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Abstract Host organisms use different innate immune mechanisms to defend against pathogenic infections, while tight control of innate immunity is essential for proper immune induction and balance. Here, we reported that apoptotic induction or caspase-3 overexpression caused dramatic reduction of differently triggered cytokine signalings in human cells, murine primary cells and mouse model, while the loss of caspase-3 or inhibiting apoptosis markedly enhances these immune signalings. Furthermore, caspase-3 can mediate the cleavage of NF-κB members p65/RelA, RelB, and c-Rel via its protease activity. And the caspase-3-resistant p65/RelA, RelB, or c-Rel mutant mostly restored the caspase-3-induced suppression of cytokine production. Interestingly, we further uncovered that apoptotic induction also dramatically inhibited Toll immune signaling in Drosophila, and the Drosophila effector caspases, drICE and DCP-1, also mediated the degradation of DIF, the NF-κB of Toll signaling. Together, our findings demonstrate apoptotic effector caspases, including mammalian caspase-3 and fly drICE/DCP-1, can function as repressors of NF-κB-mediated innate immune signalings.

Abstract Primary familial brain calcification (PFBC) is a neurogenetic disorder characterized by bilateral calcified deposits in the brain. We previously identified that MYORG as the first pathogenic gene for autosomal recessive PFBC, and established a Myorg-KO mouse model. However, Myorg-KO mice developed brain calcifications until nine months of age, which limits their utility as a facile PFBC model system. Hence, whether there is another typical animal model for mimicking PFBC phenotypes in an early stage still remained unknown. In this study, we profiled the mRNA expression pattern of myorg in zebrafish, and used a morpholino-mediated blocking strategy to knockdown myorg mRNA at splicing and translation initiation levels. We observed multiple calcifications throughout the brain by calcein staining at 2–4 days post-fertilization in myorg-deficient zebrafish, and rescued the calcification phenotype by replenishing myorg cDNA. Overall, we built a novel model for PFBC via knockdown of myorg by antisense oligonucleotides in zebrafish, which could shorten the observation period and replenish the Myorg-KO mouse model phenotype in mechanistic and therapeutic studies.

Abstract Background Gingivobuccal complex (GBC) was a relatively new concept of oral subsite that was comprises of the upper and/or lower gingiva, gingival buccal sulcus, and adjacent buccal mucosa. Squamous cell carcinoma (SCC) of the GBC had a poor prognosis, with few studies analyzing this particular entity. The objective of this study was to analyze the risk factors affecting the prognosis and complications/sequalae of gingivobuccal complex cancer. Methods Between December 2014 and August 2019, a total of 122 patients diagnosed with primary gingivobuccal complex cancer in Beijing Stomatological Hospital, Capital Medical University were enrolled in the study. Through outpatient reviewed and telephone followed-up for 2-5 years postoperatively, postoperative relapse and complications/sequalae were assessed. The primary outcome parameter was 2-year disease-free survival. Results The most common central site of the tumor was the buccal mucosa (45.1%), followed by the lower gingiva (36.9%). The most diseases were pT4a (45.1%) and there was lymph node invasion (pN+) in 41.8% of patients. Moderate differentiated squamous carcinoma (77.9%) accounted for the vast majority of the histopathological differentiation. A total of 62.3% of tumors invaded the bone, while, 5.7% invaded the skin layer. Survival analysis found that 44.3% of patients experienced relapse within two years postoperatively and the mortality rate after relapse was 75.9%. Almost 60.0% of the tumors involving the maxilla and/or mandible developed relapse. Cox proportional hazards model found that pN stage (p= 0.002) and bone invasion (p= 0.007) were significant independent predictors of 2-year disease-free survival. Importantly, 63.1% of patients had postoperative (and postradiotherapy) complications/sequalae. It was noteworthy that 18 of 43 patients (41.9%) who implanted with titanium plates had hardware-related complications/sequalae, and the most of them were titanium plate exposure (61.1%). Conclusions Squamous cell carcinoma of the gingivobuccal complex cancer, as a new subsite worthy of attention in oral cancer, has a high complication/sequalae rate, high relapse rate and poor prognosis. Trial registration Prospective, Observational, Real-world Oral Malignant Tumors Study ( clinicaltrials.gov identifier: NCT02395367). The approval of the Institutional Review Board of the Beijing Stomatological Hospital of Capital Medical University (Approval number: CMUSH-IRB-KJPJ-2015-08)

Abstract Background Chemoresistance serves as a huge obstacle for acute myeloid leukemia (AML) patients. To counteract the chemoresistance in AML cells, we discussed the role of maternally expressed gene 3 (MEG3) in arabinocytosine (AraC) chemoresistance in AML cells. Methods MEG3, microRNA (miR)-493-5p, methyltransferase-like 3 (METTL3) and MYC expression in AML cells was determined and then their interactions were also analyzed. Then, the viability and apoptosis of AML cells were determined through loss- and gain- function assay. The level of m6A modification in AML cells was examined. AML mouse models were also established to validate the potential roles of MEG3. Results MEG3 and miR-493-5p were downregulated in AML cells, and they were lower in resistant cells than in parental cells. MEG3 led to elevated expression of miR-493-5p which targeted METTL3. METTL3 increased expression of MYC by promoting its m6A levels. Overexpression of MEG3 and miR-493-5p or knockdown of METTL3 inhibited HL-60 and Molm13 cell proliferation and promoted their apoptosis. Overexpressed MEG3 induced heightened sensitivity of AML cells to AraC. However, the suppression of miR-493-5p reversed the effects of overexpressed MEG3 on AML cells. Conclusions Collectively, MEG3 could upregulate miR-493-5p expression and suppress the METTL3/MYC axis through MYC m6A methylation, by which MEG3 promoted the chemosensitivity of AML cells.

Abstract The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important target for vaccine and drug development. However, the rapid emergence of variant strains with mutated S proteins has rendered many treatments ineffective. Cleavage of the S protein by host proteases is essential for viral infection. Here, we discovered that the S protein contains two previously unidentified Cathepsin L (CTSL) cleavage sites (CS-1 and CS-2). Both sites are highly conserved among all known SARS-CoV-2 variants. Our structural studies revealed that CTSL cleavage promoted S to adopt receptor-binding domain (RBD) “up” activated conformations, facilitating receptor-binding and membrane fusion. We confirmed that CTSL cleavage is essential during infection of all emerged SARS-CoV-2 variants (including the recently emerged Omicron variant) by pseudovirus (PsV) infection experiment. Furthermore, we found CTSL-specific inhibitors not only blocked infection of PsV/live virus in cells but also reduced live virus infection of ex vivo lung tissues of both human donors and human ACE2-transgenic mice. Finally, we showed that two CTSL-specific inhibitors exhibited excellent In vivo effects to prevent live virus infection in human ACE2-transgenic mice. Our work demonstrated that inhibition of CTSL cleavage of SARS-CoV-2 S protein is a promising approach for the development of future mutation-resistant therapy.

