Search

Abstract Introduction Cisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC). Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood. Circular RNAs (circRNAs) are involved in the pathophysiology of multiple human malignancies. Methods High-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells. Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues. To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot. The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay. GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer. In vivo evaluation was conducted using patient-derived xenograft models. Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC. Results We revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells. Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model. High circ_0008315 expression predicted unfavorable survival outcome in GC patients. Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo. Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed cisplatin resistance. Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression. Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance. Conclusion Circ_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor. Circ_0008315 may function as a promising nanotherapeutic target for GC treatment. Graphical Abstract

Abstract Background Circular RNAs (circRNAs) have been implicated in the development and progression of gastric cancer (GC). However, it remains unclear whether dysregulated circRNA affects immune escape and the efficacy of immunotherapy in GC. Our aim is to investigate the molecular mechanism of circRNA affecting GC immunotherapy and identify effective molecular therapeutic targets. Methods The differential expression profile of circRNAs was established through circRNA sequencing, comparing three paired GC tissues with their adjacent non-cancerous gastric tissues. The expression level of circRHBDD1 in GC tissues was then assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological characteristics of circRHBDD1 were verified through a series of experiments, including agarose gel electrophoresis assays, RNase R treatment, and actinomycin D experiments. The prognostic value of circRHBDD1 in GC was evaluated by conducting both univariate and multivariate survival analyses. Furthermore, loss- and gain-of-function approaches were utilized to investigate the impact of circRHBDD1 on GC immune escape. RNA-sequencing, immunoprecipitation, flow cytometry, and methylated RNA immunoprecipitation (meRIP) analysis were performed to elucidate the underlying molecular mechanisms. Results We discovered that circRHBDD1 exhibited remarkably high expression levels in GC tissues and cell lines. Notably, the high expression of circRHBDD1 was significantly correlated with poor overall survival and disease-free survival among GC patients. Both in vitro and in vivo experiments revealed that circRHBDD1 upregulated the expression of PD-L1 and impeded the infiltration of CD8+ T cells. Further, we found that circRHBDD1 binds to IGF2BP2, disrupting the interaction between E3 ligase TRIM25 and IGF2BP2, and ultimately inhibiting IGF2BP2 ubiquitination and degradation. Intriguingly, IGF2BP2 enhances PD-L1 mRNA stability through m6A modification. Additionally, we developed Poly (lactide-co-glycolic acid) (PLGA)-Polyethylene glycol (PEG)-based nanoparticles loaded with circRHBDD1 siRNA. In vivo experiments validated that the combination of PLGA-PEG(si-circRHBDD1) and anti-PD-1 offers a safe and efficacious nano-drug regimen for cancer immunotherapy. Conclusion Our results demonstrated that circRHBDD1 promoted GC immune escape by upregulating the expression of PD-L1 and reprogramming T cell-mediated immune response. Inhibition of circRHBDD1 expression could potentially enhance the response of GC patients to immunotherapy, thus improving treatment outcomes. Additionally, the development of a nanodrug delivery system provides a feasible approach for future clinical applications.

Abstract Background Advanced unresectable gastric cancer (GC) patients were previously treated with chemotherapy alone as the first-line therapy. However, with the Food and Drug Administration’s (FDA) 2022 approval of programmed cell death protein 1 (PD-1) inhibitor combined with chemotherapy as the first-li ne treatment for advanced unresectable GC, patients have significantly benefited. However, the significant costs and potential adverse effects necessitate precise patient selection. In recent years, the advent of deep learning (DL) has revolutionized the medical field, particularly in predicting tumor treatment responses. Our study utilizes DL to analyze pathological images, aiming to predict first-line PD-1 combined chemotherapy response for advanced-stage GC. Methods In this multicenter retrospective analysis, Hematoxylin and Eosin (H&E)-stained slides were collected from advanced GC patients across four medical centers. Treatment response was evaluated according to iRECIST 1.1 criteria after a comprehensive first-line PD-1 immunotherapy combined with chemotherapy. Three DL models were employed in an ensemble approach to create the immune checkpoint inhibitors Response Score (ICIsRS) as a novel histopathological biomarker derived from Whole Slide Images (WSIs). Results Analyzing 148,181 patches from 313 WSIs of 264 advanced GC patients, the ensemble model exhibited superior predictive accuracy, leading to the creation of ICIsNet. The model demonstrated robust performance across four testing datasets, achieving AUC values of 0.92, 0.95, 0.96, and 1 respectively. The boxplot, constructed from the ICIsRS, reveals statistically significant disparities between the well response and poor response (all p-values

Abstract Backgound To explore the characteristics and risk factors for health-related risky behaviours (HRRBs) in adolescents with depression. Methods A total of 136 adolescents aged 12–18 years who met the diagnostic criteria for depression, and 272 healthy controls. All the subjects were assessed with the Adolescent Health-Related Risky Behavior Inventory (AHRBI), and the AHRBI scores of the two groups were compared with the Mann–Whitney U test. The depression group was assessed with the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Childhood Trauma Questionnaire (CTQ), Cognitive Emotion Regulation Questionnaire (CERQ), Egna Minnen av Barndoms Uppfostran (EMBU), and Family Adaptability and Cohesion Scale (FACES II-CV). Spearman correlation analysis and multiple linear regression were used to explore the risk factors for HRRBs in adolescents with depression. Results The AHRBI total score and five-factor scores of self-injury and suicide (SS), aggression and violence (AV), rule-breaking (RB), smoking and drinking (SD), and health-compromising behavior (HCB) in the depression group were higher than those in the control group. The severity of anxiety, catastrophizing, cognitive emotional regulation strategy (self-blame and blaming of others), the frequency of depression, physical neglect, and sexual abuse all increased the risk of HRRBs in adolescents with depression, and paternal emotional warmth and understanding had protective effects. Conclusion First, depressed adolescents exhibited significantly more HRRBs than healthy adolescents. Second, there are many risk factors for HRRBs in adolescents with depression, and the risk factors for different types of HRRBs are also different.

Abstract Primary liver cancer is the sixth most common cancer and the third leading cause of cancer‐related death worldwide. The role of the ‘Other’ subfamily of HECT E3 ligases (E3s) in hepatocellular carcinoma (HCC) remains unknown. The expression of the ‘Other’ HECT E3s was performed using The Cancer Genome Atlas (TCGA) data, and the authors found that the ‘Other’ HECT E3s were differentially expressed in HCC. Prognostic values were assessed using the Kaplan–Meier method and indicated that the high expressions of HECTD2, HECTD3, and HACE1 were associated with a worse clinical prognosis of HCC patients. The expression of HECTD2 was significantly correlated with the infiltration of CD4+T cells and neutrophils. The levels of HECTD3 and HACE1 were notably related to the dendritic cells and memory B cells infiltrated in HCC. In addition, the three previously mentioned genes have shown to be associated with immune checkpoint genes, such as FOXP3, CCR8, STAT5B, TGFB1 and TIM‐3. Moreover, HECTD2 could promote the proliferative activity, cell migration and invasive ability of HCC cells. Collectively, the authors’ study demonstrated that HECTD2 was a novel immune‐related prognostic biomarker for HCC, providing new insight into the treatment and prognosis of HCC.

