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Abstract Virtual aperture extension of small aperture array has attracted wide attention in high‐frequency surface wave radar (HFSWR). A biologically inspired coupled (BIC) system is employed to virtually extend the array aperture. However, the existing researches on BIC only consider the array signal processing model and do not combine it with actual radar signal principle. To indeed apply the BIC system to HFSWR, two detailed methods which combine the BIC and HFSWR at signal level are proposed. A three‐dimensional signal model of HFSWR considering array processing was established and the entire signal processing was derived. Then, two combination methods, namely fast‐time domain (FTD)‐BIC and slow‐time domain (STD)‐BIC are proposed. The former implements the BIC before fast‐time processing, while the latter implements the BIC before slow‐time processing. The authors demonstrate that they can virtually extend the array aperture without affecting the target detection. Meanwhile, their capabilities in multi‐target scenarios are analysed and satisfactory conclusions are obtained. By numerical simulations and experiments, the array aperture and range‐Doppler (RD) spectrum of the standard HFSWR and BIC‐HFSWR are compared. The results show that while the performance of their RD spectrum is almost the same, BIC‐HFSWR has an enlarged virtual aperture than standard HFSWR.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Amino acid metabolic remodeling is a hallmark of cancer, driving an increased nutritional demand for amino acids. Amino acids are pivotal for energetic regulation, biosynthetic support, and homeostatic maintenance to stimulate cancer progression. However, the role of phenylalanine in multiple myeloma (MM) remains unknown. Here, we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow (BM) cells. After the treatment, phenylalanine levels increase in plasma and decrease in BM. This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression. The requirement for phenylalanine by MM cells exhibits a similar pattern. Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib (BTZ) treatment in vitro and murine models. Mechanistically, phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3–CHOP–DR5 pathway. Interference with ATF3 significantly affects phenylalanine deprivation therapy. In conclusion, we have identified phenylalanine metabolism as a characteristic feature of MM metabolic remodeling. Phenylalanine is necessary for MM proliferation, and its aberrant demand highlights the importance of low-phenylalanine diets as an adjuvant treatment for MM.

Abstract Background Previous studies have demonstrated the role of N6-methyladenosine (m6A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry. Results The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m6A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis. Conclusions In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.

Summary: Hydroxycarboxylic acid receptor 3 (HCAR3), a class A G-protein-coupled receptor, is an important cellular energy metabolism sensor with a key role in the regulation of lipolysis in humans. HCAR3 is deeply involved in many physiological processes and serves as a valuable target for the treatment of metabolic diseases, tumors, and immune diseases. Here, we report four cryoelectron microscopy (cryo-EM) structures of human HCAR3-Gi1 complexes with or without agonists: the endogenous ligand 3-hydroxyoctanoic acid, the drug niacin, the highly subtype-specific agonist compound 5c (4-(n-propyl)amino-3-nitrobenzoic acid), and the apo form. Together with mutagenesis and functional analyses, we revealed the recognition mechanisms of HCAR3 for different agonists. In addition, the key residues that determine the ligand selectivity between HCAR2 and HCAR3 were also illuminated. Overall, these findings provide a structural basis for the ligand recognition, activation, and selectivity and G-protein coupling mechanisms of HCAR3, which contribute to the design of HCAR3-targeting drugs with high efficacy and selectivity.

Chemerin is an adipokine with chemotactic activity to a subset of leukocytes. Chemerin binds to 3 G protein-coupled receptors, including chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C chemokine receptor-like 2 (CCRL2). Here, we report that GPR1 is capable of Gi signaling when stimulated with full-length chemerin or its C-terminal nonapeptide (C9, YFPGQFAFS). We present high-resolution cryo-EM structures of Gi-coupled GPR1 bound to full-length chemerin and to the C9 peptide, respectively. C9 insertion into the transmembrane (TM) binding pocket is both necessary and sufficient for GPR1 signaling, whereas the full-length chemerin uses its bulky N-terminal core for interaction with a β-strand located at the N-terminus of GPR1. This interaction involves multiple β-strands of full-length chemerin, forming a β-sheet that serves as a "lid" for the TM binding pocket and is energetically expensive to remove as indicated by molecular dynamics simulations with free energy landscape analysis. Combining results from functional assays, our structural model explains why C9 is an activating peptide at GPR1 and how the full-length chemerin uses a "two-site" model for enhanced interaction with GPR1.

Abstract The High Average Utility Itemset Mining (HAUIM) technique, a variation of High Utility Itemset Mining (HUIM), uses the average utility of the itemsets. Historically, most HAUIM algorithms were designed for static databases. However, practical applications like market basket analysis and business decision-making necessitate regular updates of the database with new transactions. As a result, researchers have developed incremental HAUIM (iHAUIM) algorithms to identify HAUIs in a dynamically updated database. Contrary to conventional methods that begin from scratch, the iHAUIM algorithm facilitates incremental changes and outputs, thereby reducing the cost of discovery. This paper provides a comprehensive review of the state-of-the-art iHAUIM algorithms, analyzing their unique characteristics and advantages. First, we explain the concept of iHAUIM, providing formulas and real-world examples for a more in-depth understanding. Subsequently, we categorize and discuss the key technologies used by varying types of iHAUIM algorithms, encompassing Apriori-based, Tree-based, and Utility-list-based techniques. Moreover, we conduct a critical analysis of each mining method's advantages and disadvantages. In conclusion, we explore potential future directions, research opportunities, and various extensions of the iHAUIM algorithm.

Abstract Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894–0.4706, p

Globally, agriculture is experiencing sustainability challenges including excessive use of chemical fertilizers, pesticides, synthetic inputs, deforestation, loss of biodiversity, climate change, etc. In countries like China, farmers have experienced changes in the rainfall pattern and extreme heat and cold. Accordingly, agricultural sustainability policies support sustainable practices like integrated pest management, improved nutrient management, agroforestry systems, crop rotation, no tillage, conservation efforts, and the use of organic manure and fertilizer, as well as sustainable technologies, inputs, and innovations as a mitigation measure. However, there is little information available on farmers practices, and the concept of sustainable farming is dimly understood, resulting in divergent views among numerous stakeholders, particularly farmers, about what exactly defines sustainable agriculture. As a result, the necessity for sustainable agriculture is becoming a problem. The study therefore aims to measure smallholder farmers’ adherence to sustainable agricultural practices and assess the factors that influence farmers’ adherence to sustainable practices. Survey approach was adopted to collect data from 405 smallholder farmers using sustainable agricultural technologies to measure farmer’s adherence to the practices. Using multivariate probit analysis, the study discovered that whereas gender had no significant impact on farmers’ adherence, age had a substantial impact. Income had favourable correlation with the sustainable practices, but not significant with overall adherence. Remarkably, farmers’ commitment to adhere was encouraged by their neighbours’ activities, organic farming methods, and farmers who had engaged in organic farming. Farmers’ adherence was affected by farmers’ concern about facing penalties from market regulators or the government, but not for monitoring and regulation. Lastly, even though the smallholder farmers thought that implementing sustainable practices was essential to achieving sustainable agriculture, this did not alter their will to do so.

