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The similarity matching between the template and the search area plays a key role in Siamese-based trackers. Most Siamese-based trackers adopt correlation operation to perform feature fusion on the template branch and search branch for similarity matching. However, the correlation operation directly uses the template feature to slide the window on the search area feature without distinguishing the discriminant part of the target and the background noise, which blurs the spatial information of the response feature. To address this issue, this work proposes a novel object semantic-guided graph attention feature fusion network that both removes background information and focuses on the discriminative part of the object. The proposed network effectively removes background noise by utilizing an adaptive template instead of the fixed-size template used by the correlation operation. The network also models the contextual semantic relations of the target and uses the resulting semantic relations to guide the feature fusion process in a part-based manner, thereby accurately highlighting the discriminative parts of the target. Therefore, the problem of blurring response feature caused by correlation operation is effectively resolved. Furthermore, we propose an object-aware prediction network to learn object-aware features for classification and regression task, which effectively improves the discriminative ability of the prediction network. Experiments on many challenging benchmarks like OTB-100, LaSOT, TColor-128, GOT-10k and VOT2019, show that our methods achieves excellent performance. [ABSTRACT FROM AUTHOR]

The multi-pass caliber rolling was applied to in-situ AlN/AZ91 composite rods, and the yield strength of 295.3 MPa, ultimate tensile strength of 384.7 MPa, fracture elongation of 12.3% and a good surface morphology were obtained under the reduction ratio of 78%. The results showed that the grains of the caliber rolled AlN/AZ91 composite rods were remarkably refined due to the occurrence of dynamic recrystallization (DRX), while the in-situ AlN reinforcements induced the nucleation of { 10 1 ‾ 2 } extension twins, and preferentially promoted the formation of extension twin-induced DRX before discontinuous DRX. Especially, twinning-induced DRX weakened the texture more effectively compared with discontinuous DRX. In addition, it was also found that the increased yield strength was mainly attributed to solid solution atoms, twinning-induced DRX, discontinuous DRX, high density dislocations and nano-sized γ-Mg 17 Al 12 precipitates in the in-situ AlN/AZ91 composite rods, while the high ductility was mainly ascribed to grain size refinement, weakened texture and the activation of non-basal slip systems at room temperature. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel red-emitting two-photon fluorescent probe P1 for detecting NTRs was designed. • P1 has high selectivity, sensitivity and photostability towards NTRs. • P1 has achieved in detecting NTRs in cancer cells and tumor tissues with two-photon manner under hypoxia conditions. Nitroreductases (NTRs) are overexpressed in many cancer cells especially in hypoxia conditions. They have been acted as an essential diagnosis and treatment targets for cancers. In order to detecting NTRs with high signal to background ratios using two-photon manner, it is necessary to explore effective two-photon fluorescent probes with long emission wavelengths. Here, we designed a novel red-emitting two-photon fluorescent probe P1 for tracing NTRs. P1 was constructed based on a two-photon fluorogen P1-OH with red-emission and a NTRs recognition site p -nitrobenzene. In the presence of NTRs, P1 showed strong fluorescence emission at 647 nm. P1 had high selectivity and sensitivity with NTRs (LOD is 0.00245 U/L). Importantly, two-photon action cross section experiments showed that P1 had favorable two-photon property encountering with NTRs and NADH. Furthermore, under hypoxia conditions, P1 has succeeded in imaging NTRs in cancer cells under one- and two-photon manners with hypoxia manner. Besides, by means of three-dimensional high-resolution manner, tumor tissues imaging has been achieved using P1 with two-photon manner. Probe P1 with red-emitting two-photon property may a potential molecular tool for detecting NTRs in living biological systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • An easily-dispersed SiO 2 microspheres/MWCNTs hybrid filler was invented. • Multifunctional NR/MWCNTs nanocomposites with segregated structure was prepared. • Bionic interface of NR/MWCNTs nanocomposites was constructed by natural tannic acid. Due to the intricate entanglement and strong π-π stacking interaction, carbon nanotubes are hard to be dispersed uniformly in polymer matrix, thereof it is difficult to produce high-performance and multifunctional polymer/multiwalled carbon nanotubes (MWCNTs) nanocomposites with low filler contents by traditional polymer processing technologies. Herein, the interspersed SiO 2 microspheres (m -SiO 2)/MWCNTs hybrid fillers (ISMH), which are not only dispersed easily in rubber matrix via mechanical blending but also have a biomimetic interface with the rubber matrix via natural tannic acid (TA), have been developed successfully. Benefiting from the volume exclusion of m -SiO 2 , a small amount of MWCNTs can form a dense three-dimensional (3D) network in natural rubber (NR) matrix, endowing NR/ISMH nanocomposites with high functionalities. When MWCNTs loading is 0.33 phr, the electrical conductivity of NR/ISMH nanocomposite can reach the equilibrium value ~10-4 S·cm−1. When MWCNTs loading is 1.67 phr, the thermal conductivity and compression temperature rise of NR/ISMH nanocomposite is ~0.32 W·m−1·K−1 and 9.3 °C, respectively, corresponding to an improvement of +22% and −28% relative to the neat NR matrix. Additionally, thanks to the biomimetic interface constructed by covalent and non-covalent bonds via TA, the NR/ISMH nanocomposites also have exhibited excellent mechanical properties. When the ISMH-30 loading (mass ratio of m -SiO 2 : MWCNTs = 30: 1) is 20 phr, the comprehensive mechanical properties of NR/ISMH nanocomposite reach the best. The tensile strength, tear strength, elongation at break and DIN wear volume are 28.7 MPa, 43.7 MPa, 625% and 0.18 cm3, corresponding to an improvement of +58%, +16%, +11% and −31% relative to the neat NR matrix, respectively. In a word, the as-fabricated NR/ISMH nanocomposites have the advantages of low cost, high performance and versatile functions, endowing them with great potential applications in antistatic rubber products, vibration-isolated rubber products, and green tires, etc. [ABSTRACT FROM AUTHOR]