Cancer stem cells (CSCs) have been blamed as the main culprit of tumor initiation, progression, metastasis, chemoresistance, and recurrence. However, few anti-CSCs agents have achieved clinical success so far. Here we report a novel derivative of lonidamine (LND), namely HYL001, which selectively and potently inhibits CSCs by targeting mitochondria, with 380-fold and 340-fold lower IC50 values against breast cancer stem cells (BCSCs) and hepatocellular carcinoma stem cells (HCSCs), respectively, compared to LND. Mechanistically, we reveal that HYL001 downregulates glutaminase (GLS) expression to block glutamine metabolism, blunt tricarboxylic acid cycle, and amplify mitochondrial oxidative stress, leading to apoptotic cell death. Therefore, HYL001 displays significant antitumor activity in vivo, both as a single agent and combined with paclitaxel. Furthermore, HYL001 represses CSCs of fresh tumor tissues derived from liver cancer patients. This study provides critical implications for CSCs biology and development of potent anti-CSCs drugs.

Introduction: To achieve higher power or increased precision for a new trial, methods based on updating network meta-analysis (NMA) have been proposed by researchers. However, this approach could potentially lead to misinterpreted results and misstated conclusions. This work aims to investigate the potential inflation of type I error risk when a new trial is conducted only when, based on a p-value of the comparison in the existing network, a “promising” difference between two treatments is noticed.Methods: We use simulations to evaluate the scenarios of interest. In particular, a new trial is to be conducted independently or depending on the results from previous NMA in various scenarios. Three analysis methods are applied to each simulation scenario: with the existing network, sequential analysis and without the existing network.Results: For the scenario that the new trial will be conducted only when a promising finding (p-value

Large redundant metal structures have high stability with large cost. An excellent mechanical structure should have the lower weight when satisfying its stability. Aiming at the large redundancy of the main beam metal structure of the double-beam bridge crane, the paper extracts six important parameters to determine its quality, and the corresponding value is set. The orthogonal test table is designed to calculate the strength and stiffness. In order to avoid resonance, the fixed vibration frequency and excitation frequency are calculated. The experimental results are fitted to obtain the six parameters of the quality, strength, stiffness, and natural frequency. Moreover, particle swarm optimization algorithm is used to solve the multi-objective optimization mathematical model with the design quality as the goal and the stiffness, strength, and easy resonance interval as constraints. In view of the long calculation time and poor convergence of particle swarm optimization algorithm, a module that limits the particle forward speed is added and the generation conditions of particles are redefined. The improved particle swarm algorithm shows that the first-order vibration frequency of the main beam increases from 18 Hz to 27.55 Hz. It improves the stability of the overall structure and avoids resonance with the motor frequency. Under the condition of satisfying the stability of the main beam, the quality of the main beam is reduced from 1.23 tons to 0.53 tons, with a reduction of 6%.

The growth and health statuses of calves during the early stages of development have a significant effect on milk production during their first lactation period. Using appropriate milk replacers helps meet the long-term targets of dairy farmers. This study aimed to examine the effects of milk, milk replacer, and milk replacer plus ethoxyquin on growth performance, antioxidant status, immune function, and the gut microbiota of Holstein dairy calves. A total of 36 neonatal dairy calves were randomly divided into three groups and fed different diets: one group was fed milk, another group was fed milk replacer, and the third group was given milk replacer plus ethoxyquin. The supplementation with ethoxyquin was started on day 35 of the feeding period. The calves were weaned on day 45, and the experiment was conducted until day 49. The blood and fecal samples were collected at the end of the animal experiment. The results showed that milk replacers induced poor growth performance (body weight and average daily gain). However, milk replacer plus ethoxyquin aided in growth performance, enhanced the starter intake and blood antioxidative ability, and elevated the concentration of fecal valeric acid. Moreover, fecal fermentation and 16S rRNA analyses showed that milk replacer plus ethoxyquin altered the microbial composition (reducing Alistipes and Ruminococcaceae and increasing Bacteroides and Alloprevotella). Pearson's correlation assays showed that alterations in fecal microbiota strongly correlated with average daily gain and antioxidative ability. The results indicated the potential of milk replacer plus ethoxyquin in modulating the growth of dairy calves and in enhancing their ability to combat stress.

The girth weld is the weak link of high-grade pipeline, and its structural integrity affects the safety of pipeline operation. Herein, the state of art of the weld metal strength and toughness indicators were discussed from three aspects: the design method of weld metal strength and toughness indicators, the strength and toughness acceptance indicators proposed by pipeline engineering design standards, and the test method of weld metal strength and toughness. The fitness-for-service assessment methods of pipeline girth weld were expounded. The key problems and progress of the assessment methods were discussed: the crack tip constraint effect of fracture toughness, the numerical simulation method of fracture behavior of pipeline girth weld, the evaluation method of crack driving force, the assessment method of failure evaluation diagram, the prediction method of tensile strain capacity of pipeline girth weld, and the fracture experimental test of full-scale pipeline girth weld. Finally, the existing problems and future research directions in the mechanical properties and fitness-for-service assessment of high-grade pipeline girth weld were put forward. Generally, the research results could provide a reference for improving the intrinsic safety of high-grade pipeline girth weld.

Layer-number modulation in graphene has become a recent focus of research due to the superior degree of freedom that can be achieved in terms of magic-angle, wettability, superconductivity, and superlattices. However, the intrinsic transport of multilayer graphene is indistinguishable in atmospheric adsorbates and supporting environment, and its underlying charge transfer mechanism has not yet been thoroughly determined. In this study, a shift in the charge neutrality point of trilayer graphene (TLG) is demonstrated to be regulated by three governing factors: oxygen gas (O2), water molecules (H2O), and thermally activated electrons. Absorbed O2 ​induces a high work function in semimetallic TLG, while H2O is not an evident dopant but can strengthen binding against O2 ​desorption. A simplified model is developed to elucidate the competitive mechanism and charge transfer among these two dopants (O2, H2O) and thermal electrons, and the model is demonstrated by work function regulation and Bader charge transfer based on density functional theory calculations. This study provides a strategy to explore transport modulation of multilayer graphene in the fields of ballistic transport and low power consumption of graphene field-effect transistors.