ABSTRACTTechnologies are essential for reducing environmental impact and increasing agricultural productivity. Previous adoption studies indicate several socioeconomic, technological, and institutional variables influencing the adoption of agricultural technologies. With less than a decade to the United Nation's sustainable development agenda for 2030, there are yet reports on farmers' resistance to sustainable agricultural technologies. Using a survey and multistage sampling procedure in selecting the respondents of 405 smallholder Chinese farmers, the study models farmers' adoption intensity of sustainable agricultural technologies and their impact on productivity. A 5-point Likert scale was used to analyse farmers' SAT perception levels. The PSM was used to eliminate a major proportion of bias when estimating a more precise treatment effect or impact of SAT adoption on productivity. The findings showed that farmers have mixed perceptions (positive and negative) about SAT adoption, which is reflected in their adoption decisions. The study found that family members as extension officers positively impacted farmers' adoption behaviour. On the contrary, regular visits by agricultural extension services had no impact on farmers' adoption behaviour, but positive on productivity. The results clearly showed elements of constraints in farmers' decision-making. The ATT results showed a significant and positive impact of SATs' adoption on productivity.

Histopathology image analysis plays a crucial role in cancer diagnosis. However, training a clinically applicable segmentation algorithm requires pathologists to engage in labor‐intensive labeling. In contrast, weakly supervised learning methods, which only require coarse‐grained labels at the image level, can significantly reduce the labeling efforts. Unfortunately, while these methods perform reasonably well in slide‐level prediction, their ability to locate cancerous regions, which is essential for many clinical applications, remains unsatisfactory. Previously, CAMEL is proposed, which achieves comparable results to those of fully supervised baselines in pixel‐level segmentation. However, CAMEL requires 1280 × 1280 image‐level binary annotations for positive WSIs. Here, CAMEL2 is presented, by introducing a threshold of the cancerous ratio for positive bags, it allows one to better utilize the information, consequently enabling us to scale up the image‐level setting from 1280 × 1280 to 5120 × 5120 while maintaining accuracy. The results with various datasets demonstrate that CAMEL2, with the help of 5120 × 5120 image‐level binary annotations, which are easy to annotate, achieves comparable performance to that of a fully supervised baseline in both instance‐ and slide‐level classifications.

Summary: CXCR4 binding of its endogenous agonist CXCL12 leads to diverse functions, including bone marrow retention of hematopoietic progenitors and cancer metastasis. However, the structure of the CXCL12-bound CXCR4 remains unresolved despite available structures of CXCR4 in complex with antagonists. Here, we present the cryoelectron microscopy (cryo-EM) structure of the CXCL12-CXCR4-Gi complex at an overall resolution of 2.65 Å. CXCL12 forms a 1:1 stoichiometry complex with CXCR4, following the two-site model. The first 8 amino acids of mature CXCL12 are crucial for CXCR4 activation by forming polar interactions with minor sub-pocket residues in the transmembrane binding pocket. The 3.2-Å distance between V3 of CXCL12 and the “toggle switch” W6.48 marks the deepest insertion among all chemokine-receptor pairs, leading to conformational changes of CXCR4 for G protein activation. These results, combined with functional assays and computational analysis, provide the structural basis for CXCR4 activation by CXCL12.

Summary: Succinate, a citric acid cycle intermediate, serves important functions in energy homeostasis and metabolic regulation. Extracellular succinate acts as a stress signal through succinate receptor (SUCNR1), a class A G protein-coupled receptor. Research on succinate signaling is hampered by the lack of high-resolution structures of the agonist-bound receptor. We present cryoelectron microscopy (cryo-EM) structures of SUCNR1-Gi complexes bound to succinate and its non-metabolite derivative cis-epoxysuccinate. Key determinants for the recognition of succinate in cis conformation include R2817.39 and Y832.64, while Y301.39 and R993.29 participate in the binding of both succinate and cis-epoxysuccinate. Extracellular loop 2, through F175ECL2 in its β-hairpin, forms a hydrogen bond with succinate and caps the binding pocket. At the receptor-Gi interface, agonist binding induces the rearrangement of a hydrophobic network on transmembrane (TM)5 and TM6, leading to TM signaling through TM3 and TM7. These findings extend our understanding of succinate recognition by SUCNR1, aiding the development of therapeutics for the succinate receptor.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Abstract With the rapid development of AI and big data mining technologies, computerized medical decision-making has become increasingly prominent. The aim of high-utility pattern mining (HUPM) is to discover meaningful patterns in medical databases that contribute to maximizing the utility from the perspective of diagnosis. However, HUPM pays less attention to the interpretability and explainability of these patterns in medical decision-making scenarios. This paper proposes a novel algorithm called the Improved fuzzy high-utility pattern mining (IF-HUPM) to address this problem. First, the paper applies a fuzzy preprocessing method to divide the fuzzy intervals of a medical quantitative data set, which enhances the fuzziness and interpretability of the data. Next, in the process of IF-HUPM, both fuzzy tree and list structures are employed to calculate fuzzy high-utility values. By combining the characteristics of the one-stage and two-stage algorithms of HUPM, an adaptive-phase Fuzzy HUPM hybrid frame is proposed. The experimental results demonstrate that the proposed IF-HUPM algorithm enhances both accuracy and efficiency and the mining process requires less time and space on average.

