Search

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24–30 Fr while maintaining a balloon pressure of 25–35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16–165) with median estimated blood loss of 2 ml (range 0–150). The median postoperative hospital stay was 3 d (range 1–15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3–100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

Abstract Construction of a solid electrolyte interphase (SEI) of zinc (Zn) electrode is an effective strategy to stabilize Zn electrode/electrolyte interface. However, single-layer SEIs of Zn electrodes undergo rupture and consequent failure during repeated Zn plating/stripping. Here, we propose the construction of a robust bilayer SEI that simultaneously achieves homogeneous Zn2+ transport and durable mechanical stability for high Zn utilization rate (ZUR) and Coulombic efficiency (CE) of Zn electrode by adding 1,3-Dimethyl-2-imidazolidinone as a representative electrolyte additive. This bilayer SEI on Zn surface consists of a crystalline ZnCO3-rich outer layer and an amorphous ZnS-rich inner layer. The ordered outer layer improves the mechanical stability during cycling, and the amorphous inner layer homogenizes Zn2+ transport for homogeneous, dense Zn deposition. As a result, the bilayer SEI enables reversible Zn plating/stripping for 4800 cycles with an average CE of 99.95% (± 0.06%). Meanwhile, Zn | |Zn symmetric cells show durable lifetime for over 550 h with a high ZUR of 98% under an areal capacity of 28.4 mAh cm−2. Furthermore, the Zn full cells based on the bilayer SEI functionalized Zn negative electrodes coupled with different positive electrodes all exhibit stable cycling performance under high ZUR.

Abstract Given its nearly ubiquitous expression on plasma cells and limited expression on essential normal tissue, the G protein-coupled receptor class C group 5 member D (GPRC5D) presents a promising opportunity for utilization as an immunotherapy target in multiple myeloma (MM). The therapeutic strategies targeting GPRC5D, such as bispecific antibodies (BsAbs), chimeric antigen receptor (CAR) T cells, and antibody–drug conjugates (ADCs), have been prominently emphasized in relapsed/refractory MM (R/R MM) in recent years. Further clinical trials are necessary to confirm the long-term efficacy of GPRC5D-targeting immunotherapies alone, explore their potentials co-targeting with other specific antigens, or investigate their combinations with existing treatments to overcome MM resistance. This review provides an overview of current research progress in GPRC5D, encompassing its biological characteristics and translational journey from laboratory to clinical application.

Objective: To elucidate the small molecule peptides in Shanxi vinegar and further explore their potential mechanism of action against cardiovascular and other related diseases. Methods: The small molecule peptides of Shanxi vinegar were analyzed using ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The targets and pathways of small molecule peptides were predicted via Genecards, Drugbank 5.0, DAVID, and other databases. The "component-target-signaling pathway-disease" network was constructed using Cytoscape software. Autodock Dock 1.5.6 and Pymol 2.2.0 were used to perform molecular docking between the core targets of Shanxi vinegar and the components. Results: A total of 41 small molecule peptide compounds were identified by UPLC-Q-TOF-MS/MS, which including 27 cyclic dipeptides, 10 linear dipeptides, and 4 tripeptides. The "component-target-signaling pathway-disease" network, contributing to the health-promoting effects on cardiovascular and obesity, encompasses 14 active components and 109 drug targets. A total of 59 pathways were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking results demonstrated favorable binding interactions between the core targets (F2, MAPK1, MMP9, VCAM1) and the corresponding active components Cyclo (Leu-Pro), Val-Val, Pro-Phe, Cyclo (His-Pro) in Shanxi vinegar, which preliminarily confirming the accuracy of the network pharmacology prediction. Conclusion: Shanxi vinegar might prevent and regulate cardiovascular diseases and obesity through multiple components, targets and pathways.

Abstract Distal hereditary motor neuropathies (dHMN) are a group of heterogeneous diseases and previous studies have reported that the compound heterozygous recessive MME variants cause dHMN. Our study found a novel homozygous MME variant and a reported compound heterozygous MME variant in two Chinese families, respectively. Next-generation sequencing and nerve conduction studies were performed for two probands. The probands in two families presented with the muscle weakness and wasting of both lower limbs and carried a c.2122 A > T (p.K708*) and c.1342 C > T&c.2071_2072delinsTT (p.R448*&p.A691L) variant, respectively. Prominently axonal impairment of motor nerves and slight involvement of sensory nerves were observed in nerve conduction study. Our study reported a “novel” nonsense mutation and a missense variant of autosomal recessive late-onset dHMN and reviewed reported MME variants associated with dHMN phenotype.

Abstract Esophageal cancer (EC) mainly includes two histological subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma, which is of high morbidity and mortality. With the continuous development of medical technology, the treatment of EC has been greatly improved, but its prognosis is still unfavorable. Recent single‐cell RNA‐sequencing (scRNA‐seq) is expected to bring breakthroughs in the treatment of EC. First, we identified T cell marker genes and generated signature by analyzing scRNA‐seq data from Expression Omnibus (GEO) database and TCGA database. Then, an immune prognostic model was constructed using the least absolute shrinkage and selection operator. We found that the survival rate of ESCC varied significantly among the low‐ and high‐risk groups. Two genes from T cell signature, DCPS and CYB5R3, were expressed in ESCC cells. Collectively, our study proposed a novel prognostic signature for ESCC patients based on T cell marker genes.