In order to address the challenges of global path planning in complex and dynamic environments, where avoiding dynamic obstacles is difficult, and local paths are prone to getting stuck in local optima, this paper proposes an enhanced hybrid path planning approach based on improvements to the $\text{A}^{\ast} $ algorithm and the Artificial Potential Field (APF) algorithm. Firstly, addressing the issues of redundant path nodes and non-smooth paths generated by the $\text{A}^{\ast} $ algorithm, we introduce enhancements such as weighted heuristic function, removal of redundant path nodes, and the incorporation of a cubic quasi-uniform B-spline curve to improve search speed and generate smoother paths. Secondly, addressing the problems of unreachable target points and susceptibility to local optima associated with the APF algorithm, two key strategies are employed. On one hand, the repulsive potential field function is modified by incorporating the m-th power of the relative distance from the robot to the target point to ensure reachability. On the other hand, the CSA-APF (Constrained Simulated Annealing with Augmented Potential Field) algorithm is introduced. This algorithm combines the APF algorithm with Simulated Annealing (SA), incorporating constraints on angles and safety distances to escape local optima and generate globally optimal points. Finally, the proposed methods are compared through simulation experiments in different scenarios. The experimental results demonstrate that the proposed approach effectively achieves path planning in complex dynamic environments.

Abstract Background The role of cholesterol metabolism in gastric cancer (GC) and its implications for tumor characteristics and immunotherapy response remain poorly understood. In this study, our aim was to investigate this role, identify associated metabolic subtypes, and assess their clinical implications in GC. Methods We conducted a comprehensive analysis of cholesterol metabolism genes (CMGs) using transcriptomic data from TCGA and GEO. Based on 23 representative CMGs, we classified GC into metabolic subtypes. We evaluated clinical features and immune cell infiltration between these subtypes. Additionally, we identified a CMG signature and assessed its clinical relevance in GC. We retrospectively enrolled thirty-five GC patients receiving chemotherapy plus a PD-1 inhibitor to assess the CMG signature using multiplex immunohistochemistry. Results Our analysis revealed two cholesterol metabolism subtypes in GC: Cholesterol Metabolism Type 1 (CMT1) and Cholesterol Metabolism Type 2 (CMT2). These subtypes exhibited distinct patterns: CMT1 indicated heightened cholesterol biosynthesis, while CMT2 showed abnormal cholesterol transport. CMT2 was associated with unfavorable clinical features, enriched malignant pathways, and a pro-tumor immune microenvironment. Furthermore, we developed a five-CMG prognostic signature (ABCA1, NR1H3, TSPO, NCEH1, and HMGCR) that effectively predicted the prognosis of patients with GC and their response to chemotherapy plus a PD-1 inhibitor. This signature was validated in a clinical cohort using multiplex immunohistochemistry. Conclusion Our results highlight the effectiveness of cholesterol metabolism patterns as biomarkers for predicting the prognosis and immunotherapy response in GC. The expression of cholesterol metabolism genes and the assessment of cholesterol metabolism patterns have the potential to predict the outcome of immunotherapy and guide treatment strategies.

Abstract Background Gastrointestinal Neuroendocrine Neoplasms (GI-NENs) often result in liver metastases, and the role of Primary Tumor Resection (PTR) in managing GI-NENs with liver metastases (GI-NENLM) is still debated. This study aimed to investigate the potential benefits of PTR in treating GI-NENLM by analyzing data from the Surveillance, Epidemiology, and End Results Program (SEER) and the First Affiliated Hospital of Sun Yat-sen University (FAH). Methods The SEER Registry 17 database and the FAH clinical pathology database were used to collect clinicopathology data for GI-NENLM diagnosed between 2010 and 2019 and between 2011 and 2022, respectively. Propensity score matching (PSM) was used to match the clinicopathological characteristics of patients from both cohorts. Inverse probability weighting (IPTW) was used to weigh the PTR and non-PTR groups. The primary endpoint was overall survival (OS). Results After matching, 155 patients from the SEER database were matched to the FAH cohort. PTR was significantly associated with better prognosis in PSM-matched/unmatched SEER cohorts (P

Abstract Background Hypoxia, a common characteristic of the tumour microenvironment, is involved in tumour progression and immune evasion. Targeting the hypoxic microenvironment has been implicated as a promising antitumour therapeutic strategy. TH-302 can be selectively activated under hypoxic conditions. However, the effectiveness of TH-302 in gastric cancer combined immunotherapy remains unclear. Methods We designed mPEG-PLGA-encapsulated TH-302 (TH-302 NPs) to target the hypoxic area of tumour tissues. A particle size analyzer was used to measure the average size and zeta potential of TH-302 NPs. The morphology was observed by transmission electron microscopy and scanning electron microscopy. The hypoxic area of tumour tissues was examined by immunofluorescence assays using pimonidazole. Flow cytometry analysis was performed to measure the levels of TNF-α, IFN-γ, and granzyme B. The synergistic antitumour activity of the combination of TH-302 NPs with anti-PD-1 (α-PD-1) therapy was assessed in vitro and in vivo. Haematoxylin and eosin staining of major organs and biochemical indicator detection were performed to investigate the biological safety of TH-302 NPs in vivo. Results TH-302 NPs inhibited the proliferation and promoted the apoptosis of gastric cancer cells under hypoxic conditions. In vitro and in vivo experiments confirmed that TH-302 NPs could effectively alleviate tumour hypoxia. TH-302 NPs exhibited high bioavailability, effective tumour-targeting ability and satisfactory biosafety. Moreover, the combination of TH-302 NPs with α-PD-1 significantly improved immunotherapeutic efficacy in vivo. Mechanistically, TH-302 NPs reduced the expression of HIF-1α and PD-L1, facilitated the infiltration of CD8+ T cells and increased the levels of TNF-α, IFN-γ, and granzyme B in tumours, thereby enhancing the efficacy of α-PD-1 therapy. Conclusion TH-302 NPs alleviated the hypoxic tumour microenvironment and enhanced the efficacy of PD-1 blockade. Our results provide evidence that TH-302 NPs can be used as a safe and effective nanodrug for combined immunotherapy in gastric cancer treatment.

