, definitive conclusions require further large-scale studies.

Numerous studies have compared outcomes of liver resection (LR) of patients with non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) to those of patients with non-NAFLD-related HCC. However, results have been inconsistent. We aim to clarify this issue. We enrolled 801 patients with hepatitis B virus (HBV)-related HCC, 433 patients with hepatitis C virus (HCV)-related HCC, and 128 patients with NAFLD-related HCC undergoing LR. Overall survival (OS) and disease-free survival (DFS) of patients with different etiologies of chronic liver disease was compared using the Kaplan–Meier estimator and log-rank test after propensity score matching (PSM). After PSM, 83 patients remained in each group. The groups did not differ significantly in age, sex, the proportion of patients with pathological American Joint Committee on Cancer stage 1, tumor size > 50 mm, receipt of major resection, alpha-fetoprotein (AFP) ≥ 20 ng/ml, presence of cirrhosis, model for end-stage liver disease (MELD) score, and American Society of Anesthesiologists (ASA) classification. The five-year OS of patients with HBV-, HCV-, and NAFLD-related HCC was 78%, 75%, and 78%, respectively (p= 0.789). The five-year DFS of the HBV, HCV, and NAFLD groups was 60%, 45%, and 54%, respectively (p= 0.159). Perioperative morbidity was noted in 17 (20.5%) in the HBV group, 22 (26.5%) in the HCV group, and 15 (18.1%) in the NAFLD group (p= 0.398). The five-year OS, DFS, and perioperative morbidity of patients undergoing LR for NAFLD-related HCC and those for viral hepatitis-related HCC was similar.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel procedure for major resection in patients with insufficient future liver remnant (FLR). Effective FLR augmentation is pivotal in the completion of ALPPS. Liver fibrosis/cirrhosis associated with chronic viral hepatitis impairs liver regeneration. To investigate the augmentation of FLR in associating ALPPS between patients with fibrotic/cirrhotic livers (FL) and non-fibrotic livers (NFL) and compare their short-term clinical outcomes and long-term survival. Patients were divided into two groups based on the Ishak modified staging: non-fibrotic liver group (NFL, stage 0) and fibrotic/cirrhotic liver group (FL, stage 1–5/6). Weekly liver regeneration in FLR, perioperative data, and survival outcomes were investigated. Twenty-seven patients with liver tumors underwent ALPPS (NFL, n= 7; FL, n= 20). NFL and FL patients had viral hepatitis (28.6% [n= 2] and 95% [n= 19]), absolute FLR volume increments of 134.90 ml and 161.85 ml (p= 0.825), and rates of hypertrophy were 16.46 ml/day and 13.66 ml/day (p= 0.507), respectively. In the FL group, baseline FLR volume was 360.13 ml, postoperatively it increased to a plateau (542.30 ml) in week 2 and declined (378.45 ml) in week 3. One patient (3.7%) with cirrhotic liver (stage 6) failed to proceed to ALPPS-II. The overall ALPPS-related major complication rate was 7.4%. ALPPS is feasible for fibrotic liver patients classified by Ishak modified stages ≤ 5. After ALPPS-I, 14 days for FLR augmentation seems an appropriate waiting time to reach a maximum FLR volume in these patients.

In order to overcome the problems of low accuracy and long evaluation time of MOOC online English teaching quality evaluation, this paper proposes a MOOC online English teaching quality evaluation method based on fuzzy algorithm. Firstly, the mean method is used to calculate the cluster centre of MOOC online English teaching quality evaluation samples and the evaluation sample selection is realised by outlier detection. Secondly, the 1-9 scale method is used to compare the importance of English teaching quality evaluation indicators, so as to realise the stratification of importance level. The fuzzy discrimination matrix is constructed and the weight vector of the judgement matrix is calculated. Finally, the MOOC online English teaching quality evaluation is realised by fuzzy algorithm. The experimental results show that the accuracy of this method is 98.16%, and the evaluation time is only 1.5 min.