Due to the large amount of water supply, the water level difference between mid-layer water and shallow water increases. There is no authoritative answer whether there is a hydraulic connection between shallow and mid-layer water. Therefore, a clear understanding of hydrogeochemical characteristics and the water chemical connection of them is indispensable for groundwater protection and the safety of water supply. The results of the statistical analysis showed that shallow and mid-layer water were both neutral water. The content of SO42−, Cl− and Na+ in both exceeded the grade III standard limit in the Standard for Groundwater Quality of China. Piper diagram revealed shallow water was mainly of Na + Mg + HCO3− and Mg + Na + HCO3− type, and mid-layer water was mainly of Na + Mg + HCO3− + SO42− and Na + Mg + HCO3− type. Besides, using the coefficient variations method of comprehensive water quality index (pH, TDS, F−, and NO3−), it is found that except for a local area with thin thickness (less than 5 m) of the first aquiclude, the mid-layer water was not affected by shallow water in Sulin mining area. This study may be helpful for the safety of water supply in the study area and other mining areas in the Huaibei coalfield. HIGHLIGHTS First analysis on the hydraulic connection between shallow and mid-layer water by using comprehensive water quality indexes.; The relationship between the thickness of the first aquiclude and the vatiation of nitrate content in mid-layer water and shallow water.; Sources of fluorine in mid-layer water.;

Abstract A comparative study on the influence of different manufacturing methods (selective laser melting and hot rolling) on the microstructure, mechanical and thermal behaviours of tungsten (W) was presented for the first time. The results indicated that the selective laser melting (SLM) W exhibited a finer grain sizes, a lower strength ductility, hardness and thermal conductivity compared to hot-rolled W. The main reason for this result was that the laser underwent rapid heating and cooling when it was used to melt W powder with high energy density, resulting in large internal stress in the sample after manufacturing. Subsequently, the internal stress was released, leading to the generation of micro-cracks at the grain boundaries, thereby affecting the performance of SLM W samples. In addition, the higher fraction of high-angle grain boundaries (HAGBs) of SLM W was found to be the key factor for intrinsic brittleness. Because the HAGBs are the preferred crack paths, which could promote crack propagation and decrease fracture energy.

Abstract RNAs are rapidly degraded in samples and during collection, processing and testing. In this study, we used the same method to explore the half-lives of different RNAs and the influencing factors, and compared the degradation kinetics and characteristics of different RNAs in whole blood and experimental samples. Fresh anticoagulant blood samples were incubated at room temperature for different durations, RNAs were extracted, and genes, including internal references, were amplified by real-time quantitative PCR. A linear half-life model was established according to cycle threshold (Ct) values. The effects of experimental operations on RNA degradation before and after RNA extraction were explored. Quantitative analysis of mRNA degradation in samples and during experimental processes were explored using an orthogonal experimental design. The storage duration of blood samples at room temperature had the greatest influence on RNA degradation. The half-lives of messenger RNAs (mRNAs) was 16.4 h. The half-lives of circular RNAs (circRNAs), long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were 24.56 ± 5.2 h, 17.46 ± 3.0 h and 16.42 ± 4.2 h, respectively. RNA degradation occurred mainly in blood samples. The half-life of mRNAs was the shortest among the four kinds of RNAs. Quantitative experiments related to mRNAs should be completed within 2 h. The half-lives of circRNAs and lncRNAs were longer than those of the former two.

Military success requires retaining sufficient capable service members, but there is little research on retaining quality personnel. We propose an innovative bonus structure to retain the right quantity and quality of personnel by setting retention bonuses through a menu-of-contracts. The menu provides choices between bonus structures that encourage higher and lower-quality personnel to voluntarily select the bonus structure that best reflects their perceived quality. This addresses two essential problems in military personnel research: adverse selection (making inappropriate retention decisions due to hidden quality information) and moral hazard (incentives encouraging personnel to provide less than their best effort). A menu-of-contracts can meet the military’s retention needs without relying on past performance to measure expected future performance. This retains higher-quality personnel, increases morale and improves future retention. It also induces personnel to maximize effort throughout their careers as they strive for the highest bonus while maintaining the perception of egalitarianism.

Ultrasonic fatigue tests are performed on a magnesium alloy with and without ultrasonic peening treatment (UPT). Surface enhancement layer leads to the complete change of crack initiation sites. However, crack initiation mechanism keeps the same and results in a single-faceted morphology at crack initiation site. Microcracks initiate as Mode II crack within the original grain, but deflect to Mode I crack outside of the original cracked grain. A threshold SIF value is proposed to evaluate the retarding effect of grain boundary on microcrack propagation. Outside of the original cracked grain, Mode I crack propagation below the threshold ΔKσ-th is responsible for the formation of fine granular area (FGA, a nano-grain layer). Based on the Numerous Cyclic Pressing (NCP) model, it is proposed that crack type should be another necessary condition for the formation of FGA.

Abstract Cetuximab is a widely used drug for treating head and neck squamous cell carcinomas (HNSCCs); however, it provides restricted clinical benefits, and its response duration is limited by drug resistance. Here, we conducted randomized “Phase II-like clinical trials” of 49 HNSCC PDX models and reveal multiple informative biomarkers for intrinsic resistance to cetuximab (e.g., amplification of ANKH, up-regulation of PARP3). After validating these intrinsic resistance biomarkers in another HNSCC PDX cohort (61 PDX models), we generated acquired cetuximab resistance PDX models and analyzed them to uncover resistance mechanisms. Whole exome sequencing and transcriptome sequencing revealed diverse patterns of clonal selection in acquired resistant PDXs, including the emergence of subclones with strongly activated RAS/MAPK. Extending these insights, we show that a combination of a RAC1/RAC3 dual-target inhibitor and cetuximab could overcome acquired cetuximab resistance in vitro and in vivo. Beyond revealing intrinsic resistance biomarkers, our PDX-based study shows how clonal architecture changes underlying acquired resistance can be targeted to expand the therapeutic utility of this important drug to more HNSCC patients.

Abstract With many frameworks based on message passing neural networks proposed to predict molecular and bulk properties, machine learning methods have tremendously shifted the paradigms of computational sciences underpinning physics, material science, chemistry, and biology. While existing machine learning models have yielded superior performances in many occasions, most of them model and process molecular systems in terms of homogeneous graph, which severely limits the expressive power for representing diverse interactions. In practice, graph data with multiple node and edge types is ubiquitous and more appropriate for molecular systems. Thus, we propose the heterogeneous relational message passing network (HermNet), an end-to-end heterogeneous graph neural networks, to efficiently express multiple interactions in a single model with ab initio accuracy. HermNet performs impressively against many top-performing models on both molecular and extended systems. Specifically, HermNet outperforms other tested models in nearly 75%, 83% and 69% of tasks on revised Molecular Dynamics 17 (rMD17), Quantum Machines 9 (QM9) and extended systems datasets, respectively. In addition, molecular dynamics simulations and material property calculations are performed with HermNet to demonstrate its performance. Finally, we elucidate how the design of HermNet is compatible with quantum mechanics from the perspective of the density functional theory. Besides, HermNet is a universal framework, whose sub-networks could be replaced by other advanced models.