Chilo sacchariphagus (Lepidoptera: Pyralidae) is an economically important sugarcane pest. Although numerous studies were conducted on the physiological responses in C. sacchariphagus, little is known regarding the genes regulating these physiological processes. Gene expression analysis by qRT-PCR can offer a significant indication for functional gene studies. To our knowledge, the reference genes of C. sacchariphagus have not been screened or evaluated, which hinders the functional gene study. In the present study, the stability of seven reference genes (β-ACT, GAPDH, BTF3, 28S, RPL7, EF1α, and SDHA) was evaluated in C. sacchariphagus under different experimental conditions, including tissues (antenna, head, thorax, abdomen, leg, and wing), temperatures (4 °C, 25 °C, and 37 °C) and sexes (male and female), through RefFinder, which integrates four algorithms (Normfinder, BestKeeper, ΔCt method, and geNorm). The findings suggested that the combination of β-ACT and RPL7 is ideal to analyze gene expressions in different tissues and at distinct temperatures, and EF1α and SDHA were suitable reference genes for comparing gene expressions between sexes. Finally, the expression profiles of CsacPBP1 gene were evaluated, and the outcomes further confirm the importance of selecting fitting reference genes for normalization of qRT-PCR data. This study represents the first kind in screening out suitable reference genes for gene expression analysis in C. sacchariphagus. Information from this study is poised to galvanize future inquiry into the gene expression of C. sacchariphagus, an economically important pest of sugarcane.

Abstract Development of a malaria vaccine that blocks transmission of different parasite stages to humans and mosquitoes is considered critical for elimination efforts. A vaccine using Pfs25, a protein on the surface of zygotes and ookinetes, is under investigation as a transmission-blocking vaccine (TBV) that would interrupt parasite passage from mosquitoes to humans. The most extensively studied Pfs25 TBVs use Pichia pastoris-produced recombinant forms of Pfs25, chemically conjugated to a recombinant carrier protein, ExoProtein A (EPA). The recombinant form of Pfs25 first used in humans was identified as Pfs25H, which contained a total of 14 heterologous amino acid residues located at the amino- and carboxyl-termini including a His6 affinity tag. A second recombinant Pfs25, identified as Pfs25M, was produced to remove the heterologous amino acid residues and conjugated to EPA (Pfs25M-EPA). Here, monomeric Pfs25M was characterized biochemically and biophysically for identity, purity, and integrity including protein structure to assess its comparability with Pfs25H. Although the biological activities of Pfs25H and Pfs25M, whether generated by monomeric forms or conjugated nanoparticles, appeared similar, fine-mapping studies with two transmission-blocking monoclonal antibodies detected structural and immunological differences. In addition, evaluation of antisera generated against conjugated Pfs25H or Pfs25M nanoparticles in nonhuman primates identified polyclonal IgG that recognized these structural differences.

Abstract Background Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) was a unique molecular subtype of gastric cancer (GC). However, the clinicopathological characteristics and prognostic role of EBV infection remains unclear. We aimed to evaluate the clinicopathological features of EBVaGC and its role on prognosis. Methods EBV-encoded RNA (EBER) in situ hybridization method was used to evaluate the EBV status in GC. The serum tumor markers AFP, CEA, CA19-9 and CA125 of patients were detected before treatment. HER2 expression and microsatellite instability (MSI) status was evaluated according to established criteria. The relationship between EBV infection and clinicopathological factors as well as its role on prognosis were investigated. Results 420 patients were enrolled in the study and of 53 patients (12.62%) were identified as EBVaGC. EBVaGC was more common in males (p = 0.001) and related to early T stage (p = 0.045), early TNM stage (p = 0.001) and lower level of serum CEA (p = 0.039). No association could be found between EBV infection and HER2 expression, MSI status and other factors (p all > 0.05). Kaplan–Meier analysis revealed that both the overall survival and disease-free survival of EBVaGC patients were similar to that of EBV-negative GC (EBVnGC) patients (p = 0.309 and p = 0.264, respectively). Conclusion EBVaGC was more common in males and in patients with the early T stage and TNM stage as well as patients with lower serum CEA level. Difference in overall survival and disease-free survival between EBVaGC and EBVnGC patients cannot be detected.

Introduction: The goal of this study is to compare the prognostic performance of NETPET scores, based on gallium-68 DOTANOC (68Ga-DOTANOC) and fluorine-18 fluorodeoxyglucose (18F-FDG) Positron Emission Tomography-Computed Tomography (PET-CT), and PET-CT metabolic parameters in metastatic gastrointestinal neuroendocrine tumors (GI-NET), while constructing and validating a nomogram derived from dual-scan PET-CT. Methods: In this retrospective study, G1–G3 GI-NET patients who underwent 68Ga-DOTANOC and 18F-FDG PET scans were enrolled and divided into training and internal validation cohorts. Three grading systems were constructed based on NETPET scores and standardized uptake value maximum (SUVmax). LASSO regression selected variables for a multivariable Cox model, and nomograms predicting progression-free survival (PFS) and overall survival (OS) were created. The prognostic performance of these systems was assessed using time-dependent receiver-operating characteristic (ROC) curves, concordance index (C-index), and other methods. Nomogram evaluation involved calibration curves, decision curve analysis (DCA), and the aforementioned methods in both cohorts. Results: In this study, 223 patients (130 males; mean age ± SD: 52.6 ± 12 years) were divided into training (148) and internal validation (75) cohorts. Dual scans were classified based on NETPET scores (D1–D3). Single 68Ga-DOTANOC and 18F-FDG PET-CT scans were stratified into S1-S3 and F1-F3 based on SUVmax. The NETPET score-based grading system demonstrated the best OS and PFS prediction (C-index, 0.763 vs. 0.727 vs. 0.566). Nomograms for OS and PFS exhibited superior prognostic performance in both cohorts (all AUCs > 0.8). Conclusions: New classification based on NETPET score predicts patient OS/PFS best. PET-CT-based nomograms show accurate OS/PFS forecasts.

To achieve multiple obstacle avoidance tasks consisting of zero-space obstacle avoidance and terminal obstacle avoidance with self-avoidance permission, we propose an algorithm for multiple obstacle avoidance tasks for dual-arm robots. First, we design a self-obstacle avoidance gradient optimization function to implement the self-obstacle avoidance task between the two arms of dual-arm robots by using the pseudo-distance as the basis for the collision judgment. Second, the terminal obstacle avoidance task for dual-arm robots is implemented by applying an adaptive terminal obstacle avoidance velocity. Third, a zero-space obstacle avoidance task for dual-arm robots is realized using an adaptive virtual repulsion force. Finally, a dual-arm robot consisting of two 6-DOF Jaco2 manipulators is simulated in a Matlab environment to verify the obstacle avoidance algorithm of dual-arm robots. The simulation results show that the algorithm proposed in this paper can complete the multi-obstacle avoidance tasks of terminal obstacle avoidance and zero-space obstacle avoidance simultaneously with the premise of realizing the self-obstacle avoidance of dual-arm robots, and has a minor terminal trajectory error, which proves that the algorithm is in the feasibility of completing terminal obstacle avoidance and zero-space obstacle avoidance with the premise of realizing dual-arm robots self-obstacle avoidance.

