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1.
Int J Psychol ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38993167

ABSTRACT

Left-behind children, as a large-scale disadvantaged group, encounter an array of risk factors that impede their academic development because of parental migration. The current study aimed at investigating the roles of left-behind cumulative risk and growth mindset on academic adjustment and exploring whether growth mindset moderated the association between left-behind cumulative risk and academic adjustment in left-behind middle school students. A total of 1184 left-behind middle school students (615 males; 12-16 years) participated in the study. Results indicated that left-behind cumulative risk is negatively associated with academic adjustment in middle school students (ß = -.199, t(1183) = -7.229, p < .001). Besides, growth mindset has a protective effect on left-behind middle school students' academic adjustment (ß = .386, t(1183) = 14.070, p < .001) and a moderating effect on the relationship between left-behind cumulative risk and academic adjustment (ß = .394, t(1182) = 4.057, p < .001, ΔR2 = .012). These findings suggest that family risk factors related to left-behind status affect the academic adjustment of left-behind middle school students in a superposition way, while the positive individual factor of growth mindset could protect the negative impact caused by parental migration.

2.
Acta Pharm Sin B ; 14(6): 2669-2684, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828156

ABSTRACT

Solid oral controlled release formulations feature numerous clinical advantages for drug candidates with adequate solubility and dissolution rate. However, most new chemical entities exhibit poor water solubility, and hence are exempt from such benefits. Although combining drug amorphization with controlled release formulation is promising to elevate drug solubility, like other supersaturating systems, the problem of drug recrystallization has yet to be resolved, particularly within the dosage form. Here, we explored the potential of an emerging, non-leachable terpolymer nanoparticle (TPN) pore former as an internal recrystallization inhibitor within controlled release amorphous solid dispersion (CRASD) beads comprising a poorly soluble drug (celecoxib) reservoir and insoluble polymer (ethylcellulose) membrane. Compared to conventional pore former, polyvinylpyrrolidone (PVP), TPN-containing membranes exhibited superior structural integrity, less crystal formation at the CRASD bead surface, and greater extent of celecoxib release. All-atom molecular dynamics analyses revealed that in the presence of TPN, intra-molecular bonding, crystal formation tendency, diffusion coefficient, and molecular flexibility of celecoxib were reduced, while intermolecular H-bonding was increased as compared to PVP. This work suggests that selection of a pore former that promotes prolonged molecular separation within a nanoporous controlled release membrane structure may serve as an effective strategy to enhance amorphicity preservation inside CRASD.

3.
Opt Express ; 32(8): 14645-14658, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859403

ABSTRACT

In order to meet the ground calibration requirements of optical detection equipment to identify optical characteristics of dim targets, an optical simulation method of dim targets based on passive detection link analysis and bidirectional scattering distribution function model is proposed. The off-axis collimation system for long focal length, the simulated energy transmission model of dim targets and the simplified model of bidirectional scattering distribution function are established. An internal stray light suppression baffle was designed to effectively suppress secondary scattering, and an optical simulation system for dim targets was built. The experimental results show that the system can simulate +7 Mv∼+20 Mv, and the simulation accuracy is better than 0.07 Mv. At the same time, the detection ability of the camera is tested by using the +15 Mv point simulated by the system. The signal-to-noise of the star point target reaches 6.7, which meets the requirements of detection rate and false alarm rate, and realizes the ground test of the camera's detection ability of the dim target.

4.
Article in English | MEDLINE | ID: mdl-38923573

ABSTRACT

BACKGROUND AND AIM: Lipid metabolism disorder is the primary feature of numerous refractory chronic diseases. Fatty acid oxidation, an essential aerobic biological process, is closely related to the progression of NAFLD. The forkhead transcription factor FOXO1 has been reported to play an important role in lipid metabolism. However, the molecular mechanism through which FOXO1 regulates fatty acid oxidation remains unclear. METHODS: Transcriptomic analysis was performed to examine the cellular expression profile to determine the functional role of FOXO1 in HepG2 cells with palmitic acid (PA)-induced lipid accumulation. FOXO1-binding motifs at the promoter region of aldehyde dehydrogenase 1 family member L2 (ALDH1L2) were predicted via bioinformatic analysis and confirmed via luciferase reporter assay. Overexpression of ALDH1L2 was induced to recover the impaired fatty acid oxidation in FOXO1-knockout cells. RESULTS: Knockout of FOXO1 aggravated lipid deposition in hepatic cells. Transcriptomic profiling revealed that knockout of FOXO1 increased the expression of genes associated with fatty acid synthesis but decreased the expression of carnitine palmitoyltransferase1a (CPT1α) and adipose triglyceride lipase (ATGL), which contribute to fatty acid oxidation. Mechanistically, FOXO1 was identified as a transcription factor of ALDH1L2. Knockout of FOXO1 significantly decreased the protein expression of ALDH1L2 and CPT1α in vitro and in vivo. Furthermore, overexpression of ALDH1L2 restored fatty acid oxidation in FOXO1-knockout cells. CONCLUSION: The findings of this study indicate that FOXO1 modulates fatty acid oxidation by targeting ALDH1L2.