Abstract Background Porcine parainfluenza virus 1 (PPIV-1) is a respiratory virus in the family Paramyxoviridae and genus Respirovirus. It is closely related to bovine parainfluenza virus 3, human parainfluenza virus 1, and Sendai virus. Recent reports suggest PPIV-1 is widespread in swine herds in the United States and abroad. However, seroprevalence studies and the ability to evaluate cross neutralization between heterologous strains is not possible without validated antibody assays. This study describes the development of an indirect fluorescence antibody (IFA) assay, a whole virus enzyme-linked immunosorbent assay (wv-ELISA) and a serum virus neutralization (SVN) assay for the detection of PPIV-1 antibodies using 521 serum samples collected from three longitudinal studies and two different challenge strains in swine. Results The area under the curve (AUC) of the wv-ELISA (95% CI, 0.93–0.98) was significantly higher (p = 0.03) compared to the IFA (95% CI, 0.90–0.96). However, no significant difference was observed between the IFA and wv-ELISA when compared to the SVN (95% CI, 0.92–0.97). All three assays demonstrated relatively uniform results at a 99% true negative rate, with only 11 disagreements observed between the IFA, wv-ELISA and SVN. Conclusions All three serology assays detected PPIV-1 antibody in swine serum of known status that was collected from experimental studies. The SVN detected seroconversion earlier compared to the IFA and the wv-ELISA. Both the wv-ELISA and the SVN had similar diagnostic performance, while the IFA was not as sensitive as the wv-ELISA. All three assays are considered valid for routine diagnostic use. These assays will be important for future studies to screen seronegative swine for research, determine PPIV-1 seroprevalence, and to evaluate vaccine efficacy against PPIV-1 under experimental and field conditions.

Abstract Background Despite the continuous development and evolution of surgical methods and techniques, proximal hypospadias remains one of the most challenging issues for pediatric urologists. This study aims to evaluate the indications and postoperative complications of our new modified Duckett urethroplasty. Methods A total of 133 patients with proximal hypospadias who underwent repair of the modified Duckett urethroplasty from February 2016 to February 2021 were reviewed. The median age of patients was 3 years (range 1–16). All patients had severe chordee. One senior experienced pediatric urologist performed all the surgeries. Catheter was removed 14 days after the surgery. Results The location of the urethral meatus was proximal penile in 26 patients (19.5%), penoscrotal in 60 (45.1%), scrotal in 31 (23.3%), and perineal in 16 (12.0%). The mean length of the urethral defect was 4.5 cm (range 2.5–10). The median duration of follow-up was 46 months (range 8–67). Complications occurred in 31 patients (23.3%), including urethra-cutaneous fistula in 22 (16.5%), urethral stenosis in 7 (5.3%), and urethral diverticulum in 2 (1.5%). No recurrent chordee were found in all cases. All patients who developed complications were treated successfully at our hospital. Conclusions Our modified Duckett urethroplasty showed functionally and cosmetically favorable outcomes, with a lower incidence of postoperative complications. To the best of our knowledge, the novel Duckett technique is a feasible and suitable option for patients who suffer from proximal hypospadias with severe chordee and dysplasia of the urethral plate.

Exotic states emerge from the interplay between band topology and ferromagnetism, but it remains less known in canted-antiferromagnetic phase. Here, the authors realize a canted-antiferromagnetic Chern insulator in atomically-thin MnBi2Te4 with electrical control of chiral-edge state transport.

The two-dimensional strip-packing problem (2D-SPP) emerges as a notable variant of the cutting and packing (C&P) problem, aiming to optimize the arrangement of small rectangular items within unique strips with a fixed width and infinite height to minimize the usage of height. Despite extensive academic exploration, applying 2D-SPP solutions in industrial settings remains challenging. Two significant issues, often overlooked in academia yet frequently encountered in industrial contexts, are the uncertain demand for items, exacerbated by the bullwhip effect, and the need for diverse types of strips to cater to varying customer needs. Our paper addresses this academia–industry gap by proposing a robust optimization model for the uncertain 2D-SPP with variable-sized bins, aiming to manage the demand fluctuations within a box uncertainty set framework. Additionally, we employ the contiguous one-dimensional relaxation technique in conjunction with column generation to tighten the lower bound of the problem, thereby augmenting solution accuracy. Furthermore, we leverage the Karush–Kuhn–Tucker (KKT) condition to transform the model into a more tractable form, subsequently leading to an exact solution. Based on datasets from a real-life plastic-cutting company, comprehensive experiments validate the effectiveness and efficiency of our proposed relaxation method and algorithm, showcasing the potential for an improved industrial application of 2D-SPP solutions.

Part quality monitoring and control in wire-based directed energy deposition additive manufacturing (w-DEDAM) processes has been garnering continuous interest from both the academic and industrial sectors. However, maintaining a consistent layer height and ensuring that the wall height aligns closely with the design, as depicted in computer-aided design (CAD) models, pose significant challenges. These challenges arise due to the uncertainties associated with the manufacturing process and the working environment, particularly with extended processing times. To achieve these goals in an industrial scenario, the deposition geometry must be measured with precision and efficiency throughout the part-building process. Moreover, it is essential to comprehend the changes in the interlayer deposition height based on various process parameters. This paper first examines the behaviour of interlayer deposition height when process parameters change within different wall regions, with a particular focus on the transition areas. In addition, this paper explores the potential of geometry monitoring information in implementing interlayer wall height compensation during w-DEDAM part-building. The in-process layer height was monitored using a coherent range-resolved interferometry (RRI) sensor, and the accuracy and efficiency of this measurement were carefully studied. Leveraging this information and understanding of deposition geometry, the control points of the process parameters were identified. Subsequently, appropriate and varied process parameters were applied to each wall region to gradually compensate for wall height. The wall height discrepancies were generally compensated for in two to three layers.

The design of aerospace systems is recognized as a complex interdisciplinary process. Many studies have shown that the exchange of information among multiple disciplines often results in strong coupling and nonlinearity characteristics in system optimization. Meanwhile, inevitable multi-source uncertainty factors continuously accumulate during the optimization process, greatly compromising the system’s robustness and reliability. In this context, uncertainty-based multidisciplinary design optimization (UMDO) has emerged and has been preliminarily applied in aerospace practices. However, it still encounters major challenges, including the complexity of multidisciplinary analysis modeling, and organizational and computational complexities of uncertainty analysis and optimization. Extensive research has been conducted recently to address these issues, particularly uncertainty analysis and artificial intelligence strategies. The former further enriches the UMDO technique, while the latter makes outstanding contributions to addressing the computational complexity of UMDO. With the aim of providing an overview of currently available methods, this paper summarizes existing state-of-the art UMDO technologies, with a special focus on relevant intelligent optimization strategies.

