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1.
Heliyon ; 10(9): e30122, 2024 May 15.
Article En | MEDLINE | ID: mdl-38699048

China's crude economic development has led to high pollution and inefficiency of urban land use. Environmental regulation (Er) is crucial for governments to promote green growth and efficient land use. Using a dataset of 271 cities in China from 2011 to 2020, this paper investigates the threshold effect of green innovation in science and technology and industrial structure optimization on Er impacts of urban land green use efficiency (Ulee). The results show that (1) Er positively affects Ulee. (2) There is a threshold effect of green innovation in science and technology (Gin) and industrial structure upgrading (Ind) in Er affecting Ulee, and the force decreases as the threshold value increases. (3) Within the examination of heterogeneity, the impact of Er on Ulee is more significant in eastern, high levels of urbanization and large cities, but the force of action is smaller. Based on the nonlinear force of Er, it is crucial to maximize the effectiveness of green land use by giving full play to the interactive synergistic effect of the "combination box" and dynamically and flexibly adjusting the intensity of Er according to the time, place, and state of urban development.

2.
Chem Biodivers ; : e202400564, 2024 May 06.
Article En | MEDLINE | ID: mdl-38708558

Chlorogenic acid (Chl), isochlorogenic acid A (Isochl A), and isochlorogenic acid B (Isochl B) are naturally occurring phenolic compounds, which have been shown to exert a regulatory effect on lipid metabolism. However, the mechanism underlying this effect remains unclear. Herein, we investigated the inhibitory effects and underlying mechanisms of these three phenolic compounds on oleic acid (OA)-induced HepG2 cells and high-fat diet (HFD)-fed zebrafish. Lipid accumulation and triacylglycerol levels increased in OA-induced cells, which was attenuated by Chl, Isochl A, and Isochl B. Moreover, the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) decreased, while superoxide dismutase (SOD) levels increased by Chl, Isochl A and Isochl B treatment. Western blot analysis demonstrated that Chl, Isochl A and Isochl B reduced the expression of lipogenesis-related protein, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, peroxisome proliferator-activated receptor alpha gamma (PPARα) was increased by Chl, Isochl A, and Isochl B treatment. In addition, our results indicated that Chl, Isochl A and Isochl B decreased lipid profiles and lipid accumulation in HFD-fed zebrafish.

3.
BMC Womens Health ; 24(1): 247, 2024 Apr 18.
Article En | MEDLINE | ID: mdl-38637800

BACKGROUND: Primary lymphoma of the female genital tract (PLFGT) is a rare malignant tumor in the female reproductive system, with a low incidence and few clinical reports. The aim of this study is to report our institutional experience with this rare malignancy and emphasize the need for increasing the awareness about PLFGT presenting with gynecologic symptoms. METHODS: The medical records of patients diagnosed with PLFGT from March 2014 to November 2022 in the First Affiliated Hospital of Wannan Medical College were reviewed. Histological classification and staging were based on the World Health Organization and Ann Arbor systems, respectively. RESULTS: There were 13 patients with diagnosis of PLFGT and the median length of follow-up was 31 months (0-102 months). The main clinical symptoms included postmenopausal vaginal bleeding, pelvic mass and abdominal pain. Serum LDH increased in 10 patients and serum CA125 elevated in 2 patients. The tumor of ovarian or uterine presented as solid masses in CT or MRI, and ascites was rare. The histological subtypes were diffuse large B-cell (n = 12) and follicular (n = 1) lymphoma. Tumors were located in ovary (n = 8), uterus (n = 3), and cervix (n = 2). According to the Ann Arbor staging system, 6 cases were classified as stage II and 7 cases were classified as stage IV, respectively. A total of 10 patients underwent surgery. Combination chemotherapy was used in 10 patients. Eight patients had tumor-free survival, 1 patient had recurrent disease, 3 patients died and 1 patient lost to follow-up. The median survival time was 32 months (1-102 months). CONCLUSION: PLFGT usually presents as gynecological symptoms and solid masses in pelvis. Surgery or biopsy was the way to obtain the pathologic diagnosis, and combination chemotherapy is the efficient method for PLFGT. Making an accurate preoperative diagnosis is of paramount importance to avoid radical gynecologic surgery.


