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Abstract Background Distal gastrectomy (DG) is a commonly used surgical procedure for gastric cancer (GC), with three reconstruction methods available: Billroth I, Billroth II, and Roux-en-Y. In 2018, our team published a systematic review to provide guidance for clinical practice on the optimal reconstruction method after DG for GC. However, since then, new evidence from several randomized controlled trials (RCTs) has emerged, prompting us to conduct an updated systematic review and network meta-analysis to provide the latest comparative estimates of the efficacy and safety of the three reconstruction methods after DG for GC. Method This systematic review and network meta-analysis update followed the PRISMA-P guidelines and will include a search of PubMed, Embase, and the Cochrane Library for RCTs comparing the outcomes of Billroth I, Billroth II, or Roux-en-Y reconstruction after DG for patients with GC. Two independent reviewers will screen the titles and abstracts based on predefined eligibility criteria, and two reviewers will assess the full texts of relevant studies. The Bayesian network meta-analysis will evaluate various outcomes, including quality of life after surgery, anastomotic leakage within 30 days after surgery, operation time, intraoperative blood loss, major postoperative complications within 30 days after surgery, incidence and severity of bile reflux, and loss of body weight from baseline. Ethics and dissemination The review does not require ethical approval. The findings of the review will be disseminated through publication in an academic journal, presentations at conferences, and various media outlets. INPLASY registration number INPLASY2021100060.

Abstract Background Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, with a high mortality rate and poor prognosis. Mutated or dysregulated transcription factors (TFs) are significantly associated with carcinogenesis. The aim of this study was to develop a TF-related prognostic risk model to predict the prognosis and guide the treatment of HCC patients. Methods RNA sequencing data were obtained from the TCGA database. The ICGC and GEO databases were used as validation datasets. The consensus clustering algorithm was used to classify the molecular subtypes of TFs. Kaplan‒Meier survival analysis and receiver operating characteristic (ROC) analysis were applied to evaluate the prognostic value of the model. The immunogenic landscape differences of molecular subtypes were evaluated by the TIMER and xCell algorithms. Autodock analysis was used to predict possible binding sites of trametinib to TFs. RT‒PCR was used to verify the effect of trametinib on the expression of core TFs. Results According to the differential expression of TFs, HCC samples were divided into two clusters (C1 and C2). The survival time, signaling pathways, abundance of immune cell infiltration and responses to chemotherapy and immunotherapy were significantly different between C1 and C2. Nine TFs with potential prognostic value, including HMGB2, ESR1, HMGA1, MYBL2, TCF19, E2F1, FOXM1, CENPA and ZIC2, were identified by Cox regression analysis. HCC patients in the high-risk group had a poor prognosis compared with those in the low-risk group (p

Rolling bearings in production practice usually serve in a healthy state. Some fault state labels are scarce or even no labels, resulting in unbalanced data categories. Meanwhile, frequent working condition switching results in significant differences in data distribution among working conditions, and labeled data in some working states cannot be fully utilized. To deal with the challenge of low fault identification accuracy caused by these practical factors, this paper proposed a novel adversarial unsupervised subdomain adaption multi-channel deep convolutional network (ASMDCN). Firstly, a parallel three-channel depth feature extraction module is built, and a multi-scale convolution kernel is used to fully extract the rich features of vibration signals under various working conditions. Secondly, a novel loss function is designed to adequately consider the classification difficulty of samples and the degree of class imbalance. Finally, the adversarial training strategy is used to force the feature extractor to extract the domain invariant features, and the Local Maximum Mean discrepancy (LMMD) is used to align the global and related subdomains of the source and target domains. The experimental results show that the designed feature extraction can fully extract the domain-invariant features of the rolling bearings under different working conditions. Under the proposed objective function optimization, the network model can fully align the features of multi-source and single-target domain under unbalanced data and has strong generalization performance.

Karst geology is widely distributed in China, and karst water gushing has become a huge disaster and challenge for the safe production of limestone mines. Taking the large-flow water inflow of a karst sunken open pit mine in Guangxi as the research object, aiming at the characteristics of complex geological conditions, large concentrated water inflow and high flow rate of the mine, the karst development characteristics, data analysis and geophysical exploration methods are used to preliminarily delineate the mine runoff zone area and water source. After that, the specific location of the karst pipeline at the Y01 extra-large water gushing point of the mine was accurately found through drilling, cross-hole CT and tracer connection test. On this basis, the mine water gushing treatment technology and process were studied and implemented. The research shows that: ① In view of the characteristics of large flow and high flow rate in complex karst sunken open pit mines, a comprehensive treatment system of water gushing in karst mines is proposed and implemented, which is “discontinuous curtain closure + key channel exploration and plugging + slurry-stopping cushion to control flow and reduce speed.” According to the inhomogeneity of karst development, the idea of discontinuous curtain plugging fissure water gushing area is put forward. A slurry-stopping pad flow control device was designed for the concentrated water inflow of large-flow karst pipelines. The flow control can effectively reduce the flow velocity in the key water passage, which provides an important condition for the effective retention and deposition of grouting materials and the successful plugging of the project. ② The key hole refers to the drilling hole that directly exposes the karst water gushing pipeline or has strong connectivity with the water gushing pipeline and plays a major role in grouting and water plugging. In this paper, two key holes were successfully found for the large water inflow of Y01 karst pipeline type in the mine, both in the south of the mine. One is a short-distance borehole with a linear distance of about 50 meters from the water inflow point, which is referred to as the near hole, and the other is a long-distance borehole with a linear distance of about 150 meters from the water inflow point, which is referred to as the far hole. The simultaneous grouting process of two key holes, near hole and far hole, is adopted in the field. The near hole is mainly grouted with aggregate, and the far hole is only grouted with slurry. The near hole aggregate can not only reduce the water flow in the pipeline, but also play a better role in retaining and depositing the far hole slurry, and can be used as a plugging material to enhance the function. The far hole can ensure the length and effect of plugging due to its wide radiation range and sufficient slurry diffusion. The simultaneous grouting of near hole and far hole is an effective combination process for rapid plugging of large flow water gushing in pipeline. ③ After the implementation of the project, the Y01 super-large water gushing point with a concentrated water inflow of 71 200 m3/d in the mine was completely blocked, and the total water reduction was 84 300 m3/d (including discontinuous curtain grouting plugging), which ensured the normal and safe mining of the mine, greatly reduced the cost of pumping and drainage, and protected the surrounding environment and groundwater resources, with significant economic and social benefits. The research results can provide important theoretical technology and experience for the treatment of water inrush disaster in karst mines in China.

This paper studies a class of quasi-cyclic LDPC (QC-LDPC) codes, i.e., Tanner (3, 23)-regular QC-LDPC codes of code length $23p$ with $p$ being a prime and $p \equiv 1 (\mathrm {mod} 69)$ . We first analyze the cycle structure of Tanner (3, 23)-regular QC-LDPC codes, and divide their cycles of lengths 4, 6, 8, and 10 into five equivalent types. We propose the sufficient and necessary condition for the existence of these five types of cycles, i.e., the polynomial equations in a 69th unit root of the prime field $\mathbb {F}_{p}$ . We check the existence of solutions for such polynomial equations by using the Euclidean division algorithm and obtain the candidate girth values of Tanner (3, 23)-regular QC-LDPC codes. We summarize the results and determine the girth distribution of Tanner (3, 23)-regular QC-LDPC codes.