Abstract Purpose To present the experience of ileal ureter with ileocystoplasty (IUC), and compare the outcomes of IUC in minimally invasive procedures to open procedures. Patients and methods From December 2017 to April 2023, twenty patients underwent IUC in open or minimally invasive (including laparoscopic and robotic) procedures. The baseline characteristics, perioperative data and follow-up outcomes were collected. Success was defined as relief of clinical symptoms, stable postoperative serum creatine and absence of radiographic obstruction. The perioperative and follow-up outcomes of open procedures and minimally invasive procedures were compared. Results The etiology included pelvic irradiation (14/20), urinary tuberculosis (3/20) and surgical injury (3/20). Bilateral ureter strictures were repaired in 15 cases. The surgeries conducted consisted of open procedures in 9 patients and minimally invasive procedures in 11 patients. Compared to open procedures, minimally invasive surgeries had less median estimated blood loss (EBL) (100 ml vs. 300 min, p = 0.010) and shorter postoperative hospitalization (27 d vs. 13 d, p = 0.004). Two patients in the open group experienced grade 3 complications (sigmoid fistula and acute cholecystitis in one patient, and pulmonary embolism in another patient). Over a median follow-up period of 20.1 months, the median bladder functional capacity was 300 ml, with a 100% success rate of IUC. Conclusion IUC is feasible in both open and minimally invasive procedures, with acceptable complications and a high success rate. Minimally invasive procedures can have less EBL and shorter postoperative hospitalization than open procedure. However, prospective studies with larger groups and longer follow-up are needed.

Accumulation of acylcarnitines is a characteristic feature of various metabolic disorders affecting fatty acid metabolism. Despite extensive research, no specific molecules have been identified to induce ferroptosis through the regulation of acylcarnitine metabolism. In this study, acylcarnitine accumulation was identified based on cell metabolomics study after the treatment with Stemona alkaloid derivative (SA-11), which was proved to induce ferroptosis in our previous research. Furthermore, the CPT-1 level was proved to significantly increase, while the CPT-2 level indicated no significant difference, which resulted in the accumulation of acylcarnitine. Besides, the ferroptosis-inducing ability of SA-11 was significantly enhanced by the addition of exogenous acylcarnitine, presumably due to the production of additional ROS. This hypothesis was corroborated by the observation of increased ROS levels in HCT-116 cells treated with SA-11 compared to the control group. These findings suggest that targeting acylcarnitine metabolism, particularly through CPT-1, may offer a novel therapeutic strategy for cancer treatment by enhancing ferroptosis induction.

Abstract Practical application of lithium–sulfur (Li–S) batteries is severely impeded by the random shuttling of soluble lithium polysulfides (LiPSs), sluggish sulfur redox kinetics, and uncontrollable growth of lithium dendrites, particularly under high sulfur loading and lean electrolyte conditions. Here, nitrogen‐doped bronze‐phase TiO2(B) nanosheets with oxygen vacancies (OVs) grown in situ on MXenes layers (N‐TiO2−x(B)‐MXenes) as multifunctional interlayers are designed. The N‐TiO2−x(B)‐MXenes show reduced bandgap of 1.10 eV and high LiPSs adsorption‐conversion‐nucleation‐decomposition efficiency, leading to remarkably enhanced sulfur redox kinetics. Moreover, they also have lithiophilic nature that can effectively suppress dendrites growth. The cell based on the N‐TiO2−x(B)‐MXenes interlayer under sulfur loading of 2.5 mg cm−2 delivers superior cycling performance with a high specific capacity of 690.7 mAh g−1 over 600 cycles at 1.0 C. It still has a notable areal capacity of 6.15 mAh cm−2 after 50 cycles even under a high sulfur loading of 7.2 mg cm−2 and a low electrolyte‐to‐sulfur (E/S) ratio of 6.4 µL mg−1. The Li‐symmetrical battery with the N‐TiO2−x(B)‐MXenes interlayer showcases a low over‐potential fluctuation with 21.0 mV throughout continuous lithium plating/stripping for 1000 h. This work offers valuable insights into the manipulation of defects and heterostructures to achieve high‐energy Li–S batteries.

Abstract Background and Objective To explore the association between protein quantitative trait loci (pQTL‐SNPs) and the risk of LUAD. Methods “Blood +” high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non‐tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL‐SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL‐SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein. Results A total of 7 pQTL‐SNPs were significantly associated with altered LUAD risk (p 1, p

The effectiveness, tolerance, and safety of pesticides must be established before their scientific or rational. This study evaluates the field control efficacy of broflanilide, tetraniliprole, and chlorantraniliprole in combating Spodoptera frugiperda in maize crops, as well as the resistance of S. frugiperda to these three diamide pesticides after exposure. By assessing field control efficiency, toxicity, effects on development and reproduction, and detoxification enzyme activity of these diamide pesticides on S. frugiperda, highlights broflanilide's significant insecticidal potential. A highly sensitive and efficient method using QuEChERS/HPLCMS/MS was developed to simultaneously detect residues of these three pesticides on maize. Initial concentrations of broflanilide, tetraniliprole, and chlorantraniliprole ranged from 2.13 to 4.02 mg/kg, with their respective half-lives varying between 1.23 and 1.51 days. Following foliar application, by the time of harvest, the terminal residue concentrations of these pesticides were all under 0.01 mg/kg. Chronic dietary intake risk assessments and cumulative chronic dietary exposure for three pesticides indicated that the general population's terminal residue concentration was within acceptable limits. Not only does this research provide valuable insights into field control efficiency, insecticidal effects, resistance, residues, and risk assessment results of broflanilide, tetraniliprole, and chlorantraniliprole on maize, but additionally, it also paves the way for setting suitable Maximum Residue Limits (MRLs) values based on pre-harvest interval values, rational dosage, and application frequency.