Abstract Objective To evaluate the effectiveness, safety, and convenience of in‐class transition (iCT) from intravenous bortezomib‐based induction to ixazomib‐based oral regimens. Methods This retrospective real‐world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first‐line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib‐based induction therapy, followed by an ixazomib‐based oral regimen for 2 year or until disease progression or intolerable toxicity. Results The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M‐FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib‐based treatment spanning 6 months. At the 20‐month median follow‐up, 53% of patients remained on therapy. The 24‐month PFS rate was 84.3% from the initiation of bortezomib‐based induction and 83.4% from the start of ixazomib‐based treatment. Overall response rate (ORR) was 100% post‐bortezomib induction and 90% following 6 cycles of the ixazomib‐based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. Conclusion In the real‐world Chinese MM population, NDMM and FRMM patients responded favorably to PI‐based continuous therapy, demonstrating substantial response rates. The ixazomib‐based iCT allows for sustained PI‐based treatment, offering promising efficacy and tolerable AEs.

Abstract Background Nonsecretory multiple myeloma (NSMM) is a rare type of multiple myeloma (MM). Few studies have described the clinical features and outcomes of NSMM in novel agents. Additionally, the prognostic characteristics have remained controversial in recent years. Purpose To investigate the clinical and prognostic features of NSMM and explore the prognostic value of involved free light chain (FLC) levels in NSMM patients in the Chinese population. Methods We retrospectively enrolled 176 newly diagnosed NSMM cases between January 2005 and December 2021 from 19 clinical centers in China. The control group was selected using a 1:4 propensity score matching technique of newly diagnosed secretory MM, with age, sex and diagnosis time as the matching variables. Results The median age of NSMM patients was 60 years, and 22.6% of patients were classified as ISS stage 3. The ORR of the NSMM patients was 87.4%, and the CR was 65.8%. Compared to the matched secretory MM patients, more NSMM patients achieved CR after first-line treatment (65.8% vs. 36%, p = 0.000). The ORR of first-line treatment was not significantly different between NSMM and secretory MM (89.45% vs. 84.7%, p = 0.196). The first-line PFS was 27.5 m and 23 m (p = 0.063), and the median OS was 81 m and 70 months (p = 0.401). However, for CR-achieved NSMM and CR-not-achieved NSMM patients, the median PFS was 37 m vs. 16 m (p = 0.021), while the median OS showed no difference (107 m vs. 87 m, p = 0.290). In multivariate analysis, the significant factors for PFS were age ≥ 65 and ISS-3. ISS-3 was the only independent prognostic factor of OS. The iFLC ≥ 50 mg/L group had a high ORR of 97.3%, and the median PFS and OS were 48 m and NR, respectively. Compared to the matched secretory MM, the iFLC ≥ 50 mg/L group also showed more CR and longer OS (NR vs. 70 m, p = 0.006) and PFS (48 m vs. 23 m, p = 0.003). Conclusions Our results revealed that Chinese NSMM patients are younger and have a higher CR but not superior survival. The subgroup of NSMM patients with iFLC ≥ 50 mg/L had better outcomes than secretory MM.

Abstract Crystal-field perturbation is theoretically the most direct and effective method of achieving highly efficient photoluminescence from trivalent lanthanide (Ln3+) ions through breaking the parity-forbidden nature of their 4f-transitions. However, exerting such crystal-field perturbation remains an arduous task even in well-developed Ln3+-doped luminescent nanocrystals (NCs). Herein, we report crystal-field perturbation through interstitial H+-doping in orthorhombic-phase NaMgF3:Ln3+ NCs and achieve a three-orders-of-magnitude emission amplification without a distinct lattice distortion. Mechanistic studies reveal that the interstitial H+ ions perturb the local charge density distribution, leading to anisotropic polarization of the F− ligand, which affects the highly symmetric Ln3+-substituted [MgF6]4− octahedral clusters. This effectively alleviates the parity-forbidden selective rule to enhance the 4f–4 f radiative transition rate of the Ln3+ emitter and is directly corroborated by the apparent shortening of the radiative recombination lifetime. The interstitially H+-doped NaMgF3:Yb/Er NCs are successfully used as bioimaging agents for real-time vascular imaging. These findings provide concrete evidence for crystal-field perturbation effects and promote the design of Ln3+-doped luminescent NCs with high brightness.

This study explores the effect of steel ball size and proportion on mineral grinding characteristics using Discrete Element Method (DEM) simulations. Based on batch grinding kinetics, this paper analyzes the contact behavior during grinding, discussing particle breakage conditions and critical breakage energy. The results indicate that while increasing the size of the steel balls leads to higher collision energy, the collision probability decreases significantly; the opposite is true for smaller steel balls. Simulation results with different ball size combinations show that increasing the proportion of smaller balls does not significantly change the collision energy but greatly increases the collision probability, providing a basis for optimizing ball size distribution to improve grinding performance. Furthermore, appropriately increasing the proportion of smaller balls can reduce fluctuations in grinding energy consumption, thereby enhancing collision energy and collision probability while reducing energy costs. Liner wear results demonstrate that larger ball sizes increase liner wear, but different ball size combinations can effectively distribute the forces on the liner, reducing wear.

Light is a key environmental factor regulating reproduction in avians. However, the mechanism of light intensity regulating ovarian development is still unclear. In this study, 5-week-old (5 wk) partridge broiler breeders were randomly divided into a low-light-intensity group (LL group) and a natural-light-intensity group (NL group) (n = 100). In the rearing period (5 wk to 22 wk), the light intensity of the LL group and NL group were 0.41 ± 0.05 lux and 45.39 ± 1.09 lux, and in the laying period (23 wk to 32 wk) they were 23.92 ± 0.06 lux and 66.93 ± 0.76 lux, respectively. Samples were collected on 22 wk and 32 wk. The results showed that the LL group had a later age at first egg and a longer laying period than the NL group. Serum P4 and LH levels in the LL group were higher than in the NL group on 22 wk (p < 0.05). On 32 wk, P4, E2, LH and FSH levels in the LL group were lower than in the NL group (p < 0.05). Ovarian transcriptomics and metabolomics identified 128 differentially expressed genes (DEGs) and 467 differential metabolites (DMs) on 22 wk; 155 DEGs and 531 DMs on 32 wk between two groups. An enrichment analysis of these DEGs and DMs identified key signaling pathways, including steroid hormone biosynthesis, neuroactive ligand-receptor interaction. In these pathways, genes such as CYP21A1, SSTR2, and NPY may regulate the synthesis of metabolites, including tryptamine, triglycerides, and phenylalanine. These genes and metabolites may play a dominant role in the light-intensity regulation of ovarian development and laying performance in broiler breeders.