A high-selectivity hybrid-technology bandpass filter (BPF) at the K band using an inverted microstrip gap waveguide (MGW) approach is reported. The resonant frequencies of the modes TE102 and TE103 (i.e., $f_{102}$ and $f_{103}$ ) of its non-perturbed groove gap waveguide cavity resonator—as example TE resonant modes being contained within the extracted stopband range of the mushroom-type EBG cells—are firstly analyzed. By perturbing the referred cavity with a pin-loaded patch, a second-order BPF block with an adjustable transmission zero (TZ) is implemented. Moreover, by adding a source-load coupling structure among its inverted microstrip feeding sections, one more close-to-passband TZ is created. Next, in order to further increase the filter order and the number of stopband TZs, a stub-loaded microstrip ring resonator is introduced. In this way, by exploiting the perturbed- groove-gap-waveguide-cavity-resonator-based second-order BPF block along with the microstrip ring resonator, a three-pole BPF response is achieved. Furthermore, owing to the multiple signal paths being created in this mixed-technology filter, two additional close-to-passband TZs are produced. Consequently, an overall sharp-rejection third-order BPF with four TZs is realized. The RF operational foundations of the devised mixed-technology BPF are detailed. Besides, for practical-validation purposes, a third-order BPF prototype is developed and tested. The measured BPF circuit exhibits a passband centered at 21.21 GHz with 3-dB fractional bandwidth (FBW) of 4.72%, four out-of-band TZs, and stopband power-attenuation levels above 17.68 dB from 18.65 to 25.7 GHz.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4)gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

In this article, we first reveal the performance degradation and physical failure mechanism of a lab-designed GaN power amplifier (PA) module based on a commercial GaN high-electron-mobility transistor (HEMT) with high-power electromagnetic pulse injected. We carried out a systematic step pulse injection experiment to hunt out the degradation and failure threshold of PA module by monitoring its S-parameter and the gate-source resister (RGS) of GaN HEMT. Moreover, the performance indexes of GaN PA, including gain, power-added efficiency, output power, and signal-to-noise ratio, have been measured before/after degradation for comparative analysis. The intact surface circuit microscope of PA module and the degradation electrical characteristics of GaN HEMT demonstrated that the GaN HEMT is the vulnerable component of GaN PA. Furthermore, the numerical simulations and decapsulation experiments are carried out for GaN HEMT to gain insight into the failure process and physical failure mechanism. The results reveal that the failure mode is thermal-induced gate metal melting of the GaN HEMT. The failure mechanism is mainly attributable to the impact ionization, which induced by the high pulse voltage under the gate near the source. This is followed by the thermal–electrical feedback state in the device internal until the temperature finally reaching the melting point of the gate metal.

Overactivation of the NLRP3 inflammasomes induces production of pro-inflammatory cytokines and drives pathological processes. Pharmacological inhibition of NLRP3 is an explicit strategy for the treatment of inflammatory diseases. Thus far no drug specifically targeting NLRP3 has been approved by the FDA for clinical use. This study was aimed to discover novel NLRP3 inhibitors that could suppress NLRP3-mediated pyroptosis. We screened 95 natural products from our in-house library for their inhibitory activity on IL-1β secretion in LPS + ATP-challenged BMDMs, found that Britannin exerted the most potent inhibitory effect with an IC50value of 3.630 µM. We showed that Britannin (1, 5, 10 µM) dose-dependently inhibited secretion of the cleaved Caspase-1 (p20) and the mature IL-1β, and suppressed NLRP3-mediated pyroptosis in both murine and human macrophages. We demonstrated that Britannin specifically inhibited the activation step of NLRP3 inflammasome in BMDMs via interrupting the assembly step, especially the interaction between NLRP3 and NEK7. We revealed that Britannin directly bound to NLRP3 NACHT domain at Arg335 and Gly271. Moreover, Britannin suppressed NLRP3 activation in an ATPase-independent way, suggesting it as a lead compound for design and development of novel NLRP3 inhibitors. In mouse models of MSU-induced gouty arthritis and LPS-induced acute lung injury (ALI), administration of Britannin (20 mg/kg, i.p.) significantly alleviated NLRP3-mediated inflammation; the therapeutic effects of Britannin were dismissed by NLRP3 knockout. In conclusion, Britannin is an effective natural NLRP3 inhibitor and a potential lead compound for the development of drugs targeting NLRP3.