Cellular vehicle-to-everything(C-V2X) technology can protect vulnerable road users(VRUs) in traffic accidents. Smartphones are the most common portable devices for VRUs, but they do not support direct communication between vehicles and pedestrians. To address this problem, we propose a vehicle-to-pedestrian collision warning system that includes a phone case designed for the smartphone. It allows VRUs to communicate directly with connected vehicles(CVs) through C-V2X. A collision warning method based on s-t-coordinates is proposed to help VRUs to avoid collision with CVs on both straight and curved roads. Firstly, the World Geodetic System-1984(WGS-84) coordinates of the VRU and CV are transformed to Universal Transverse Mercator(UTM) coordinates. Then the s-t-coordinates of the VRU and CV are calculated. The lateral and longitudinal distance between them is determined. Finally, the time-to-collision(TTC) is used to determine the time to alert the VRU and the driver. To verify the effectiveness of this system, we conduct experiments on communication, positioning, and scenario. The communication experiments show that the system can communicate effectively with low latency and its reliable communication range is more than 200 meters in different scenarios. The positioning experiments show that the average positioning accuracy of the phone case is 0.83 meters in the open-sky scenario, which satisfies the lane-level positioning requirement for VRU applications. The scenario experiments indicate that our method can alert the driver and VRU on both straight and curved roads. The comparative experiments illustrate that our method outperforms the conventional method(CM) and the existing pedestrian alert system(PAS).

With the evolution of society, the world has entered a moderate stage of aging. Not surprisingly, the aging problem in the world is getting more intense, resulting in the increasing demand for higher-quality and well-organized medical and elderly care services. To cope with that, many researchers have dedicated themselves to advancing the medical care system based on data or platforms. However, they have ignored the life cycle, health service and management and the inevitable shift of living scenarios for the elderly. Therefore, the study aims to improve health conditions and enhance senior citizens' life quality and happiness index. In this paper, we build a unified body for people in their old age, bridging the disconnection between medical care and elderly care and constructing the "five-in-one" comprehensive medical care framework. It should be mentioned that the system takes the human life cycle as its axis, relies on the supply side and supply chain management, integrates medicine, industry, literature and science as methods, and takes health service management as a requirement. Furthermore, a case study on upper limb rehabilitation is elaborated along the "five-in-one" comprehensive medical care framework to confirm the effectiveness of the novel system.

Healthcare is the method of keeping or enhancing physical and mental well-being with its aid of illness and injury prevention, diagnosis, and treatment. The majority of conventional healthcare practices involve manual management and upkeep of client demographic information, case histories, diagnoses, medications, invoicing, and drug stock upkeep, which can result in human errors that have an impact on clients. By linking all the essential parameter monitoring equipment through a network with a decision-support system, digital health management based on Internet of Things (IoT) eliminates human errors and aids the doctor in making more accurate and timely diagnoses. The term "Internet of Medical Things" (IoMT) refers to medical devices that have the ability to communicate data over a network without requiring human-to-human or human-to-computer interaction. Meanwhile, more effective monitoring gadgets have been made due to the technology advancements, and these devices can typically record a few physiological signals simultaneously, including the electrocardiogram (ECG) signal, the electroglottography (EGG) signal, the electroencephalogram (EEG) signal, and the electrooculogram (EOG) signal. Yet, there has not been much research on the connection between digital health management and multi-modal signal monitoring. To bridge the gap, this article reviews the latest advancements in digital health management using multi-modal signal monitoring. Specifically, three digital health processes, namely, lower-limb data collection, statistical analysis of lower-limb data, and lower-limb rehabilitation via digital health management, are covered in this article, with the aim to fully review the current application of digital health technology in lower-limb symptom recovery.

Wernicke's encephalopathy (WE) is a severe neuropsychiatric disorder, mainly resulting from a nutritional deficiency of thiamine. WE is hard to detect at an early stage. Less than 20% of WE can be diagnosed during a patient’s lifetime, and WE tends to occur in patients with chronic alcoholism. Therefore, a large proportion of non-alcoholic WE patients are misdiagnosed. Lactate is an important by-product of anaerobic metabolism when the aerobic metabolism is blocked without thiamine, which can potentially serve as an alerting index for WE. Here, we report a case of a patient with WE who suffered gastric outlet obstruction following postoperative fasting, accompanied by lactic acidosis and refractory thrombocytopenia. A 67-year-old non-alcoholic woman who suffered hyperemesis for 2 months was diagnosed with gastric outlet obstruction (GOO). Gastric biopsies with endoscopy revealed gastric cancer, and total gastrectomy, together with D2 nodal dissection, was performed. She developed a coma with refractory thrombocytopenia rapidly after the surgical procedures were performed. The above conditions were treated not by the administration of antibiotics but by that of thiamine. We also found before the start of the procedures that she had a high level of blood lactate for a long period of time. Early diagnosis of WE is important because permanent injury can be caused to the central nervous system. Even today, the diagnosis of WE mainly depends on clinical symptoms, but occasionally, a typical triad occurs among WE patients. Therefore, a sensitive index for early diagnosis is critical for WE. Rising levels of blood lactate as a result of thiamine deficiency can serve as a warning for WE. In addition, we noted that this patient had a non-typical thiamine-sensitive refractory thrombocytopenia.

As one of the most densely populated, economically developed, and outwardly open urban agglomerations in China, the Pearl River Delta (PRD) urban agglomeration is a key player in achieving China’s carbon peak and carbon neutrality targets. This study analyzes low-emission development by examining the evolutionary patterns of carbon dioxide (CO2) emissions and the decoupling relationship between economic growth and CO2 emissions, using the latest available data from 2000 to 2020. Here are the main findings: (1) We found a significant fluctuation in the decoupling statuses between economic advancements and CO2 emissions within the PRD domain. Predominantly, a weak decoupling scenario was observed, where economic proliferations were paralleled by nearly equivalent increments in CO2 emissions. (2) The growth rate of carbon emissions increased significantly relative to economic expansion during 2015–2020, especially pronounced in cities such as Guangdong, Zhuhai, Foshan, and Dongguan. This delineates the persistent challenges in steering towards a pathway of energy conservation and emission abatement in the region. (3) Furthermore, a differential role of elasticity factors was noted across cities: Guangzhou and Shenzhen witnessed a significant influence of energy-saving elasticity in fostering a decoupling between economic surge and CO2 emissions, whereas in other cities, the emphasis shifted towards emission-reduction elasticity as a more vital determinant. The results of this study are of great significance for guiding policy makers and stakeholders in urban clusters across China and in similar regions globally to achieve low carbon development goals.

The traditional A* algorithm has several problems in practical applications, such as many path turning points, redundant nodes, and long running time. it is sometimes impossible to plan the theoretical optimal route. To solve the above problem, this paper presents an optimized A* algorithm, the adaptive adjustment step algorithm and the three-time Bezier curve are used to solve the problems of many turning points, large turning angles, and long running time in the search path. Moreover, aiming at the path planning problem of mobile robots facing dynamic obstacle interference in complex environments, an algorithm that integrates the improved A* algorithm with the dynamic window method is proposed, which not only solves the shortcomings of the A* algorithm in which the dynamic obstacles cannot be avoided, but also prevents the mobile robot from falling into local optimization. The results show that the fusion algorithm of the improved A* algorithm and the dynamic window method with the traditional A* algorithm reduces the number of turns by 50% and the path length by 3.62% compared with the original algorithm. In the same environment, compared with the traditional algorithm, the hybrid algorithm in this paper reduces the average time consumption by 10.27%, the number of path inflection points by 57.14%, and the accuracy is higher than 33.33%, which is more effective in complex dynamic environments.