Genital Neoplasms, Female , Lymphoma, Large B-Cell, Diffuse , Female , Humans , Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/pathology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Genitalia, Female , Gynecologic Surgical Procedures , Neoplasm Staging
4.
Biomed Pharmacother ; 175: 116669, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38677243

BACKGROUND: The lack of an efficient way to screen patients who are responsive to immunotherapy challenges PD1/CTLA4-targeting cancer treatment. Immunotherapeutic efficacy cannot be clearly determined by peripheral blood analyses, tissue gene markers or CT/MR value. Here, we used a radionuclide and imaging techniques to investigate the novel dual targeted antibody cadonilimab (AK104) in PD1/CTLA4-positive cells in vivo. METHODS: First, humanized PD1/CTLA4 mice were purchased from Biocytogen Pharmaceuticals (Beijing) Co., Ltd. to express hPD1/CTLA4 in T-cells. Then, mouse colon cancer MC38-hPD-L1 cell xenografts were established in humanized mice. A bispecific antibody targeting PD1/CTLA4 (AK104) was labeled with radio-nuclide iodine isotopes. Immuno-PET/CT imaging was performed using a bispecific monoclonal antibody (mAb) probe 124I-AK104, developed in-house, to locate PD1+/CTLA4+ tumor-infiltrating T cells and monitor their distribution in mice to evaluate the therapeutic effect. RESULTS: The 124I-AK104 dual-antibody was successfully constructed with ideal radiochemical characteristics, in vitro stability and specificity. The results of immuno-PET showed that 124I-AK104 revealed strong hPD1/CTLA4-positive responses with high specificity in humanized mice. High uptake of 124I-AK104 was observed not only at the tumor site but also in the spleen. Compared with PD1- or CTLA4-targeting mAb imaging, 124I-AK104 imaging had excellent standard uptake values at the tumor site and higher tumor to nontumor (T/NT) ratios. CONCLUSIONS: The results demonstrated the potential of translating 124I-AK104 into a method for screening patients who benefit from immunotherapy and the efficacy, as well as the feasibility, of this method was verified by immuno-PET imaging of humanized mice.

5.
Zhen Ci Yan Jiu ; 49(4): 398-402, 2024 Apr 25.
Article En, Zh | MEDLINE | ID: mdl-38649208

OBJECTIVES: To compare the clinical effect of combined therapy of acupotomy and electroacupuncture (EA) with the simple application of EA on knee osteoarthritis (KOA), and their influence on knee function. METHODS: Sixty-eight KOA patients were randomly divided into 2 groups, an acupotomy group and an EA group. In the acupotomy group, the combined therapy of acupotomy and EA was adopted. In the EA group, EA was simply used, delivered once every two days, 3 treatments a week;and the duration of treatment was 4 weeks. In the acupotomy group, besides the treatment as the EA group, acupotomy was combined once weekly, and the duration of treatment was 4 weeks. Separately, before and after treatment, and in 4 and 12 weeks after treatment completion (1-month and 3-month follow-up), the results of the timed up and go test (TUG), the 9-step stair climb test (9-SCT) and the knee function (Western Ontario and McMaster University osteoarthritis index visualization scale [WOMAC]) were measured in the two groups. RESULTS: By the intention-to-treat analysis, the results of TUG, 9-SCT and WOMAC scores were reduced after treatment and in 1-month and 3-month follow-up when compared with those before treatment in the patients of the two groups (P<0.05). Compared with the EA group at the same time point, TUG results were decreased after treatment and in 1-month follow-up, and WOMAC score was reduced after treatment in the acupotomy group. WOMAC score in 1-month follow-up was reduced when compared with that before treatment within the acupotomy group (P<0.05). CONCLUSIONS: Either the simple application of EA or the combined therapy of acupotomy and EA can improve knee function, but the combined therapy obviously increases the walking speed and relieves the symptoms such as joint pain and morning stiffness. The treatment with acupotomy and EA is safe and effective on KOA and the long-term effect is satisfactory.


Acupuncture Therapy , Electroacupuncture , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/therapy , Osteoarthritis, Knee/physiopathology , Female , Male , Middle Aged , Aged , Treatment Outcome , Combined Modality Therapy , Knee Joint/physiopathology , Acupuncture Points
6.
Signal Transduct Target Ther ; 9(1): 96, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38653754

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.