Though the evidence for antibiotic resistance spread via plant microbiome is mounting, studies regarding antibiotic resistome in the plant seed, a reproductive organ and important food resource, are still in their infancy. This study investigated the effects of long-term organic fertilization on seed bacterial endophytes, resistome, and their intergenerational transfer in the microcosm. A total of 99 antibiotic resistance genes (ARGs) and 26 mobile genetic elements (MGEs) were detected by high-throughput quantitative PCR. The amount of organic fertilizer applied was positively correlated to the number and relative abundance of seed-associated ARGs and MGEs. Moreover, the transmission of ARGs from the rhizosphere to the seed was mainly mediated by the shared bacteria and MGEs. Notably, the rhizosphere of progeny seedlings derived from seeds harboring abundant ARGs was found to have a higher relative abundance of ARGs. Using structural equation models, we further revealed that seed resistome and MGEs were key factors affecting the ARGs in the progeny rhizosphere, implying the seed was a potential resistome reservoir for rhizosphere soil. This study highlights the overlooked role of seed endophytes in the dissemination of resistome in the soil-plant continuum, and more attention should be paid to plant seeds as vectors of ARGs within the “One-Health” framework.

Abstract:This article systematically reviews the diplomatic activities carried out by China's leaders, aiming to gain insights into the nation's strategic approach to foreign affairs. The research commenced by compiling and analyzing a dataset comprising 1,908 reports on "leaders' activities" sourced from the Ministry of Foreign Affairs website, spanning the period from November 2017 to January 2020. We examined patterns and trends in areas such as the reception of foreign dignitaries, international visits, the timing of diplomatic activities, and the specific regions for which each leader was responsible for in overseeing policy. Analyzing these patterns unveils the scheduling and division of diplomatic responsibilities among leaders, along with the specific regions associated with each leader's focus. Our systematic analysis sheds light on the nature and structure of Chinese leaders' diplomatic activities. It also provides policymakers with essential information to reassess their strategies and reallocate their resources as they engage with China.

Background and aim: Endoscopic resection (ER) has been used to remove submucosal tumors (SMTs) in recent years; however, duodenal ER is associated with high rates of immediate or delayed bleeding and perforation. Whether ER can be recommended for the treatment of duodenal SMTs remains controversial. Therefore, we aimed to investigate the clinical outcomes associated with the ER of duodenal SMTs and to assess possible predictive factors for complications and incomplete resection. Methods: This retrospective study included 141 patients with duodenal SMTs. The therapeutic outcomes from ER and procedure-related complications were analyzed. Results: Of the 141 patients, 78.7% achieved complete resection and nine (6.4%) developed complications. The multivariate analysis suggested that location near the duodenal papilla (P= 0.010) and diameter exceeding 15 mm (P= 0.091) of duodenal SMTs were independent risk factors for complications in ER. Besides, submucosal fibrosis (P= 0.042), location near the duodenal papilla (P= 0.049), and irregular morphology (P= 0.067) were independent risk factors for incomplete resection. Conclusions: ER can be recommended as an effective and minimally invasive treatment for duodenal SMTs.

Constraint handling is a core part when using surrogate-assisted evolutionary algorithms (SAEAs) to solve expensive constrained optimization problems (ECOPs). However, most existing SAEAs for ECOPs train a surrogate for each constraint. With the number of constraints increasing, the training burden of surrogates becomes heavy and the efficiency of the algorithm is greatly reduced. To solve this issue, this article proposes an efficient two-stage surrogate-assisted differential evolution (eToSA-DE) algorithm to handle expensive inequality constraints. eToSA-DE trains one surrogate for the degree of constraint violation and the type of the surrogate varies during the evolution process. In the first stage when there are only a few feasible individuals, a Gaussian process regression model is trained to fit the degree of constraint violation. In the second stage when more feasible individuals are accumulated, a support vector machine classification model is trained to classify whether candidates are feasible. Both types of surrogates are constructed by individuals which are chosen by the boundary training data selection strategy. These selected individuals are located around the feasible boundaries and helpful for the surrogate to approximate the feasibility structure. Besides, a feasible exploration strategy is devised to search for promising areas. To alleviate the error caused by the regression model, a nearest neighbor rectification is adopted to modify the prediction results. Extensive experiments on benchmark test functions and two formulated engineering optimization problems demonstrate that the proposed method can get satisfactory optimization results and significantly improve the efficiency of the algorithm.