As flammable natural rubber (NR) becomes more ubiquitous in industrial fields, there is a growing need for safe and effective flame retardant treatments through efficient techniques. Remarkably, our developed highly efficient natural tannic acid (TA)-based intumescent flame-retardant system (AGT) has the unique function in the rubber flame retardant aspect. Meanwhile, the developed coating method through polyurethane elastomer (PU) both as adhesive medium and a carbonforming agent can not only minimize the influence of flame retardant on the desirable intrinsic properties of base polymer and also maximize the efficiency of flame retardant. The flame-retardant coating (AGT/PU) exhibits highly efficient flame retardant performances reflected by a 31.9% reduction in peak heat release rate and a 27.3% reduction in total heat release and a 26.2% reduction in total smoke production with 50 wt% loading in 1 mm thick coating due to synergistic flame retardant effects. More importantly, the excellent flame retardancy performance are obtained by the PU@AGT10, as reflected in flame retardancy index (FRI) value of 11.88 makes it as excellent flame retardancy performance. While many physically mixed flame retardants are usually seriously detrimental to mechanical properties of NR, the influence of AGT/PU coating on mechanical properties of NR decreases obviously because fire retardant just directly impacts on PU adhesive layer rather than NR matrix, and the reinforcement function of graphene is also much significant. Moreover, the coating method requires just less flame retardant to achieve high flame retardant effect for NR. These findings suggest that significant opportunities for flame retardant polymer materials in industry. We develop an highly efficient polyurethane elastomer-based intumescent fire-retardant and smoke suppression protective coating method. Specially, while many physically mixed methods are usually seriously detrimental to mechanical properties of rubber, the influence of coating method on mechanical properties decreases obviously because fire retardant just directly impact on PU adhesive layer rather than rubber matrix, moreover, the coating method requires less flame retardant to achieve high flame retardant effect. Image 1 • An efficient elastomer-based intumescent fire-retardant and smoke suppression protective coating method is studied. • The developed intumescent flame-retardant exhibits highly efficient flame retardant performances for NR. • The influence of coating method on mechanical properties of NR decreases obviously. [ABSTRACT FROM AUTHOR]

Air-to-ground (A2G) communication has been attracted great attention due to the gradual popularization of unmanned aerial vehicle (UAV). In this paper, a 3D geometry-based stochastic model (GBSM) for A2G channels is proposed. Meanwhile, the Gauss-Markov mobile model is adopted to generate dynamic trajectories. According to different scattering environments, we establish a reference model and a statistical simulation model for A2G channels, and derive their respective time correlation functions. In particular, the purpose of establishing the statistical simulation model is to reduce complexity, and we verify the consistency of the two models. Then, we analyze the dynamic motion scenarios generated by Gauss-Markov process, and their effects on A2G channel correlation. Finally, the good conformities of time correlation curves with the existing measurement data and sphere model verify the reliability of our proposed models. [ABSTRACT FROM AUTHOR]

In this study, a stochastic model is used to reconstruct the uncompressed gas diffusion layer (GDL) microstructures. Subsequently, the finite element method (FEM) is conducted for assembly pressure simulation to generate the compressed GDL microstructures. The effects of assembly pressure on GDL deformation are investigated. It is found that assembly pressure causes non-uniform deformation of the GDL along the thickness direction. Finally, a volume of fluid (VOF) model is developed to investigate two-phase flow in the compressed GDL. The results show that when the capillary pressure is higher than 4 kPa, the water saturation decreases as the compression ratio increases. But when the capillary pressure is below 3 kPa, compression has little effect on water saturation. Based on the above findings, three regions namely weak deformation region (WDR), moderate deformation region (MDR), and strong deformation region (SDR) are defined. Impacts of compression on water saturation differ in these three regions. Moreover, compression increases the pressure of water breakthrough, but has minor effects on preferential pathways of water breakthrough. Quantitative correlations between water saturation and capillary pressure in the uncompressed and compressed GDL microstructures are also concluded. • Microstructures of compressed GDL are digitally reconstructed. • Pore-scale two-phase flow in compressed GDL is investigated using VOF model. • Effects of compression on water transport in GDL are discussed. • Quantitative correlations between P c and s are concluded. [ABSTRACT FROM AUTHOR]

Mitochondrial sulfur dioxide (SO 2 ) plays important roles in physiological and pathological activities. Unfortunately, it is lack of a reliable tool to precisely visualize the mitochondrial SO 2 and elaborate its complicated functions in various cytoactivities. Here we report a mitochondrial-immobilized fluorescent probe PM-Cl consisting of coumarin and benzyl chloride modified benzothiazole, which enables selective visualization of mitochondrial SO 2 via chemical immobilization. The spectral results demonstrated that probe PM-Cl could respond to SO 2 with high selectivity and sensitivity. Co-localization and the fluorescence of cytolysis extraction verified the excellent mitochondrial targeting and anchoring abilities. Due to the chemical immobilization, probe PM-Cl could firmly retain into mitochondria after stimulation of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and H 2 O 2 . Significantly, a series of fluorescence images are indicative of capability for detecting the fluctuations of SO 2 in mitochondria during ferroptosis. Furthermore, PM-Cl also could visualize SO 2 in myocardium and muscle tissues after the stimulation of CCCP. Taken together, probe PM-Cl is a very potential molecular tool for precisely detecting mitochondrial SO 2 to explore its complex functions in physiological and pathological activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel Lindau (VHL) gene loss of function mutation, which leads to the accumulation of hypoxia-inducible factor 2α (HIF2α). HIF2α has been well-established as one of the major oncogenic drivers of ccRCC, however, its therapeutic targeting remains a challenge. Through an analysis of proteomic data from ccRCCs and adjacent non-tumor tissues, we herein revealed that Ubiquitin-Specific Peptidase 7 (USP7) was upregulated in tumor tissues, and its depletion by inhibitors or shRNAs caused significant suppression of tumor progression in vitro and in vivo. Mechanistically, USP7 expression is activated by the transcription factors FUBP1 and FUBP3, and it promotes tumor progression mainly by deubiquitinating and stabilizing HIF2α. Moreover, the combination of USP7 inhibitors and afatinib (an ERBB family inhibitor) coordinately induce cell death and tumor suppression. In mechanism, afatinib indirectly inhibits USP7 transcription and accelerates the degradation of HIF2α protein, and the combination of them caused a more profound suppression of HIF2α abundance. These findings reveal a FUBPs-USP7-HIF2α regulatory axis that underlies the progression of ccRCC and provides a rationale for therapeutic targeting of oncogenic HIF2α via combinational treatment of USP7 inhibitor and afatinib., (© 2024. The Author(s).)