ABSTRACT Purpose: It has been reported that exhaustive exercise (EE) causes myocyte injury, and eventually damages the function of the myocardia. Albiflorin (AF) has anti-inflammatory, antioxidant, and anti-apoptosis effects. In this study, we determined whether AF could mitigate the EE-induced myocardial injury and research the potential mechanisms. Methods: The rat model of EE was built by forced treadmill running method. Rats were intraperitoneally injected with AF before EE once daily for one week. The relative factors levels were examined by commercial kits. The apoptosis was appraised using a TdT-mediated dUTP nick end labeling assay kit. The ACSL4, GPX4, Nrf2, pAKT/AKT, and HO-1 contents were assessed by western blot. Results: AF lessened EE-induced cardiac myocytes ischemic/hypoxic injury and reduced the contents of myocardial injury biomarkers in the serum. AF lessened EE-induced cardiac myocyte apoptosis, inflammatory response, oxidative stress, and ferroptosis in myocardial tissues. However, the influences of AF were overturned by the co-treatment of AF and LY294002. AF activated the AKT/Nrf2/HO-1 signaling pathway in myocardial tissues in vivo. Conclusions: AF could curb cardiac myocytes ferroptosis, thus diminishing the EE-induced myocardial injury through activating the AKT/Nrf2/HO-1 cascade.

Abstract Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM.

Abstract The Ningdong coalfield has played a pivotal role in advancing local economic development and meeting national energy. Nevertheless, mining operations have engendered ecological challenges encompassing subterranean water depletion, land desertification, and ground subsidence, primarily stemming from the disruption of coal seam roof strata. Consequently, the local ecosystem has incurred substantial harm. Water-preserved coal mining presently constitutes the pivotal technology in mitigating this problem. The primary challenge of this technique lies in identifying critical aquifer layers and understanding the heights of water-conducting fracture zones. To obtain a precise comprehension of the seepage patterns within the upper coal seam aquifer during mining, delineate the extent of water-conducting fracture zones, non-invasive geophysical techniques such as time-lapse electrical resistivity tomography (TL-ERT), magnetic resonance sounding (MRS), and spontaneous potential (SP) have been employed to monitor alterations within the shallow coalfield’s aquifer throughout the mining process in the Ningdong coalfield. By conducting meticulous examinations of fluctuations in resistivity, moisture content, and self-potential within the superjacent strata during coal seam extraction, the predominant underground water infiltration strata were ascertained, concurrently enabling the estimation of the development elevation of water-conducting fracture zones. This outcome furnishes a geophysical underpinning for endeavors concerning local water-preserved coal mining and ecological rehabilitation.

Abstract Background Chronic graft-versus-host disease (cGVHD) is an immune-related disorder that is the most common complication post-allogenic hematopoietic stem cell transplant. Corticosteroids with or without calcineurin inhibitors (CNIs) remain the mainstay of cGVHD treatment for first-line therapy. However, for many patients, cGVHD symptoms cannot be effectively managed and thus require second-line therapy. Currently, there is no approved treatment for second-line cGVHD treatment in China. In this study, belumosudil, a highly selective and potent rho-associated coiled-coil-containing protein kinase-2 inhibitor demonstrated to be effective for cGVHD in the United States and other Western countries, is investigated in patients with cGVHD in China for its overall benefit–risk balance. Methods This multicenter, open-label phase II study evaluated the safety, efficacy, and pharmacokinetics of oral belumosudil 200 mg once daily in cGVHD patients who had been treated with at least one line of systemic therapy in China. The primary endpoint was overall response rate (ORR); each individual patient’s response was assessed by the investigator using the 2014 National Institutes of Health consensus criteria. Secondary endpoints were duration of response (DOR), time to response (TTR), changes in Lee Symptom Scale (LSS) score, organ response rate, corticosteroid dose change, CNI dose change, failure-free survival, time-to-next-treatment, overall survival, and safety. Results Thirty patients were enrolled in the study with a median follow-up time of 12.9 months. ORR was 73.3% (95% confidence interval: 54.1–87.7%) and all responders achieved partial response. Median DOR among responders was not reached and median TTR was 4.3 weeks (range: 3.9–48.1). Fifteen patients (50.0%) achieved clinically meaningful response in terms of reduction in LSS score by ≥ 7 points from baseline. Corticosteroid and CNI dose reductions were reported in 56.7% (17/30) and 35.0% (7/20) of patients, respectively. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity, with 11 patients (36.7%) experiencing grade ≥ 3 TEAEs. The most common grade ≥ 3 TEAE was pneumonia (n = 5, 16.7%). Conclusions Belumosudil treatment demonstrated a favorable benefit–risk balance in treating cGVHD patients who previously have had standard corticosteroid therapy in China where approved second-line setting is absent. Trial registration ClinicalTrials.gov identifier NCT04930562.

Abstract. Continuous cutaneous urinary diversion is challenging when the appendix is physically unavailable. The Yang–Monti channel is an alternative to the tunneled appendix for urinary diversion. We present a case involving a 49-year-old man who underwent total urethrectomy and cystostomy 10 months previously. No tumor recurrence was observed; however, the patient experienced severe catheter-related bladder irritation after the procedure. The patient was readmitted to the authors’ hospital and underwent laparoscopic continent cutaneous urinary diversion using extracorporeal construction of a modified Yang–Monti channel. The operation lasted 232 minutes, with an estimated blood loss of 10 mL. The patient was discharged from hospital 6 days after surgery and removal of the cystostomy tube. After this, clean intermittent catheterization was performed every 3 hours for 4 weeks. Five years after the procedure, the modified Yang–Monti channel was still used for clean intermittent catheterization without any stomal stenosis being observed. The patient was satisfied with his postoperative quality of life.

Abstract Message passing neural networks such as graph convolutional networks (GCN) can jointly consider various types of features for social bot detection. However, the expressive power of GCN is upper-bounded by the 1st-order Weisfeiler–Leman isomorphism test, which limits the detection performance for the social bots. In this paper, we propose a subgraph encoding based GCN model, SEGCN, with stronger expressive power for social bot detection. Each node representation of this model is computed as the encoding of a surrounding induced subgraph rather than encoding of immediate neighbors only. Extensive experimental results on two publicly available datasets, Twibot-20 and Twibot-22, showed that the proposed model improves the accuracy of the state-of-the-art social bot detection models by around 2.4%, 3.1%, respectively.

