Search

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

Highlights The hierarchical nanogrid-in-nanofiber-structured dual-type carbon-confined CoTe2 nanodots (CoTe2@NC@NSPCNFs) were synthesized via facile templates and an electrospinning approach. Hierarchical nanogrid-in-nanofiber structure effectively suppresses the volume change of CoTe2 and the shuttle of potassium polytelluride (K-pTe x ) through robust physical restraint and strong chemisorption. CoTe2@NC@NSPCNFs hybrid achieves ultralong lifespan potassium-storage performance over 3500 cycles, and the deep mechanisms underlying the evolution, dissolution, and shuttle of K-pTe x have been clearly revealed.

Abstract Background Transthoracic single-port assisted laparoscopic five-step maneuver inferior mediastinal lymphadenectomy for Siewert type II adenocarcinoma of esophagogastric junction (AEG) has superiority in lower mediastinal lymph nodes dissection and digestive tract reconstruction. However, the right pleura was probably ruptured in this surgical technique. The aim of this study was to explore whether the infracardiac bursa (ICB) exposed could protect right pleura. Methods We retrospectively collected and evaluated the clinical and pathological data of patients who underwent five-step maneuver of transthoracic single-port assisted laparoscopic lower mediastinal lymphadenectomy for Siewert II AEG at Guangdong Provincial Hospital of Chinese Medicine between May 2017 and February 2022. Results A total of 49 patients were eligible, including 31 patients in ICB exposed group (group A) and 18 patients in ICB unexposed group (group B). There were no statistically significant differences in baseline characteristics between the two groups. 4 patients (12.9%) had right pleura rupture in group A, while 14 patients (77.8%) in group B, and the difference was statistically significant (p

Abstract The accurate evaluation of telomerase activity, a typical cancer biomarker, is vital for early cancer screening. In this study, we developed a dark‐field microscopy (DFM) visual single‐particle detection scheme to detect telomerase activity based on automatic counting gold nanoparticles (AuNPs). This method started with attaching the telomerase substrate (TS) primer to the magnetic beads (MBs) through streptavidin‐biotin interaction. In the presence of telomerase and dNTPs, the TS primer was expanded with (TTAGGG)n repeat units to form the telomerase extension product (MBs‐telomerase extension product), which could be hybridized with the complementary DNA (cDNA) modified with AuNPs through Au‐S bonds (AuNPs‐SH‐cDNA). After magnetic separation and DNA double‐strand unwinding, AuNPs were collected from the supernatant, and the telomerase activity was quantitatively measured by visually counting bright spots based on DFM. This strategy achieved a limit of detection as low as 1 HeLa cell and distinguished telomerase activity among different cell lines, thus verifying its excellent sensitivity and specificity. Further, two common telomerase inhibitors (BIBR1532 and curcumin) were screened with the consistent IC50 values with other methods, respectively. It is worth mentioning that this strategy can clearly identify bladder cancer among various urinary diseases. Consequently, the visualized automatic particle counting strategy is potential as a powerful tool in early and noninvasive diagnosis of bladder cancer.

ObjectivesVenous thromboembolism (VTE) is a common complication among patients with newly diagnosed multiple myeloma (NDMM). Therefore, this study aimed to analyze the incidence and risk factors associated with VTE in the current era of thromboprophylaxis and to propose appropriate nursing measures.MethodsA total of 1,539 NDMM patients were retrospectively analyzed. All patients underwent VTE risk assessment and received aspirin or low molecular weight heparin (LMWH) to prevent thrombosis, followed by appropriate care based on their individual thrombosis risk. The incidence of VTE and its related risk factors were then analyzed.ResultsAll patients received at least four cycles of therapy containing immunomodulators (IMiDs) and/or proteasome inhibitors (PIs). We assigned 371 patients (24.1%) to the moderate-risk thrombosis group, who received daily aspirin (75 mg) for thrombosis prevention and 1,168 patients (75.9%) to the high-risk group, who received daily low molecular weight heparin (3,000 IU) for thrombosis prevention two times a day. Among all the patients, 53 (3.4%) experienced lower extremity venous thromboembolism events, with three of those patients experiencing a concurrent pulmonary embolism. A multivariate analysis indicated that bed rest lasting more than 2 months and plasma cells of ≥60% were independent factors associated with thrombosis.ConclusionMore effective risk assessment models are needed to predict thrombosis accurately. In addition, nurses involved in the treatment and management of thrombosis should continually engage in professional development to enhance their knowledge and skills.