Oxidative stress is closely associated with neurodegenerative, cardiovascular and metabolic diseases. Resveratrol and related compounds have shown great potential as antioxidants via either direct scavenging of abundant reactive oxygen species (ROS) or activation of the Kelch‐like ECH‐associated protein 1‐nuclear factor (erythroid‐derived 2)‐like 2‐antioxidant response elements pathway. In the present study, we evaluated imine resveratrol analogs (IRAs) for their neuroprotective effects against ROS in PC12 cells, which are a commonly employed model system for studies of neuronal development and function. We identified that IRA‐3 (4‐[[(4‐hydroxyphenyl)methylene]amino]‐phenol) was more potent than resveratrol at rescuing PC12 cells from H2O2‐induced oxidative damage, exhibiting a recovery percentage of 60.4% at 50 μm. Our findings suggest that the neuroprotective effect of IRA‐3 was achieved via multiple routes, including direct scavenging of ROS, rescue of endogenous antioxidants and activation of the Kelch‐like ECH‐associated protein 1‐nuclear factor (erythroid‐derived 2)‐like 2‐antioxidant response elements pathway. Our results suggest that IRA‐3 may have potential for development into a possible treatment for neurodegenerative diseases.

Photodynamic therapy (PDT) is a promising alternative and palliative therapeutic strategy for colorectal cancer (CRC). A novel photosensitizer with higher selectivity for CRC and fewer side effects is vital for clinical application. Given that the overexpression of hydrogen sulfide (H2S) in CRC, it is expected to provide a selective stimulus for activatable photosensitizers that in respond to the specific microenvironment. Herein, we report a novel development of metal-organic frameworks (MOFs) composed of meso-Tetra (4-carboxyphenyl) porphine (TCPP) and ferric ion (Fe3+) through a facile one-pot process. Experiments both in vitro and in vivo reveal that the MOF is capable of depredating in response to the high content of H2S in tumor microenvironment of CRC. Accompanying with the degradation and release of TCPP, the fluorescence and photosensitivity effect is switched from “off” to “on”, enabling the MOF to serve as a H2S activatable nano-photosensitizer for real-time fluorescence imaging-guided and targeted PDT of CRC.

Aims: Colon adenocarcinoma (COAD) is responsible for 90% of all colorectal cancer cases and is one of the most common causes of cancer-related deaths worldwide. ATP6V1s (cytosolic V1 domain of vacuolar adenosine triphosphatase) participate in the biological process of transporting hydrogen ions and are implicated in tumor growth and metastasis. ATP6V1C2 as a family member has been documented to associate with esophageal carcinoma and renal clear cell carcinoma, while its roles in COAD remain elusive.Methods: The expression status, potential molecular mechanism, and prognostic value of ATP6V1C2 in COAD were investigated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, its biological roles in COAD were explored through in vitro studies.Results: ATP6V1C2 showed a significantly higher expression level in COAD compared with matched non-cancerous tissues. High expression of ATP6V1C2 predicted a shorter overall survival both in TCGA and GEO COAD datasets, and ATP6V1C2 was identified as an independent factor associated with overall survival in COAD. Bioinformatic analyses showed that high expression of ATP6V1C2 was associated with high epithelial–mesenchymal transition (EMT) score and Wnt signaling pathway was significantly enriched from differentially expressed genes between ATP6V1C2-high and -low group. We also found that high expression of ATP6V1C2 could decrease pathway activity of CD8 T effector implicated in tumor microenvironment (TME). In vitro study revealed that ATP6V1C2 knockdown resulted in aberrant expression of Wnt- and EMT-related genes and inhibited COAD cell proliferation and growth.Conclusion: This is the first study to reveal the molecular functions of ATP6V1C2 in COAD. Our study suggests that overexpressed ATP6V1C2 might promote EMT by activating Wnt signaling pathway, resulting in cancer metastasis and poor prognosis. This study paves the way for understanding potential molecular mechanisms and therapeutic perspectives in COAD.

As the aging process is springing up around the whole world, the problem of sit-to-stand (STS) for the elderly has become the focal point of older people themselves, their families, and society. The key challenge in solving this problem is developing and applying the technology of auxiliary robots for standing up and auxiliary stands. The research is not only to find the appropriate fundamentals from a healthcare perspective in the center of gravity movement (COM) curve of the elderly during STS but also to meet the psychological needs of the elderly during STS in a comfortable, pleasant, and safe way. To obtain the skeleton tracking technology used in this study, we used the Vicon optical motion capture system and automatic moving target indicator (AMTI) 3-D force measuring table to obtain a COM curve of the elderly during STS. The stationary process, speed, and sitting posture analysis during STS were combined in this paper to seek a solution to the psychological needs of the elderly. The analysis is conducted with the integration of medicine, engineering, art, and science into this research. Finally, a movement curve and related dynamic parameters that can truly reflect the STS of the elderly are obtained, and the discussion is provided. The research result can provide theoretical and technical support for the later development of auxiliary robots for standing up and auxiliary stands technology products, so that the elderly can STS comfortably, happily, and safely with the assistance of human–robot interaction.

This study aims to explore the joint usage of multisource scatterometer measurements in polar sea water and ice discrimination. All radar backscatter measurements from current operating satellite scatterometers are considered, including the C-band ASCAT scatterometer on board the MetOp series satellites, the Ku-band scatterometer on board the HY-2B satellite (HSCAT), and the Ku-band scatterometer on board the CFOSAT satellite (CSCAT). By performing seven experiments that use the same support vector machine (SVM) classifier method but with different input data, we find that the SVM model with all available HSCAT, CSCAT, and ASCAT scatterometer data as inputs gives the best performance. In addition to the SVM outputs, we employ the image erosion/dilation techniques and area growth method to reduce misclassifications of sea water and ice. The sea ice extent obtained in this study shows a good agreement with the National Snow and Ice Data Center (NSIDC) sea ice concentration data from the years 2019 to 2021. More specifically, the sea ice areas are closer to the sea ice areas calculated using 15% as the threshold for NSIDC sea ice concentration data in both Arctic and Antarctic. The sea ice edges acquired by the multisource scatterometer show a close correlation with sea ice edges from the Sentinel-1 Synthetic Aperture Radar (SAR) images. In addition, we found that the coverage of multisource scatterometer data in a half-day is usually above 97%, and more importantly, the sea ice areas obtained on the basis of half-day and daily multisource scatterometer data are very close to each other. The presented work can serve as guidance on the usage of all available scatterometer measurements in sea ice monitoring.