Sirtuin 6 (SIRT6), a member of the SIRT family, plays essential roles in the regulation of metabolism, inflammation, aging, DNA repair, and cancer development, making it a promising anticancer drug target. Herein, we present our use of proteolysis-targeting chimera (PROTAC) technology to formulate a series of highly potent and selective SIRT6 degraders. One of the degraders, SZU-B6 , induced the near-complete degradation of SIRT6 in both SK-HEP-1 and Huh-7 cell lines and more potently inhibited hepatocellular carcinoma (HCC) cell proliferation than the parental inhibitors. In preliminary mechanistic studies, SZU-B6 hampered DNA damage repair, promoting the cellular radiosensitization of cancer cells. Our SIRT6 degrader SZU-B6 displayed promising antitumor activity, particularly when combined with the well-known kinase inhibitor sorafenib or irradiation in an SK-HEP-1 xenograft mouse model. Our results suggest that these PROTACs might constitute a potent therapeutic strategy for HCC.

Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, with a high rate of disability and mortality. Due to the complicated pathological process of SCI, there is no effective clinical treatment strategy at present. Although mesenchymal stem cells (MSCs) are effective in the treatment of SCI, their application is limited by factors such as low survival rate, cell dedifferentiation, tumorigenesis, blood-brain barrier, and immune rejection. Fortunately, there is growing evidence that most of the biological and therapeutic effects of MSCs may be mediated by the release of paracrine factors, which are extracellular vesicles called exosomes. Exosomes are small endosomal vesicles with bilaminar membranes that have recently been recognized as key mediators for communication between cells and tissues through the transfer of proteins, lipids, nucleic acids, cytokines, and growth factors. Mesenchymal stem cell-derived exosomes (MSC-exos) play a critical role in SCI repair by promoting angiogenesis and axonal growth, regulating inflammation and immune response, inhibiting apoptosis, and maintaining the integrity of the blood-spinal cord barrier. Furthermore, they can be used to transport genetic material or drugs to target cells, and their relatively small size allows them to permeate the blood-brain barrier. Studies have demonstrated that some exosomal miRNAs derived from MSCs play a significant role in the treatment of SCI. In this review, we summarize recent research advances in MSC-exos and exosomal miRNAs in SCI therapy to better understand this emerging cell-free therapeutic strategy and discuss the advantages and challenges of MSC-exos in future clinical applications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Viscosity and hypoxia, as microenvironment parameters, play important roles in maintaining normal biological processes and homeostasis. Therefore, simultaneous and sensitive detection of these elements with simple and effective methods could offer precise information in biology. Here, we report a two-site lysosome-targeting fluorescent probe, NVP, for monitoring viscosity and nitroreductase with dual emission channels (emission shift is 86 nm). The NVP probe has displayed highly sensitive and selective responses towards viscosity and nitroreductase, respectively. Significantly, the fluctuations of viscosity and NTR have been detected in vitro and in vivo . We expect that the dual-responsive fluorescent NVP probe will become a potential molecular tool for the exploration of deeper functions of viscosity and hypoxia.

Undergraduate medical education in China has shifted from educator-centered learning to self-directed learning (SDL) over the past few decades. Careful design of public engagement activities can enable SDL and empower medical students to pioneer public health and patient safety education. In this study, we aimed to innovate nervous system education by implementing a public engagement model that empowers students to learn about the nervous system by teaching the public. Our goal was to generate greater interest in the nervous system at the undergraduate stage, inspire students' enthusiasm to pursue a career in neurology, and ultimately, contribute to health promotion. During the nervous system module of the second year of the undergraduate curriculum, students were given the option to participate in the public engagement model. Participants were tasked with the creation of educational videos focusing on knowledge, attitudes, and behaviors associated with the prevention and management of neurological diseases and their complications. The videos were made accessible to the general public through the university's official channel at the end of the semester. A total of 117 students (67.24% of all students) chose to participate in the public engagement model. Female students and those with higher Grade Point Averages in the present semester were more likely to participate. The model received strong positive feedback from participants, as students found the public engagement task helpful in learning about the nervous system module as well as in enhancing their public engagement skills. Despite the time and effort consumption, participating in the public engagement task did not affect students' exam scores. The public engagement task is an innovative model in the nervous system curriculum and has the potential to be integrated into a broader range of undergraduate courses. It empowers medical students to pioneer public health and patient safety education.