With the advancement of the wood processing industry, the demand for the detection of surface defects in wood has become increasingly urgent. The application of automated production technology has enhanced the efficiency and precision of wood processing, which can significantly impact product quality and competitiveness. However, current methods for detecting surface defects in wood suffer from issues such as low detection accuracy, high computational complexity, and poor real-time performance. In response to these challenges, this paper proposes a high-precision, lightweight, real-time wood surface defect detection method based on YOLO(GBCD-YOLO) model. Firstly, the Ghost Bottleneck is introduced to improve the computational efficiency and inference speed of deep neural networks. Furthermore, the BiFormer is incorporated in the neck to enhance the performance of natural language processing tasks. Simultaneously, CARAFE is utilized as an upsampling replacement to enhance perceptual and capture abilities for details. In addition, the Dynamic Head is introduced to enhance the method’s flexibility and generalization ability, and the loss function is replaced with complete intersection over union (CIoU). The proposed method was evaluated using an optimized dataset and the YOLOv5s model was chosen as the baseline. The experimental results show that compared with the original YOLOv5s, the mAP (0.5) has been improved by 13.45%, reaching 88.72%. The mAP (0.5:0.95) increased by 11.95%, and FPS increased by 6.25%. In addition, the parameter of the improved model has been reduced by 15.49%. These results indicate that the proposed GBCD-YOLO improves the real-time detection performance of wood surface defects.

The increasing integration of distributed household photovoltaics (PVs) and electric vehicles (EVs) may further aggravate voltage violations and unbalance of low-voltage distribution networks (LVDNs). DC distribution networks can increase the accommodation of PVs and EVs and mitigate mutilple power quality problems by the flexible power regulation capability of voltage source converters. This paper proposes schemes to establish hybrid AC/DC LVDNs considering the conversion of the existing three-phase four-wire low-voltage AC systems to DC operation. The characteristics and DC conversion constraints of typical LVDNs are analyzed. In addition, converter configurations for typical LVDNs are proposed based on the three-phase four-wire characteristics and quantitative analysis of various DC configurations. Moreover, an optimal planning method of hybrid AC/DC LVDNs is proposed, which is modeled as a bi-level programming model considering the annual investments and three-phase unbalance. Simulations are conducted to verify the effectiveness of the proposed optimal planning method. Simulation results show that the proposed optimal planning method can increase the integration of PVs while simultaneously reducing issues related to voltage violation and unbalance.

This study explores the consensus of multi-agent systems in the presence of ambient noise using intermittent Brownian noise stabilization. Firstly, the research provides a mathematical explanation of multi-agent systems and intermittent stochastic noise, and establishes a sufficient condition for multi-agent systems to achieve consensus using intermittent stochastic noise control input. Secondly, a consensus criterion is proposed for a class of multi-agent systems that are affected by ambient noise. Finally, the simulation results demonstrate that the intermittent stochastic noise stabilization technique can facilitate the establishment of consensus in multi-agent systems.

Abstract Background The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not. Methods A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately. Results After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model. Conclusion The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and its molecular mechanisms are unclear. Nucleolar and spindle-associated protein 1 (NUSAP1), an indispensable mitotic regulator, has been reported to be involved in the development of several types of tumors. The biological function and molecular mechanism of NUSAP1 in PDAC remain controversial. This study explored the effects and mechanism of NUSAP1 in PDAC. Methods Differentially expressed genes (DEGs) were screened. A protein‒protein interaction (PPI) network was constructed to identify hub genes. Experimental studies and tissue microarray (TMA) analysis were performed to investigate the effects of NUSAP1 in PDAC and explore its mechanism. Results Network analysis revealed that NUSAP1 is an essential hub gene in the PDAC transcriptome. Genome heterogeneity analysis revealed that NUSAP1 is related to tumor mutation burden (TMB), loss of heterozygosity (LOH) and homologous recombination deficiency (HRD) in PDAC. NUSAP1 is correlated with the levels of infiltrating immune cells, such as B cells and CD8 T cells. High NUSAP1 expression was found in PDAC tissues and was associated with a poor patient prognosis. NUSAP1 promoted cancer cell proliferation, migration and invasion, drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation. Conclusions NUSAP1 is an essential hub gene that promotes PDAC progression and leads to a dismal prognosis by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation.

The eastern margin of the Tibetan Plateau is composed of multiple secondary tectonic units which constitute typical “multi-level extrusion-rotation active tectonic system”. It is the tectonic transformation belt that regulates the eastward extrusion of plateau blocks, and contains high-density active faults. This area is characterized by frequent and high intensity strong earthquakes and complex geological and geomorphological features. Therefore, this region is one of the areas in China where the problem of earthquake disaster is particularly significant. In recent years, with the research deepening of the national earthquake disaster risk survey, active fault detection of urban，seismic experimental site construction, seismic safety evaluation of engineering sites, identification of active faults and evaluation of crustal stability in major projects sites and urban areas，and the wide application of high-precision remote sensing, tectonic geomorphology, paleoseismic and Quaternary chronology methods. The investigation of seismogenic structures around the eastern margin of the Tibetan Plateau and its adjacent areas has been significantly improved. In order to timely exchange the latest study results in this field support regional earthquake prevention and disaster reduction and geological safety evaluation of important projects sites and infrastructure construction, the journal editorial department of Progress in Earthquake Science organized the special topic “The strong earthquakes and seismogenic structures in eastern margin of Tibetan Plateau and adjacent areas”. More than 20 representative academic papers such as active faults and earthquakes, Jishishan earthquake in Gansu Province，and research reviews in related fields have been collected. In this issue, 10 papers are selected in the special topic I “The strong earthquakes and seismogenic structures in eastern margin of Tibetan Plateau and adjacent areas”. It is hoped that these newly study results may improve the understanding of characteristics of strong earthquake activity and seismogenic structural mechanism in the region, and provide scientific basis for regional strong earthquake risk analysis and effective prevention of strong earthquake disaster risk.

Daqingshan piedmont fault is located in the northern margin of Hetao basin and has been active strongly since the Late Quaternary. Previous researchers had conducted extensive research on the characteristics of paleoseismic in this area, but limited by the dating techniques and the fact that there were fewer data available on the same fault profile that can effectively constrain paleoseismic events, and fewer profiles that can reveal more paleoseismic events. This paper explores the excavation of an paleoseismic trench on the east side of Lianhuashan in the western section of Tuyouqi of the Daqingshan piedmont fault, using Optically Stimulated Luminescence data, and combineing with the age data of previous exploration trenches. By using the fault successive limit method, it is found that the western section of the Tuyouqi fault has experienced five paleoseismic events approximately 11500 years ago, with an average recurrence interval of 2260 years. The five paleoseismic events in this section of the fault, from new to old, are 1.28 to 1.42 ka, 3.41 to 3.60 ka, 4.08 to 5.01 ka, 8.26 to 9.32 ka, and 10.70 to 11.30 ka, respectively. The latest event of activity should be the earthquake of 849 AD. Meanwhile, the trench exploration revealed that the fault in this section exhibits a normal fault nature, with an inclination angle between 58 and 77 degrees. According to empirical formula, the potential seismic capacity of the Baotou section, the western section of Tuyouqi, and the western section of Tuzuoqi are around MW6.8～7.1, MW6.8～7.1 and MW7.1～7.2, respectively. The magnitude obtained by the empirical formula in this paper is relatively small, and there may be cascade rupture. In the later stage, it is necessary to conduct a comprehensive evaluation of the risk of the western section of Daqingshan piedmont fault combined with other means.