Current theoretical models for tree relative growth rate (RGR) have considered physiological processes based on carbon economy and nutrient-productivity relations, but have not taken water relations into account. According to the ecological energetics and Lockhart equation theories, if more energy is needed to maintain water balance in plants, less energy should be invested towards growth, resulting in a trade-off between growth and drought tolerance. Leaf pressure–volume (PV) curve parameters are the best recognised classical indicators of plant drought tolerance, however, the relationships between tree growth and leaf PV parameters have rarely been investigated in forest communities. In the study, we selected two evergreen (Lithocarpus glaber, Cyclobalanopsis oxyodon) and two deciduous species (Quercus serrata, Platycarya strobilacea) that dominate northern subtropical forests on Mt. Shennongjia, central China. For each species, we selected individuals at different developmental stages (growth vs. mature stage), and measured the relative growth rate of diameter at breast height (RGRDBH) and leaf PV curve parameters, including leaf saturated osmotic potential (Ψsat), maximum bulk elastic modulus (εmax), turgor loss osmotic potential (Ψtlp) and leaf water capacity (Cleaf). Correlation analysis and structural equation models (SEM) were applied to explore the relationships between RGRDBH and PV parameters. The results showed that: 1) at both stages, RGRDBH was positively correlated with Ψsat, but not with Ψtlp and Cleaf; 2) εmax was negatively related to RGRDBH at the growth stage; 3) the relationship between PV parameters and RGRDBH was determined mainly by inter-specific difference; 4) SEM showed that both Ψtlp and Ψsat were affected by εmax; and 5) due to the interaction between the PV parameters, Ψsat and εmax had a direct effect on RGRDBH only during the growth stage. Our results showed that the functional/structural coordination between PV parameters adjusted the RGRDBH of trees, and among different species, there exists a tradeoff between energy allocation for drought tolerance and growth. These findings can be applied to improve RGR models, and show how forests respond to warm-induced drought, which is a major threat to global forests in a future warmer climate.

The most significant technical challenges of current aerial image object-detection tasks are the extremely low accuracy for detecting small objects that are densely distributed within a scene and the lack of semantic information. Moreover, existing detectors with large parameter scales are unsuitable for aerial image object-detection scenarios oriented toward low-end GPUs. To address this technical challenge, we propose efficient-lightweight You Only Look Once (EL-YOLO), an innovative model that overcomes the limitations of existing detectors and low-end GPU orientation. EL-YOLO surpasses the baseline models in three key areas. Firstly, we design and scrutinize three model architectures to intensify the model’s focus on small objects and identify the most effective network structure. Secondly, we design efficient spatial pyramid pooling (ESPP) to augment the representation of small-object features in aerial images. Lastly, we introduce the alpha-complete intersection over union (α-CIoU) loss function to tackle the imbalance between positive and negative samples in aerial images. Our proposed EL-YOLO method demonstrates a strong generalization and robustness for the small-object detection problem in aerial images. The experimental results show that, with the model parameters maintained below 10 M while the input image size was unified at 640 × 640 pixels, the APS of the EL-YOLOv5 reached 10.8% and 10.7% and enhanced the APs by 1.9% and 2.2% compared to YOLOv5 on two challenging aerial image datasets, DIOR and VisDrone, respectively.

Nowadays, because of the energy crisis, combined heat and power systems have notable benefits. One of the best devices is SOFC (Solid Oxide Fuel Cell) which joins heat and power frameworks. Some considerable failure modes arise that can affect these devices’ productivity. Generally, failure modes evaluations need an experts team to achieve uncertainties belongs to the risk assessment procedure. To improve the efficiency of the routine FMEA methodology and to represent a suitable hybrid fuzzy MCDM approach for FMEA, in this work, fully fuzzy best-worst method (FF-BWM) is employed to achieve the risk factors weights then fuzzy weighted aggregated sum product assessment (F-WASPAS) approach to detect the failure modes priorities is utilized. Ultimately, the sensitivity analyses demonstrate that the offered framework is verified and can make applicable data in risk management decision-making evaluation.