Aberrant expression of gene is driven by its promoter methylation and is the key molecular basis of carcinogenic processes. This study aimed at identifying a risk signature of methylation-driven (MD) genes and evaluating its prognostic value for colon cancer (CC) patients. The expression profiles of methylation and mRNA in CC samples were obtained from the TCGA database, and the MethylMix algorithm was used to identify MD genes. The relationships between their expression levels and overall survival (OS) of CC patients were analyzed, and a prognostic signature of MD genes was established. The risk score of gene signature was calculated, and the median was used to divide all patients into high (H) and low (L) risk groups. The prognostic value of gene signature was tested by the TCGA cohort and an independent validation cohort (GSE17538 dataset). In total, 69 MD genes were identified, and 7 were associated with OS of CC patients. Ultimately, 4 (TWIST1, LDOC1, EPHX3, and STC2) were screened out to establish a risk signature. The H-risk patients (>0.923) had a worse OS than L-risk patients (≤0.923) in both the TCGA (5-year cumulative survival: 52.9% vs 72.0%, P=0.005) and GSE17538 cohort (49.4% vs 69.3%, P=0.004). The AUC values of MD genes signature for the prediction of 3- and 5-year OS were 0.648 and 0.643 in the TCGA dataset and 0.634 and 0.624 in the GSE17538 dataset, respectively. The risk signature of four MD genes was identified as an independent predictor of OS for CC patients (HR for TCGA dataset: 2.071, 95% CI=1.196-3.586, P=0.009; HR for GSE17538 dataset: 2.021, 95% CI=1.290-3.166, P=0.002). The risk signature of four MD genes might be a useful prognostic tool and help doctors improve the clinical management of CC patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Triple-negative breast cancer (TNBC) cells are often resistant to FAS (CD95)-mediated apoptosis, but the underlying molecular mechanism(s) is not fully understood yet. Notably, the expression of the type II transmembrane protein, CD74, is correlated with chemotherapy-resistant and more invasive forms of cancers via unknown mechanisms. Here, we analyzed gene expression pattern of cancer patients and/or patient-derived xenograft (PDX) models and found that mRNA and protein levels of CD74 are highly expressed in TNBC and correlated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) properties. Mechanistically, we found that AKT activation is likely critical for maintaining CD74 expression and protein stability to favor its oncogenic functions. Physiologically, epidermal growth factor (EGF) along with CD74 could activate AKT signaling, likely through binding of phosphorylated AKT (S473) to CD74, whereas inhibition of AKT could impair stability of CD74. We also revealed that CD74 binds to FAS and interferes with the intrinsic signaling of FAS-mediated apoptosis. As such, selective targeting of the CD74/FAS complex using the AKT inhibitor along with the CD74-derived peptide could synergistically restore and activate FAS-mediated apoptosis. Therefore, our approach of mobilizing apoptosis pathways likely provides a rationale for TNBC treatment by targeting the CD74/FAS and CD74-AKT axes.

Glioblastoma multiform (GBM) is categorized as the most malignant subtype of gliomas, which comprise nearly 75% of malignant brain tumors in adults. Increasing evidence suggests that network pharmacology will be a novel method for identifying the systemic mechanism of therapeutic compounds in diseases like cancer. The present study aimed to use a network pharmacology approach to establish the predictive targets of sciadopitysin against GBM and elucidate its biological mechanisms. Firstly, targets of sciadopitysin were obtained from the SwissTargetPrediction database, and genes associated with the pathogenesis of GBM were identified from the DiGeNET database. Sixty-four correlative hits were identified as anti-glioblastoma targets of sciadopitysin. Functional enrichment and pathway analysis revealed significant biological mechanisms of the targets. Interaction of protein network and cluster analysis using STRING resulted in two crucial interacting hub genes, namely, HSP90 and AKT1. Additionally, the in vitro cytotoxic potential of sciadopitysin was assessed on GBM U87 cells. The findings indicate that the pharmacological action of sciadopitysin against GBM might be associated with the regulation of two core targets: HSP90 and AKT1. Thus, the network pharmacology undertaken in the current study established the core active targets of sciadopitysin, which may be extensively applied with further validations for treatment in GBM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

To analyze the expression profile of fatty acid metabolism (FAM)-related genes, identify a prognostic signature, and evaluate its clinical value for gastric cancer (GC) patients. The mRNA expression profiles of 493 FAM-related genes were obtained from TCGA database. Differentially expressed genes (DEGs) between cancer and non-cancer samples were identified, and their relationships with overall survival (OS) of GC patients were evaluated. A prognostic signature of FAM-related genes was identified by the LASSO regression model, and its predictive performance was tested by an independent external cohort. Ninety-three DEGs were identified, of which 44 were downregulated and 49 were upregulated. After optimizing risk characteristics, a prognostic signature of four FAM-related genes (ACBD5, AVPR1A, ELOVL4, and FAAH) were developed. All patients were divided into high-risk (>1.020) and low-risk groups (≤1.020) on the basis of the median risk score. Survival analysis indicated that high-risk patients had a shorter OS than low-risk patients (5-year OS rate, 26.3% vs. 45.0%, p < 0.001). The AUC values for the prediction of 3-year and 5-year OS were 0.664 and 0.624, respectively. In the GSE62254 data set, the 5-year OS rate of high-risk and low-risk patients were 44.7% versus 61.5%, respectively (p = 0.003). The AUC values were 0.632 and 0.627 at 3-year and 5-year prediction. The prognostic signature of FAM-related genes was an independent predictor of OS (hanzard ratio [HR] for TCGA cohort: 1.851, 95% confidence interval [CI]: 1.394-2.458, p < 0.001; HR for GSE62254: 1.549, 95% CI: 1.098-2.185, p = 0.013). The risk signature of four FAM-related genes was a valuable prognostic tool, and it might be helpful for clinical management and therapeutic decision of gastric cancer patients., (© 2024 Wiley Periodicals LLC.)