Objective:. The size and morphology of the right ventricular outflow tract (RVOT) in patients suffering from long-term pulmonary regurgitation (PR) after native RVOT (NRVOT) reconstruction are important factors affecting the feasibility, safety, and effectiveness of transcatheter pulmonary valve replacement. The purpose of this study was to evaluate the feasibility, safety, and effectiveness of a transthoracic Salus valve (Balance Medical Technology Co., Ltd, Beijing, China) in patients with moderate-to-severe PR after NRVOT reconstruction. Methods:. Patients with moderate-to-severe PR after NRVOT reconstruction were selected between June 2021 and November 2021 at Beijing Anzhen Hospital. Demographic data as well as preoperative, intraoperative, and follow-up data were reviewed. Results:. Ten patients with moderate-to-severe PR after NRVOT reconstruction underwent physical examination, transthoracic echocardiography, and cardiovascular magnetic resonance imaging. Seven patients were selected for transthoracic Salus valve replacement. Six patients underwent implantation of the Salus valve successfully. One valve migrated and was embolized during recovery of the delivery device; the Salus valve was surgically explanted and sutured to the inner wall of the main pulmonary artery. At a mean follow-up of (5.5 ± 1.1) months, dysfunction or migration of the Salus valve embolism was not observed. Conclusions:. This early feasibility study demonstrates the feasibility, safety, and effectiveness of transthoracic implantation of a Salus valve in patients with moderate-to-severe PR after NRVOT reconstruction. The short-term effectiveness is clear, medium and long-term effectiveness requires longer follow-up.

Summary: The integration of stereoelectroencephalography with therapeutic deep brain stimulation (DBS) holds immense promise as a viable approach for precise treatment of refractory disorders, yet it has not been explored in the domain of headache or pain management. Here, we implanted 14 electrodes in a patient with refractory migraine and integrated clinical assessment and electrophysiological data to investigate personalized targets for refractory headache treatment. Using statistical analyses and cross-validated machine-learning models, we identified high-frequency oscillations in the right nucleus accumbens as a critical headache-related biomarker. Through a systematic bipolar stimulation approach and blinded sham-controlled survey, combined with real-time electrophysiological data, we successfully identified the left dorsal anterior cingulate cortex as the optimal target for the best potential treatment. In this pilot study, the concept of the herein-proposed data-driven approach to optimizing precise and personalized treatment strategies for DBS may create a new frontier in the field of refractory headache and even pain disorders.

Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction and plaque formation. Under pro-inflammatory conditions, endothelial cells can undergo endothelial-to-mesenchymal transition (EndMT), contributing to atherosclerosis development. However, the specific regulatory mechanisms by which EndMT contributes to atherosclerosis remain unclear and require further investigation. Dan-Shen-Yin (DSY), a traditional Chinese herbal formula, is commonly used for cardiovascular diseases, but its molecular mechanisms remain elusive. Emerging evidence indicates that competing endogenous RNA (ceRNA) networks play critical roles in atherosclerosis pathogenesis. In this study, we constructed an EndMT-associated ceRNA network during atherosclerosis progression by integrating gene expression profiles from the Gene Expression Omnibus (GEO) database and weighted gene co-expression network analysis. Functional enrichment analysis revealed this EndMT-related ceRNA network is predominantly involved in inflammatory responses. ROC curve analysis showed the identified hub genes can effectively distinguish between normal vasculature and atherosclerotic lesions. Furthermore, Kaplan-Meier analysis demonstrated that high expression of IL1B significantly predicts ischemic events in atherosclerosis. Molecular docking revealed most DSY bioactive components can bind key EndMT-related lncRNAs, including AC003092.1, MIR181A1HG, MIR155HG, WEE2-AS1, and MIR137HG, suggesting DSY may mitigate EndMT in atherosclerosis by modulating the ceRNA network.

Agriculture in China is undergoing a swift transformation to modify labour relocation. This change is spearheaded by commercial farms and other Chinese government interventions thereby promoting agricultural production and rural growth. The input-dependent industrial model of agriculture is also considered in conflict with attaining a safe and healthy environment for its inhabitants. The current approaches initiated in the tea sector have witnessed several enriched sustainable agricultural technologies (SATs). The SATs seek to increase yield while ensuring agricultural sustainability via ecological strategies. However, reports have shown farmers have low desire resulting in a lower acceptance rate of SATs among Chinese farmers. We provide a systematic review with a focus on the key determinants of SATs adoption rate in tea production in China from 2000 to 2022. The results revealed the significance and suitability of different approaches in establishing farmers’ adoption behaviour. The specificity of farmers’ SAT adoption behaviour is essentially not compromised by any codified variables but the interrelationship among the determinants, including socio-demographic, agroecological and environmental, technological, institutional, and social networks, and informational, and farmer behavioural factors. We recommend that the government increase awareness of SATs to promote public demand for agricultural sustainability, particularly in developing countries.

BackgroundTransformation of endometriosis to malignancy is a rare occurrence. Clear cell ovarian cancer and endometrioid ovarian cancer are the two histotypes most consistently linked to endometriosis. The exact pathways leading to malignant transformation of endometriosis remain elusive.Case presentationA 41-year-old woman presented to our hospital with a ten days history of abdominal pain which was not responsive to medication. Pathological examination revealed an unexpected finding of bilateral endometriosis associated with distinct malignancies: a clear cell carcinoma in the right ovary and a well-differentiated endometrioid carcinoma in the left ovary. Molecular analysis indicated a shared somatic driver mutation in ING1 in the eutopic endometrium and the bilateral ovaries while simultaneously exhibiting specific genetic alterations unique to each carcinoma. Notably, several common mutation sites were also identified, including previously reported common oncogenes (KRAS, PIK3CA, ARID1A). This finding prompts the hypothesis of a possible monoclonal origin of the two tumours.ConclusionThis case represents an exceedingly rare occurrence of two different histotypes of ovarian endometriosis-associated cancer manifesting simultaneously in bilateral ovaries. Based on genetic analysis, we hypothesize that these malignancies may have a monoclonal origin, providing insights into understanding the different biological mechanisms underlying carcinogenesis.