ABSTRACTBackground: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL.Methods: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24.Results: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, β2-microglobulin (β2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P

IntroductionThis study aims to investigate whether exercise adherence and positive mental character significantly affect subjective well-being among Chinese college students during the COVID-19 pandemic and whether positive mental character plays a mediating role.MethodsThe study employed questionnaires, including the Exercise Adherence Scale, the Positive Mental Character Scale, and the Subjective Well-Being Scale, which were administered to students across seven universities in Henan Province, China. A total of 1,001 participants were analyzed in the final sample. Data were analyzed using SPSS 21.0 for descriptive statistics, independent samples T-test, correlation, and regression analyses. Furthermore, structural equation model with AMOS was conducted to examine the potential mediating effect of positive mental characteristics on the relationship between exercise adherence and subjective well-being.ResultsThe results indicated significant differences in exercise adherence, positive mental character, and subjective well-being between male and female participants, with males scoring higher in all three domains. Among Chinese university students during the COVID-19 pandemic, there was a significant correlation among exercise adherence, positive mental character, and subjective well-being. Exercise adherence was found to have a significant and positive impact on both positive mental character and subjective well-being. Additionally, it was found that positive mental character had a significant positive association with subjective well-being. The mediating role of positive mental character in the relationship between exercise adherence and subjective well-being was partially supported.DiscussionExercise adherence among Chinese college students had a significant positive association on both positive mental character and subjective well-being throughout the COVID-19 pandemic. The exercise adherence can directly or indirectly enhance subjective well-being through its association with positive mental character. Therefore, positive mental and subjective well-being can be enhanced by consistent physical activity even during a pandemic.

The research on energy storage resource management is an important measure to cope with the present problem of uncertainty in the use of renewable energy, in order to explore the evolution of the research focus and future trend of energy storage resource management under the uncertainty of renewable energy, this paper adopts the method of bibliometric analysis, and conducts a visual analysis of the relevant 800 documents in the core collection of the Web of Science by using the CiteSpace to draw co-occurrence maps and analyze the collaborative networks of different countries/regions, institutions and authors in this field, and further conducted journal co-citation analysis, literature co-citation analysis and author co-citation analysis. The keyword co-occurrence, emergent analysis, and cluster co-occurrence analysis reveal the current research focus and trend in this field, and summarize and propose four future key focus directions: energy storage technology improvement, energy storage system integration, expansion of business models for energy storage resource management, and intelligent control of energy storage system, which provide new research paths for solving the problem of renewable energy uncertainty in the future.

Summary: Background: MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively. Methods: This multicentre, single-arm, phase 1b/2 trial aimed to explore the efficacy, pharmacokinetics, and safety of MIL62 combined with lenalidomide in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Eligible patients included those who had histopathologically confirmed CD20 positive FL (grade 1–3a) or MZL and failed to be treated with rituximab. Patients received intravenously infused MIL62 1000 mg (cycle 1: day 1, 15; cycles 2–8: day 1, cycles 10 and 12: day 1) combined with oral lenalidomide (once a day, days 2–22, the initial dose was 10 mg, and the maximum dose was 20 mg) for 12 cycles, 28 days as a cycle. The primary endpoint was objective response rate (ORR) assessed by investigator per Lugano 2014 criteria every 3 cycles. This study was registered in ClinicalTrials.gov (NCT04110301). Findings: Between November 22, 2019 and December 22, 2020, 54 patients were enrolled from 11 hospitals in China and received study treatment. Fifty patients were included in the efficacy analysis set, and 43 patients (86%, 95% CI: 73, 94) achieved objective response, meeting the pre-specified primary endpoint. Disease control rate was 96% (48/50, 95% CI: 86, 100), proportion of patients with duration of response (DoR) > 6 months was 77% (33/43). The median follow-up for survival was 12.3 months (IQR 12.0–12.6). The 1-year progression-free survival rate was 72% (95% CI: 57, 83), 9-month DoR rate was 74% (95% CI: 58, 85), and 1-year overall survival rate was 98% (95% CI: 85, 100). Most common TRAEs were neutropenia (93%, 50/54), leukopenia (85% 46/54), thrombocytopenia (61% 33/54), lymphopenia (32% 17/54), and alanine aminotransferase increased (20% 11/54). Interpretation: MIL62 combined with lenalidomide showed promising efficacy in patients with R/R FL and MZL. A multicentre, randomized, open-label, phase Ⅲ trial of MIL62 combined with lenalidomide versus lenalidomide in anti-CD20 monoclonal antibody refractory FL patients is ongoing (NCT04834024). Funding: Beijing Mabworks Biotech Co. Ltd, Beijing China and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

E-commerce with the immersive scene of live streaming gives users a new interaction and consumption experience, extending a new path for traditional marketing. Live barrage, being the primary means of users’ social engagement in live e-commerce, encapsulates their inclination to purchase products, commonly referred to as consumption intention. The mining of live barrage enables the exploration of latent user behavior and consumption intention. The current methods employed for mining consumption intention in e-commerce live barrage encounter challenges including insufficient corpus, excessively brief text, and significant semantic deficiencies. Therefore, this study proposes a paradigm of consumption intention recognition by combining the text features of barrage: by constructing a dataset of Live barrage, cleaning the original dataset, and then using a fused BERT’s feature network model BERT-BiLSTM to identify the consumption intention in live e-commerce Live barrage. The experimental results demonstrate the efficacy of the proposed method for recognizing consumption intention. Finally, this study conducted text mining on live barrage containing consumption intent, including word cloud visualization, topic extraction, and co-occurrence analysis, further investigating consumers’ purchasing needs and intentions.