Objective: The purpose of this study was to explore the appropriate surgical procedure and clinical decision for appendiceal adenocarcinoma., Methods: A total of 1,984 appendiceal adenocarcinoma patients from 2004 to 2015 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were divided into three groups based on the extent of surgical resection: appendectomy (N = 335), partial colectomy (N = 390) and right hemicolectomy (N = 1,259). The clinicopathological features and survival outcomes of three groups were compared, and independent prognostic factors were assessed., Results: The 5-year OS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 58.3%, 65.5% and 69.1%, respectively (right hemicolectomy vs appendectomy, P < 0.001; right hemicolectomy vs partial colectomy, P = 0.285; partial colectomy vs appendectomy, P = 0.045). The 5-year CSS rates of patients who underwent appendectomy, partial colectomy and right hemicolectomy were 73.2%, 77.0% and 78.7%, respectively (right hemicolectomy vs appendectomy, P = 0.046; right hemicolectomy vs partial colectomy, P = 0.545; partial colectomy vs appendectomy, P = 0.246). The subgroup analysis based on the pathological TNM stage indicated that there was no survival difference amongst three surgical procedures for stage I patients (5-year CSS rate: 90.8%, 93.9% and 98.1%, respectively). The prognosis of patients who underwent an appendectomy was poorer than that of those who underwent partial colectomy (5-year OS rate: 53.5% vs 67.1%, P = 0.005; 5-year CSS rate: 65.2% vs 78.7%, P = 0.003) or right hemicolectomy (5-year OS rate: 74.2% vs 53.23%, P < 0.001; 5-year CSS rate: 65.2% vs 82.5%, P < 0.001) for stage II disease. Right hemicolectomy did not show a survival advantage over partial colectomy for stage II (5-year CSS, P = 0.255) and stage III (5-year CSS, P = 0.846) appendiceal adenocarcinoma., Conclusions: Right hemicolectomy may not always be necessary for appendiceal adenocarcinoma patients. An appendectomy could be sufficient for therapeutic effect of stage I patients, but limited for stage II patients. Right hemicolectomy was not superior to partial colectomy for advanced stage patients, suggesting omission of standard hemicolectomy might be feasible. However, adequate lymphadenectomy should be strongly recommended., (© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Response: Pixels with location affinity, which can be also called "pixels of affinity," have similar semantic information. Group convolution and dilated convolution can utilize them to improve the capability of the model. However, for group convolution, it does not utilize pixels of affinity between layers. For dilated convolution, after multiple convolutions with the same dilated rate, the pixels utilized within each layer do not possess location affinity with each other. To solve the problem of group convolution, our proposed quaternion group convolution uses the quaternion convolution, which promotes the communication between to promote utilizing pixels of affinity between channels. In quaternion group convolution, the feature layers are divided into 4 layers per group, ensuring the quaternion convolution can be performed. To solve the problem of dilated convolution, we propose the quaternion sawtooth wave-like dilated convolutions module (QS module). QS module utilizes quaternion convolution with sawtooth wave-like dilated rates to effectively leverage the pixels that share the location affinity both between and within layers. This allows for an expanded receptive field, ultimately enhancing the performance of the model. In particular, we perform our quaternion group convolution in QS module to design the quaternion group dilated neutral network (QGD-Net). Extensive experiments on Dermoscopic Lesion Segmentation based on ISIC 2016 and ISIC 2017 indicate that our method has significantly reduced the model parameters and highly promoted the precision of the model in Dermoscopic Lesion Segmentation. And our method also shows generalizability in retinal vessel segmentation.

Introduction: The Metagenomics next-generation sequencing (mNGS) and GeneXpert MTB/RIF assay (Xpert) exhibited a sensitivity for tuberculosis (TB) diagnostic performance. Research that directly compared the clinical performance of ddPCR analysis, mNGS, and Xpert in mycobacterium tuberculosis complex (MTB) infection has not been conducted., Methods: The study aimed to evaluate the diagnostic performance of ddPCR compared to mNGS and Xpert for the detection of MTB in multiple types of clinical samples. The final clinical diagnosis was used as the reference standard., Results: Out of 236 patients with suspected active TB infection, 217 underwent synchronous testing for tuberculosis using ddPCR, Xpert, and mNGS on direct clinical samples. During follow-up, 100 out of 217 participants were diagnosed with MTB infection. Compared to the clinical final diagnosis, ddPCR produced the highest sensitivity of 99% compared with mNGS (86%) and Xpert (64%) for all active MTB cases., Discussion: Twenty-two Xpert-negative samples were positive in mNGS tests, which confirmed the clinical diagnosis results from ddPCR and clinical manifestation, radiologic findings. Thirteen mNGS-negative samples were positive in ddPCR assays, which confirmed the clinical final diagnosis.ddPCR provides a higher sensitive compared to Xpert and mNGS for MTB diagnosis, as defined by the high concordance between ddPCR assay and clinical final diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Yu, Han, Chen, Yuan, Xie, Zheng, Wang, Lou, Zheng and Chen.)

Background: Pancreatic adenocarcinoma (PAAD) is a lethal malignancy with high levels of heterogeneity. Pyroptosis is thought to influence the development of various tumors. Nevertheless, the role of pyroptosis-related genes (PRGs) in prognostic risk stratification and therapeutic guidance for PAAD remains ambiguously., Methods: Transcriptome profile and clinical information of PAAD patients were retrieved from The Cancer Genome Atlas (TCGA) as well as Gene Expression Omnibus (GEO) databases, followed by differential analysis. Patients were divided into distinct pyroptosis phenotype subtypes based on the characteristic of differently expressed PRGs (DEPRGs). Then a PRG signature was established through univariate analysis and LASSO algorithm in the training set to assess the prognostic risk, and its reliability was verified in the validation set using receiver operating characteristic(ROC) curve. The correlation of risk score with tumor microenvironment(TME), TMB and chemotherapeutic drug sensitivity were also analyzed. In addition, a nomogram was constructed to promote better clinical application., Results: A total of 28 DEPRGs were determined in the integrated TCGA-GEO datasets. Patients were divided into three pyroptosis phenotype subtypes, Kaplan-Meier curve suggested patients in cluster B had a worse prognosis than those in cluster A and C. Then a price signature comprised of 8 PRGs was generated. TME analysis suggested that the low-risk subgroup displayed potential stronger antitumor immune effect and might respond better to immune checkpoint inhibitors (ICIs) therapy. Furthermore, PRG signature exhibited favorable discriminatory ability for TMB status and the sensitivity of multiple conventional chemotherapeutic agents including paclitaxel. Ultimately, we constructed a promising nomogram according to the risk score and N stage with good predictive accuracy compared with the actual overall survival (OS) probabilities., Conclusion: We established an 8-gene signature that could be regarded as an independent prognostic risk factor for PAAD patients. The 8-gene signature could provide rationale for immunotherapy and chemotherapy, which might help clinicians make precise individualized treatment regimens., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: As a rare gastrointestinal neoplasm, the demographic, clinicopathological, and prognostic characteristics of mixed adenoneuroendocrine carcinoma (MANEC) remain unclear. The purpose of this study was to evaluate its biological features, survival outcome, and prognostic factors., Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, we retrospectively reviewed clinicopathological and survival data of 513 patients who were histopathologically diagnosed with MANEC of the appendix and colorectum bettween 2004 and 2015. The clinicopathological features and survival outcomes of MANEC located at different anatomical locations were compared, and predictive factors for cancer-specific survival (CSS) and overall survival (OS) were assessed., Results: In terms of anatomical distribution of MANEC, the appendix (64.5%, 331/513) was more frequently involved, followed by colon (28.1%, 144/513) and rectum (7.4%, 38/513). The MANEC at different anatomical locations had a distinct clinicopathological characteristic, and colorectal MANEC was significantly associated with more aggressive biological features. The survival outcomes of appendiceal MANEC were significantly better than that of colorectal MANEC (3-year CSS rate 73.8% vs 59.4%, P = 0.010; 3-year OS 69.2% vs 48.3%, P < 0.001). In addition, hemicolectomy had a better survival benefit than appendicectomy for patients with appendiceal MANEC, regardless of lymph node metastasis (P < 0.05). Tumor location, histology grade III, tumor size > 2 cm, T3-T4 stage, lymph node metastasis, and distant metastasis were independent prognostic factors for patients with MANEC., Conclusions: Tumor location had an important prognostic significance for MANEC. As an uncommon clinical entity, colorectal MANEC had more aggressive biological features and worse prognosis than its appendiceal counterpart. The standard surgical procedure and clinical management strategy for MANEC need to be established., (© 2023. Springer Nature Switzerland AG.)