5.
Research (Wash D C) ; 7: 0387, 2024.
Article in English | MEDLINE | ID: mdl-38939041

ABSTRACT

Hepatocellular carcinoma (HCC) was characterized as being hypervascular. In the present study, we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73 (GP73) HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development. Specifically, we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc, lactate, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, and endoplasmic reticulum stress (ERS) signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo. Mechanistically, we found that GP73, the pivotal hub gene, was activated by histone lactylation and c-Myc, which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78 (GRP78)-induced ERS. STAT3 potentiates GP73-mediated pro-angiogenic functions. Clinically, serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy. Taken together, the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.

6.
Bioresour Technol ; 406: 131007, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901747

ABSTRACT

This study investigated the effects of carbon/nitrogen (C/N) ratio on microbial community in moving bed biofilm reactor (MBBR) using metagenomic analysis, and the dynamic changes of relevant antibiotic resistance genes (ARGs) were also analyzed. The results showed that under low C/N ratio, MBBR exhibited average removal rates of 98.41 % for ammonia nitrogen and 75.79 % for total nitrogen. Metagenomic analysis showed low C/N ratio altered the structure of biofilm and water microbiota, resulting in the detachment of bacteria such as Actinobacteria from biofilm into water. Furthermore, sulfamethazine (SMZ)-resistant bacteria and related ARGs were released into water under low C/N ratio, which lead to the increase of SMZ resistance rate to 90%. Moreover, most dominant genera are potential hosts for both nitrogen cycle related genes and ARGs. Specifically, Nitrosomonas that carried gene sul2 might be released from biofilm into water. These findings implied the risks of antibiotic resistance dissemination in MBBR under low C/N ratio.

7.
J Immunother Cancer ; 12(6)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886114

ABSTRACT

BACKGROUND: Epstein-Barr virus (EBV) is a double-stranded DNA oncogenic virus. Several types of solid tumors, such as nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and lymphoepithelioma-like carcinoma of the lung, have been linked to EBV infection. Currently, several TCR-T-cell therapies for EBV-associated tumors are in clinical trials, but due to the suppressive immune microenvironment of solid tumors, the clinical application of TCR-T-cell therapy for EBV-associated solid tumors is limited. Figuring out the mechanism by which EBV participates in the formation of the tumor immunosuppressive microenvironment will help T cells or TCR-T cells break through the limitation and exert stronger antitumor potential. METHODS: Flow cytometry was used for analyzing macrophage differentiation phenotypes induced by EBV-infected and EBV-uninfected tumors, as well as the function of T cells co-cultured with these macrophages. Xenograft model in mice was used to explore the effects of M2 macrophages, TCR-T cells, and matrix metalloprotein 9 (MMP9) inhibitors on the growth of EBV-infected tumors. RESULTS: EBV-positive tumors exhibited an exhaustion profile of T cells, despite the presence of a large T-cell infiltration. EBV-infected tumors recruited a large number of mononuclear macrophages with CCL5 and induced CD163+M2 macrophages polarization through the secretion of CSF1 and the promotion of autocrine IL10 production by mononuclear macrophages. Massive secretion of MMP9 by this group of CD163+M2 macrophages induced by EBV infection was an important factor contributing to T-cell exhaustion and TCR-T-cell therapy resistance in EBV-positive tumors, and the use of MMP9 inhibitors improved the function of T cells cocultured with M2 macrophages. Finally, the combination of an MMP9 inhibitor with TCR-T cells targeting EBV-positive tumors significantly inhibited the growth of xenografts in mice. CONCLUSIONS: MMP9 inhibitors improve TCR-T cell function suppressed by EBV-induced M2 macrophages. TCR-T-cell therapy combined with MMP9 inhibitors was an effective therapeutic strategy for EBV-positive solid tumors.