Abstract Background Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)—derived from exons 2–6 of EYA3–facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions. Methods CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model. Results CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells. Conclusions Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

Abstract. Background:. The KangDuo-Surgical Robot-01 (KD-SR-01) system is a new surgical robot recently developed in China. The aim of this study was to present our single-center experience and mid-term outcomes of urological procedures using the KD-SR-01 system. Methods:. From August 2020 to April 2023, consecutive urologic procedures were performed at Peking University First Hospital using the KD-SR-01 system. The clinical features, perioperative data, and follow-up outcomes were prospectively collected and analyzed. Results:. A total of 110 consecutive patients were recruited. Among these patients, 28 underwent partial nephrectomy (PN), 41 underwent urinary tract reconstruction (26 underwent pyeloplasty, 3 underwent ureteral reconstruction and 12 underwent ureterovesical reimplantation [UR]), and 41 underwent radical prostatectomy (RP). The median operative time for PN was 112.5 min, 157.0 min for pyeloplasty, 151.0 min for ureteral reconstruction, 142.5 min for UR, and 138.0 min for RP. The median intraoperative blood loss was 10 mL for PN, 10 mL for pyeloplasty, 30 mL for ureteral reconstruction, 20 mL for UR, and 50 mL for RP. All procedures were successfully completed without conversion, and there were no major complications in any patient. The median warm ischemia time of PN was 17.3 min, and positive surgical margin was not noted in any patient. The overall positive surgical margin rate of RP was 39% (16/41), and no biochemical recurrence was observed in any RP patient during the median follow-up of 11.0 months. The surgical success rates of pyeloplasty and UR were 96% (25/26) and 92% (11/12) during the median follow-up of 29.5 months and 11.5 months, respectively. Conclusion:. The KD-SR-01 system appears feasible, safe, and effective for most urological procedures, based on our single-center experience.

There are great challenges in the field of natural product isolation and purification and in the pharmacological study of oligosaccharide monomers. And these isolation and purification processes are still universal problems in the study of natural products (NPs), traditional Chinese medicine (TCM), omics, etc. The same polymer-modified materials designed for the special separation of oligosaccharides, named Sil-epoxy-PEI and Sil-chloropropyl-PEI, were synthesized via two different methods and characterized by scanning electron microscopy combined with energy spectrum analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential as well as surface area analysis, etc. Several nucleotide/nucleoside molecules with different polarities and selectivities were successfully isolated in our laboratory using stainless-steel columns filled with the synthesized material. In addition, the separation of saccharide probes and oligosaccharides mixtures in water extracts of Morinda officinalis were compared in HILIC mode. The results showed that the resolution of separations for the representative analytes of the Sil-epoxy-PEI column was higher than for the Sil-chloropropyl-PEI column, and the developed stationary phase exhibited improved performance compared to hydrothermal carbon, amide columns and other HILIC materials previously reported.

The purpose of this study was to analyze ‘sharing’ as an operational framework for waterfront industrial heritage revitalization in the context of sustainable urban regeneration. This research study was conducted to better understand the public accessibility of heritage preservation projects in a densely populated waterfront urban area and to determine to what extent heritage could be made available to the general public. We examined the development of industrial heritage along Suzhou Creek, Shanghai, and its process of regeneration. The focus area covered a waterway stretch of 19.2 km and an adjacent land area of 11.7 km2 managed as a single planning entity on both sides of the creek. We analyzed the present preservation practices and discovered a growing desire to increase the historical buildings’ visibility in the context of urban regeneration. We argue that ‘sharing’ can serve as a pivotal framework for sustainable waterfront regeneration, as its implementation can (1) increase the public value of waterfront heritage and (2) incorporate comprehensive objectives, design strategies, evaluation methods, and public participation into the space revitalization process.

During the manufacturing of surgical forceps, the flashes of the blanks need to be removed. Manual production has problems such as high labor intensity, low efficiency, and high-risk factors. To solve this problem and realize fully automatic resection, a novel modular workstation was designed and a corresponding process method was proposed. The workstation adopts robots, non-standard automation equipment, and image recognition technology instead of manual loading and blanking, but the blank storage still needs to be performed manually. The critical components were selected according to the workstation design scheme and process method, and the control system design was completed. The reliability of the separation unit was studied through a test platform, and the failure problem caused by uneven force was solved using a blank locking device, which showed that the separation success rate was stabilized at 100%. The detection speed of the image recognition system can reach 100 ms/piece, and the product qualification rate can reach 95.7%. The advantages of the workstation in terms of output and productivity were further analyzed by comparing it to manual production, where the average daily output increased by 12.5% (4500 pieces). In addition, the results of long-term test experiments and power consumption comparison tests showed that the workstations are highly stable and consume little additional power.

In order to accurately simulate the actual road driving resistance of four-wheel drive motor vehicles based on the chassis dynamometer and efficiently test the vehicle performance, it is necessary to analyze the influencing factors of the additional loss resistance and the loading resistance of the chassis dynamometer bench system. In this paper, the effects of the drum speed, the sampling speed interval, and basic inertia on the test results of the additional loss resistance are tested and analyzed based on the self-developed chassis dynamometer of a four-wheel drive motor vehicle. The static and dynamic components of the additional loss resistance are defined by linear regression through ordinary least squares, and the additional loss resistance of the four-axis eight-drum chassis dynamometer and mainstream chassis dynamometer system for four-wheel drive motor vehicles are compared. In addition, the effects of the dynamometer type and the control strategy on the loading resistance are discussed, and the transient condition, steady-state condition, and overall operating condition deviation coefficient of loading force are defined, according to which the advantages and disadvantages of the control strategy of the chassis dynamometer system for four-wheel drive motor vehicles are evaluated. The analysis of the influencing factors and laws of the resistance of the four-wheel drive motor vehicle chassis dynamometer bench system can provide a reference basis for accurately simulating the resistance of vehicle road driving based on the bench testing.