Background: Metagenomic next-generation sequencing (mNGS) is a promising tool for improving antimicrobial therapy and infection control decision-making in complex infections. Secondary infection surveillance using mNGS in COVID-19 patients has rarely been reported., Methods: Respiratory pathogen and antibiotic resistance prediction were evaluated by BALF mNGS for 192 hospitalized COVID-19 patients between December 2022 and February 2023., Results: Secondary infection was confirmed in 83.3% (160/192) of the COVID-19 patients, with bacterial infections (45%, 72/160) predominating, followed by mixed bacterial and fungal infections (20%, 32/160), and fungal infections (17.5%, 28/160). The incidence of bacterial or viral secondary infection was significantly higher in patients who were admitted to the ICU, received mechanical ventilation, or developed severe pneumonia (all p<0.05). Klebsiella pneumoniae (n=30, 8.4%) was the most prevalent pathogen associated with secondary infection followed by Acinetobacter baumannii (n=29, 8.1%), Candida albicans (n=29, 8.1%), Aspergillus fumigatus (n=27, 7.6%), human herpes simplex virus type 1 (n=23, 6.4%), Staphylococcus aureus (n=20, 5.6%) and Pneumocystis jiroveci (n=14, 3.9%). The overall concordance between the resistance genes detected by mNGS and the reported phenotypic resistance in 69 samples containing five clinically important pathogens (ie, K. pneumoniae, A. baumannii, S. aureus, P. aeruginosa and E. coli ) that caused secondary infection was 85.5% (59/69)., Conclusion: mNGS can detect pathogens causing secondary infection and predict antimicrobial resistance for COVID19 patients. This is crucial for initiating targeted treatment and rapidly detect unsuspected spread of multidrug-resistant pathogens., Competing Interests: The authors declare no competing interests in this work., (© 2023 Chen et al.)

The prolyl hydroxylation of hypoxia-inducible factor 1α (HIF-1α) mediated by the EGLN-pVHL pathway represents a classic signalling mechanism that mediates cellular adaptation under hypoxia. Here we identify RIPK1, a known regulator of cell death mediated by tumour necrosis factor receptor 1 (TNFR1), as a target of EGLN1-pVHL. Prolyl hydroxylation of RIPK1 mediated by EGLN1 promotes the binding of RIPK1 with pVHL to suppress its activation under normoxic conditions. Prolonged hypoxia promotes the activation of RIPK1 kinase by modulating its proline hydroxylation, independent of the TNFα-TNFR1 pathway. As such, inhibiting proline hydroxylation of RIPK1 promotes RIPK1 activation to trigger cell death and inflammation. Hepatocyte-specific Vhl deficiency promoted RIPK1-dependent apoptosis to mediate liver pathology. Our findings illustrate a key role of the EGLN-pVHL pathway in suppressing RIPK1 activation under normoxic conditions to promote cell survival and a model by which hypoxia promotes RIPK1 activation through modulating its proline hydroxylation to mediate cell death and inflammation in human diseases, independent of TNFR1., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Adenosine monophosphate-activated protein kinase (AMPK) activity is stimulated to promote metabolic adaptation upon energy stress. However, sustained metabolic stress may cause cell death. The mechanisms by which AMPK dictates cell death are not fully understood. We report that metabolic stress promoted receptor-interacting protein kinase 1 (RIPK1) activation mediated by TRAIL receptors, whereas AMPK inhibited RIPK1 by phosphorylation at Ser 415 to suppress energy stress-induced cell death. Inhibiting pS415-RIPK1 by Ampk deficiency or RIPK1 S415A mutation promoted RIPK1 activation. Furthermore, genetic inactivation of RIPK1 protected against ischemic injury in myeloid Ampkα1 -deficient mice. Our studies reveal that AMPK phosphorylation of RIPK1 represents a crucial metabolic checkpoint, which dictates cell fate response to metabolic stress, and highlight a previously unappreciated role for the AMPK-RIPK1 axis in integrating metabolism, cell death, and inflammation.