The epicenter of the 2017 Qinghai Zeku MS4.9 earthquake was located near the SN-striking Riyueshan fault, while the focal mechanism solutions and the dominant arrangement of seismic sequence are inconsistent with the Riyueshan fault. In this paper, we have discovered EW- and NW-trending faults near the epicenter, by methods of remote sensing interpretation and field investigation. These faults are western terminal structures of Xiahe fault, in which the EW-trending faults are north-dipping and associated with kinematics including both left-lateral and vertical slip. Meanwhile, we use double differential positioning to relocate seismic sequences of Zeku MS4.9 earthquake. Results show that seismic arrangements consist of two segments striking NW and EW. The seismic profile crossing EW-striking segment indicates a north-dipping fault plane. Well consistence is found between Xiahe fault and seismic arrangements of Zeku MS4.9 earthquake, which leads us to the speculation that the seismogenic fault of Zeku earthquake is Xiahe fault. From a regional perspective, the Xiahe fault might be one strand of dissipating faults in the western end of the West Qinling fault, and the Zeku MS4.9 earthquake represents tectonic activity of the western end of the West Qinling fault. Besides，the northwestward turn of fault striking and reverse slipping of Xiahe fault might also be attributed to the right-lateral shearing effects of Riyueshan fault. Results of this paper highlight the significance of improving active fault traces, especially for the secondary or pre-existing faults in a tectonic active area.

Accurately classifying tree species in urban forests remains a major challenge due to the limitations of existing methods. While hyperspectral imaging is capable of capturing detailed spectral information, it struggles with the issue of ‘similar reflectance curves for different species’. On the other hand, the intensity frequency curve also has the problem of ‘similar intensity frequency curves for different species’. To overcome these challenges, a new method is proposed in this study. The method combines UAV LiDAR intensity frequency features (IF) and hyperspectral features (HF) to accurately identify tree species, abbreviated as HICM. The results of the study demonstrate that HICM can accurately identify 16 common urban tree species with an overall accuracy (OA) of 92.0% and kappa of 91.2%. Compared with using only IF or HF for identification, HICM improves OA by 16.9% and 12%, and kappa by 21.6% and 10.1%, respectively. This shows that HF and IF have complementarity, and the combination of these two features effectively addresses the problems of “same species different frequency” and “same species different spectrum”.

The hollow mold revolutionizes conventional dense mold design as it can optimize the solidification and cooling processes of casting and offer potential to improve performance of castings. In this paper, the effect of hollow mold structures on the microstructure and mechanical properties of a low pressure thin-walled aluminum alloy conical cabin casting was investigated. A hollow mold combined by four sectors with different shell thicknesses was tactfully designed. The hollow mold structures delayed the cooling and solidification of casting. They significantly reduced the pore defect from 0.4 % to 0.03 % at the lower, from 0.68 % to 0.04 % at the middle and from 0.3 % to 0.03 % at the top, compared to dense mold. In the lower and middle areas of casting, improvements of 1.0 % and 1.1 % in mechanical properties were respectively achieved when applying 50 mm-thick-shell hollow sand molds compared with using dense sand mold, while an improvement of 1.1 % was achieved in the upper area of casting with 70 mm-thick-shell. This allows designers to create hollow molds with different shell thicknesses depending on the position in the casting to meet specific needs. For example, thin shell for the bottom to achieve high fluid flow and feeding while thick shell for the top for improved cooling. For castings with wall thickness of 10 mm–20 mm, the most effective shell thickness for the hollow mold is 50 mm–70 mm. The hollow mold provides the feasibility to differentiated semi-quantitatively control the solidification and cooling processes of castings, which can be applied in production of high-end castings in the future.

Abstract Background Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying mechanism and bring a potential preventive strategy for postmenopausal osteoporosis in the future. Methods An ovariectomy (OVX)-induced rat osteoporosis model was established for in vivo experiments. Micro-computed tomography and three-point bending test were used to evaluate bone strength. Histological femur slices were processed for immunohistochemistry (IHC). Bone turnover markers and nitric oxide (NO) concentrations in serum were determined with enzyme-linked immunosorbent assay (ELISA). The mouse embryo osteoblast precursor (MC3T3-E1) cells were used for in vitro experiments. The cell viability was analysed with a Cell Counting Kit‑8. We performed Alizarin Red S staining and alkaline phosphatase (ALP) activity assay to observe the differentiation status of osteoblasts. Western blotting was adopted to detect the expression of osteogenesis related proteins and AMP-activated protein kinase/endothelial nitric oxide synthase (AMPK/eNOS) in osteoblasts. DAF-FM diacetate was used for semi-quantitation of intracellular NO. Results In OVX rats, alamandine alleviated osteoporosis and maintained bone strength. The IHC showed alamandine increased osteocalcin and collagen type I α1 (COL1A1) expression. The ELISA revealed alamandine decreased bone turnover markers and restored NO level in serum. In MC3T3-E1 cells, alamandine promoted osteogenic differentiation. Western blotting demonstrated that alamandine upregulated the expression of osteopontin, Runt-related transcription factor 2 and COL1A1. The intracellular NO was also raised by alamandine. Additionally, the activation of AMPK/eNOS axis mediated the effects of alamandine on MC3T3-E1 cells and bone tissue. PD123319 and dorsomorphin could repress the regulating effect of alamandine on bone metabolism. Conclusion Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.

Abstract There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney’s active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.

Abstract Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy.

Abstract There is significant heterogeneity in individual responses to antipsychotic drugs, but there is no reliable predictor of antipsychotics response in first-episode psychosis. This study aimed to investigate whether psychotic symptom-related alterations in fractional anisotropy (FA) and mean diffusivity (MD) of white matter (WM) at the early stage of the disorder may aid in the individualized prediction of drug response. Sixty-eight first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single atypical antipsychotic throughout the first 12 weeks. Clinical symptoms were evaluated using the eight “core symptoms” selected from the Positive and Negative Syndrome Scale (PANSS-8). Follow-up assessments were conducted at the 4th, 8th, and 12th weeks by trained psychiatrists. LASSO regression model and cross-validation were conducted to examine the performance of baseline symptom-related alterations FA and MD of WM in the prediction of individualized treatment outcome. Fifty patients completed both clinical follow-up assessments by the 8th and 12th weeks. 30 patients were classified as responders, and 20 patients were classified as nonresponders. At baseline, the altered diffusion properties of fiber tracts in the anterior thalamic radiation, corticospinal tract, callosum forceps minor, longitudinal fasciculi (ILF), inferior frontal-occipital fasciculi (IFOF) and superior longitudinal fasciculus (SLF) were related to the severity of symptoms. These abnormal fiber tracts, especially the ILF, IFOF, and SLF, significantly predicted the response to antipsychotic treatment at the individual level (AUC = 0.828, P

Abstract Leakage is one of the most serious challenges for the safe production of high‐pressure gas wells for its high risks, including abnormal annular pressure, natural gas accumulation, and environment pollution, but available methods can hardly accurately measure the leakage type and depth, which are the key parameters for the rigless leakage repair and risk assessment. Therefore, this paper proposes a method to measure the leakage based on the characteristics, which combines qualitative and quantitative measurement together. Qualitative measurement considers the annular pressure, tubing pressure, liquid level, cement quality, and workover history. Quantitative measurement is determined by noise logging, electromagnetic logging, pressure logging, and temperature logging. The logging should be optimized according to the qualitative measurement. The method was successfully applied in high‐pressure gas well belonging to Tarim Oilfield. Two potential leakage types are provided based on the annular pressure, liquid level, cement quality, and workover history, including tubing leakage and linger hanger leakage. Based on the potential leakage types, the pressure difference, logging devices string, stopping length, and time are optimized to make the engineering logging reliable. Through measurement, two leakage points are found in tubing string. One is tubing body crack at the depth of 2724 m and the other is tubing thread leakage at the depth of 5211.7 m, which well matches the production data.