A detailed examination of the traffic in production data centers (DCs) suggests a new way to build optical network architectures (ONAs). As a result, recent efforts have pursued high-fan-out and cluster-based ONAs. A high-fan-out and flexible-cluster (HFFC) ONA for DCs is proposed in this article. The HFFC architecture is made up of an optical switch and a number of clusters, with the latter consisting of a number of top-of-rack (ToR) switches. Compared to a high-fan-out, scalable, and cluster-based optical interconnect (FSCOI), the HFFC architecture solves a congestion problem by removing the FSCOI's couplers and increasing the available bandwidth between clusters. By removing the couplers, the value of fan-out can be increased. In addition, one or several clusters can constitute a flexible cluster. The flexible cluster can be tailored for diverse intra-flexible-cluster traffic. The performance of the HFFC architecture is evaluated by simulation using synthetic traffic patterns. Compared to the FSCOI architecture, our approach has better performance in various traffic scenarios. In addition, the HFFC architecture has a flexible cluster capacity, making it more suited to large-scale intra-flexible-cluster traffic.

Abstract Background Cold inducible RNA-binding protein (CIRP) is a key protein in the hypothermic therapy. Highly expressed CIRP exerts a neuroprotective effect on neurons. The aim of this study is to provide the evidence of the protective effects of CIRP on the glial cells and explore the downstream pathway of CIRP. Results The results of this study demonstrated that the cell viability of the glial cells with CIRP overexpression was increased significantly compared to the control. With CIRP overexpression, the epidermal growth factor (EGF) mRNA expression was found increasing significantly and the mRNA expressions of derived neurotrophic factor (BDNF), bcl-2, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) were not upregulated compared to the control. EGF and CIRP co-expression was demonstrated on the glial cells. With CIRP expression, EGF expression on the glial cells was increased statistically compared to the control. Conclusion CIRP overexpression increases the cell viability of the glial cells, exerting a neuroprotective effect. EGF expression is activated on the glial cells with CIRP overexpression, implying a pathway of CIRP neuroprotection via EGF activation.

This study examines the optimal pricing and production strategy of a closed-loop supply chain consisting of a manufacturer, a recycler, and consumers. Considering the cannibalization and promotion effects of remanufactured products on new and secondhand products, we constructed Stackelberg game models under different scenarios. We analyze the impact of the changes in the two effects on the optimal prices and production strategies of the manufacturer and recycler, as well as their countermeasures. We find that (i) how the cannibalization and promotional effects influence the manufacturer and the recycler's pricing and production strategies differ under different scenarios; (ii) when the two effects exceed a threshold, the manufacturer abandons new or remanufactured products, and the recycler prefers to stop production on its new products or continue to remanufacture products; and (iii) the two effects always reduce the profits of the manufacturer and increase the profits of the recycler.

Abstract Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first “tumor agnostic” drugs approved for pan‐cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second‐generation drugs designed to overcome first‐generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and (DNA and/or RNA‐based) next‐generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first‐ and second‐generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

Abstract Skin metastasis of ovarian cancer is extremely rare. We report an unusual case of ovarian carcinosarcoma with cutaneous metastasis of carcinomatous component that displayed distinct clinical manifestation. A 48-year-old woman presented to the dermatologist complaining of a new onset of erythematous, plaque-like skin rash with multiple small nodules on the left inner thigh, the area measuring 8 × 5cm. While the patient had no history of dermatologic conditions, she underwent a total hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection 16 months ago with a pathology confirmed stage IIIC ovarian carcinosarcoma. Of note, the carcinomatous component, mainly adenocarcinoma with hybrid features of seromucinous, endometrioid and minor high-grade serous carcinoma, involved bilateral fallopian tubes, omentum, and parametrium with extensive lymph node metastases. A skin biopsy specimen revealed an adenocarcinoma involving epidermis, dermis, and subcutaneous tissue with nodular contours, consistent with metastatic carcinomatous component of carcinosarcoma. Both carcinomatous component of primary ovarian carcinosarcoma and metastatic adenocarcinoma in the skin demonstrated Pax8, WT-1, and ER positivity and a mutation pattern of p53. The patient passed away 15 months after identification of skin metastasis. This case represents a unique example of cutaneous metastasis of ovarian carcinosarcoma with distinct clinical manifestation and detailed histopathological description. Alertness to the possibility of cutaneous metastasis, in combination with clinical history, morphological and immunohistochemical findings, is critical for a definitive classification.

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, the authors report human papillomavirus features and genomic landscape in SCCC via high-throughput sequencing methods and identify MYC, SOX, NR4A, ANKRD and CEA family genes as HPV-integrated hotspots.

The organic movement have considered itself the growing drive for today’s consumers purchasing behaviour and growing attention from mainstream media. However, it has not fully received the attention to increase the organic tea industry to benefit humanity and natural ecosystems. The effect is that the future is uncertain as current challenges continue to pose threats to the industry. A systematic review was done to examine the overview of organic tea production challenges and prospects within the scope of sustainable farming. The findings showed that the unprecedented challenges are currently facing the global organic tea industry, which includes high competition for agricultural land, convention of organic lands for other purposes and urbanization activities in tea-growing countries. Biotic and abiotic stresses are major limits to agricultural production. Lack of knowledge on organic practices and high input costs affect the adoption of organic farming. However, the growth and new marketing trends in Asia-Pacific is an excellent sustainable indicator. Besides, stakeholders commitment is needed to implement and comply with applicable laws and supports to ensure industry development and sustainability. The current study is the first to have put together literatures on the global challenges and prospects of the organic tea industry within sustainable agriculture.

The demand for mealworms as food is expected to increase over the coming years globally due to the recent sector development; however, consumer acceptance could vary among countries, hence, identifying drivers towards insects as food could help to develop different strategies to increase consumer acceptance, based on the location. Thus, this study aimed to explore consumers’ motivations to accept or reject whole and processed mealworms (Tenebrio molitor) in Belgium, China, Italy, Mexico, and the US (N = 3006). To reach this aim, an online survey with two open-ended questions was performed and responses were categorized into semantic groups based on their meaning. We identified what motivates consumers among different acceptance levels (“Yes, because…”, “Yes, but…”, “Maybe if…”, “No, because…”), and cross-country differences were investigated using hierarchical cluster analysis. “Healthiness” was the most frequent driver to accept whole and processed mealworms, except in Italy. “Aversion” and “dislike” were the most important barriers that led to rejecting these products across all five countries. However, some country differences exist. For example, Italian consumers often reported different motivations to either accept or reject mealworms, e.g., by giving less importance to health-related aspects and by showing more aversion towards the insect compared to the other countries. Reported reasons to reject mealworms were common between the traditional and non-traditional insect-eating countries.