Objective: The purpose of this study was to develop and validate a nomogram model for the prediction of survival outcome in rectal cancer patients who underwent surgical resection. Methods: A total of 9,919 consecutive patients were retrospectively identified using the Surveillance, Epidemiology, and End Results (SEER) database. Significant prognostic factors were determined by the univariate and multivariate Cox analysis. The nomogram model for the prediction of cancer-specific survival (CSS) in rectal cancer patients were developed based on these prognostic variables, and its predictive power was assessed by the concordance index (C-index). Calibration curves were plotted to evaluate the associations between predicted probabilities and actual observations. The internal and external cohort were used to further validate the predictive performance of the prognostic nomogram. Results: All patients from the SEER database were randomly split into a training cohort ( n = 6,944) and an internal validation cohort ( n = 2,975). The baseline characteristics of two cohorts was comparable. Independent prognostic factors were identified as age, pT stage, lymph node metastasis, serum CEA level, tumor size, differentiation type, perineural invasion, circumferential resection margin involvement and inadequate lymph node yield. In the training cohort, the C-index of the nomogram was 0.719 (95% CI: 0.696-0.742), which was significantly higher than that of the TNM staging system (C-index: 0.606, 95% CI: 0.583-0.629). The nomogram had a C-index of 0.726 (95% CI: 0.691-0.761) for the internal validation cohort, indicating a good predictive power. In addition, an independent cohort composed of 202 rectal cancer patients from our institution were enrolled as the external validation. Compared with the TNM staging system (C-index: 0.573, 95% CI: 0.492-0.654), the prognostic nomogram still showed a better predictive performance, with the C-index of 0.704 (95% CI: 0.626-0.782). Calibration plots showed a good consistency between predicted probability and the actual observation in the training and two validation cohorts. Conclusion: The nomogram showed an excellent predictive ability for survival outcome of rectal cancer patients, and it might provide an accurate prognostic stratification and help clinicians determine individualized treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wang, Ma, Ye, Yang and Meng.)

Plasma metagenomic next-generation sequencing (mNGS) testing is a promising diagnostic modality for infectious diseases, but its real-world clinical impact is poorly understood. We reviewed patients who had undergone plasma mNGS at a general hospital to evaluate the clinical utility of plasma mNGS testing. A total of 76.9% (113/147) of plasma mNGS tests had a positive result. A total of 196 microorganisms (58) were identified and reported, of which 75.6% (148/196) were clinically relevant. The median stringent mapped read number (SMRN) of clinically relevant organisms was 88 versus 22 for irrelevant organisms ( P = 0.04). Based on the clinically adjudicated diagnosis, the positive and negative percent agreements of plasma mNGS testing for identifying a clinically defined infection were 95.2% and 67.4%, respectively. The plasma mNGS results led to a positive impact in 83 (57.1%) patients by diagnosing or ruling out infection and initiating targeted therapy. However, only 32.4% (11/34) of negative mNGS tests showed a positive impact, suggesting that plasma mNGS testing alone may not be a powerful tool to rule out infection in clinical practice. In the subset of 37 patients positive for both plasma mNGS and conventional testing, mNGS identified the pathogen(s) 2 days (IQR = 0.75 to 4.25) earlier than conventional testing. mNGS enables pathogen identification within 24 h, but given that the detection of clinically irrelevant organisms and nearly half of the tests result in no or a negative clinical impact, more clinical practice and studies are required to better understand who and when to test and how to optimally integrate mNGS into the infectious disease diagnostic workup. IMPORTANCE In this study, we show that although plasma mNGS testing significantly improved the detection rate of tested samples, nearly one in four (24.5%, 48/196) mNGS tests reported organisms were not clinically relevant, emphasizing the importance of cautious interpretation and infectious disease consultation. Moreover, based on clinical adjudication, plasma mNGS testing resulted in no or a negative impact in nearly half (43.5%, 64/147) of patients in the current study, indicating that how best to integrate this advanced method into current infectious disease diagnostic frameworks to maximize its clinical utility in real-world practice is an important question. Therefore, recommending plasma mNGS testing as a routine supplement to first-line diagnostic tests for infectious diseases faces great challenges. The decision to conduct mNGS testing should take into account the diagnostic performance, turnaround time and cost-effectiveness of mNGS, as well as the availability of conventional tests.

We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions. The CLS was tested with seven independent datasets and compared with 21 physicians, and the system's diagnostic ability exceeded 20 physicians by training stage six. The optimal integrated method we developed is expected accurately diagnose breast masses. This method can also be extended to the intelligent diagnosis of masses in other organs. Overall, our findings have potential value in further promoting the application of AI diagnosis in precision medicine., (© 2023. The Author(s).)

Our world needs to develop clean energy to reach the target of carbon peak and carbon neutralization. As one of clean energy, wind energy should contribute to energy conservation and emission reduction. Wind power generation is an important field of wind energy application. However, the fluctuation and intermittency of wind can affect the safety of power system. Therefore, prediction of wind power accurately for wind power safety, dispatching, and power grid development is significant. This paper proposes a prediction model of wind power, and predicts the wind power of two wind farms. For the complex wind speed series, the variational modal decomposition (VMD) method is used to reduce its volatility before prediction. And this paper presents an improved method to improve the prediction efficiency when least square support vector machine (LSSVM) predicts stationary series. The prediction result shows that the proposed model improves the prediction of wind power effectively, provides an effective method for wind farm to predict the wind power, and makes contributions to reducing carbon emissions and environmental protection., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study investigated the pathogenesis of age-related macular degeneration (AMD) using histological methods that are commonly used for atherosclerotic vascular disease (ASVD). 1 normal, 3 early dry AMD, and 1 late dry AMD eyes were obtained from the Lions Eye Bank of Oregon and systematically dissected. They were stained with hematoxylin and eosin, Oil red O, Masson, Elastica van Gieson, Alizarin red, and Prussian blue. Additionally, the normal and late dry AMD eyes were immunostained for a-smooth muscle actin, CD45, and CD68 with Nile red and DAPI. Correlations were found between severity of AMD and lipid accumulation in the deep sclera (+), numbers of drusen between the Bruch's membrane and retinal pigment epithelium (RPE) (+), amount of collagen in the deep sclera (+), and amount of elastin in the deep sclera (-) (P < 0.1). Geographic atrophy, RPE detachment, and abnormal capillary shape and distribution in the choriocapillaris were observed in the fovea of late AMD. There were no stenosis, plaque, hemorrhage, and calcification. Additionally, late AMD tended to have higher smooth muscle thicknesses of the choroidal vascular walls, lower numbers of T lymphocytes in the choroid, and higher numbers of macrophages near the RPE and in the choroid relative to normal (P < 0.1). Macrophages-derived foam cells were detected near the Bruch's membrane in late AMD. Therefore, the present study showed many histological characteristics of ASVD in AMD, which suggests an association between them; however, there were also some histological characteristics of ASVD that were not found in AMD, which indicates that there exist pathogenic differences between them. The results generally support the vascular model of AMD, but some details still need clarification., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Tumor cells must rewire cellular metabolism to satisfy the demands of unbridled growth and proliferation. How these metabolic processes are integrated to fuel cancer cell growth remains largely unknown. Deciphering the regulatory mechanisms is vital to develop targeted strategies for tumor-selective therapies. We herein performed an unbiased and functional siRNA screen against 96 deubiquitinases, which play indispensable roles in cancer and are emerging as therapeutic targets, and identified USP29 as a top candidate essential for metabolic reprogramming that support biosynthesis and survival in tumor cells. Integrated metabolic flux analysis and molecular investigation reveal that USP29 directly deubiquitinates and stabilizes MYC and HIF1α, two master regulators of metabolic reprogramming, enabling adaptive response of tumor cells in both normoxia and hypoxia. Systemic knockout of Usp29 depleted MYC and HIF1α in MYC-driven neuroblastoma and B cell lymphoma, inhibited critical metabolic targets and significantly prolonged survival of tumor-bearing mice. Strikingly, mice homozygous null for the Usp29 gene are viable, fertile, and display no gross phenotypic abnormalities. Altogether, these results demonstrate that USP29 selectively coordinates MYC and HIF1α to integrate metabolic processes critical for cancer cell growth, and therapeutic targeting of USP29, a potentially targetable enzyme, could create a unique vulnerability given deregulation of MYC and HIF1α frequently occurs in human cancers., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