Subject(s)
Antigens, CD , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Macrophages , Matrix Metalloproteinase 9 , Receptors, Cell Surface , Animals , Mice , Humans , Matrix Metalloproteinase 9/metabolism , Macrophages/immunology , Macrophages/metabolism , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/virology , Receptors, Cell Surface/metabolism , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Receptors, Antigen, T-Cell/metabolism , Tumor Microenvironment , Cell Line, Tumor , Xenograft Model Antitumor Assays , Female , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Immunotherapy, Adoptive/methods
8.
Pest Manag Sci ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877543

ABSTRACT

BACKGROUND: Cationic antimicrobial peptides (AMPs) possess broad-spectrum biological activities with less inclination to inducing antibiotic resistance. Herein a battery of amphiphilic amidines were designed by mimicking the characteristics of AMPs. The antifungal activities and the effects to the hyphal morphology and membrane permeability were investigated. RESULTS: The results indicated the inhibitory rates of ten compounds were over 80% to Botrytis cinerea and ten compounds over 90% to Valsa mali Miyabe et Yamada at 50 mg L-1. The half maximal effective concentration (EC50) values of compound 5g and 6g to V. mali were 1.21 and 1.90 mg L-1 respectively. The protective rate against apple canker of compound 5g reached 93.4% at 100 mg L-1 on twigs, superior to carbendazim (53.3%). When treated with 5g, the cell membrane permeability and leakage of content of V. mali increased, accompanied with the decrease of superoxide dismutase (SOD) and catalase (CAT) level. Concurrently, the mycelial hyphae contracted, wrinkled, and collapsed, providing evidence of membrane perturbation. A three-dimensional quantitative structure-activity relationship (3D-QSAR) between the topic compounds and the EC50 to V. mali was established showing good predictability (r2 = 0.971). CONCLUSION: Amphiphilic amidines can acquire antifungal activities by acting on the plasmic membrane. Compound 5g could be a promising lead in discovering novel fungicidal candidates. © 2024 Society of Chemical Industry.

9.
J Neuroeng Rehabil ; 21(1): 98, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851703

ABSTRACT

PURPOSE: This pilot study aimed to investigate the effects of REX exoskeleton rehabilitation robot training on the balance and lower limb function in patients with sub-acute stroke. METHODS: This was a pilot, single-blind, randomized controlled trial. Twenty-four patients with sub-acute stroke (with the course of disease ranging from 3 weeks to 3 months) were randomized into two groups, including a robot group and a control group. Patients in control group received upright bed rehabilitation (n = 12) and those in robot group received exoskeleton rehabilitation robot training (n = 12). The frequency of training in both groups was once a day (60 min each) for 5 days a week for a total of 4 weeks. Besides, the two groups were evaluated before, 2 weeks after and 4 weeks after the intervention, respectively. The primary assessment index was the Berg Balance Scale (BBS), whereas the secondary assessment indexes included the Fugl-Meyer Lower Extremity Motor Function Scale (FMA-LE), the Posture Assessment Scale for Stroke Patients (PASS), the Activities of Daily Living Scale (Modified Barthel Index, MBI), the Tecnobody Balance Tester, and lower extremity muscle surface electromyography (sEMG). RESULTS: The robot group showed significant improvements (P < 0.05) in the primary efficacy index BBS, as well as the secondary efficacy indexes PASS, FMA-LE, MBI, Tecnobody Balance Tester, and sEMG of the lower limb muscles. Besides, there were a significant differences in BBS, PASS, static eye-opening area or dynamic stability limit evaluation indexes between the robotic and control groups (P < 0.05). CONCLUSIONS: This is the first study to investigate the effectiveness of the REX exoskeleton rehabilitation robot in the rehabilitation of patients with stroke. According to our results, the REX exoskeleton rehabilitation robot demonstrated superior potential efficacy in promoting the early recovery of balance and motor functions in patients with sub-acute stroke. Future large-scale randomized controlled studies and follow-up assessments are needed to validate the current findings. CLINICAL TRIALS REGISTRATION: URL: https://www.chictr.org.cn/index.html.Unique identifier: ChiCTR2300068398.