In this work, the bending behavior of high-strength Al–Mg–Si–Cu alloys and AA6061 under different artificial aging condition was investigated. The existing springback prediction formula is suitable for commercial AA6061 alloy, but not for high-strength Al–Mg–Si–Cu alloy. Subsequently, the microstructure, mechanical properties and residual stress of AA6061 and high-strength Al– Mg–Si–Cu alloys were investigated. The results show that the yield strength and residual stress play important roles on the springback of high-strength Al–Mg–Si–Cu alloy. In addition, a springback prediction formula based on residual tensile stress has been proposed, which makes the prediction accuracy higher than 96 %. This provides theoretical guidance and data support for the application of high-strength Al–Mg–Si–Cu alloys in lightweight automotive materials.

Porthole die extrusion experiments were carried out on 6005A aluminum alloy under the billet heating temperatures of 420–570 °C and ram speeds of 1–120 mm/min. The effects of extrusion parameters on the microstructure and mechanical properties in the longitudinal weld of profiles were investigated. It was found that the crystal orientation of longitudinal weld region showed the characteristics of gradient arrangement with different oriented grains wrapped in layers and symmetric along the welding line. The Copper{112} grains are formed at the welding line under the combined effect of shear and compression, and the Goss{110} grains are formed on their both sides due to dynamic recrystallization. A shear band is formed when part of metals flow through the 45° inclination angle of port bridge due to a sudden change in velocity, causing the Goss{110} texture in local region to rotate to Brass{110} texture. The 6005A aluminum alloy profiles mainly contain β (Mg2Si) phase, Q (Al3Mg9Si7Cu2) phase, AlCrMnSi phase and AlFeMnCrSi phase. Appropriately increasing billet heating temperature and ram speed can promote dynamic recrystallization and the dissolution of β-phase and Q-phase, thus improving the strength and hardness of the profile. However, when the billet heating temperature is too high, the strength and hardness are reduced instead due to grain coarsening. The profile extruded at billet heating temperature of 510 °C and ram speed of 120 mm/min has the best mechanical properties, with the tensile strength in 0° direction and hardness at the welding line of 179.93 MPa and 52.2 HV, respectively.

In this paper, the effect of Ce addition on high temperature oxidation behavior of hot-formed steel was studied by high temperature oxidation experiment. The structure and phase composition of surface oxide layer of specimens with different Ce content were systematically analyzed by SEM, EDS, XPS. The results showed that the addition of Ce promoted the formation of a dense oxide layer during the initial oxidation stage, and effectively weaken the oxidation degree of the steel surface. Meanwhile, the Ce2O3 particles segregation in Si–Cr rich phase reduced the concentration of vacancy defects in oxide layer and enhanced the adhesion between oxide layer and substrate. After Ce addition, the surface oxidation resistance of hot-formed steel is significantly improved.

In this work, a novel microstructure-informed machine learning (MIML) framework is proposed for the longitudinal ultimate tensile strength (UTS) evaluation and the construction of microstructure-property linkages of titanium matrix composites (TMCs). The main components of the MIML framework include (i) high-fidelity simulation and dataset generation using finite element method (FEM), (ii) the quantitative characterization of microstructures obtained by 2-point cross-correlation analysis and principal component analysis, (iii) the extraction of structure-property linkages based on support vector regression model and (iv) the validation of MIML by experimental data. The fiber breakage observed by advanced microstructure characterization is considered as the dominant failure mode during mechanical tests of TMCs, which is embedded in the FEM simulations. The MIML approach reaches capable accuracy in UTS prediction of TMCs using FEM-generated datasets and trained MIML is validated by experimental data. In addition, the permutation importance-based method is utilized to accurately identify the key feature parameters related to UTS. The first two principal components of microstructural reduced-order representation are recognized as highly relevant features for UTS. The well-trained MIML model is a promising tool in the evaluation of the mechanical property, and further provides a technical chain for the establishment of microstructure-property linkages of multi-phase composites.

NASA's (National Aeronautics and Space Administration) ICESat-2 with a Photon Counting LiDAR (Light Detection And Ranging) Sensor sensitively detects signal photons at high speed with an advanced detection system called the Advanced Topographic Laser Altimeter System (ATLAS). However, the sensor also extracts a large amount of background photon noise coming from the atmosphere, ground, sun, or other radiation. This condition is particularly evident in forest areas. This study proposes an automatic machine learning approach to utilize data for forestry applications to improve data availability compared to NASA's official product. Our method uses only a very limited number (10%) of sample points for training, ensuring operational efficiency and training accuracy. We conclude that the integrated learning performance generally outperforms single models, and the mean F1 score of all tests is approximately 0.9. The mean F1 score of the Stacked Ensembles model is 0.957 ahead of the other models. The top three variables used in training models are kNNdist5, kNNdist10, and h. These three variables could explain 51.6% of the components of the models. Over the regions tested, the proposed method could improve the proportion of signals correctly identified by 6.4%, 12.2%, 2.7%, 9.3%, and 1.4% in five datasets. The model performs better in low signal-to-noise (SNR) datasets less than 7.5. The method would be largely unaffected by differences in topography, noise distribution, and SNR. The classifiers could correct misclassified labels in ATL08 products and show good stability in different conditions.

Abstract Corpus callosotomy (CC) is a palliative treatment for drop seizures in patients with drug‐resistant nonlocalizable epilepsy. We compared drop seizure outcomes between patients undergoing anterior CC versus complete CC and examined factors impacting outcomes for drop seizures including age at CC and duration of epilepsy. A retrospective review of patients who underwent CC between 2003 and 2022 with a minimum of 6 months postsurgical follow‐up was included. Outcome measure for drop seizures included seizure reduction ≥50% from baseline as well as elimination of drop seizures. Thirty‐eight patients were included. Overall, ≥50% reduction in drop seizures occurred in nearly 70% (23 out of 33) patients with complete elimination in 58% (19 out of 33). Compared with anterior CC (n = 13), patients undergoing complete CC (n = 25) had increased likelihood of ≥50% reduction (p = 0.006) or elimination (p = 0.024) of drop seizures. Regression analysis showed that complete CC was the primary predictor for improved drop seizure outcomes (elimination, p = 0.014 or ≥50% reduction, p = 0.006), while age at CC and duration of epilepsy did not impact the outcomes. Compared to anterior CC, complete CC was significantly more likely to lead to improvement/freedom from drop seizures. Age at CC or duration of epilepsy did not influence drop seizure outcomes.

Abstract Interferon (IFN) exerts its effects through interferon-stimulated genes (ISGs), but its efficacy is limited by interferon resistance, which can be caused by the ubiquitination of key proteins. UBE2O was initially identified as a promising therapeutic target based on data from the TCGA and iUUCD 2.0 databases. Through the inhibition of UBE2O, interferon α/β signaling and overall interferon signaling were activated. Integrating data from proteomic, mass spectrometry, and survival analyses led to the identification of IFIT3, a mediator of interferon signaling, as a ubiquitination substrate of UBE2O. The results of in vitro and in vivo experiments demonstrated that the knockdown of UBE2O can enhance the efficacy of interferon-α by upregulating IFIT3 expression. K236 was identified as a ubiquitination site in IFIT3, and the results of rescue experiments confirmed that the effect of UBE2O on interferon-α sensitivity is dependent on IFIT3 activity. ATO treatment inhibited UBE2O and increased IFIT3 expression, thereby increasing the effectiveness of interferon-α. In conclusion, these findings suggest that UBE2O worsens the therapeutic effect of interferon-α by targeting IFIT3 for ubiquitination and degradation.