This study utilized transmission electron microscopy (TEM) and on-axis transmission Kikuchi diffraction (TKD) to investigate the fatigue-induced HCP-to-FCC phase transformation in industrial pure zirconium under a stress ratio of R = 0.1. The results show that fatigue damages result from phase deformations during cyclic loadings. The fatigue-induced FCC-Zr phases exhibit a B-type orientation relationship with the HCP-Zr matrix. Notedly, due to the different growth directions of Shockley partial dislocations relative to nucleation points, there are two FCC-Zr variants after the HCP-to-FCC phase transformation. The content of these two variants accounts for 65% and 35% of the total FCC-Zr, respectively, appearing as lamellae morphology embedded parallelly within the matrix. The distribution of the two variants includes isolated distribution and adjacent distribution. For the adjacent distribution, a twinning relationship is observed between the two variants. Meanwhile, as an intermediate transition stage of the HCP-to-FCC phase transformation, stacking faults are observed at the boundaries of the FCC-Zr lamellae. These findings offer insights into the microstructural features and formation mechanisms of fatigue-induced HCP-to-FCC phase transformation.

The box-counting dimension, which can effectively reflect the complexity and self-similarity of models, is an important method for calculating the fractal dimension of models. To improve the precision of the box-counting dimension algorithm, in this study, we propose an improved 3D box-counting dimension algorithm for models composed of triangular meshes. Through linear coding and optimization of intersection detection between triangles and octree cells, we can accurately calculate the box dimension of models with less memory expense. Through the results of measuring regular geometric bodies and spatial Voronoi bodies, it can be seen that the method has good performance, and the ability of filling space of fractal bodies can be calculated accurately. In the circumstance of 3D box-counting dimension algorithm cannot work well for comparing curvature changes of non-fractal surfaces, the weighted box-counting dimension algorithm can be used to quantitatively analyze the complexity of surface curvature.

Body fluid identification through messenger RNA (mRNA) has been proposed as a useful supplement to presumptive and confirmatory tests by previous laboratory studies; however, its application in routine clinical forensic examination was rare. We report a case of sexual assault in which body fluid identification by mRNA profiling was used. Vaginal secretions mRNA markers (MUC4, HBD1, and CYP2B7P1) were used to test the sample, being obtained positive results. This case demonstrates that mRNA profiling of body fluids could be applied to routine case examinations as an aid, acting as a scientific collaborative evidence to strengthen the medicolegal opinion.

Abstract Background More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. Methods Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. Results Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo, while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. Conclusions Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention.

Abstract Background The association of cough with Mycoplasma hyopneumoniae (MHP) DNA detection in specimens was evaluated under conditions in which the MHP status of inoculated and contact-infected pen mates was closely monitored for 59 days post-inoculation (DPI). Methods Seven-week-old pigs (n = 39) were allocated to five rooms (with one pen). Rooms contained 9 pigs each, with 1, 3, 6, or 9 MHP-inoculated pigs, respectively, except Room 5 (three sham-inoculated pigs). Cough data (2 × week) and specimens, tracheal swabs (2 × week), oral fluids (daily), drinker wipes (~ 1 × week), and air samples (3 × week) were collected. At 59 DPI, pigs were euthanized, and lung and trachea were evaluated for gross and microscopic lesions. Predictive cough value to MHP DNA detection in drinker and oral fluid samples were estimated using mixed logistic regression. Results Following inoculation, MHP DNA was first detected in tracheal swabs from inoculated pigs (DPI 3), then oral fluids (DPI 8), air samples (DPI 10), and drinker wipes (21 DPI). MHP DNA was detected in oral fluids in 17 of 59 (Room 1) to 43 of 59 (Room 3) samples, drinker wipes in 4 of 8 (Rooms 2 and 3) to 5 of 8 (Rooms 1 and 4) samples, and air samples in 5 of 26 (Room 2) or 3 of 26 (Room 4) samples. Logistic regression showed that the frequency of coughing pigs in a pen was associated with the probability of MHP DNA detection in oral fluids (P

Abstract Nanomaterials (NMs) have received considerable attention in the field of agrochemicals due to their special properties, such as small particle size, surface structure, solubility and chemical composition. The application of NMs and nanotechnology in agrochemicals dramatically overcomes the defects of conventional agrochemicals, including low bioavailability, easy photolysis, and organic solvent pollution, etc. In this review, we describe advances in the application of NMs in chemical pesticides and fertilizers, which are the two earliest and most researched areas of NMs in agrochemicals. Besides, this article concerns with the new applications of NMs in other agrochemicals, such as bio-pesticides, nucleic acid pesticides, plant growth regulators (PGRs), and pheromone. We also discuss challenges and the industrialization trend of NMs in the field of agrochemicals. Constructing nano-agrochemical delivery system via NMs and nanotechnology facilitates the improvement of the stability and dispersion of active ingredients, promotes the precise delivery of agrochemicals, reduces residual pollution and decreases labor cost in different application scenarios, which is potential to maintain the sustainability of agricultural systems and improve food security by increasing the efficacy of agricultural inputs. Graphical Abstract

Unlike DNA profiling, mRNA profiling is greatly affected by external factors. To analyze the influence of different stain carriers on the detectability of mRNA markers from bloodstains, this study examined 10 carriers, including a knife, cotton swab, paper, plastic, leather, cement, chopsticks, clothes, ceramic block, and wall. After detecting five specific mRNA markers (HBA, HBB, ALAS2, GYPA, and SPTB) and the housekeeping gene B2M in peripheral blood samples, no statistically significant differences in the effects of the carriers were found. The results suggest that when performing mRNA testing on bloodstains, the effect of the stain carrier has little influence.

Abstract Optical biosensors are platforms that translate biological information into detectable optical signals, and have extensive applications in various fields due to their characteristics of high sensitivity, high specificity, dynamic sensing, etc. The development of optical sensing materials is an important part of optical sensors. In this review, we emphasize the role of microfluidic technology in the preparation of optical sensing materials and the application of the derived optical sensors in the biomedical field. We first present some common optical sensing mechanisms and the functional responsive materials involved. Then, we describe the preparation of these sensing materials by microfluidics. Afterward, we enumerate the biomedical applications of these optical materials as biosensors in disease diagnosis, drug evaluation, and organ‐on‐a‐chip. Finally, we discuss the challenges and prospects in this field.