Background & Aims: Recent studies have implicated platelets, particularly α-granules, in the development of non-alcoholic steatohepatitis (NASH). However, the specific mechanisms involved have yet to be determined. Notably, thrombospondin 1 (TSP1) is a major component of the platelet α-granules released during platelet activation. Hence, we aimed to determine the role of platelet-derived TSP1 in NASH. Methods: Platelet-specific Tsp1 knockout mice (TSP1Δpf4) and their wild-type littermates (TSP1F/F) were used. NASH was induced by feeding the mice with a diet enriched in fat, sucrose, fructose, and cholesterol (AMLN diet). A human liver NASH organoid model was also employed. Results: Although TSP1 deletion in platelets did not affect diet-induced steatosis, TSP1Δpf4 mice exhibited attenuated NASH and liver fibrosis, accompanied by improvements in plasma glucose and lipid homeostasis. Furthermore, TSP1Δpf4 mice showed reduced intrahepatic platelet accumulation, activation, and chemokine production, correlating with decreased immune cell infiltration into the liver. Consequently, this diminished proinflammatory signaling in the liver, thereby mitigating the progression of NAFLD. Moreover, in vitro data revealed that co-culturing TSP1-deficient platelets in a human liver NASH organoid model attenuated hepatic stellate cell activation and NASH progression. Additionally, TSP1-deficient platelets play a role in regulating brown fat endocrine function, specifically affecting Nrg4 (neuregulin 4) production. Crosstalk between brown fat and the liver may also influence the progression of NAFLD. Conclusions: These data suggest that platelet α-granule-derived TSP1 is a significant contributor to diet-induced NASH and fibrosis, potentially serving as a new therapeutic target for this severe liver disease. Impact and implications: Recent studies have implicated platelets, specifically α-granules, in the development of non-alcoholic steatohepatitis, yet the precise mechanisms remain unknown. In this study, through the utilization of a tissue-specific knockout mouse model and human 3D liver organoid, we demonstrated that platelet α-granule-derived TSP1 significantly contributes to diet-induced non-alcoholic steatohepatitis and fibrosis. This contribution is, in part, attributed to the regulation of intrahepatic immune cell infiltration and potential crosstalk between fat and the liver. These findings suggest that platelet-derived TSP1 may represent a novel therapeutic target in non-alcoholic fatty liver disease.

Sentiment analysis measures user experience on social media. With the emergence of pre-trained models, text classification tasks have become homogeneous, without a significant improvement in accuracy. Therefore, we present a hybrid model called PLASA to classify the sentiment polarity of short comments, particularly barrages. PLASA introduces a collaborative attention module that integrates information about relative position and knowledge from summarized lexicons to better adjust the relationship between word representations. Our model is evaluated using three new curated sentiment analysis datasets: SentiTikTok-2023 (4613 items), SentiBilibili-2023 (7755 items), and SentiWeibo-2023 (5614 items). Although the comment length varies across datasets, all maintain a consistent punctuation percentage at approximately 13%. Consequently, PLASA with the optimal combination demonstrates notable performance improvements compared to both the baseline and commonly used models. It achieves micro-F1 scores of 93.94%, 90.34%, and 88.79% on the respective datasets. We also observed that the representation capacity of the pre-trained model decreases as the text length increases. Moreover, the proposed collaborative attention module effectively addresses this limitation, as confirmed by our ablation study.

Objective Lumbar fractures are the most common spinal injuries, and surgery is required for severe fracture. This study aimed to investigate the variations in motion and stress in varying states of activity after minimally invasive and traditional open pedicle screw placement for L1 vertebral fracture stabilization. Methods We studied a male volunteer (26 years old) with no history of chronic back pain or lumbar spine trauma. We used the finite element method for this investigation. Using finite element software, we created a three-dimensional model of L1 vertebral compression fracture. We also constructed models for four percutaneous pedicle screws spanning the fractured vertebra and four screws traversing the damaged vertebra with transverse fixation. Results In all three-dimensional movement directions, the open pedicle fixation system experienced maximum stress higher than its percutaneous counterpart. With axial spinal rotation, von Mises stress on the traditional open pedicle screw was considerably lower than that with percutaneous pedicle fixation, but peak stress was elevated at the transverse connection. Traditional open pedicle fixation displayed less maximum displacement than percutaneous pedicle internal fixation. Conclusions During axial spinal movements, high peak stress is observed at the transverse connection. Patients should avoid excessive axial rotation of the spine during recovery.

Objective: To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy (rRAPN) with a new robotic platform called KangDuo Surgical Robot-01 (KD-SR-01) system (Suzhou KangDuo Robot Co., Ltd., Suzhou, China) and discuss its surgical technique. Methods: A 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney. The R.E.N.A.L. nephrometry score of this patient was 4x. This patient underwent rRAPN with KD-SR-01. The perinephric fat between the tumor and Gerota's fascia was preserved, which was used for internal suspension traction during tumor resection. Postoperative follow-up data were collected. Results: The surgery was successfully carried out with a duration of 127 min, in which the docking time was 6 min 25 s and console time was 60 min. The warm ischemia time was 19 min 53 s, and the estimated blood loss was 0 mL. The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma, with a negative surgical margin. The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of this patient was Grade 2. No recurrence was observed during the 6-month follow-up. Conclusion: Internal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1–BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination–deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Abstract Human MutT Homolog 1 (MTH1) is a nucleotide pool sanitization enzyme that hydrolyzes oxidized nucleotides to prevent their mis-incorporation into DNA under oxidative stress. Expression and functional roles of MTH1 in platelets are not known. Here, we show MTH1 expression in platelets and its deficiency impairs hemostasis and arterial/venous thrombosis in vivo. MTH1 deficiency reduced platelet aggregation, phosphatidylserine exposure and calcium mobilization induced by thrombin but not by collagen-related peptide (CRP) along with decreased mitochondrial ATP production. Thrombin but not CRP induced Ca2+-dependent mitochondria reactive oxygen species generation. Mechanistically, MTH1 deficiency caused mitochondrial DNA oxidative damage and reduced the expression of cytochrome c oxidase 1. Furthermore, MTH1 exerts a similar role in human platelet function. Our study suggests that MTH1 exerts a protective function against oxidative stress in platelets and indicates that MTH1 could be a potential therapeutic target for the prevention of thrombotic diseases.