The increasing proportion of distributed photovoltaics (DPVs) and electric vehicle charging stations in low-voltage distribution networks (LVDNs) has resulted in challenges such as distribution transformer overloads and voltage violations. To address these problems, we propose a coordinated planning method for flexible interconnections and energy storage systems (ESSs) to improve the accommodation capacity of DPVs. First, the power-transfer characteristics of flexible interconnection and ESSs are analyzed. The equipment costs of the voltage source converters (VSCs) and ESSs are also analyzed comprehensively, considering the differences in installation and maintenance costs for different installation locations. Second, a bilevel programming model is established to minimize the annual comprehensive cost and yearly total PV curtailment capacity. Within this framework, the upper-level model optimizes the installation locations and capacities of the VSCs and ESSs, whereas the lower-level model optimizes the operating power of the VSCs and ESSs. The proposed model is solved using a non-dominated sorting genetic algorithm with an elite strategy (NSGA-II). The effectiveness of the proposed planning method is validated through an actual LVDN scenario, which demonstrates its advantages in enhancing PV accommodation capacity. In addition, the economic benefits of various planning schemes with different flexible interconnection topologies and different PV grid-connected forms are quantitatively analyzed, demonstrating the adaptability of the proposed coordinated planning method.

Glycosylated volatiles are considered as hidden aroma precursors that affect fruit flavor and are involved in plant defense response. Several uridine-diphosphate (UDP)-glycosyltransferase (UGT) members related to the glycosylation of volatiles have been identified from grapevine berries. Although grapevine leaves produced much higher levels of glycosylated volatiles than berries, UGTs responsible for the production of glycosylated volatiles in leaves have not yet been identified. Here, eight novel UGT genes were cloned, among these four members that belong to UGT85A family (named UGT85A24, UGT85A25, UGT85A26, and UGT85A27) were localized in the cytoplasm and their recombinant proteins showed activity toward volatiles detected in grapevine, with geraniol as the preferred substrate in vitro. Two UGT genes with 98.1% homology differ in R/S-linalool selection. The UGT85A26-catalyzed substrate showed enrichment in S-linalool, whereas UGT85A27 showed a strong preference for R-linalool. UGT85A24 and UGT85A25 were expressed mainly in berries, and UGT85A26 and UGT85A27 were expressed predominantly in grapevine mature leaves and correlated with the highest content of glycosylated volatiles in the mature leaves. Methyl jasmonate (MeJA) induced the expression of UGT85A26 and UGT85A27 as well as the production of linalyl-β-glucoside, citronellyl-β-glucoside and phenethyl-β-glucoside. Transient overexpression of UGT85A26 and UGT85A27 in tobacco leaves led to the accumulation of linalyl-β-glucoside and an increase in citronellyl-β-glucoside in vivo. These results indicate that the expression of UGT85A26 and UGT85A27 is a major regulator affecting the content of glycosylated volatiles in grapevine.

Objective Hounsfield units (HU), vertebral bone quality (VBQ), and bone mineral density (BMD) can all serve as predictive indicators for thoracolumbar fragility fractures. This study aims to explore which indicator provides better risk prediction for thoracolumbar fragility fractures. Methods Patients who have received medical attention from The First Affiliated Hospital of Anhui Medical University for thoracolumbar fragility fractures were selected. A total of 78 patients with thoracolumbar fragility fractures were included in the study. To establish a control group, 78 patients with degenerative spinal diseases were matched to the fracture group on the basis of gender, age, and body mass index. The lumbar vertebral HU, the VBQ, and the BMD were obtained for all the 156 patients through computed tomography, magnetic resonance imaging, and dual-energy x-ray absorptiometry (DEXA). The correlations among these parameters were analyzed. The area under curve (AUC) analysis was employed to assess the predictive efficacy and thresholds of lumbar vertebral HU, VBQ, and BMD in relation to the risk of thoracolumbar fragility fractures. Results Among the cohort of 156 patients, lumbar vertebral HU exhibited a positive correlation with BMD (p < 0.01). Conversely, VBQ showed a negative correlation with HU, BMD (p < 0.05). HU and BMD displayed a favorable predictive efficacy for thoracolumbar fragility fractures (p < 0.01), with HU (AUC = 0.863) showcasing the highest predictive efficacy, followed by the DEXA-measured BMD (AUC = 0.813). VBQ (AUC = 0.602) ranked lowest among the 3 indicators. The thresholds for predicting thoracolumbar fragility fractures were as follows: HU (88),VBQ (3.37), and BMD (0.81). Conclusion All 3 of these indicators, HU, VBQ, and BMD, can predict thoracolumbar fragility fractures. Notably, lumbar vertebral HU exhibits the highest predictive efficacy, followed by the BMD obtained through DEXA scanning, with VBQ demonstrating the lowest predictive efficacy.

Objective This study assessed biomechanical properties of pedicle screws enhanced or revised with 3 materials. We aimed to compare the efficacy of these materials in pedicle augmentation and revision. Methods One hundred twenty human cadaveric vertebrae were utilized for in vitro testing. Vertebrae bone density was evaluated. Allograft bone particles (ABP), calcium phosphate cement (CPC), and demineralized bone matrix (DBM) were used to augment or revise pedicle screw. Post the implantation of pedicle screws, parameters such as insertional torque, pullout strength, cycles to failure and failure load were measured using specialized instruments. Results ABP, CPC, and DBM significantly enhanced biomechanical properties of the screws. CPC augmentation showed superior properties compared to ABP or DBM. ABP-augmented screws had higher cycles to failure and failure loads than DBM-augmented screws, with no difference in pullout strength. CPC-revised screws exhibited similar strength to the original screws, while ABP-revised screws showed comparable cycles to failure and failure loads but lower pullout strength. DBM-revised screws did not match the original screws’ strength. Conclusion ABP, CPC, and DBM effectively improve pedicle screw stability for pedicle augmentation. CPC demonstrated the highest efficacy, followed by ABP, while DBM was less effective. For pedicle revision, CPC is recommended as the primary choice, with ABP as an alternative. However, using DBM for pedicle revision is not recommended.

Structure plane is one of the important factors affecting the stability and failure mode of rock mass engineering. Rock mass structure characterization is the basic work of rock mechanics research and the important content of numerical simulation. A new 3-dimensional rough discrete fracture network (RDFN3D) model and its modeling method based on the Weierstrass-Mandelbrot (W-M) function were presented in this paper. The RDFN3D model, which improves and unifies the modelling methods for the complex structural planes, has been realized. The influence of fractal dimension, amplitude, and surface precision on the modeling parameters of RDFN3D was discussed. The reasonable W-M parameters suitable for the roughness coefficient of JRC were proposed, and the relationship between the mathematical model and the joint characterization was established. The RDFN3D together with the smooth 3-dimensional discrete fracture network (DFN3D) models were successfully exported to the drawing exchange format, which will provide a wide application in numerous numerical simulation codes including both the continuous and discontinuous methods. The numerical models were discussed using the COMSOL Multiphysics code and the 3-dimensional particle flow code, respectively. The reliability of the RDFN3D model was preliminarily discussed and analyzed. The roughness and spatial connectivity of the fracture networks have a dominant effect on the fluid flow patterns. The research results can provide a new geological model and analysis model for numerical simulation and engineering analysis of jointed rock mass.