ABSTRACT Herpes simplex virus 1 (HSV-1) is a DNA virus belonging to the family Herpesviridae. HSV-1 infection causes severe neurological disease in the central nervous system (CNS), including encephalitis. Ferroptosis is a nonapoptotic form of programmed cell death that contributes to different neurological inflammatory diseases. However, whether HSV-1 induces ferroptosis in the CNS and the role of ferroptosis in viral pathogenesis remain unclear. Here, we demonstrate that HSV-1 induces ferroptosis, as hallmarks of ferroptosis, including Fe2+ overload, reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, and mitochondrion shrinkage, are observed in HSV-1-infected cultured human astrocytes, microglia cells, and murine brains. Moreover, HSV-1 infection enhances the E3 ubiquitin ligase Keap1 (Kelch-like ECH-related protein 1)-mediated ubiquitination and degradation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidative genes, thereby disturbing cellular redox homeostasis and promoting ferroptosis. Furthermore, HSV-1-induced ferroptosis is tightly associated with the process of viral encephalitis in a mouse model, and the ferroptosis-activated upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) and prostaglandin E2 (PGE2) plays an important role in HSV-1-caused inflammation and encephalitis. Importantly, the inhibition of ferroptosis by a ferroptosis inhibitor or a proteasome inhibitor to suppress Nrf2 degradation effectively alleviated HSV-1 encephalitis. Together, our findings demonstrate the interaction between HSV-1 infection and ferroptosis and provide novel insights into the pathogenesis of HSV-1 encephalitis. IMPORTANCE Ferroptosis is a nonapoptotic form of programmed cell death that contributes to different neurological inflammatory diseases. However, whether HSV-1 induces ferroptosis in the CNS and the role of ferroptosis in viral pathogenesis remain unclear. In the current study, we demonstrate that HSV-1 infection induces ferroptosis, as Fe2+ overload, ROS accumulation, GSH depletion, lipid peroxidation, and mitochondrion shrinkage, all of which are hallmarks of ferroptosis, are observed in human cultured astrocytes, microglia cells, and murine brains infected with HSV-1. Moreover, HSV-1 infection enhances Keap1-dependent Nrf2 ubiquitination and degradation, which results in substantial reductions in the expression levels of antiferroptotic genes downstream of Nrf2, thereby disturbing cellular redox homeostasis and promoting ferroptosis. Furthermore, HSV-1-induced ferroptosis is tightly associated with the process of viral encephalitis in a mouse model, and the ferroptosis-activated upregulation of PTGS2 and PGE2 plays an important role in HSV-1-caused inflammation and encephalitis. Importantly, the inhibition of ferroptosis by either a ferroptosis inhibitor or a proteasome inhibitor to suppress HSV-1-induced Nrf2 degradation effectively alleviates HSV-1-caused neuro-damage and inflammation in infected mice. Overall, our findings uncover the interaction between HSV-1 infection and ferroptosis, shed novel light on the physiological impacts of ferroptosis on the pathogenesis of HSV-1 infection and encephalitis, and provide a promising therapeutic strategy to treat this important infectious disease with a worldwide distribution.

Metal halide perovskites (MHPs) have demonstrated great advances for photovoltaic and optoelectronic applications. However, owing to the presence of the synergy from lattice strain, defects of MHPs, and environment, MHPs suffer from phase transitions and degradation, resulting in the restriction of their practical applications and further commercialization. Multiple metal elements can coexist in MHPs to form alloys due to the high tolerance of lattice and the composition replaceability, which provides a novel strategy for improvement of performance and stability. In this review, the recent advances of alloy engineering of MHPs, focusing on the cation and the metal ion (A‐ and B‐site) alloy strategies, are reviewed. The alloy effects on the crystalline structure, optoelectronic properties, ferroelectricity, carrier dynamics, and stability of perovskites are interpreted. Finally, the prospect of this study is the challenges in the MHPs alloy engineering.

Randomized clinical trials (RCTs) are designed for measuring the effectiveness of the treatments and testing a hypothesis regarding the relative effect between two or more treatments. Trial designers are often interested in maximizing power when the total sample size is fixed or minimizing the required total sample size to reach a pre-specified power. One approach to maximizing power proposed by previous researchers is to leverage prior evidence using meta-analysis (NMA) to inform the sample size determination of a new trial. For example, researchers may be interested in designing a two-arm trial comparing treatments A and B which are already in the existing trial network but do not have any direct comparison. The researchers' intention is to incorporate the result into an existing network for meta-analysis. Here we develop formulas to address these options and use simulations to validate our formula and evaluate the performance of different analysis methods in terms of power. We also implement our proposed method into the R package OssaNMA and publish an R Shiny app for the convenience of the application. The goal of the package is to enable researchers to readily adopt the proposed approach which can improve the power of an RCT and is therefore resource-saving. In the R Shiny app, We also provide the option to include the cost of each treatment which would enable researchers to compare the total treatment cost associated with each design and analysis approach. Further, we explore the effect of allocation to treatment group on study power when the a priori plan is to incorporate the new trial result into an existing network for meta-analysis.

The study takes 10 urban agglomerations in China as the research object, focusing on the Chengdu-Chongqing urban agglomeration, and applies Data Envelopment Analysis (DEA) to measure and compare their scientific input and output efficiency of universities. First, this paper analyzes the input and output of scientific research in universities in major provinces in China in detail. Second, according to the construction principles of the indicator system, using qualitative interview to construct evaluation indicators of university research efficiency. Third, using DEA method, first analyze the input and output profile of some urban agglomeration universities such as Chengdu-Chongqing economic circle, measure and compare their research input and output efficiency, then compare and analyze the research efficiency of research-type sample universities within Chengdu-Chongqing economic circle, and conduct a projection study of non-DEA effective sample universities. The main conclusions are as follows: first, the average efficiency of scientific research in universities in Chengdu-Chongqing and other urban agglomerations in 2020 has slightly increased compared with that in 2016, but the gap between urban agglomerations is prominent, and the innovation level of scientific research in higher education institutions in urban agglomerations needs to be improved. Second, there is a mismatch between the themes of research, funding and human resources in research-oriented universities in the Chengdu-Chongqing economic circle. Third, there is considerable room for improvement in research efficiency, and the influence of scale on overall efficiency is weak. We found that excessive investment in scientific research in universities is the main reason for the non-effect.

Photodynamic therapy with reactive oxygen species production is a prospective treatment to combat cancer stem cells (CSCs). However, the innate drawbacks, including short lifetime and diffusion distance of reactive oxygen species and hypoxia within solid tumors, have become bottlenecks for clinical applications of photodynamic therapy. Here, we develop a mitochondria-targeting hemicyanine–oleic acid conjugate (CyOA), which can self-assemble into supramolecular nanoparticles (NPs) without any exogenous excipients. CyOA is also shown for targeting the mitochondrial complex II protein succinate dehydrogenase to inhibit oxidative phosphorylation and reverse tumor hypoxia, resulting in 50.4-fold higher phototoxicity against breast cancer stem cells (BCSCs) compared to SO3-CyOA NPs that cannot target to mitochondria. In 4T1 and BCSC tumor models, CyOA NPs achieve higher tumor inhibition and less lung metastasis nodules compared to the clinically used photosensitizer Hiporfin. This study develops a self-assembled small molecule that can serve as both oxidative phosphorylation inhibitor and photosensitizer for eradication of CSCs and treatment of solid tumors.

Drug therapy is among the most widely used methods in disease treatment. However, there remains a trade-off problem between drug dosage and toxicity. Blood purification by adsorption of excessive drugs during clinical treatment could be a solution for enhancing therapeutic efficacy while maintaining normal body function. Here, inspired by the intrinsic action mechanism of chemotherapeutic agents in targeting DNA in the cell nucleus, we present DNA–polyelectrolyte composite responsive microparticles for chemotherapeutics cleaning. The presence of DNA in the microparticles enabled the adsorption of multiple common chemotherapy drugs. Moreover, the microparticles are endowed with a porous structure and a photothermal-responsive ability, both of which contribute to improved adsorption by enhancing the contact of the microparticles with the drug solution. On the basis of that, the microparticles are integrated into a herringbone-structured microfluidic chip. The fluid mixing capacity and the enhanced drug cleaning efficiency of the microfluidic platform are validated on-chip. These results indicate the value of the DNA–polyelectrolyte composite responsive microparticles for drug capture and blood purification. We believe the microparticle-integrated microfluidic platform could provide a solution for settling the dosage–toxicity trade-off problems in chemotherapy.