The Ku-band scatterometer called CSCAT onboard the Chinese–French Oceanography Satellite (CFOSAT) is the first spaceborne rotating fan-beam scatterometer (RFSCAT). A new algorithm for classification of Arctic sea ice types on CSCAT measurement data using a random forest classifier is presented. The random forest classifier is trained on the National Snow and Ice Data Center (NSIDC) weekly sea ice age and sea ice concentration product. Five feature parameters, including the mean value of horizontal and vertical polarization backscatter coefficient, the standard deviation of horizontal and vertical polarization backscatter coefficient and the copol ratio, are innovatively extracted from orbital measurement for the first time to distinguish water, first-year ice (FYI) and multi-year ice (MYI). The overall accuracy and kappa coefficient of sea ice type model are 93.35% and 88.53%, respectively, and the precisions of water, FYI, and MYI are 99.67%, 86.60%, and 79.74%, respectively. Multi-source datasets, including daily sea ice type from the EUMETSAT Ocean and Sea Ice Satellite Application Facility (OSI SAF), NSIDC weekly sea ice age, multi-year ice concentration (MYIC) provided by the University of Bremen, and SAR-based sea ice type released by Copernicus Marine Environment Monitoring Service (CMEMS) have been used for comparison and validation. It is shown that the most obvious difference in the distribution of sea ice types between the CSCAT results and OSI SAF sea ice type are mainly concentrated in the marginal zones of FYI and MYI. Furthermore, compared with OSI SAF sea ice type, the area of MYI derived from CSCAT is more homogeneous with less noise, especially in the case of younger multiyear ice. In the East Greenland region, CSCAT identifies more pixels as MYI with lower MYIC values, showing better accuracy in the identification of areas with obvious mobility of MYI. In conclusion, this research verifies the capability of CSCAT in monitoring Arctic sea ice classification, especially in the spatial homogeneity and detectable duration of sea ice classification. Given the high accuracy and processing speed, the random forest-based algorithm can offer good guidance for sea ice classification with FY-3E/RFSCAT, i.e., a dual-frequency (Ku and C band) scatterometer called WindRAD.

The Chinese HY-2C satellite was launched on Sep. 21, 2020, carrying the new Ku-band scatterometer (HSCAT-C). Different from the other currently operating scatterometers, the HSCAT-C is in a nonsun-synchronous orbit and as such it will be useful for the cross-calibration of sea surface wind products from current space-borne scatterometers and radiometers. In this article, the HSCAT-C wind products are validated by comparing to collocated winds from buoys, European Centre for Medium-Range Weather Forecasts model, and several other scatterometers. The results show that the quality of HSCAT-C winds is very good: in comparison with buoy winds, the wind speed standard deviation and direction root-mean-square error are 1.03 m/s and 15.9°, respectively. The HSCAT-C winds show very good agreements with the HSCAT-B winds, especially in the range of [4, 17] m/s. In addition, as HSCAT-C is a rotating pencil-beam scatterometer, some common error characteristics are also clearly found in the wind products. Based on the validation results and existing scatterometer application experience, it is believed that the availability of the HSCAT-C wind product would greatly benefit the scientific and user community.

Sustainable agriculture is a vital part of the UN Sustainable Development Goals. While tremendous achievements in the agriculture sector in China have been made, a series of problems are challenging the sustainable development of the agriculture management and agriculture economy. In this paper, the level of sustainable agriculture development was evaluated by constructing an entropy-TOPSIS model. The sustainable agricultural development level evaluation system was subsequently established, including 4 first-level criteria (economy, society, environment and resources) and 25 second-level criteria. Corresponding data on 13 cities in Jiangsu Province, China (from 2016 to 2019) were collected. Moreover, the main obstacle factors restricting the sustainable agriculture development level were analyzed through the obstacle diagnosis model. The Tobit regression model was established for an empirical study on its influencing factors. The results showed that the agricultural sustainable development level in Jiangsu Province is going upward, and the development level gaps between various prefecture-level cities are narrowing; the output values in agriculture, forestry, animal husbandry and fishery services, per capita disposable income of farmers and other aspects are the main obstacle factors for agricultural sustainable development. The research objective of this paper was to improve the index system of agricultural sustainable development, analyze the influencing mechanism and obstacle factors, and explore the promotion path of agricultural sustainable development in Jiangsu by optimizing the spatial layout. The main innovation of this paper was bringing the five interrelated and interactive dimensions of “economy, society, environment, ecology, and resources” into the same analytical framework to analyze the concept and connotation of agricultural sustainable development.

The launch of the Haiyang-2 (HY-2) satellite constellation fosters the quick acquisition of global sea surface vector winds from the perspective of remote sensing. This study intends to develop a six-hourly mesoscale analysis of sea surface winds based on the microwave scatterometers onboard the HY-2 satellite series, with the objective of meeting the considerable demand for accurate and gap-free ocean wind forcing products. First, the accuracy of HY-2 scatterometers (HSCATs) in measuring wind is evaluated. In particular, the standard deviation (SD) errors of HSCATs data are assessed using the collocated buoy measurements with different temporal windows in order to account for the temporal representativeness errors in the blending analysis. Afterwards, a two-dimensional variational (2D-Var) method is implemented to blend the HSCATs measured winds and the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis winds over the global ocean surface. This approach is different from existing methods in that it takes both wind error and background error correlation into account. The results show that the blended wind product is of a promising quality compared with independent wind references. Interestingly, the blended winds derived from 2D-Var in combination with an empirical background error correlation show smaller SD errors than those using a Gaussian error correlation function. Overall, the blended wind product should be valuable for forcing global ocean models or describing air-sea interaction processes on a scale close to the scatterometer measurements.

BackgroundLymph node metastasis of rectal neuroendocrine tumors (RNETs) predicts poor prognosis. However, the assessment of lymph node metastasis remains a challenge. It has been reported that 68Ga-DOTANOC and 18F-FDG PET-CT scans could be employed in the work-up of rectal neuroendocrine tumors (RNETs). This study aimed to assess both tracers’ ability to identify primary tumors and lymph node (LN) metastasis in RNETs.MethodsA total of 537 patients with RNETs were enrolled from January 2014 to January 2021. Both 68Ga-DOTANOC and 18F-FDG PET-CT scans were used to evaluate primary tumors and LN group metastasis. PET images were evaluated through visual and semiquantitative assessment. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of SUVmax of 68Ga-DOTANOC and 18F-FDG PET in predicting LN group metastasis.ResultsFifty-two patients with preoperative 68Ga-DOTANOC with 18F-FDG PET-CT scans underwent endoscopic biopsy or dissection of the primary tumor, while 11 patients underwent rectal surgery together with regional LN dissection. For primary tumors, 68Ga-DOTANOC had a sensitivity of 89.58% and a positive predictive value (PPV) of 95.56% through visual assessment, while 18F-FDG PET-CT showed 77.08% sensitivity and 97.37% PPV. For the prediction of LN group metastasis, 68Ga-DOTANOC PET-CT had 77.78% sensitivity and 91.67% specificity, while 18F-FDG PET-CT had 38.89% sensitivity and 100% specificity according to visual assessment. The area under the ROC curves (AUC) for 68Ga-DOTANOC PET/CT was 0.852 (95%CI:0.723-0.981) with an optimal SUVmax cut-off value of 2.25, while the AUC for 18F-FDG PET were 0.664 (95%CI:0.415-0.799) with an optimal SUVmax cut-off value of 1.05.ConclusionsThis study showed that 68Ga-DOTANOC PET-CT was a promising tool for detecting LN metastasis in RNETs with high sensitivity and specificity in visual assessment and semiquantitative assessment, which was better than 18F-FDG PET-CT.