Abstract Objective Resilience has been reported as an important predictor of better mental health and prognoses in cancer patients, while its mechanisms were not clearly elucidated. In this study, we surveyed a large sample of nasopharyngeal carcinoma patients to investigate the mediating role of illness‐related cognition (illness perception, stigma and meaning in life) on the associations between resilience and symptoms of anxiety and depression. Methods This cross‐sectional study involved 773 participants diagnosed with nasopharyngeal carcinoma. Participants completed a self‐reported structured questionnaire to assess their illness perception, stigma and meaning in life, resilience and symptoms of anxiety and depression. Structural equation models (SEM) were employed to explore the relationship between resilience and symptoms of anxiety and depression in the entire sample, as well as in two subgroups: Subgroup I (0–1 year since diagnosis), and Subgroup II (over 1 year since diagnosis). Results In the entire sample, after adjusting for potential confounders, illness perception, stigma and meaning in life were found to mediate the protective effect of resilience on symptoms of depression (mediating effect proportion: 65.25%) and anxiety (mediating effect proportion: 67.63%). In Subgroup I, direct effects were dominant in the associations between resilience and symptoms of anxiety (mediating effect proportion: 37.95%) and depression (mediating effect proportion: 29.13%). However, in Subgroup II, the associations between resilience and symptoms of anxiety (mediating effect proportion: 98.92%) and depression (mediating effect proportion: 81.04%) were completely mediated. Conclusions Our study suggests that direct and indirect effects of resilience on depression and anxiety dominate in early periods (0–1 year) and long‐term periods (over 1 year) following the cancer diagnosis, respectively. The findings indicate that comprehensive intervention considering both the direct effect of resilience in early stages (e.g., health education prescription and social support groups) and the indirect effects of illness cognition in long‐term periods (e.g., cognitive behavioral therapies) are likely to yield the most favorable outcomes for cancer patients.

Abstract Introduction Durvalumab is a check‐point inhibitor against programmed death ligand‐1 (PD‐L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs. However, it is unclear that whether this combination is effective when initiated as maintenance treatment in ES‐SCLC patients. Methods This is a multicenter, randomized, phase II study. A total of 64 eligible patients who do not experience disease progression after four cycles platinum‐based chemotherapy combined with durvalumab will be randomized to durvalumab with anlotinib or durvalumab alone until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is PFS (from randomization); secondary endpoint was OS and PFS (from diagnosis), objective response rate (ORR); disease control rate (DCR) and duration of response (DOR), safety and tolerability assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Discussion We conduct a phase II study to investigate the safety and efficacy of durvalumab combined with anlotinib as maintenance treatment in ES‐SCLC patients.

Abstract The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate that VRC01 influenced viral loads in AMP participants who acquired HIV. Instantaneous inhibitory potential (IIP), which integrates VRC01 serum concentration and VRC01 sensitivity of acquired viruses in terms of both IC50 and IC80, follows a dose-response relationship with first positive viral load (p = 0.03), which is particularly strong above a threshold of IIP = 1.6 (r = -0.6, p = 2e-4). Mathematical modeling reveals that VRC01 activity predicted from in vitro IC80s and serum VRC01 concentrations overestimates in vivo neutralization by 600-fold (95% CI: 300–1200). The trained model projects that even if future therapeutic HIV trials of combination monoclonal antibodies do not always prevent acquisition, reductions in viremia and reservoir size could be expected.

Abstract Background Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. A large number of studies have shown that pulmonary vascular endothelial cells (PVECs) dysfunction plays an important role in the initiation and development stages of HPH, but the mechanism of PVECs dysfunction after hypoxia remains unclear. In this study, we explored the exact mechanism of PVECs dysfunction after hypoxia. Methods In vitro, we used primary cultured PVECs hypoxia model to mimic HPH injury. We detected the expressions of mitochondrial biogenesis markers, mitochondrial transcription factor A (TFAM) level inside mitochondria, mitochondrial quantity and function, and the components expressions of translocase of outer mitochondrial membrane (TOM) at 24 h after hypoxia. To explore the effects of Tom70 on mitochondrial biogenesis and functions of PVECs after hypoxia, Tom70 overexpression adenovirus was constructed, and the expressions of mitochondrial biogenesis markers, TFAM level inside mitochondria, mitochondrial quantity and function, and the functions of PVECs were detected. And in vivo, we used cre-dependent overexpression adenovirus of Tom70 in the Cdh5-CreERT2 mouse model of HPH to verify the role of upregulating PVECs Tom70 in improving HPH. Results Hypoxia obviously increased the expressions of mitochondrial biogenesis markers for PGC-1α, NRF-1 and TFAM, but reduced the content of TFAM in mitochondria and the quantity and functions of mitochondria. In addition, only Tom70 expression among the TOM components was significantly decreased after hypoxia, and up-regulation of Tom70 significantly increased the content of TFAM in mitochondria of PVECs by transporting TFAM into mitochondria after hypoxia, enhanced the quantity and functions of mitochondria, improved the functions of PVECs, and ultimately alleviated HPH. Conclusion The findings of present study demonstrated that hypoxia induced the decreased expression of Tom70 in PVECs, reduced the mitochondrial biogenesis-associated TFAM protein transporting into mitochondria, inhibited mitochondrial biogenesis, caused PVECs injury, and prompted the formation of HPH. However, up-regulation of Tom70 abolished the hypoxia-induced injurious effects on PVECs and alleviated HPH.

Abstract Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.

Abstract Background Beta-cell replacement methods such as transplantation of isolated donor islets have been proposed as a curative treatment of type 1 diabetes, but widespread application is challenging due to shortages of donor tissue and the need for continuous immunosuppressive treatments. Stem-cell-derived islets have been suggested as an alternative source of beta cells, but face transplantation protocols optimization difficulties, mainly due to a lack of available methods and markers to directly monitor grafts survival, as well as their localization and function. Molecular imaging techniques and particularly positron emission tomography has been suggested as a tool for monitoring the fate of islets after clinical transplantation. The integral membrane protein DGCR2 has been demonstrated to be a potential pancreatic islet biomarker, with specific expression on insulin-positive human embryonic stem-cell-derived pancreatic progenitor cells. The candidate Affibody molecule ZDGCR2:AM106 was radiolabeled with fluorine-18 using a novel click chemistry-based approach. The resulting positron emission tomography tracer [18F]ZDGCR2:AM106 was evaluated for binding to recombinant human DGCR2 and cryosections of stem-cell-derived islets, as well as in vivo using an immune-deficient mouse model transplanted with stem-cell-derived islets. Biodistribution of the [18F]ZDGCR2:AM106 was also assessed in healthy rats and pigs. Results [18F]ZDGCR2:AM106 was successfully synthesized with high radiochemical purity and yield via a pretargeting approach. [18F]ZDGCR2:AM106 retained binding to recombinant human DCGR2 as well as to cryosectioned stem-cell-derived islets, but in vivo binding to native pancreatic tissue in both rat and pig was low. However, in vivo uptake of [18F]ZDGCR2:AM106 in stem-cell-derived islets transplanted in the immunodeficient mice was observed, albeit only within the early imaging frames after injection of the radiotracer. Conclusion Targeting of DGCR2 is a promising approach for in vivo detection of stem-cell-derived islets grafts by molecular imaging. The synthesis of [18F]ZDGCR2:AM106 was successfully performed via a pretargeting method to label a site-specific covalently bonded fluorine-18 to the Affibody molecule. However, the rapid washout of [18F]ZDGCR2:AM106 from the stem-cell-derived islets graft indicates that dissociation kinetics can be improved. Further studies using alternative binders of similar classes with improved binding potential are warranted.

Abstract Background To ensure emergency infection prevention and control (IPC) can be fully supervised and monitored in coronavirus disease (COVID-19) epidemic period, a three-level inspector mechanism called "Internal self-check, Departmental cross-check, and Verification of outstanding key and difficult issues" was established in southwest China. The present study aimed to explore the effectiveness of inspector mechanism for the emergency IPC. Methods A self-control real-world study was conducted during COVID-19 epidemic period from 2020 to 2022. An innovative designed mobile phone application was used to realize paperless information transmission and data management. Data were compared between inspection levels using SPSS 19.0 software. Results A total of 2,800,132 supervision records were collected, including 149,137 comprehensive epidemic IPC projects, 1,410,093 personal protective equipment (PPE) use, 1,223,595 wearing and removing process of PPE and 17,307 ultraviolet light-detectable fluorescent (UV/F) surface marker. During the study period, the inspectors and subjects explored many optimized IPC measures. The compliance rate of check items has exceeded 98%, and internal self-check has a statistically significant higher rate than departmental cross-check (99.95% versus 98.74%, χ 2 = 26111.479, P < 0.001). Compare with the failure rate in internal self check, the failure rate of PPE usage and wearing/removing process was statistically higher in departmental cross-check (χ 2 = 1957.987, P < 0.001, χ 2 = 465.610, P < 0.001, respectively). The overall clearance rate of UV/F surface markers is 87.88%, but there is no statistically significant difference over the three years of the present study (F = 2.902, P = 0.071). Conclusions Inspector mechanism for the emergency IPC completed an incredible inspection workload and offered creative assistance to combat the COVID-19 outbreak. These methods and accumulated experiences should be helpful for us to strengthen IPC for future epidemic.