Parkinson’s disease (PD) is a common neurodegenerative movement disorder with undetermined etiology. A major pathological hallmark of PD is the progressive degeneration of dopaminergic neurons in the substantia nigra. Loss-of-function mutations in the RAB39B gene, which encodes a neuronal-specific small GTPase RAB39B, have been associated with X-linked intellectual disability and pathologically confirmed early-onset PD in multiple families. However, the role of RAB39B in PD pathogenesis remains elusive. In this study, we treated Rab39b knock-out (KO) mice with MPTP to explore whether RAB39B deficiency could alter MPTP-induced behavioral impairments and dopaminergic neuron degeneration. Surprisingly, we found that MPTP treatment impaired motor activity and led to loss of tyrosine hydroxylase-positive dopaminergic neurons and gliosis in both WT and Rab39b KO mice. However, RAB39B deficiency did not alter MPTP-induced impairments. These results suggest that RAB39B deficiency does not contribute to PD-like phenotypes through compromising dopaminergic neurons in mice; and its role in PD requires further scrutiny.

ObjectiveThe purpose of this study was to investigate the clinical efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) for lumbar spinal stenosis (LSS).MethodsPatients who underwent UBE-TLIF due to single-segment LSS between August 2019 and July 2021 were retrospectively included in the study. Clinical outcomes evaluated include operative time, estimated blood loss (including postoperative drainage), time to ambulation, postoperative hospital stay, complications, visual analog scale (VAS) scores of low back pain and leg pain, Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), and modified Macnab criteria. Interbody bony fusion at the index level was assessed using Bridwell grading criteria.ResultsA total of 73 patients (29 males and 44 females) were enrolled in this study. All surgeries were successfully performed without intraoperative conversion to open surgery. Magnetic resonance imaging (MRI) revealed optimal direct neural decompression after UBE-TLIF. The mean operative time was 150.89 ± 15.58 min. The mean estimated blood loss was 126.03 ± 17.85 ml (postoperative drainage was 34.84 ± 8.31 ml). Time to ambulation was 2.0 ± 0.75 days after the procedure. Postoperatively, the mean hospital stay was 5.96 ± 1.38 days. VAS scores of low back pain and leg pain, JOA, and ODI were significantly improved postoperatively compared with those before the operation, and differences were statistically significant (P

Meiotic recombination starts with the programmed formation of double-strand breaks (DSB) in DNA, which are catalyzed by SPO11, a type II topoisomerase that is evolutionarily conserved, and several other accessary proteins. Homologs of MEIOSIS INHIBITOR 4 (MEI4/REC24/PRD2) are proteins that are also essential for the generation of meiotic DSBs in budding yeast, mice and Arabidopsis thaliana. In Arabidopsis, the protein ARABIDOPSIS THALIANA PUTATIVE RECOMBINATION INITIATION DEFECTS 2/MULTIPOLAR SPINDLE 1 (AtPRD2/MPS1) has been shown to have additional roles in spindle assembly, indicating a functional diversification. Here we characterize the role of the rice MEI4/PRD2 homolog in meiosis. The osprd2 mutant was completely male and female sterile. In male meiocytes of osprd2, no γH2AX foci were detected and twenty-four univalents were produced at diakinesis, suggesting that OsPRD2 is essential for DSB generation. OsPRD2 showed a dynamic localization during meiosis. For instance, OsPRD2 foci first appeared as discrete signals across chromosome at leptotene, and then became confined to the centromeres during zygotene, suggesting that they might be involved in assembly of the spindle. However we did not observe any obvious aberrant morphologies in neither the organization of the bipolar spindle nor in the orientation of the kinetochore in the mutant. These findings suggest that in rice PRD2 might not be required for spindle assembly and organization, as it does in Arabidopsis. Taken together our results indicate that plant MEI4/PRD2 homologs do play a conserved role in the formation of meiotic DSBs in DNA, but that their involvement in bipolar spindle assembly is rather species-specific.

The archeological site at Sanxingdui preserves a considerable amount of ancient ivory tusks in its artifact pits, and accurately and quantitatively analyzing the original chemical signatures of these ivory tusks is a critical step in interpreting their buried history. In this study, 123 unearthed ivory tusks were characterized using Fourier-transformed infrared spectroscopy (FTIR), and seven in situ heating experiments were conducted. The hydroxylapatite crystallinity and carbonate concentration were quantitatively determined in line with the absorbance peak intensities of the corresponding bands. The average values of splitting factor (SF), type B carbonate/type A carbonate ratio (BC/AC), carbonate/phosphate ratio (C/P), type B carbonate/phosphate ratio (BPI), type A carbonate/phosphate ratio (API), and water–amide on the phosphate index (WAMPI) were calculated to be 3.84, 0.98, 0.12, 0.37, 0.38, and 0.11, respectively. The ratios of the 1,416 cm−1–1,454 cm−1 carbonate bands of the ivory tusks were used to quantitatively estimate the different types of carbonate content in the ivory tusks. Heating experiments were designed to simulate the effect of heat on the hydroxylapatite structures. We suggest that the SF and the C/P indices can serve as distinctive preservation indices of ancient ivory tusks as well as the BC/AC index and hydroxyl types.

The basin effects alter the frequency content, amplitude and duration of seismic waves with different depth and shape basin. In this paper, we selected 2-D geophysical profiles spanning the Weihe Basin with large area and the Luoquanli Basin with small area. Based on the velocity structure data of the two geophysical profiles, 2-D finite element models were established to analyze the influences of the sedimentary layer in a broad basin and the basement geometry of a small basin on the basin effects using the spectral element method. The results showed that the sedimentary deposits in the basin could significantly amplify the ground motion, and the diffraction waves generated by the lateral inhomogeneity of the basin could prolong the duration of the ground motion. The highlight of this paper, our results showed that the amplification characteristics were controlled by the velocity mean in the vertical direction of sedimentary deposits (vp < 4.5 km/s) for a broad basin with small depth-to-width ratio as Weihe Basin, while the amplification characteristics were dominated by basement geometry of the small basin with large depth-to-width ratio as Luoquanli Basin. In this study, a high-resolution 2-D geophysical refraction profile was directly used to construct a finite element model to study the basin effects, which provided a new method of studying the basin effects.