Subject(s)
Exoskeleton Device , Lower Extremity , Postural Balance , Robotics , Stroke Rehabilitation , Humans , Stroke Rehabilitation/instrumentation , Stroke Rehabilitation/methods , Male , Pilot Projects , Female , Middle Aged , Lower Extremity/physiopathology , Postural Balance/physiology , Single-Blind Method , Robotics/instrumentation , Aged , Adult , Stroke/physiopathology , Electromyography , Treatment Outcome , Recovery of Function
10.
Oncogene ; 43(28): 2143-2159, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38778160

ABSTRACT

Angiogenesis is one of the characteristics of malignant tumors, and persistent generation of abnormal tumor blood vessels is an important factor contributing to tumor treatment resistance. Epstein-Barr virus (EBV) is a highly prevalent DNA oncogenic virus that is associated with the development of various epithelial malignancies. However, the relationship between EBV infection and tumor vascular abnormalities as well as its underlying mechanisms is still unclear. In this study, we found that compared to EBV-uninfected tumors, EBV-infected tumors were more angiogenic, but the neovascularization was mostly immature vessels without pericyte attachment in both clinical patient tumor samples and mouse xenograft models; These immature vessels exhibited aberrant functionality, characterized by poor blood perfusion and increased vascular permeability. The vascular abnormalities caused by EBV infection exacerbated tumor hypoxia and was responsible for accelerated tumor growth. Mechanistically, EBV infection upregulated ANXA3-HIF-1α-VEGF pathway. Silencing the ANXA3 gene or neutralizing ANXA3 with an antibody can diminish vascular abnormalities, thereby increasing immune cell infiltration and alleviating treatment resistance. Finally, a new therapy combining ANXA3 blockade and NK cell + PD1 antibody significantly inhibited the growth of EBV-infected xenografts in mice. In conclusion, our study identified a previously unrecognized role for EBV infection in tumor vascular abnormalities and revealed its underlying mechanism that upregulated the ANXA3-HIF-1α-VEGF pathway. ANXA3 is a potential therapeutic target for EBV-infected tumors and ANXA3 blockade to improve vascular conditions, in combination with NK cell + PD1 antibody therapy, holds promise as an effective treatment strategy for EBV-associated epithelial malignancies.


Subject(s)
Epstein-Barr Virus Infections , Herpesvirus 4, Human , Hypoxia-Inducible Factor 1, alpha Subunit , Neovascularization, Pathologic , Vascular Endothelial Growth Factor A , Humans , Animals , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mice , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/pathology , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/virology , Neovascularization, Pathologic/metabolism , Cell Line, Tumor , Up-Regulation , Signal Transduction , Xenograft Model Antitumor Assays , Female
11.
Int Immunopharmacol ; 135: 112310, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38788453

ABSTRACT

Chronic obstructive pulmonary disease (COPD) poses a significant health threat characterized by lung inflammation primarily triggered by pulmonary monocytes. Despite the centrality of inflammation in COPD, the regulatory mechanisms governing this response remain elusive, presenting a challenge for anti-inflammatory interventions. In this study, we assessed the expression of exportins in COPD mouse models, revealing a notable upregulation of XPO6 in the mouse lung (P = 0.0011). Intriguingly, we observed a consistent upregulation of XPO6 in pulmonary monocytes from both human and mouse COPD subjects (P < 0.0001). Furthermore, in human lung tissue, XPO6 expression exhibited a positive correlation with TLR2 expression (P = 0). In vitro investigations demonstrated that XPO6 enhances TLR2 expression, activating the MyD88/NF-κB inflammatory signaling pathway. This activation, in turn, promotes the secretion of pro-inflammatory cytokines such as TNFα, IL-6, and IL-1ß in monocytes. Mechanistically, XPO6 facilitates the nuclear export of TLR2 mRNA, ensuring its stability and subsequent protein expression in monocytes. In conclusion, our findings unveil that the upregulation of XPO6 in COPD pulmonary monocytes activates the MyD88/NF-κB inflammatory signaling pathway by facilitating the nuclear export of TLR2 mRNA, thereby identifying XPO6 as a promising therapeutic target for anti-inflammatory interventions in COPD.