Abstract Active matter demonstrates complex spatiotemporal self-organization not accessible at equilibrium and the emergence of collective behavior. Fluids comprised of microscopic Quincke rollers represent a popular realization of synthetic active matter. Temporal activity modulations, realized by modulated external electric fields, represent an effective tool to expand the variety of accessible dynamic states in active ensembles. Here, we report on the emergence of shockwave patterns composed of coherently moving particles energized by a pulsed electric field. The shockwaves emerge spontaneously and move faster than the average particle speed. Combining experiments, theory, and simulations, we demonstrate that the shockwaves originate from intermittent spontaneous vortex cores due to a vortex meandering instability. They occur when the rollers’ translational and rotational decoherence times, regulated by the electric pulse durations, become comparable. The phenomenon does not rely on the presence of confinement, and multiple shock waves continuously arise and vanish in the system.

Abstract A long dispersal distance is widely used to indicate high invasiveness, but it ignores the temporal dimensions of plant invasion. Faster dispersal rates (= distance/time) of invasive species than native ones have been widely used in modeling species invasion and planning control management. However, the comparison of dispersal rate between invasive and native plants, particularly for dispersal on a local or landscape scale, has not been tested with a comprehensive dataset. Moreover, both the effects of plant functional traits on the dispersal rate and variation in the functional-trait effects between invasive and native plants remain elusive. Compiling studies from 30 countries globally, we compared seed dispersal rates (km/year) on a local or landscape scale between 64 observations of invasive and 78 observations of native plants given effects of plant life forms, disturbance levels, and measurement methods. Furthermore, we compared the effects of functional traits on dispersal rate between invasive and native species. We found that: (1) Trait values were similar between the invasive and native plants except for the greater height of woody native plants than woody invasive ones; (2) Compared within the same plant life form, the faster dispersal rates of invasive species were found in herbaceous plants, not in woody plants, and disturbance level and measurement methods did not affect the rate comparison; (3) Plant height and seed length had significant effects on dispersal rates of both invasive and native plants, but the effect of leaf dry matter content (LDMC) was only significant on herbaceous invasive plants. The comparison of dispersal rate between invasive and native plants varied by plant life form. The convergent values but divergent dispersal effects of plant traits between invasive and native species suggest that the trait effects on invasiveness could be better understood by trait association with key factors in invasiveness, e.g., dispersal rate, than the direct trait comparison between invasive and native plants.

Abstract Background Compassionate use is a system that provides patients with expedited access to drugs which has not yet been approved, but currently in clinical trials. The investigational drugs have been authorized for compassionate use in cases involving patients suffered from life-threatening diseases and with no alternative treatments. For instance, patients afflicted with highly heterogeneous rare diseases are eligible for treatment assistance through the compassionate use program. This study aims to investigate the characteristics of compassionate use in the context of rare diseases, evaluate the efficacy and safety of compassionate use for rare diseases, and analyze the marketing approval of investigational drugs. Methods The case reports/case series of compassionate use were collected by conducting searches on Embase, PubMed, Web of Science, CNKI and SinoMed, spanning from January 1991 to December 2022. Subsequently, two independent reviewers evaluated these reports. Case reports/case series that met the inclusion criteria and exclusion criteria were enrolled. Information extracted from these reports and series included patients' basic information, the investigational drug's name, its indication, adverse events, treatment outcomes, and other relevant data. Results A total of forty-six studies were included, encompassing 2079 patients with an average age of 38.1 years. Thirty-nine different drugs were involved in 46 studies. Furthermore, neoplasms emerged as the most common therapeutic area for compassionate use in rare disease management (23/46, 50.0%). Regarding the treatment efficacy, four studies reported successful disease resolution, while 35 studies observed symptom improvement among patients. Conversely, four studies documented no significant effects on patients' diseases. Moreover, one study reported worsened results following compassionate use, while the efficacy was not described in 2 studies. Adverse events were reported in 31 studies (67.4%) because of the compassionate use, while no adverse events occurred in 13 studies (28.3%). In other 2 studies, there was no description about whether treatment-emergent adverse events (TEAEs) were happened. 136 patients (6.5%) had Grade 5 adverse events (death), of which 19 deaths (0.9%) were considered to be related to compassionate use. Furthermore, the investigational drugs in 33 studies (33/46, 71.7%) received new drug approval at the end of January 31, 2023.The time lag from the start of the compassionate use to the formal approval of the investigational drug was 790.5 (IQR 359–2199.3) days. We found that in 11 studies, encompassing 9 different drugs, some compassionate use indications had not received regulatory authorities at the end of January 31, 2023. Conclusion The current status of compassionate use for rare diseases was clarified systematically in this study. Compassionate use of investigational drug is a significant treatment option for rare disease. In general, compassionate use appears to demonstrate favorable efficacy in the context of rare diseases, with a significant proportion of compassionate use drugs subsequently receiving marketing approval. However, the safety of drugs for compassionate use cannot be fully evaluated due to the safety data were not covered in some enrolled studies. Therefore, the establishment of an adverse event reporting system specific to compassionate use is warranted.

Magnesium (Mg) and its alloys have been intensively studied to develop the next generation of bone implants recently, but their clinical application is restricted by rapid degradation and unsatisfied osteogenic effect in vivo. A bioactive chemical conversion Mg-phenolic networks complex coating (eEGCG) was stepwise incorporated by epigallocatechin-3-gallate (EGCG) and exogenous Mg2+ on Mg-2Zn magnesium alloy. Simplex EGCG induced chemical conversion coating (cEGCG) was set as compare group. The in vitro corrosion behavior of Mg-2Zn alloy, cEGCG and eEGCG was evaluated in SBF using electrochemical (PDP, EIS) and immersion test. The cytocompatibility was investigated with rat bone marrow mesenchymal stem cells (rBMSCs). Furthermore, the in vivo tests using a rabbit model involved micro computed tomography (Micro-CT) analysis, histological observation, and interface analysis. The results showed that the eEGCG is Mg-phenolic multilayer coating incorporated Mg-phenolic networks, which is rougher, more compact and much thicker than cEGCG. The eEGCG highly improved the corrosion resistance of Mg-2Zn alloy, combined with its lower average hemolytic ratios, continuous high scavenging effect ability and relatively moderate contact angle features, resulting in a stable and suitable biological environment, obviously promoted rBMSCs adhesion and proliferation. More importantly, Micro-CT, histological and interface elements distribution evaluations all revealed that the eEGCG effectively inhibited degradation and enhanced bone tissue formation of Mg alloy implants. This study puts forward a promising bioactive chemical conversion coating with Mg-phenolic networks for the application of biodegradable orthopedic implants.