In this communication, a $2\times2$ balanced filtering antenna array parallel-fed by a differential broadband network is presented. The array has four identical stacked filtering antenna elements, each of which consists of a main patch etched with a folded U-shaped slot, a pair of ear-shaped parasitic patches, a stacked patch, and a folded T-shaped strip. The conceived antenna topology can enhance the gain flatness, improve selectivity, and increase the number of radiation nulls. Meanwhile, by introducing a novel ring-shaped transition structure (RSTS) to the balanced-to-single-ended (BTSE) four-way feeding network, a broad bandwidth, low insertion losses, low phase difference errors, and high common-mode (CM) suppression are realized. To validate the method, an integrated antenna array with a center frequency of 2.5 GHz is fabricated and measured. Experimental results exhibit a boresight gain of 13.7 dBi, four radiation nulls, and a square factor ( $SF_{10}$ ) of 1.21.

In-memory computing is an emerging computing paradigm to breakthrough the von-Neumann bottleneck. The SRAM based in-memory computing (SRAM-IMC) attracts great concerns from industries and academia, because the SRAM is technology compatible with the widely-used MOS devices. The digital SRAM-IMC scheme has advantages on stability and accuracy of computing results, compared with the analog SRAM-IMC schemes. However, few logic operations can be implemented by the current digital SRAM-IMC architectures. Designers have to insert some special logic modules to facilitate the complex computation. To address this issue, this work proposes an area-efficient implementation method of arbitrary Boolean function in SRAM array. Firstly, a two-input SRAM LUT is designed to realize the arbitrary two-input Boolean functions. Then, the logic merging and the spatial merging techniques are proposed to reduce the area consumption of the SRAM-IMC scheme. Finally, the SOP-based SRAM-IMC architecture is proposed, and the merged SOPs are mapped into and computed in it. The evaluation results on LGsynth’91, IWLS’93 and EPFL benchmarks show that, the area of the synthesis results based on the ABC tool is 3.69, 5.72 and 1.86 times of the circuit area from the proposed SRAM-IMC scheme in average respectively. Furthermore, the circuit area from the original SOP-based SRAM-IMC scheme is 2.07, 1.99 and 1.86 times in average of the circuit area from the proposed SRAM-IMC scheme respectively. The performance evaluation results show that the cycle consumption of the proposed SRAM-IMC scheme is independent to the scale of the input Boolean functions.

Predicting recurrence patterns of hepatocellular carcinoma (HCC) can be helpful in developing surveillance strategies. This study aimed to use the hazard function to investigate recurrence hazard and peak recurrence time transitions in patients with HCC undergoing liver resection (LR). We enrolled 1204 patients with HCC undergoing LR between 2007 and 2018 at our institution. Recurrence hazard, patterns, and peak rates were analyzed. The overall recurrence hazard peaked at 7.2 months (peak hazard rate [pHR]: 0.0197), but varied markedly. In subgroups analysis based on recurrence risk factors, patients with a high radiographic tumor burden score (pHR: 0.0521), alpha-fetoprotein level ≥ 400 ng/ml (pHR: 0.0427), and pT3–4 (pHR: 0.0656) showed a pronounced peak within the first year after LR. Patients with cirrhosis showed a pronounced peak within three years after LR (pHR: 0.0248), whereas those with Barcelona Clinic Liver Cancer stage B (pHR: 0.0609) and poor tumor differentiation (pHR: 0.0451) showed multiple peaks during the 5-year follow-up period. In contrast, patients without these recurrence risk factors had a relatively flat hazard function curve. HCC recurrence hazard, patterns, and peak rates varied substantially depending on different risk factors of HCC recurrence.

In this brief, a filtering power divider (FPD) based on a novel tri-mode resonator (TMR) is proposed firstly. Characteristic mode analysis (CMA) method is utilized to analyze the three modes of TMR in detail. Meanwhile, two transmission zeros (TZs) are generated due to TMR, which can improve the passband selectivity greatly. Then for the purpose of meeting the connecting requirement between single-ended and balanced components, a single-ended-to-balanced (SETB) FPD is realized on the basis of the FPD. In order to realize the miniaturization, a multilayer microstrip-slotline (M-S) transition structure is applied. As a result, the additional half-wavelength transmission slotline is not required. To validate the design method, the prototype has been manufactured and measured. The overall size is about $0.38\,\,\lambda _{\mathrm{ g}} \times 1.04\,\,\lambda _{\mathrm{ g}}$ and the common-mode (CM) suppression level is better than 28.5 dB at all frequencies (the fractional bandwidth is 200%). Furthermore, the in-band insertion loss is lower than 1.2 dB and the isolation is higher than 17.6 dB in the passband.

Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)-mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.