Subject(s)
Karyopherins , Mice, Inbred C57BL , Monocytes , Myeloid Differentiation Factor 88 , NF-kappa B , Pulmonary Disease, Chronic Obstructive , RNA, Messenger , Signal Transduction , Toll-Like Receptor 2 , Up-Regulation , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 2/genetics , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/immunology , Animals , Humans , Myeloid Differentiation Factor 88/metabolism , Monocytes/metabolism , Monocytes/immunology , Monocytes/drug effects , NF-kappa B/metabolism , Mice , Male , Karyopherins/metabolism , RNA, Messenger/metabolism , RNA, Messenger/genetics , Active Transport, Cell Nucleus , Lung/pathology , Lung/immunology , Lung/metabolism , Disease Models, Animal , Female
12.
Plants (Basel) ; 13(10)2024 May 10.
Article in English | MEDLINE | ID: mdl-38794388

ABSTRACT

The glutathione S-transferases (GSTs, EC 2.5.1.18) constitute a versatile enzyme family with pivotal roles in plant stress responses and detoxification processes. Recent discoveries attributed the additional function of facilitating anthocyanin intracellular transportation in plants to GSTs. Our study identified 178 VcGST genes from 12 distinct subfamilies in the blueberry genome. An uneven distribution was observed among these genes across blueberry's chromosomes. Members within the same subfamily displayed homogeneity in gene structure and conserved protein motifs, whereas marked divergence was noted among subfamilies. Functional annotations revealed that VcGSTs were significantly enriched in several gene ontology and KEGG pathway categories. Promoter regions of VcGST genes predominantly contain light-responsive, MYB-binding, and stress-responsive elements. The majority of VcGST genes are subject to purifying selection, with whole-genome duplication or segmental duplication serving as key processes that drive the expansion of the VcGST gene family. Notably, during the ripening of the blueberry fruit, 100 VcGST genes were highly expressed, and the expression patterns of 24 of these genes demonstrated a strong correlation with the dynamic content of fruit anthocyanins. Further analysis identified VcGSTF8, VcGSTF20, and VcGSTF22 as prime candidates of VcGST genes involved in the anthocyanin intracellular transport. This study provides a reference for the exploration of anthocyanin intracellular transport mechanisms and paves the way for investigating the spectrum of GST functions in blueberries.

13.
Sci Rep ; 14(1): 12036, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802650

ABSTRACT

Two low-pressure ultraviolet (UV) lamps at 185/254 nm with sodium persulfate in a pilot UV device were utilized for the degradation of reactive red (B-3BF) dye wastewater compared with two UV lamps at 185/185 nm and two UV lamps at 254/254 nm. The degradation performances of UV irradiation (254/185 nm) with sodium persulfate under different degradation times, flow rates, initial pH, initial Na2S2O8 concentrations and initial dye concentrations were investigated. The experimental results illustrated that the degradation percentage of B-3BF dye could reduce to 90.42% with the energy consumption of 85.1 kWh/kg and the residual dye concentration of 1.92 mg/L by UV irradiation (254/185 nm) with initial Na2S2O8 concentration of 1.5 mmol/L and initial dye concentration of 20 mg/L. In addition, degradation performance of B-3BF dye wastewater by UV irradiation (254/185 nm) with sodium persulfate was more effective than those of UV irradiation (254/254 nm) and UV irradiation (185/185 nm). Therefore UV irradiation (254/185 nm) with sodium persulfate was promising for the degradation of B-3BF dye wastewater.

14.
Adv Healthc Mater ; : e2400659, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700840

ABSTRACT

The exploration of sonodynamic therapy (SDT) as a possible replacement for antibiotics by creating reactive oxygen species (ROS) is suggested as a non-drug-resistant theranostic method. However, the low-efficiency ROS generation and complex tumor microenvironment which can deplete ROS and promote tumor growth will cause the compromised antibacterial efficacy of SDT. Herein, through an oxygen vacancy engineering strategy, TiO2- x microspheres with an abundance of Ti3+ are synthesized using a straightforward reductant co-assembly approach. The narrow bandgaps and Ti3+/Ti4+-mediated multiple-enzyme catalytic activities of the obtained TiO2- x microspheres make them suitable for use as sonosensitizers and nanozymes. When graphene quantum dot (GQD) nanoantibiotics are deposited on TiO2- x microspheres, the resulting GQD/TiO2- x shows an increased production of ROS, which can be ascribed to the accelerated separation of electron-hole pairs, as well as the peroxidase-like catalytic activity mediated by Ti3+, and the depletion of glutathione mediated by Ti4+. Moreover, the catalytic activities of TiO2- x microspheres are amplified by the heterojunctions-accelerated carrier transfer. In addition, GQDs can inhibit Topo I, displaying strong antibacterial activity and further enhancing the antibacterial activity. Collectively, the combination of GQD/TiO2- x-mediated SDT/NCT with nanoantibiotics can result in a synergistic effect, allowing for multimodal antibacterial treatment that effectively promotes wound healing.