ObjectiveThis study aims to investigate the effectiveness and feasibility of biportal endoscopic decompression, debridement, and interbody fusion, combined with percutaneous screw fixation for lumbar brucellosis spondylitis (LBS).MethodsThe data of 13 patients with LBS were retrospectively analyzed, who underwent biportal endoscopic decompression, debridement, and interbody fusion, combined with percutaneous screw fixation from May 2020 to June 2022. The patients’ clinical data, the duration of operation, the estimated blood loss (including postoperative drainage), and complications were recorded. Clinical outcomes include serum agglutination test (SAT) measures Brucella antibody titer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the visual analog scale (VAS) scores of low back and leg, Japanese Orthopaedic Association (JOA) score, Oswestry Disability Index (ODI), American Spinal Injury Association neurological classification, and lordotic angle were analyzed. All patients were assessed using the modified Macnab criteria at the final follow-up. The intervertebral bone graft fusion was assessed using the Bridwell grading criteria.ResultsThe mean operation duration was 177.31 ± 19.54 min, and the estimated blood loss was 176.15 ± 43.79 ml (including postoperative drainage was 41.15 ± 10.44 ml). The mean follow-up period was 13.92 ± 1.5 months. SAT showed that the antibody titers of 13 patients were normal 3 months after the operation and at the final follow-up. ESR and CRP levels returned to normal by the end of the 3-month follow-up. VAS scores of low back and leg, JOA score, and ODI significantly improved after the operation throughout the follow-up period (P

The efficiency of photovoltaic(PV) panels decreases as their temperature increases, so effective cooling of them is necessary. The cooling of PV panels based on phase change materials(PCMs) is an emerging cooling method that has recently received the attention of scholars around the world. Herein, the cooling characteristics of PCM on PV panels are experimentally investigated to study the cooling effect of PCM on solar PV panel cooling technology (PV-PCM) and explore the effect of inverse process of PCM from molten to solidified state on the temperature of solar PV panels after cooling. The results reveal that the PCM can effectively reduce the temperature of solar PV panels under the condition of no wind, irradiance of 1000 W/m2 and ambient temperature of 7.3 °C. The PCM can reduce the average temperature of the upper and back surfaces of solar PV panels by 33.94 °C and 36.51 °C within 300 min, respectively. Moreover, the PCM increased the average maximum power generation efficiency of solar PV panels by 1.63% and the average maximum output power by 1.35 W. The solar PV panels cooled without PCM took only 60 min to cool from the maximum temperature to room temperature, whereas the solar PV panels in PV-PCM system took 480 min to cool down to room temperature.

Abstract Background Network meta-analysis (NMA) is a statistical method used to combine results from several clinical trials and simultaneously compare multiple treatments using direct and indirect evidence. Statistical heterogeneity is a characteristic describing the variability in the intervention effects being evaluated in the different studies in network meta-analysis. One approach to dealing with statistical heterogeneity is to perform a random effects network meta-analysis that incorporates a between-study variance into the statistical model. A common assumption in the random effects model for network meta-analysis is the homogeneity of between-study variance across all interventions. However, there are applications of NMA where the single between-study assumption is potentially incorrect and instead the model should incorporate more than one between-study variances. Methods In this paper, we develop an approach to testing the homogeneity of between-study variance assumption based on a likelihood ratio test. A simulation study was conducted to assess the type I error and power of the proposed test. This method is then applied to a network meta-analysis of antibiotic treatments for Bovine respiratory disease (BRD). Results The type I error rate was well controlled in the Monte Carlo simulation. We found statistical evidence (p value = 0.052) against the homogeneous between-study variance assumption in the network meta-analysis BRD. The point estimate and confidence interval of relative effect sizes are strongly influenced by this assumption. Conclusions Since homogeneous between-study variance assumption is a strong assumption, it is crucial to test the validity of this assumption before conducting a network meta-analysis. Here we propose and validate a method for testing this single between-study variance assumption which is widely used for many NMA.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) as a binding receptor to enter cells via clathrin-mediated endocytosis (CME). However, receptors involved in other steps of SARS-CoV-2 infection remain largely unknown. Here, we found that metabotropic glutamate receptor subtype 2 (mGluR2) is an internalization factor for SARS-CoV-2. Our results show that mGluR2 directly interacts with the SARS-CoV-2 spike protein and that knockdown of mGluR2 decreases internalization of SARS-CoV-2 but not cell binding. Further, mGluR2 is uncovered to cooperate with ACE2 to facilitate SARS-CoV-2 internalization through CME and mGluR2 knockout in mice abolished SARS-CoV-2 infection in the nasal turbinates and significantly reduced viral infection in the lungs. Notably, mGluR2 is also important for SARS-CoV spike protein- and Middle East respiratory syndrome coronavirus spike protein-mediated internalization. Thus, our study identifies a novel internalization factor used by SARS-CoV-2 and opens a new door for antiviral development against coronavirus infection.

ObjectivesThe "cost plus 5% profit" pricing method has been adopted for ship equipment scheduled repair for many years, but it does not reflect quality and schedule of repair project, so it is unable to motivate contractors to cost-effectively improve their repair work.MethodsThis paper chooses cost, schedule and quality as the incentive factors, and develops an incentive fee method which distinguishes between the fixed and incentive parts of the cost, with a schedule-based incentive fee to encourage the elimination of delays by Party A and a quality-based incentive fee to encourage the construction of a quality evaluation index based on the features of ship equipment scheduled repair.ResultsThe example analyses show that the contractors can thus earn reasonable profits from contracts adopting this method, Among the examples,projects with better overall performance can break the 5% profit margin limit.Conclusions The method put forward in this paper can effectively motivate contractors to control their costs, improve their quality and accelerate their schedule. This is of great practical significance for perfecting the incentive fee mechanism and promoting effective ship equipment scheduled repair.

Abstract A 6.0‐magnitude (Mw) earthquake was reported to have occurred in Jiashi County, Xinjiang at 21:27 on 19 January 2020, Beijing time (13:27 UTC). This study applied a stochastic finite‐fault approach based on the dynamic corner frequency (EXSIM) to simulate 23 near‐field stations within a distance of 120 km from the epicenter. The stochastic finite‐fault approach is the simplest and most effective method for simulating high‐frequency ground motions. According to studies and empirical relationships, we estimated a region‐specific parameter (κ0) for use in simulations. In this study, two different slip models, namely, random and inverted slip models, were used to explain their influence on the simulation results. For most stations, the simulated seismic characteristics, such as the peak ground acceleration (PGA), pseudo spectral acceleration ,and Fourier acceleration spectrum, are highly compatible with the observed values in the frequency range (f > 1 Hz), indicating that the stochastic finite‐fault approach is not highly sensitive to input slip distributions and fault dimensions. The simulation results indicated no significance between the two slip models under high‐frequency conditions. Finally, based on the predicted PGA values of 1891 field points selected near the fault, the acceleration field of the Jiashi earthquake is plotted. The results show that the use of the acceleration time history predicted by modified EXSIM is feasible and practical in the high‐frequency band above 1 Hz.