Danhong injection (DHI) is a compound Chinese medicine widely used in China for treatment of ischemic cardio-cerebrovascular diseases. However, limited data are available regarding the protective effect of DHI on the ischemic penumbra in ischemic stroke. This study aimed to investigate the effect of intravenous DHI on neuronal injure in the ischemic penumbra after cerebral ischemia/reperfusion (CI/R), focusing especially on the involvement of intracellular energy metabolism coupling. Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion for 60 min followed by reperfusion with or without intravenous DHI (0.5, 1.0, or 2.0 mL/kg) once daily for 7 days. Post-treatment with DHI ameliorated neurological defects, diminished cerebral infarction, alleviated cerebral edema, improved microcirculatory perfusion after 7days of reperfusion, and inhibited apoptosis and enhanced neuronal survival in the ischemic penumbra. In addition, DHI significantly ameliorated oxidative stress, reduced DNA damage, and inhibited the activation of PARP1/AIF pathway, thereby restoring cytoplasmic glycolytic activity. Furthermore, this drug increased PDH activity by inhibiting the HIF1α/PDK1 signaling pathway, thus eliminating the inhibitory effect of CI/R on mitochondrial metabolism. The results of this study suggest that DHI can alleviate cerebral edema after CI/R and rescue the ischemic penumbra, and these protective effects are due to the regulation of intracellular energy metabolic coupling.

Traditional Chinese Medicine formulas, which are usually considered exerting their holistic clinical benefits via multi-component, multi-target manner, are unique resources for the discovery of multi-component drug combinations. In order to screen and optimize the functional compound combination (FCC) from TCM, we established a novel four-step ‘GCIC’ strategy, including ‘Global profiling’, ‘Chemical structural classification’, ‘Intra-group screening’ and ‘Component-knockout optimization’. Following this strategy, an FCC consisted of four components from Danhong Injection (DHI) was identified, containing ferulic acid, cryptotanshinone, quercetin and anhydrosafflor yellow B. The holistic neuroprotective effects of the FCC were further investigated, indicating that the combination can both activate the antioxidative and anti-inflammatory responses in PC12 cells to protect them from oxidative stress. Major signaling pathways as Nrf2/ARE and Nrf2/AMPK/GSK3β were involved in the protective process of FCC. The ‘GCIC’ strategy established in this study might provide an alternation to traditional strategies in discovering the bioactive components from herbal medicines, especially compounded TCM formulas.

MicroRNA (miR) sponges containing miR binding sequences constitute a potentially powerful molecular therapeutic strategy. Recently, naturally occurring circular RNAs (circRNAs) were shown to function as efficient miR sponges in cancer cells. We hypothesized that synthetic circRNA sponges could achieve therapeutic loss-of-function targeted against specific miRs. Linear RNA molecules containing miR-21 binding sites were transcribed in vitro; after dephosphorylation and phosphorylation, circularization was achieved using 5′-3′ end-ligation by T4 RNA ligase 1. circRNA stability was assessed using RNase R and fetal bovine serum. Competitive inhibition of miR-21 activity by a synthetic circRNA sponge was assessed using luciferase reporter, cell proliferation, and cell apoptosis assays in three gastric cancer cell lines. circRNA effects on downstream proteins were also delineated by Tandem Mass Tag (TMT) labeling (data available via ProteomeXchange identifier PRIDE: PXD008584), followed by western blotting. We conclude that artificial circRNA sponges resistant to nuclease digestion can be synthesized using simple enzymatic ligation steps. These sponges inhibit cancer cell proliferation and suppress the activity of miR-21 on downstream protein targets, including the cancer protein DAXX. In summary, synthetic circRNA sponges represent a simple, effective, convenient strategy for achieving targeted loss of miR function in vitro, with potential future therapeutic application in human patients. Keywords: synthetic circular RNA, microRNA sponge, microRNA loss-of-function, gastric carcinoma, molecular therapy

The estimation of tropical cyclone (TC) intensity using Ku-band scatterometer data is challenging due to rain perturbation and signal saturation in the radar backscatter measurements. In this paper, an alternative approach to directly taking the maximum scatterometer-derived wind speed is proposed to assess the TC intensity. First, the TC center location is identified based on the unique characteristics of wind stress divergence/curl near the TC core. Then the radial extent of 17-m/s winds (i.e., R17) is calculated using the wind field data from the Haiyang-2B (HY-2B) scatterometer (HSCAT). The feasibility of HSCAT wind radii in determining TC intensity is evaluated using the maximum sustained wind speed (MSW) in the China Meteorological Administration best-track database. It shows that the HSCAT R17 value generally better correlates with the best-track MSW than the HSCAT maximum wind speed, therefore indicating the potential of using the HSCAT data to improve the TC nowcasting capabilities.

Chimeric antigen receptor (CAR) T-cell immunotherapy still faces many challenges in the treatment of solid tumors, one of which is T-cell dysfunction or exhaustion. Immunomodulator lenalidomide may improve CAR T-cell function. In this study, the effects of lenalidomide on CAR T-cell functions (cytotoxicity, cytokine secretion, and cell proliferation) were investigated. Two different CAR T cells (CD133-specific CAR and HER2-specific CAR) were prepared, and the corresponding target cells including human glioma cell line U251 CD133-OE that overexpress CD133 and human breast cancer cell line MDA-MB-453 were used for functional assay. We found that lenalidomide promoted the killing of U251 CD133-OE by CD133-CAR T cells, the cytokine secretion, and the proliferation of CD133-CAR T cells. Lenalidomide also enhanced the cytotoxicity against MDA-MB-453 and the cytokine secretion of HER2-CAR T cells but did not affect their proliferation significantly. Furthermore, lenalidomide may regulate the function of CAR T cells by inducing the degradation of transcription factors Ikaros and Aiolos.