Ship detection has been an area of focus for high-frequency surface wave radar (HFSWR). The detection and identification of ship formation have proven significant in early warning, while studies on the formation identification are limited due to the complex background and low resolution of HFSWR. In this paper, we first establish a spatial distribution model of ship formation in HFSWR. Then, we propose a cascade identification algorithm of ship formation in the clutter edge. The proposed algorithm includes a preprocessing stage and a two-stage formation identification stage. The Faster R-CNN is introduced in the preprocessing stage to locate the clutter regions. In the first stage, we propose an extremum detector based on connected regions to extract suspicious regions. The suspicious regions contain ship formations, single-ship targets, and false targets. In the second stage, we design a network connected by a convolutional neural network (CNN) and an extreme learning machine (ELM) to identify two densely distributed ship formations from inhomogeneous clutter and single-ship targets. The experimental results based on the factual HFSWR background demonstrate that the proposed cascade identification algorithm is superior to the extremum detector combined with the classical CNN algorithm for ship formation identification. Meanwhile, the proposed algorithm performs well in weak formation and deformed formation identification.

The influenza BM2 transmembrane domain (BM2TM), an acid-activated proton channel, is an attractive antiviral target due to its essential roles during influenza virus replication, whereas no effective inhibitors have been reported for BM2. In this study, we draw inspiration from the properties of cyclodextrins (CDs) and hypothesize that CDs of appropriate sizes may possess the potential to act as inhibitors of the BM2TM proton channel. To explore this possibility, molecular dynamics simulations were employed to assess their inhibitory capabilities. Our findings reveal that CD4, CD5, and CD6 are capable of binding to the BM2TM proton channel, resulting in disrupted water networks and reduced hydrogen bond occupancy between H19 and the solvent within the BM2TM channel necessary for proton conduction. Notably, CD4 completely obstructs the BM2TM water channel. Based on these observations, we propose that CD4, CD5, and CD6 individually contribute to diminishing the proton transfer efficiency of the BM2 protein, and CD4 demonstrates promising potential as an inhibitor for the BM2 proton channel.

Investigating the dynamic evolution process of the ocean and ionosphere in sudden sea conditions poses a challenging problem. To address this objective, this study utilizes actual data from high-frequency surface wave radar (HFSWR) to analyze, validate, summarize, and characterize the echo properties of the ocean and ionosphere during the severe Typhoon Muifa. By employing the short-time Fourier transform (STFT) method, the HFSWR ocean and ionosphere echoes stimulated by typhoon-induced gravity waves are observed, and the joint gravity wave features of the ocean and ionosphere echoes at different time scales are extracted. Additionally, the phase-space reconstruction method is employed to characterize the dynamical evolution of the joint gravity wave features in higher-dimensional space. Furthermore, the chaotic dynamics behavior of the joint gravity wave features is analyzed using the largest Lyapunov exponents. By combining the gravity wave features with chaotic dynamics, this study introduces a method to characterize the joint gravity wave features. The extraction of joint gravity wave features in HFSWR echoes stimulated by typhoons, along with the construction of a chaotic characterization scheme for the gravity wave features, provides an innovative approach and a solid technical foundation for studying the ocean and ionosphere using HFSWR under sudden sea conditions.

This paper proposes a method for the intelligent detection of high-frequency surface wave radar (HFSWR) targets. This method cascades the adaptive constant false alarm (CFAR) detector variability index (VI) with the convolutional neural network (CNN) to form a cascade detector (VI)CFAR-CNN. First, the (VI)CFAR algorithm is used for the first-level detection of the range–Doppler (RD) spectrum; based on this result, the two-dimensional window slice data are extracted using the window with the position of the target on the RD spectrum as the center, and input into the CNN model to carry out further target and clutter identification. When the detection rate of the detector reaches a certain level and cannot be further improved due to the convergence of the CNN model, this paper uses a dual-detection maps fusion method to compensate for the loss of detection performance. First, the optimized parameters are used to perform the weighted fusion of the dual-detection maps, and then, the connected components in the fused detection map are further processed to achieve an independent (VI)CFAR to compensate for the (VI)CFAR-CNN detection results. Due to the difficulty in obtaining HFSWR data that include comprehensive and accurate target truth values, this paper adopts a method of embedding targets into the measured background to construct the RD spectrum dataset for HFSWR. At the same time, the proposed method is compared with various other methods to demonstrate its superiority. Additionally, a small amount of automatic identification system (AIS) and radar correlation data are used to verify the effectiveness and feasibility of this method on completely measured HFSWR data.

The problem of accurate source localization has been an area of focus in high-frequency surface wave radar (HFSWR) applications. However, antenna pattern distortion (APD) decreases the direction-of-arrival (DOA) estimation performance of the multiple signal classification (MUSIC) algorithm. Up to now, limited studies have been conducted on the calibration of antenna pattern distortion for phased arrays in HFSWR. In this paper, we first analyze the effect of APD on the performance of the MUSIC algorithm through estimation of accuracy and angular resolution. We demonstrate that using the actual pattern (or say APD) can improve DOA estimation performance. Based on this proposition, we propose a novel iterative calibration method that employs the first-order sea clutter data and can jointly estimate DOA and APD in an iterative way. To obtain available calibration points, we introduce the extraction methods of the first-order sea clutter spectrum and single-DOA spectrum points. Meanwhile, in each iteration, the Beamspace MUSIC algorithm and artificial hummingbird algorithm (AHA) are utilized to estimate the DOA and APD, respectively. Numerical results reveal a good coincidence between the actual pattern and the estimated APD. We also apply this method to process the experimental data of HFSWR. We obtain the APD vector of the real phased array and improve the direction-finding performance of several real ship targets using this vector. Both numerical and experimental results prove the correctness of our proposed calibration method.