Abstract Machine learning (ML) has been extensively involved in assistant disease diagnosis and prediction systems to emancipate the serious dependence on medical resources and improve healthcare quality. Moreover, with the booming of pre-training language models (PLMs), the application prospect and promotion potential of machine learning methods in the relevant field have been further inspired. PLMs have recently achieved tremendous success in diverse text processing tasks, whereas limited by the significant semantic gap between the pre-training corpus and the structured electronic health records (EHRs), PLMs cannot converge to anticipated disease diagnosis and prediction results. Unfortunately, establishing connections between PLMs and EHRs typically requires the extraction of curated predictor variables from structured EHR resources, which is tedious and labor-intensive, and even discards vast implicit information.In this work, we propose an Input Prompting and Discriminative language model with the Mixture-of-experts framework (IPDM) by promoting the model’s capabilities to learn knowledge from heterogeneous information and facilitating the feature-aware ability of the model. Furthermore, leveraging the prompt-tuning mechanism, IPDM can inherit the impacts of the pre-training in downstream tasks exclusively through minor modifications. IPDM remarkably outperforms existing models, proved by experiments on one disease diagnosis task and two disease prediction tasks. Finally, experiments with few-feature and few-sample demonstrate that IPDM achieves significant stability and impressive performance in predicting chronic diseases with unclear early-onset characteristics or sudden diseases with insufficient data, which verifies the superiority of IPDM over existing mainstream methods, and reveals the IPDM can powerfully address the aforementioned challenges via establishing a stable and low-resource medical diagnostic system for various clinical scenarios.

Abstract The steganalysis for JPEG image is an important research topic, as the enormous popularity of JPEG image on Internet. However, the stego noise feature extraction process of the existing deep learning‐based steganalytic methods are not adaptive enough to the content of the image, which may lead to suboptimal steganalysis performance. In order to solve this issue, an adaptive stego noise extraction network, named SNENet, for JPEG image steganalysis is proposed. The stego noise extraction module of the network is specifically designed for steganalysis, which consists of parallel dilated convolutional layer and inverted bottleneck layer. This specific design expands the receptive field of the network, which makes the extraction of the stego noise more global and adaptive to the content of the image. The experimental results indicate that proposed network outperforms the state‐of‐the‐art steganalytic method by as much as 6.25% for UED‐JC and 3.35% for J‐UNIWARD. The design of the network is also justified in the extensive ablation experiments.

In scenarios where the global navigation satellite system is unavailable, unmanned aerial vehicles (UAVs) can employ visual algorithms to process aerial images. These images are integrated with satellite maps and digital elevation models (DEMs) to achieve global localization. To address the localization challenge in unfamiliar areas devoid of prior data, an iterative computation-based localization framework is commonly used. This framework iteratively refines its calculations using multiple observations from a downward-facing camera to determine an accurate global location. To improve the rate of convergence for localization, we introduced an innovative observation model. We derived a terrain descriptor from the images captured by a forward-facing camera and integrated it as supplementary observation into a point-mass filter (PMF) framework to enhance the confidence of the observation likelihood distribution. Furthermore, within this framework, the methods for the truncation of the convolution kernel and that of the probability distribution were developed, thereby enhancing the computational efficiency and convergence rate, respectively. The performance of the algorithm was evaluated using real UAV flight sequences, a satellite map, and a DEM in an area measuring 7.7 km × 8 km. The results demonstrate that this method significantly accelerates the localization convergence during both takeoff and ascent phases as well as during cruise flight. Additionally, it increases localization accuracy and robustness in complex environments, such as areas with uneven terrain and ambiguous scenes. The method is applicable to the localization of UAVs in large-scale unknown scenarios, thereby enhancing the flight safety and mission execution capabilities of UAVs.

In order to solve the problems of methods that use a single form of sensing, the ease of causing deformation damage to the targets with a low hardness during grasping, and the slow sliding inhibition of a prosthetic hand when the grasping target slides, which are problems that exist in most current intelligent prosthetic hands, this study introduces an adaptive control strategy for prosthetic hands based on multi-sensor sensing. Using a force-sensing resistor (FSR) to collect changes in signals generated after contact with a target, a prosthetic hand can classify the target’s hardness level and adaptively provide the desired grasping force so as to reduce the deformation of and damage to the target in the process of grasping. A fiber-optic sensor collects the light reflected by the object to identify its surface roughness, so that the prosthetic hand adaptively adjusts the sliding inhibition method according to the surface roughness information to improve the grasping efficiency. By integrating information on the hardness and surface roughness of the target, an adaptive control strategy for a prosthetic hand is proposed. The experimental results showed that the adaptive control strategy was able to reduce the damage to the target by enabling the prosthetic hand to achieve stable grasping; after grasping the target with an initial force and generating sliding, the efficiency of slippage inhibition was improved, the target could be stably grasped in a shorter time, and the hardness, roughness and weight ranges of targets that could be grasped by the prosthetic hand were enlarged, thus improving the success rate of stable grasping under extreme conditions.

Children with severe aplastic anemia (SAA) face heterogeneous prognoses after immunosuppressive therapy (IST). There are few models that can predict the long-term outcomes of IST for these patients. The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA. In the early stage, a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques. Among the indicators related to long-term efficacy, white blood cell count, lymphocyte count, absolute reticulocyte count, lymphocyte ratio in bone-marrow smears, C-reactive protein, and the level of IL-6, IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy (P < .05). Taken together, we analyzed the long-term outcomes of rabbit anti-thymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques, which may shorten the observation period of therapeutic effects and reduce treatment costs and time.