15.
Signal Transduct Target Ther ; 9(1): 79, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38565886

ABSTRACT

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.


Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Oxaloacetates , Humans , Bevacizumab/therapeutic use , Capecitabine/therapeutic use , Oxaliplatin , Colorectal Neoplasms/drug therapy , Fluorouracil/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Immunotherapy
16.
Mol Cancer Ther ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647536

ABSTRACT

Hepatocellular carcinoma (HCC) has a pathogenesis that remains elusive with restricted therapeutic strategies and efficacy. This study aimed to investigate the role of SMG5, a crucial component in nonsense-mediated mRNA decay (NMD) that degrades mRNA containing a premature termination codon (PTC), in HCC pathogenesis and therapeutic resistance. We demonstrated an elevated expression of SMG5 in HCC and scrutinized its potential as a therapeutic target. Our findings revealed that SMG5 knockdown not only inhibited the migration, invasion, and proliferation of HCC cells but also influenced sorafenib resistance. Differential gene expression analysis between the control and SMG5 knockdown groups showed an upregulation of MAT1A in the latter. High expression of MAT1A, a catalyst for S-adenosylmethionine (SAM) production, as suggested by TCGA data, was indicative of a better prognosis for HCC. Further, an enzyme-linked immunosorbent assay showed a higher concentration of SAM in SMG5 knockdown cell supernatants. Furthermore, we found that exogenous SAM supplementation enhanced the sensitivity of HCC cells to sorafenib alongside changes in the expression of Bax and Bcl 2, apoptosis-related proteins. Our findings underscore the important role of SMG5 in HCC development and its involvement in sorafenib resistance, highlighting it as a potential target for HCC treatment.

17.
BMC Plant Biol ; 24(1): 286, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627660

ABSTRACT

Fruit length is a crucial agronomic trait of snake gourd (Trichosanthes anguina L); however, genes associated with fruit length have not been characterised. In this study, F2 snake gourd populations were generated by crossing the inbred lines, S1 and S2 (fruit lengths: 110 and 20 cm, respectively). Subsequently, bulk segregant analysis, sequencing, and fine-mapping were performed on the F2 population to identify target genes. Our findings suggest that the fruit length of snake gourd is regulated by a major-effect regulatory gene. Mining of genes regulating fruit length in snake gourd to provide a basis for subsequent selection and breeding of new varieties. Genotype-phenotype association analysis was performed on the segregating F2 population comprising 6,000 plants; the results indicate that the target gene is located on Chr4 (61,846,126-61,865,087 bp, 18.9-kb interval), which only carries the annotated candidate gene, Tan0010544 (designated TFL). TFL belongs to the MADS-box family, one of the largest transcription factor families. Sequence analysis revealed a non-synonymous mutation of base C to G at position 202 in the coding sequence of TFL, resulting in the substitution of amino acid Gln to Glu at position 68 in the protein sequence. Subsequently, an InDel marker was developed to aid the marker-assisted selection of TFL. The TFL in the expression parents within the same period was analysed using quantitative real-time PCR; the TFL expression was significantly higher in short fruits than long fruits. Therefore, TFL can be a candidate gene for determining the fruit length in snake gourd. Collectively, these findings improve our understanding of the genetic components associated with fruit length in snake gourds, which could aid the development of enhanced breeding strategies for plant species.