Adaptor Proteins, Signal Transducing , Cell Nucleus , SOX9 Transcription Factor , Transcription Factors , YAP-Signaling Proteins , Humans , YAP-Signaling Proteins/genetics , YAP-Signaling Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Cell Nucleus/metabolism , Cell Nucleus/genetics , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Protein-Arginine N-Methyltransferases/genetics , Protein-Arginine N-Methyltransferases/metabolism , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Active Transport, Cell Nucleus/genetics , Mice , Cell Line, Tumor , Animals , Repressor Proteins/genetics , Repressor Proteins/metabolism
7.
Lipids Health Dis ; 23(1): 110, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38627726

BACKGROUND: There is evidence for an association between the gut microbiome and endometriosis. However, their causal relationship and the mediating role of lipid metabolism remain unclear. METHODS: Using genome-wide association study (GWAS) data, we conducted a bidirectional Mendelian randomization (MR) analysis to investigate the causal relationships between gut microbiome and endometriosis. The inverse variance weighted (IVW) method was used as the primary model, with other MR models used for comparison. Sensitivity analysis based on different statistical assumptions was used to evaluate whether the results were robust. A two-step MR analysis was further conducted to explore the mediating effects of lipids, by integrating univariable MR and the multivariate MR method based on the Bayesian model averaging method (MR-BMA). RESULTS: We identified four possible intestinal bacteria genera associated with the risk of endometriosis through the IVW method, including Eubacterium ruminantium group (odds ratio [OR] = 0.881, 95% CI: 0.795-0.976, P = 0.015), Anaerotruncus (OR = 1.252, 95% CI: 1.028-1.525, P = 0.025), Olsenella (OR = 1.110, 95% CI: 1.007-1.223, P = 0.036), and Oscillospira (OR = 1.215, 95% CI: 1.014-1.456, P = 0.035). The further two-step MR analysis identified that the effect of Olsenella on endometriosis was mediated by triglycerides (proportion mediated: 3.3%; 95% CI = 1.5-5.1%). CONCLUSION: This MR study found evidence for specific gut microbiomes associated with the risk of endometriosis, which might partially be mediated by triglycerides.


Endometriosis , Gastrointestinal Microbiome , Female , Humans , Gastrointestinal Microbiome/genetics , Endometriosis/genetics , Bayes Theorem , Genome-Wide Association Study , Mendelian Randomization Analysis , Lipids , Triglycerides
9.
Microbiol Res ; 282: 127661, 2024 May.
Article En | MEDLINE | ID: mdl-38432016

In yeasts, ferric reductase catalyzes reduction of ferric ion to ferrous form, which is essential for the reductive iron assimilation system. However, the physiological roles of ferric reductases remain largely unknown in the filamentous fungi. In this study, genome-wide annotation revealed thirteen ferric reductase-like (Fre) proteins in the filamentous insect pathogenic fungus Beauveria bassiana, and all their functions were genetically characterized. Ferric reductase family proteins exhibit different sub-cellular distributions (e.g., cell periphery and vacuole), which was due to divergent domain architectures. Fre proteins had a synergistic effect on fungal virulence, which was ascribed to their distinct functions in different physiologies. Ten Fre proteins were not involved in reduction of ferric ion in submerged mycelia, but most proteins contributed to blastospore development. Only two Fre proteins significantly contributed to B. bassiana vegetative growth under the chemical-induced iron starvation, but most Fre proteins were involved in resistance to osmotic and oxidative stresses. Notably, a bZIP-type transcription factor HapX bound to the promoter regions of all FRE genes in B. bassiana, and displayed varying roles in the transcription activation of these genes. This study reveals the important role of BbFre family proteins in development, stress response, and insect pathogenicity, as well as their distinctive role in the absorption of ferric iron from the environment.


Beauveria , FMN Reductase , Animals , Virulence/genetics , Beauveria/genetics , Fungal Proteins/genetics , Fungal Proteins/metabolism , Spores, Fungal , Insecta , Iron/metabolism
10.
Cell Death Dis ; 15(2): 110, 2024 02 03.
Article En | MEDLINE | ID: mdl-38310091