Objectives: To examine the disparities between COVID-19 studies conducted in high-income countries (HICs) and low-and middle-income countries (LMICs). Methods: We used the International Clinical Trials Registry Platform to identify COVID-19-related studies registered from December 31, 2019 to December 31, 2021. The World Bank definition was used to classify countries as high-, upper-middle-, lower-middle-, and low-income. The last three were considered to be LMICs. We examined the disparities in response speed, classification of medicines and vaccines, and registration and results reporting compliance between COVID-19 studies conducted in HICs and LMICs. Results: We included 12,396 COVID-19 studies, with 6631 (53.5%) from HICs. HIC-registered studies reached a peak of 1039 in April 2020, whereas LMICs had only 440 studies. Of the 6969 interventional trials, those from HICs showed higher registration compliance (2199, 62.3% vs 1979, 57.6%, P

Abstract To enable the development of all-solid-state batteries, an inorganic solid-state electrolyte should demonstrate high ionic conductivity (i.e., > 1 mS cm−1 at 25 °C), compressibility (e.g., > 90% density under 250−350 MPa), and cost-effectiveness (e.g.,

Abstract More than 60 years ago, disulfiram (DSF) was employed for the management of alcohol addiction. This promising cancer therapeutic agent inhibits proliferation, migration, and invasion of malignant tumor cells. Furthermore, divalent copper ions can enhance the antitumor effects of DSF. Molecular structure, pharmacokinetics, signaling pathways, mechanisms of action and current clinical results of DSF are summarized here. Additionally, our attention is directed towards the immunomodulatory properties of DSF and we explore novel administration methods that may address the limitations associated with antitumor treatments based on DSF. Despite the promising potential of these various delivery methods for utilizing DSF as an effective anticancer agent, further investigation is essential in order to extensively evaluate the safety and efficacy of these delivery systems.

Abstract B cell maturation antigen (BCMA)-targeted immunotherapy has shown unprecedented results in the treatment of relapsed or refractory (R/R) multiple myeloma (MM). However, disease progression remains an issue attributed to variable BCMA expression, BCMA downregulation, and heterogeneity of tumor antigens in MM. Therefore, additional treatment options with novel therapeutic targets are warranted. G protein-coupled receptor, class C group 5 member D (GPRC5D), an orphan receptor expressed on malignant plasma cells with limited expression in normal tissue, has emerged as a promising therapeutic target for R/R MM. GPRC5D-targeted chimeric antigen receptor (CAR)-T and CAR-NK cell therapy, as well as bispecific T cell engagers, offer remarkable anti-tumor activities. We summarized some latest reports on GPRC5D-targeted treatments for R/R MM from the 2022 ASH Annual Meeting (ASH 2022).

Litsea cubeba essential oil is a pure natural plant essential oil. In this paper, the inhibitory effect of Litsea cubeba essential oil on the growth, metabolism and toxin production of Aspergillus flavus was investigated. In this study, peanuts were placed in a natural environment to infect bacteria, and the target bacteria were isolated and purified. Morphology and ITS sequence methods were used to classify and identify the strains. The inhibition ability of essential oil on Aspergillus flavus was discussed by the determination of inhibition zone, inhibition rate and minimum inhibitory concentration (MIC). The effects of essential oil on the germination rate, growth curve and aflatoxin B1 production of Aspergillus flavus, as well as the effects of cell membrane permeability and cellular enzyme activity, were tested. The results showed that strain HB2 was isolated and screened from spoilage peanuts and was identified as Aspergillus flavus by the ITS sequence method. The results of aflatoxin determination showed that aflatoxin B1 (AFB1) had a mass concentration of 3.4×103 μg·kg−1 (pure wet bacteria). The bacteriostatic zone significantly increased with increasing essential oil concentration, and the minimum inhibitory concentration (MIC) for Aspergillus flavus was 0.800 μL·mL−1. The germination rate, the length of the dental tube, the growth of Aspergillus flavus, and the concentration of AFB1 showed a significant decreasing trend with increasing concentrations of essential oil in the culture medium. When the concentration of Litsea cubeba essential oil was 0.100 μL·mL−1, the growth of the bacteria was invisible to the naked eye. With the increase in the concentration of essential oil, the conductivity of the culture medium increased, the utilization rate of reducing sugars and the protein content of the bacteria decreased, and the activities of malate dehydrogenase and succinate dehydrogenase in the bacteria decreased. These results indicated that Litsea cubeba essential oil caused irreversible damage to Aspergillus flavus. It is speculated that Litsea cubeba essential oil damaging the cell wall and cell membrane, affecting cell growth and metabolism and ultimately leading to cell death. Therefore, Litsea cubeba essential oil has a good inhibitory effect on Aspergillus flavus and can be widely used in grain storage and food antimolding.

Dynamic voltage restorer (DVR) needs to turn off the anti-parallel bypass thyristor (SCR) at the output terminal when dealing with voltage sag phenomenon. When applying traditional methods to force the thyristor off, it is essential to determine the direction of thyristor current according to the sensor sampling information, which has the risk of misjudgment under actual conditions. A novel fast switching strategy (FSS) for DVR is proposed in this paper. DVR-FSS uses the current control algorithm to force off the bypass SCR, which can realize the smooth transition from bypass state to compensation state. Firstly, the basic working principle of the DVR-FSS is introduced based on which the FSS operating modes are analyzed in detail. And the mathematical model of DVR-FSS in key modes is established to analyze the influence of FSS control algorithm parameters on the dynamic or steady performance of DVR. Secondly, the modeling and quantitative analysis of the fundamental voltage drop introduced by DVR in the steady-state mode are used to explain that the impact of FSS on the primary side load supply voltage is within the acceptable range. Finally, the correctness and feasibility of the proposed FSS are fully verified by experiments, which indicate that FSS has strong robustness at the same time.