T-cell acute lymphoblastic leukemias (T-ALLs) are aggressive and heterogeneous hematologic tumors resulting from the malignant transformation of T-cell progenitors. The major challenges in the treatments of T-ALL are dose-limiting toxicities of chemotherapeutics and drug resistance. Despite important progress in deciphering the genomic landscape of T-ALL, translation of these findings into effective targeted therapies remains largely unsuccessful. New targeted agents with significant antileukemic efficacy and less toxicity are in urgent need. We herein report that the expression of WEE1, a nuclear tyrosine kinase involved in cell cycle G2-M checkpoint signaling, is significantly elevated in T-ALL. Mechanistically, oncogenic MYC directly binds to the WEE1 promoter and activates its transcription. T-ALL cells particularly rely on the elevated WEE1 for cell viability. Pharmacological inhibition of WEE1 elicits global metabolic reprogramming which results in a marked suppression of aerobic glycolysis in T-ALL cells, leading to an increased dependency on glutaminolysis for cell survival. As such, dual targeting of WEE1 and glutaminase (GLS1) induces synergistic lethality in multiple T-ALL cell lines and shows great efficacy in T-ALL patient-derived xenografts. These findings provide mechanistic insights in the regulation of WEE1 kinase in T-ALL and suggest an additional vulnerability during WEE1 inhibitor treatments. In aggregate, we highlight a promising combination strategy of dual inhibition of cell cycle kinase and metabolic enzymes for T-ALL therapeutics.

Ligand-induced chirality in core/shell nanocrystals (NCs) has attracted extensive attention because of many valuable potential applications. However, the cause of chirality especially in semiconductor nanomaterials is still under debate despite the creation of chiral type I core/shell structures. Herein, we synthesized a kind of new Cu 2 S/CdSe core/shell nanostructure to study the underlying reason. Four samples of Cu 2 S/CdSe were synthesized utilizing successive ion layer adsorption and reaction to vary the thickness of the CdSe shell upon a Cu 2 S core with 5 nm diameter. The chirality of type II Cu 2 S/CdSe NCs is imparted by l-/d-cysteine and penicillamine, which could be modulated with an increasing thickness of the CdSe shell. To the best of our knowledge, this is the first report of chiral type II core/shell semiconductor NCs. The hybridization theory can explain the variation trend of g factors with every increase in shell thickness from four monolayers (4 ML) to 7 ML. The results indicate that the chiroptical activity of semiconductor NCs is mainly due to hybridization between the holes in the valence band of NCs and the highest occupied molecular orbitals of the chiral ligands. In addition, Cu 2 S/CdSe NCs show a better chiroptical intensity in comparison with the type I structure according to previous work. The first design of chiral type II Cu 2 S/CdSe core/shell NCs and a detailed investigation of chiral variation trend help to give a better understanding of the chiral interaction between ligands and core/shell semiconductor nanostructures.

New ordered architectures or morphologies could be obtained through the self-assembly process and usually generate new physical and chemical properties. Here we report an adjustable self-assembly research study on copper sulphide nanocrystals (Cu1.94S NCs) forming five kinds of plant-like morphologies. Hydrophobic Cu1.94S quantum dots were prepared in the CHCl3 phase and transferred to the aqueous phase and capped with cysteine or penicillamine through a ligand exchange technique. Afterwards, a facile and eco-friendly self-assembly process (without using any template or surfactant) was employed. Through regulating the conditions including the solvent composition, surface ligand and starting concentration of Cu1.94S NCs, five delicate architectures were obtained. In addition, the possible formation process and growth mechanism of the obtained three-dimensional (3D) Cu1.94S architectures was also proposed and discussed. The assembled Cu1.94S architectures show improved molar extinction coefficients compared with individual Cu1.94S NCs, and in this way, better photothermal performance is achieved.

Arsenic (As) is a highly toxic metalloid that is classified as a non-threshold class-1 carcinogen. Millions of people worldwide suffer from As toxicity due to the intake of As-contaminated drinking water and food. Reducing the As concentration in drinking water and food is thus of critical importance. Phytoremediation of soil contaminated with As and the reduction of As contamination in food depend on a detailed understanding of As uptake and transport in plants. As transporters play essential roles in As uptake, translocation and accumulation in plant cells. In this review, we summarize the current understanding of As transport in plants, with an emphasis on As uptake, mechanisms of As resistance and the long-distance translocation of As, especially the accumulation of As in grains through phloem-mediated transport., (© The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)