Abstract The effective storage and utilization of hydrogen energy is expected to solve the problems of energy shortage and environmental pollution currently faced by human society. Metal–organic framework materials (MOFs) have been shown by scientists to be very potential hydrogen storage materials. However, the current design methods and strategies for MOFs are still generally in the trial‐and‐error stage, and the research works are at the overall level. To solve the problems of directional design and rational construction of new MOFs, this work uses the principles and methods of coordination chemistry and crystal engineering to carry out the theoretical design and mechanism research of new MOFs for high‐efficiency hydrogen storage application scenarios. In this study, the structures selected for theoretical calculation were divided into two types: different ligands for the same metal (IRMOFs, MOF‐205, and DUT‐23‐Zn) and different metals for the same ligand (DUT‐23‐M [(M = Co, Ni, Cu, and Zn]). The model construction process, hydrogen loading with temperature, specific surface area, hydrogen adsorption energy, charge density and hydrogen storage mechanism of the above structures were analyzed, and the key indicators that may affect the hydrogen storage performance of MOFs were summarized: type and quantity of coordination metals, temperature, pressure, adsorption site and specific surface area.

Pancreatic cancer is a malignant tumor of the digestive system that is highly malignant, difficult to treat, and confers a poor prognosis for patients. BRAF-activated noncoding RNA (BANCR) has been proven to play an important role in the invasion and metastasis of pancreatic cancer. In this study, we focused on BANCR as a potential therapeutic target for human pancreatic cancer. The BANCR level in pancreatic cancer tissues and cells is affected by m6A methylation. Based on this, the aim of our study was to investigate the effect of a highly potent and selective first-in-class catalytic inhibitor of METTL3 (STM2457) on BANCR m6A methylation and its malignant biological behaviors in pancreatic cancer. The relationship between BANCR expression and BANCR m6A modification was detected with RT-qPCR and MeRIP-PCR. The expression of methyltransferase-like 3 (METTL3), the key enzyme involved in m6A methylation, in pancreatic cancer tissues was detected using a Western blot. STM2457 was used in vitro to investigate its resistance to the proliferation, invasion, and metastasis of pancreatic cancer cells. BANCR was overexpressed in pancreatic cancer tissues and cells, which was associated with poor clinical outcomes and validated in pancreatic cancer cell lines. m6A modification was highly enriched within BANCR and enhanced its expression. Remarkably, STM2457 inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells by down-regulating BANCR m6A modifications. This study demonstrates the promise of BANCR as a new diagnostic and therapeutic target for pancreatic cancer and reveals the therapeutic effect that STM2457 exerts on pancreatic cancer by down-regulating BANCR m6A modifications.

Abstract Polyploidization is a major driver of genome diversification and environmental adaptation. However, the merger of different genomes may result in genomic conflicts, raising a major question regarding how genetic diversity is interpreted and regulated to enable environmental plasticity. By analyzing the genome-wide binding of 191 trans-factors in allopolyploid wheat, we identified like heterochromatin protein 1 (LHP1) as a master regulator of subgenome-diversified genes. Transcriptomic and epigenomic analyses of LHP1 mutants reveal its role in buffering the expression of subgenome-diversified defense genes by controlling H3K27me3 homeostasis. Stripe rust infection releases latent subgenomic variations by eliminating H3K27me3-related repression. The simultaneous inactivation of LHP1 homoeologs by CRISPR–Cas9 confers robust stripe rust resistance in wheat seedlings. The conditional repression of subgenome-diversified defenses ensures developmental plasticity to external changes, while also promoting neutral-to-non-neutral selection transitions and adaptive evolution. These findings establish an LHP1-mediated buffering system at the intersection of genotypes, environments, and phenotypes in polyploid wheat. Manipulating the epigenetic buffering capacity offers a tool to harness cryptic subgenomic variations for crop improvement.

With the increasing penetration of clean energy sources such as wind power and photovoltaic in the grid, the volatility, intermittency, and randomness of their power output have impacted the safe and stable operation of the grid. To address the challenges posed by scheduling and the potential wastage of renewable energy due to these factors, a two-layer optimal scheduling model for a virtual power plant that takes into account source-load synergy is proposed in this paper. In the upper model, emphasis is placed on demand response strategies to optimize load-side dispatch. This includes encouraging customers to adjust their electricity consumption patterns through time-of-use pricing and effectively managing controllable loads for peak shaving and valley filling. These actions collectively aim to maximize the virtual power plant's overall performance. The upper-tier model then communicates the power output to the lower-tier model. In the lower model, we consider the costs associated with wind, photovoltaic, thermal, and energy storage power generation to optimize power-side scheduling. This approach ensures a comprehensive optimization process, addressing both demand and power generation aspects of the virtual power plant's operations. Compared to existing research, this paper takes into account the impact of various clean energy sources, meticulously categorizes controllable loads, and conducts in-depth modeling and analysis of demand response. Finally, the results of optimal scheduling of the virtual power plant under different scenes are compared and analyzed using examples, to validate the effectiveness of the proposed method.

Improvement of corrosion resistance in high-strength Al–Si–Cu–Mg casting alloy is an important issue for its application in humid and corrosion environment. In this paper, the effect of Cr on microstructure, mechanical properties and corrosion behavior of Al–9Si-1.2Cu-0.5 Mg alloy were investigated. The results indicate that 0.052 % and 0.106 % Cr addition shows a slight strengthening for mechanical properties by introducing AlSiFeCr dispersoids, 0.052 % Cr addition effectively enhances the corrosion resistance of the alloy. The addition of 0.052%Cr not only increase the thickness and stability of the passive film, but also has an obvious effect on the charge transfer process. 0.052 % Cr addition reduces the potential difference between cathode phases and Al matrix. The results of first-principles calculations indicate that the (001) surface of CrO2 would have an effect of adsorbing Cl− ions in the passive film/solution interface, the interaction between Cl and neighboring Cr atoms implies the formation of chemical bonds between Cl atoms and the surrounding Cr atoms at adsorption sites. It contributes to weaken the attack of the passive film by Cl− ions. When Cr level increases to 0.106 %, the appearance of AlSiFeCr dispersoids may result in the additional electrochemical process and weaken the protection on the matrix. This paper designs a novel Al–Si–Cu–Mg–Cr casting alloy with high mechanical properties and high corrosion resistance, expanding automotive industry application of casting aluminum alloy.

Introduction: Flavor is a major contributor to consumer preference. Despite being effective at extending the fruit’s commercial life, cold storage also results in a significant loss of flavor volatiles. To date, there has been few studies on the metabolic dynamics and the mechanism underlying the regulatory networks that modulate flavor loss during cold storage for fruit. Methods: The volatile contents were detected by Gas Chromatography–Mass Spectrometer (GC–MS). Weighted gene co-expression network analysis (WGCNA) was used to identify structure genes and transcription factors (TFs). DNA methylation was analyzed by whole-genome methylation sequencing during cold storage. Results: We generated a temporal map, over hourly to weekly timescales, for the effects of chilling on flavor volatiles by combining metabolome, transcriptome, and DNA methylome in peach fruit. Based on the big data analysis, we developed a regulatory network for volatile formation and found that a decrease in volatiles during cold storage was significantly correlated with a decrease in the expression of synthesis genes. Moreover, TFs associated with these structure genes were identified. Expression of genes involved in ethylene biosynthesis was reduced while cold tolerance pathway was activated in response to low temperature. Functions of those genes were confirmed through transgenic experiments and across peach cultivars, suggesting our dataset is a useful tool for elucidating regulatory factors that have not yet been clarified in relation to flavor and cold tolerance. Genome wide DNA methylation was induced by chilling and peaked at 7 d followed by a decline during 28 d cold storage. Reduction of gene expression was accompanied by major changes in the methylation status of their promoters, including PpACS1, PpAAT1, PpTPS3 and PpMADS2. Conclusion: Our study revealed the mechanism for chilling-induced flavor loss of peach fruit through time-course transcriptome and DNA methylome analysis.