In this paper, the authors presented a study on the discrimination of handlebar grip samples, to provide effective forensic science service for hit and run traffic cases. 50 bicycle handlebar grip samples, 49 electric bike handlebar grip samples, and 96 motorcycle handlebar grip samples have been randomly collected by the local police in Beijing (China). Fourier transform infrared microspectroscopy (FTIR) was utilized as analytical technology. Then, target absorption selection, data pretreatment, and discrimination of linked samples and unlinked samples were chosen as three steps to improve the discrimination of FTIR spectrums collected from different handlebar grip samples. Principal component analysis and receiver operating characteristic curve were utilized to evaluate different data selection methods and different data pretreatment methods, respectively. It is possible to explore the evidential value of handlebar grip residue evidence through instrumental analysis and statistical treatments. It will provide a universal discrimination method for other forensic science samples as well.

HIV-1 maturation inhibitors (MIs) disrupt the final step in the HIV-1 protease-mediated cleavage of the Gag polyprotein between capsid p24 capsid (CA) and spacer peptide 1 (SP1), leading to the production of infectious virus. BMS-955176 is a second generation MI with improved antiviral activity toward polymorphic Gag variants compared to a first generation MI bevirimat (BVM). The underlying mechanistic reasons for the differences in polymorphic coverage were studied using antiviral assays, an LC/MS assay that quantitatively characterizes CA/SP1 cleavage kinetics of virus like particles (VLPs) and a radiolabel binding assay to determine VLP/MI affinities and dissociation kinetics. Antiviral assay data indicates that BVM does not achieve 100% inhibition of certain polymorphs, even at saturating concentrations. This results in the breakthrough of infectious virus (partial antagonism) regardless of BVM concentration. Reduced maximal percent inhibition (MPI) values for BVM correlated with elevated EC50 values, while rates of HIV-1 protease cleavage at CA/SP1 correlated inversely with the ability of BVM to inhibit HIV-1 Gag polymorphic viruses: genotypes with more rapid CA/SP1 cleavage kinetics were less sensitive to BVM. In vitro inhibition of wild type VLP CA/SP1 cleavage by BVM was not maintained at longer cleavage times. BMS-955176 exhibited greatly improved MPI against polymorphic Gag viruses, binds to Gag polymorphs with higher affinity/longer dissociation half-lives and exhibits greater time-independent inhibition of CA/SP1 cleavage compared to BVM. Virological (MPI) and biochemical (CA/SP1 cleavage rates, MI-specific Gag affinities) data were used to create an integrated semi-quantitative model that quantifies CA/SP1 cleavage rates as a function of both MI and Gag polymorph. The model outputs are in accord with in vitro antiviral observations and correlate with observed in vivo MI efficacies. Overall, these findings may be useful to further understand antiviral profiles and clinical responses of MIs at a basic level, potentially facilitating further improvements to MI potency and coverage.

Herein, the quality and accuracy to manufacture delicate parts from NiTi powder using electron beam powder bed fusion (EB-PBF) technology is investigated. Therefore, benchmarks with thin cylinders and thin walls are designed and fabricated using two distinct scan strategies of EB-PBF manufacturing (i.e., continuous melting and spotmelting) with different process parameter sets. After these optimizations, four different lattice structures (i.e., octahedron, cell gyroid, sheet gyroid, and channel) are manufactured and characterized. It is shown both continuous melting and spot melting modes are able to manufacture lattices with relative densities over 97%. And as-built lattice structures exhibit an excellent pseudoelasticity up to 8% depending on the design of the structure, e.g., the channel structure shows more deformation recoverability than the cell gyroid. This is attributed to the integrity of geometry as well as compressive mode of the mechanical loading. Of course, the compressive strength and ultimate compressive strength also increase with the increasing volume fraction. Moreover, the spotmelting can be used as an engineering tool to customize a delicate beamshaped structure with a superior pseudoelasticity. [ABSTRACT FROM AUTHOR]