Subject(s)
Trichosanthes , Trichosanthes/genetics , Fruit/genetics , Plant Breeding , Phenotype , Genes, Plant/genetics
18.
ACS Appl Mater Interfaces ; 16(17): 21689-21698, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38629436

ABSTRACT

Plasmonic nanozymes bring enticing prospects for catalytic sterilization by leveraging plasmon-engendered hot electrons. However, the interface between plasmons and nanozymes as the mandatory path of hot electrons receives little attention, and the mechanisms of plasmonic nanozymes still remain to be elucidated. Herein, a plasmonic carbon-dot nanozyme (FeCG) is developed by electrostatically assembling catalytic iron-doped carbon dots (Fe-CDs) with plasmonic gold nanorods. The energy harvesting and hot-electron migration are remarkably expedited by a spontaneous organic-inorganic heterointerface holding a Fermi level-induced interfacial electric field. The accumulated hot electrons are then fully utilized by conductive Fe-CDs to boost enzymatic catalysis toward overproduced reactive oxygen species. By synergizing with localized heating from hot-electron decay, FeCG achieves rapid and potent disinfection with an antibacterial efficiency of 99.6% on Escherichia coli within 5 min and is also effective (94.2%) against Staphylococcus aureus. Our work presents crucial insights into the organic-inorganic heterointerface in advanced plasmonic biocidal nanozymes.


Subject(s)
Anti-Bacterial Agents , Carbon , Escherichia coli , Gold , Staphylococcus aureus , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Carbon/chemistry , Catalysis , Gold/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Quantum Dots/chemistry , Electron Transport , Iron/chemistry
19.
Sci Total Environ ; 928: 172462, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38615761

ABSTRACT

Carbonaceous aerosols were collected in the valley city of Baoji city in Northern China in August 2022. The light absorption characteristics and influencing factors of black carbon (BC) and brown carbon (BrC) were analyzed, and their radiative forcing was estimated. The results showed that the light absorption of secondary brown carbon [AbsBrC,sec (370)] was 7.5 ± 2.4 Mm-1, which was 2.5 times that of primary brown carbon [AbsBrC,pri (370), 3.0 ± 1.2 Mm-1]. During the study period, the absorption Ångström exponent (AAE) of aerosol was 1.6, indicating that there was obvious secondary aerosol formation or carbonaceous aerosol aging in the valley city of Baoji. Except for secondary BrC (BrCsec), the light absorption coefficient (Abs) and mass absorption efficiency (MAE) of BC and primary BrC (BrCpri) during the persistent high temperature period (PHT) were higher than those during the normal temperature period (NT) and the precipitation period (PP), which indicated that the light absorption capacity of black carbon and primary brown carbon increased, while the light absorption capacity of secondary brown carbon decreased under persistent high temperature period. Secondary aerosols sulfide (SO42-), nitrate (NO3-) and secondary organic carbon (SOC) are important factors for promoting the light absorption enhancemen of BC and BrCpri and photobleaching of BrCsec during persistent high temperature period. The Principal Component Analysis-Multiple Linear Regression (PCA-MLR) model showed that traffic emissions was the most important source of pollution in Baoji City. Based on this, the secondary source accelerates the aging of BC and BrC, causing changes in light absorption. During PHT, the radiative forcing of BC and BrCpri were enhanced, while the radiative forcing of BrCsec was weakened, but the positive radiative forcing generated by them may aggravate the high-temperature disaster.

20.
Front Neurorobot ; 18: 1338189, 2024.
Article in English | MEDLINE | ID: mdl-38566892

ABSTRACT

In real-world scenarios, making navigation decisions for autonomous driving involves a sequential set of steps. These judgments are made based on partial observations of the environment, while the underlying model of the environment remains unknown. A prevalent method for resolving such issues is reinforcement learning, in which the agent acquires knowledge through a succession of rewards in addition to fragmentary and noisy observations. This study introduces an algorithm named deep reinforcement learning navigation via decision transformer (DRLNDT) to address the challenge of enhancing the decision-making capabilities of autonomous vehicles operating in partially observable urban environments. The DRLNDT framework is built around the Soft Actor-Critic (SAC) algorithm. DRLNDT utilizes Transformer neural networks to effectively model the temporal dependencies in observations and actions. This approach aids in mitigating judgment errors that may arise due to sensor noise or occlusion within a given state. The process of extracting latent vectors from high-quality images involves the utilization of a variational autoencoder (VAE). This technique effectively reduces the dimensionality of the state space, resulting in enhanced training efficiency. The multimodal state space consists of vector states, including velocity and position, which the vehicle's intrinsic sensors can readily obtain. Additionally, latent vectors derived from high-quality images are incorporated to facilitate the Agent's assessment of the present trajectory. Experiments demonstrate that DRLNDT may achieve a superior optimal policy without prior knowledge of the environment, detailed maps, or routing assistance, surpassing the baseline technique and other policy methods that lack historical data.

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