Abstract Background The Sheng-ji Hua-yu (SJHY) formula is a quite effective Traditional Chinese Medicines (TCM) in the treatment of delayed diabetic wounds. Previous research has shown that the SJHY formula has significant anti-inflammatory and wound-healing effects, but the precise mechanism remains unknown. The purpose of this study was to evaluate the effects of rhein, a compound extracted from SJHY formula, in keratinocytes and to investigate the underlying mechanisms. Methods Microscale thermophoresis (MST) technology was used to confirm that rhein binds directly to oestrogen receptors (ERs). Rhein was then used to treat keratinocytes in vitro. Cell cycle and proliferation analysis, Real-time polymerase chain reaction (RT-PCR) and Western-blot were conducted. Results Rhein increased the proportion of cells in the S phase of the cell cycle and promoted keratinocyte proliferation. ICI 182,780, an ER inhibitor, was also used to treat keratinocytes. The expression of c-myc mRNA and protein induced by rhein was antagonized by ICI 182,780, indicating that this induction is ER dependent. Intervention with ICI 182,780 had no effect on the upregulation of FosB and JunD, indicating that activator protein 1 (AP-1) members (FosB and JunD) are involved in rhein-induced c-myc mRNA and protein expression but does not require the ER. Conclusion The present study found that rhein stimulates keratinocyte proliferation by activating the oestrogen signalling pathway via the oestrogen receptor, which induces the expression of c-myc in collaboration with FosB and JunD, thereby accelerating the process of re-epithelialization.

Nsun4-mediated m5C and Mettl3-mediated m6A are found to be required for Sox9-regulated chondrogenic differentiation, whereby Nsun4 and Mettl3 interact with each other and recruit Ythdf2 and eEF1a-1 to form a complex at the 3’UTR of Sox9.

As an important infrastructure of the national information system, the satellite internet is of great signifi cance to the national security.Thus, it needs to ensure the validity and reliability of the data transmission in the hostile jamming environment.The threat of smart jamming and the limitation of classical link-layer anti-jamming methods give rise to the new demand of intelligent and networked antijamming solutions.In view of the structural characteristics of the satellite internet and the development trend of modern communication jamming technologies, this paper analyzed the basic architecture of intelligent and networked anti-jamming.Based on the closed-loop strategic of sense-learn-prediction-decision-feedback, intelligent and active anti-jamming decision was made to realized self-confi guration and self-optimization.Based on the cooperative communication between nodes, networked anti-jamming ability was improved by the means of topology control and reconstruction, adjacent resources reallocation, and traffi c load balancing.It provided certain theoretical support for the construction of anti-jamming strategy system to achieved the cross-layer optimization, multi-domain combination, and adaptive intelligence.

In the current globalized business environment, multinational competition has become the norm for companies. This paper considers technology spillovers among manufacturers and develops a global supply chain network equilibrium model. Firstly, the optimal decision-making behaviors of manufacturers, retailers, and demand markets are characterized separately. Secondly, based on the variational inequality theory, the optimal decision-making behaviors of global supply chain members are transformed. Finally, the model is solved and analyzed using the Euler algorithm. The primary objective is to explore the impact of research and development (R&D) subsidies and intellectual property protection (IPP) strategies on manufacturers’ research and development technological levels. Furthermore, the study delves into their effects on the production and transactions of the global supply chain network and social welfare. The following conclusions are drawn: (1) Technology spillovers have a positive effect on the technological level achieved by manufacturers through research and development investment and social welfare. However, intense technological competition may harm manufacturers’ profits. (2) Under the symmetric subsidy policy, higher subsidies may lead to a decrease in social welfare. (3) Under symmetric intellectual property protection policies, increasing the intensity of intellectual property protection benefits manufacturers but is detrimental to retailers and social welfare. However, under an asymmetric intellectual property protection strategy, implementing high-intensity intellectual property protection by high-technology countries is advantageous for retailers and social welfare. This conclusion has contributed to the technical research and development and production operation decision making of global supply chain members, as well as government policy formulation, and has also provided a new perspective for theoretical research in the field of global supply networks.

The interest in edible insects as food is growing, both in traditional and non-traditional insect-eating countries given their advantages in terms of sustainability and nutritional content. However, only a few studies have conducted cross-country investigations on the acceptance of including processed or whole insects in the diet. Thus, this study aimed to examine to which extent consumers were accepting (i) whole and visible mealworms, (ii) processed mealworms in their diet and (iii) to explore the factors affecting the acceptance level of consuming mealworms in countries with and without entomophagy tradition. An online survey was applied to collect responses (3,006) from five countries-i.e., Belgium, China, Italy, Mexico, and the US-using a quota sampling method. Moreover, an information treatment was included with about half of the participants receiving information about the advantages of edible insects as food (ingredient) and the presence of food safety regulations. Across countries, gender was the main factor affecting acceptance level as men accepted mealworms more than women. Entomophagy tradition mainly explained the differences among countries. Countries with entomophagy traditions (Mexico and China) showed higher acceptance of including whole or processed mealworms in the diet compared to countries with no entomophagy traditions (i.e., Belgium, Italy, and the US). While information and age did affect differently the acceptance of including processed mealworms in countries with entomophagy traditions showing that consumer acceptance was affected by information in Mexico and by age in China. Whereas it was found that younger people (below 42 years old) in countries without entomophagy tradition were more open to accepting processed mealworms in their diet. Moreover, across countries, the acceptance of including processed mealworms was higher compared to whole mealworms. These findings provide insights into which consumer segments to target and the potential impact of information when introducing new insect-based foods in countries with and without entomophagy traditions.

Objective: This study aimed to identify the clinical significance of TP53 and common cytogenetic abnormalities. Materials and Methods: A total of 114 patients with newly diagnosed multiple myeloma (MM) and TP53 abnormalities were selected from two large patient cohorts of collaborating hospitals from 2010 to 2017. The characteristics and outcomes of these patients were analyzed. TP53 and other common mutations in MM patients were quantified by fluorescence in situ hybridization. Kaplan-Meier curves and logrank tests were applied for survival analysis. A Cox proportional hazard model for covariate analysis was used to determine the prognostic factors. Results: By extensive data analysis, we found that TP53 amplification is a strong positive predictor for complete response (CR) to therapy and positively correlated with patient survival. The number of simultaneous genomic abnormalities with TP53 mutation has a modest impact on patient survival. Among these mutations, 1q21 amplification is associated with decreased CR (odds ratio: 4.209) and FGFR3 levels are positively correlated with progression-free and overall survival. Conclusion: TP53 abnormalities at the diagnosis of MM are of great clinical significance in predicting patient response to therapy and survival. Furthermore, 1q21 and FGFR3 mutations could potentially be used in combination with TP53 status to better predict patient survival and guide the selection of high-risk patients to advance patient treatment strategies.