Chimeric antigen receptor (CAR) T cell therapy still faces the challenge of immunosuppression when treating solid tumors. TGF-β is one of the critical factors in the tumor microenvironment to help tumors escape surveillance by the immune system. Here we tried using the combination of a small molecule inhibitor of TGF-β receptor I, Galunisertib, and CAR T cells to explore whether Galunisertib could enhance CAR T cell function against solid tumor cells. In vitro experiments showed Galunisertib could significantly enhance the specific cytotoxicity of both CD133- and HER2-specific CAR T cells. However, Galunisertib had no direct killing effect on target cells. Galunisertib significantly increased the cytokine secretion of CAR T cells and T cells that do not express CAR (Nontransfected T cells). Galunisertib did not affect the proliferation of T cells, the antigen expression on target cells and CD69 on CAR T cells. We found that TGF-β was secreted by T cells themselves upon activation, and Galunisertib could reduce TGF-β signaling in CAR T cells. Our findings can provide the basis for further preclinical and clinical studies of the combination of Galunisertib and CAR T cells in the treatment of solid tumors.

The Chinese HY-2D satellite was launched on 19 May 2021, carrying a Ku-band scatterometer. Together with the operating scatterometers onboard the HY-2B and HY-2C satellites, the HY-2 series scatterometer constellation was built, constituting different satellite orbits and hence opportunity for mutual intercomparison and intercalibration. To achieve intercalibration of backscatter measurements for these scatterometers, this study presents and performs three methods including: (1) direct comparison using collocated measurements, in which the nonlinear calibrations can also be derived; (2) intercalibration over the Amazon rainforest; (3) and the double-difference technique based on backscatter simulations over the global oceans, in which a geophysical model function and numerical weather prediction (NWP) model winds are needed. The results obtained using the three methods are comparable, i.e., the differences among them are within 0.1 dB. The intercalibration results are validated by comparing the HY-2 series scatterometer wind speeds with NWP model wind speeds. The curves of wind speed bias for the HY-2 series scatterometers are quite similar, particularly in wind speeds ranging from 4 to 20 m/s. Based on the well-intercalibrated backscatter measurements, consistent sea surface wind products from HY-2 series scatterometers can be produced, and greatly benefit data applications.

The Ku-band scatterometer called CSCAT onboard the Chinese–French Oceanography Satellite (CFOSAT) is the first spaceborne rotating fan-beam scatterometer (RFSCAT). This paper performs sea ice monitoring with the CSCAT backscatter measurements in polar areas. The CSCAT measurements have the characteristics of diverse incidence and azimuth angles and separation between open water and sea ice. Hence, five microwave feature parameters, which show different sensitivity to ice or water, are defined and derived from the CSCAT measurements firstly. Then the random forest classifier is selected for sea ice monitoring because of its high overall accuracy of 99.66% and 93.31% in the Arctic and Antarctic, respectively. The difference of features ranked by importance in different seasons and regions shows that the combination of these parameters is effective in discriminating sea ice from water under various conditions. The performance of the algorithm is validated against the sea ice edge data from the EUMETSAT Ocean and Sea Ice Satellite Application Facility (OSI SAF) on a global scale in a period from 1 January 2019 to 10 May 2021. The mean sea ice area differences between CSCAT and OSI SAF product in the Arctic and Antarctic are 0.2673 million km2 and −0.4446 million km2, respectively, and the sea ice area relative errors of CSCAT are less than 10% except for summer season in both poles. However, the overall sea ice area derived from CSCAT is lower than the OSI SAF sea ice area in summer. This may be because the CSCAT is trained by radiometer sea ice concentration data while the radiometer measurement of sea ice is significantly affected by melting in the summer season. In conclusion, this research verifies the capability of CSCAT in monitoring polar sea ice using a machine learning-aided random forest classifier. This presented work can give guidance to sea ice monitoring with radar backscatter measurements from other spaceborne scatterometers, particular for the recently launched FY-3E scatterometer (called WindRad).

There have been no reports describing the effects of cancer cell–derived extracellular vesicles (EVs) on three-dimensional organoids. In this study, we delineated the proneoplastic effects of esophageal adenocarcinoma (EAC)–derived EVs on gastric organoids (gastroids) and elucidated molecular mechanisms underlying these effects. EVs were identified using PKH-67 staining. Morphologic changes, Ki-67 immunochemistry, cell viability, growth rates, and expression levels of miR-25 and miR-210, as well as of their target mRNAs, were determined in gastroids co-cultured with EAC-derived extracellular vesicles (c-EVs). C-EVs were efficiently taken up by gastroids. Notably, c-EV–treated gastroids were more crowded, compact, and multilayered and contained smaller lumens than did those cultured in organoid medium alone or in EAC-conditioned medium that had been depleted of EVs. Moreover, c-EV–treated gastroids manifested increased proliferation and cellular viability relative to medium-only or EV-depleted controls. Expression levels of miR-25 and miR-210 were significantly higher, and those of PTEN and AIFM3 significantly lower, in c-EV–treated versus medium-only or EV-depleted control groups. Inhibitors of miR-25 and miR-210 reversed the increased cell proliferation induced by c-exosomes in co-cultured gastroids by lowering miR-25 and miR-210 levels. In conclusion, we have constructed a novel model system featuring the co-culture of c-EVs with three-dimensional gastroids. Using this model, we discovered that cancer-derived EVs induce a neoplastic phenotype in gastroids. These changes are due, at least in part, to EV transfer of miR-25 and miR-210.

A sea ice detection algorithm based on Fisher’s linear discriminant analysis is developed to segment sea ice and open water for the Ku-band scatterometer onboard the China’s Hai Yang 2A Satellite (HY-2A/SCAT). Residual classification errors are reduced through image erosion/dilation techniques and sea ice growth/retreat constraint methods. The arctic sea-ice-type classification is estimated via a time-dependent threshold derived from the annual backscatter trends based on previous HY-2A/SCAT derived sea ice extent. The extent and edge of the sea ice obtained in this study is compared with the Special Sensor Microwave Imager/Sounder (SSMIS) sea ice concentration data and the Sentinel-1 SAR imagery for verification, respectively. Meanwhile, the classified sea ice type is compared with a multi-sensor sea ice type product based on data from the Advanced Scatterometer (ASCAT) and SSMIS. Results show that HY-2A/SCAT is powerful in providing sea ice extent and type information, while differences in the sensitivities of active/passive products are found. In addition, HY-2A/SCAT derived sea ice products are also proved to be valuable complements for existing polar sea ice data products.

An objectively trained model for tropical cyclone intensity estimation from routine satellite infrared images over the Northwestern Pacific Ocean is presented in this paper. The intensity is correlated to some critical signals extracted from the satellite infrared images, by training the 325 tropical cyclone cases from 1996 to 2007 typhoon seasons. To begin with, deviation angles and radial profiles of infrared images are calculated to extract as much potential predicators for intensity as possible. These predicators are examined strictly and included into (or excluded from) the initial predicator pool for regression manually. Then, the “thinned” potential predicators are regressed to the intensity by performing a stepwise regression procedure, according to their accumulated variance contribution rates to the model. Finally, the regressed model is verified using 52 cases from 2008 to 2009 typhoon seasons. The R2 and Root Mean Square Error are 0.77 and 12.01 knot in the independent validation tests, respectively. Analysis results demonstrate that this model performs well for strong typhoons, but produces relatively large errors for weak tropical cyclones.