This paper reviews the primary scientific articles applicable to the logistics industry, and specifically those relating to cross-border e-commerce in China. The authors focused on reviewing the articles about the current status of cross-border e-commerce in China and the factors affecting its development, with the aim of highlighting literature gaps. The authors used a systematic literature review (SLR) to identify, gather, and analyze 60 primary papers selected from international peer-reviewed journals and international conference proceedings between 2001 and 2020. Chinese cross-border e-commerce has experienced a trend of steady progress, although several challenges remain. These challenges include, but are not limited to, low custom clearance efficiency, complex monitoring and supervision, tax rebate settlement challenges, payment risks, insufficient talent within the Chinese industry, and the lack of scientific management guidelines. The significant contributions of this paper include critical highlights of the current gaps and future research themes.

Abstract In sports data analysis and visualization, understanding collective tactical behavior has become an integral part. Interactive and automatic data analysis is instrumental in making use of growing amounts of compound information. In professional team sports, gathering and analyzing sportsperson monitoring data are common practice, intending to evaluate fatigue and succeeding adaptation responses, analyze performance potential, and reduce injury and illness risk. Data visualization technology born in the era of big data analytics provides a good foundation for further developing fitness tools based on artificial intelligence (AI). Hence, this study proposed a video-based effective visualization framework (VEVF) based on artificial intelligence and big data analytics. This study uses the machine learning method to categorize the sports video by extracting both the videos' temporal and spatial features. Our system is based on convolutional neural networks united with temporal pooling layers. The experimental outcomes demonstrate that the recommended VEVF model enhances the accuracy ratio of 98.7%, recall ratio of 94.5%, F1-score ratio of 97.9%, the precision ratio of 96.7%, the error rate of 29.1%, the performance ratio of 95.2%, an efficiency ratio of 96.1% compared to other existing models.

Termination of eukaryotic RNA polymerase III (Pol III)-mediated transcription occurs when the polymerase reaches a stretch of four or more deoxythymidine nucleotides (poly-dT) on the non-template strand. Here, the authors present the 3.6 Å cryo-EM structure of a human Pol III pre-termination complex (PTC) that was assembled on a 7 dT-containing DNA template and discuss the mechanism of poly-dT-dependent transcription termination of Pol III.

BackgroundTertiary lymphoid structures (TLSs) are crucial in promoting and maintaining positive anti-tumor immune responses. The tumor stroma has a powerful immunosuppressive function that could exclude tumor-infiltrating lymphocytes from the tumor beds and lead to a “cold” phenotype. TLSs and tumor stroma percentage (TSP) are significantly associated with the prognosis of patients with certain cancers. However, the exact roles of TLSs and TSP and their intrinsic relationship are still largely unknown in colorectal cancer (CRC).MethodsTLSs and TSP were assessed using hematoxylin-eosin (H&E) and/or immunohistochemistry (IHC) staining from 114 CRC patients in the training set and 60 CRC patients in the external validation set. The correlation between TILs, TLS and clinicopathological characteristics and their prognostic values were assessed. Finally, we plotted a Nomogram including the TLS, TSP and tumor-node-metastasis (TNM) stage to predict the probability of recurrence-free survival (RFS) at 2- and 5-years in non-metastatic colorectal cancer (nmCRC) patients.ResultsPeritumoral TLS (P-TLS), intratumoral TLS (In-TLS) and high TSP (H-TSP, >50%) were present in 99.1%, 26.3% and 41.2% patients, respectively. H-TSP tumor tends to be associated with lower P-TLS density (P =0.0205). The low P-TLS density (< 0.098/mm2) was significantly associated with reduced RFS (HR=6.597 95% CI: 2.882-15.103, P

Abstract Background Coarctation of the aorta (CoA) is a serious innate heart disease. Although surgery results are generally good, some complications such as recoarctation and aortic aneurysm or persistent hypertension were serious threats to patient’s health. To better understand the pathology of CoA and its underlying molecular mechanism is particularly important for early diagnosis and preventing the occurrence of its complications. However, the mechanisms of CoA remain unclear, especially for infants. Methods RNA sequencing (RNA-seq) was used to identify the differentially expressed genes (DEGs) in vascular tissues of 12 patients with CoA and 10 normal participants form 3- to 34-month-old infants. The characteristic of DEGs were validated by quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and immunochemical staining (IHC) in vessels of patients with CoA and normal infants. Results A total of 2491 DEGs with the false discovery rate less than 0.05(> 1.5-fold, P

Abstract Background The urea breath test (UBT) is widely used for diagnosing Helicobacter pylori infection. In the Shenzhen Kuichong People’s Hospital, some UBT findings were contradictory to the histology outcomes, therefore this study aimed to assess and compare the diagnostic performance of both 13C- and 14C-UBT assays. Methods We recruited 484 H. pylori-treatment naïve patients, among which 217 and 267 were tested by the 13C-UBT or 14C-UBT, respectively. The cutoff value for H. pylori positivity based on manufacturer’s instruction was 4% delta over baseline (DOB) for the 13C-UBT, and 100 disintegrations per minute (DPM) for the 14C-UBT. Gastric biopsies of the antrum and corpus were obtained during endoscopy for histopathology. Results In patients who were tested using the 13C-UBT kit, histopathology was positive in 136 out of 164 UBT-positive patients (82.9% concordance), and negative in 46 out of 53 UBT-negative cases (86.8% concordance). For the 14C-UBT-tested patients, histopathology was positive for H. pylori in 186 out of 220 UBT-positive patients (84.5% concordance), and negative in 41 out of 47 UBT-negative cases (87.2% concordance). While the 13C-UBT and 14C-UBT each had a high sensitivity level of 95.1% and 96.9%, respectively, their specificity was low, at 62.2% and 54.7%, respectively. By using new optimal cutoff values and including an indeterminate range (3–10.3% DOB for 13C-UBT and 87–237 DPM for 14C-UBT), the specificity values can be improved to 76.7% and 76.9% for the 13C- and 14C-UBT, respectively. Conclusions The establishment of an indeterminate range is recommended to allow for repeated testing to confirm H. pylori infection, and thereby avoiding unnecessary antibiotic treatment. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000041570. Registered 29 December 2020- Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=66416&htm=4