Hepatocellular carcinoma (HCC) is an aggressive malignancy without effective therapeutic approaches. Here, we evaluate the tumor-intrinsic mechanisms that attenuate the efficacy of immune checkpoint inhibitor (ICI) that is observed in patients with advanced HCC who progress on first-line tyrosine kinase inhibitor (TKI) therapy. Upregulation of AXL observed in sorafenib- and lenvatinib-resistant HCCs is correlated with poor response towards TKI and ICI treatments. AXL upregulation protects sorafenib-resistant HCC cells from oxidative stress, mitochondrial damage, and accompanying immunogenic cell death through suppressed tumor necrosis factor-α (TNF-α) and STING-type I interferon pathways. Pharmacological inhibition of AXL abrogates the protective effect and re-sensitizes TKI-resistant HCC tumors to anti-PD-1 treatment. We suggest that targeting AXL in combination with anti-PD-1 may provide an alternative treatment scheme for HCC patients who progress on TKI treatment.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Sorafenib/pharmacology , Sorafenib/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use
11.
BMC Med Inform Decis Mak ; 23(Suppl 4): 299, 2024 Feb 07.
Article En | MEDLINE | ID: mdl-38326827

BACKGROUND: In this era of big data, data harmonization is an important step to ensure reproducible, scalable, and collaborative research. Thus, terminology mapping is a necessary step to harmonize heterogeneous data. Take the Medical Dictionary for Regulatory Activities (MedDRA) and International Classification of Diseases (ICD) for example, the mapping between them is essential for drug safety and pharmacovigilance research. Our main objective is to provide a quantitative and qualitative analysis of the mapping status between MedDRA and ICD. We focus on evaluating the current mapping status between MedDRA and ICD through the Unified Medical Language System (UMLS) and Observational Medical Outcomes Partnership Common Data Model (OMOP CDM). We summarized the current mapping statistics and evaluated the quality of the current MedDRA-ICD mapping; for unmapped terms, we used our self-developed algorithm to rank the best possible mapping candidates for additional mapping coverage. RESULTS: The identified MedDRA-ICD mapped pairs cover 27.23% of the overall MedDRA preferred terms (PT). The systematic quality analysis demonstrated that, among the mapped pairs provided by UMLS, only 51.44% are considered an exact match. For the 2400 sampled unmapped terms, 56 of the 2400 MedDRA Preferred Terms (PT) could have exact match terms from ICD. CONCLUSION: Some of the mapped pairs between MedDRA and ICD are not exact matches due to differences in granularity and focus. For 72% of the unmapped PT terms, the identified exact match pairs illustrate the possibility of identifying additional mapped pairs. Referring to its own mapping standard, some of the unmapped terms should qualify for the expansion of MedDRA to ICD mapping in UMLS.


Adverse Drug Reaction Reporting Systems , International Classification of Diseases , Humans , Unified Medical Language System , Pharmacovigilance , Algorithms
12.
Nat Commun ; 15(1): 1300, 2024 Feb 12.
Article En | MEDLINE | ID: mdl-38346942

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.


Bone Resorption , Osteoclasts , Animals , Mice , Osteoclasts/metabolism , Kisspeptins/genetics , Kisspeptins/metabolism , Receptors, G-Protein-Coupled/metabolism , src-Family Kinases/genetics , src-Family Kinases/metabolism , Mice, Knockout , Bone Resorption/genetics , Receptors, Kisspeptin-1
13.
Front Microbiol ; 15: 1349151, 2024.
Article En | MEDLINE | ID: mdl-38333587

Eight new 12,8-eudesmanolide sesquiterpenes, eutypellaolides A-H (1-8), and two new eudesmane-type sesquiterpenes, eutypellaolides I-J (9-10), along with four known 12,8-eudesmanolide compounds 11-14, were isolated from the culture extract of the polar fungus Eutypella sp. D-1 by one strain many compounds (OSMAC) approach. The structures of these compounds were determined through comprehensive spectroscopic data and experimental and calculated ECD analysis. Antibacterial, immunosuppressive, and PTP1B inhibition activities of these compounds were evaluated. Compounds 1 and 11 exhibited strong inhibitory activities against Bacillus subtilis and Staphylococcus aureus, with each showing an MIC value of 2 µg/mL. Compound 9 displayed weak immunosuppressive activity against ConA-induced T-cell proliferation with an inhibitory rate of 61.7% at a concentration of 19.8 µM. Compounds 5, 11, and 14 exhibited weak PTP1B inhibition activities with IC50 values of 44.8, 43.2, and 49.5 µM, respectively.

14.
Child Adolesc Psychiatry Ment Health ; 18(1): 17, 2024 Jan 28.
Article En | MEDLINE | ID: mdl-38282053

BACKGROUND: School bullying victimization (SBV) occurs more frequently in students with autism spectrum disorder (ASD) in general education than in special classes, and there is a cumulative risk effect on SBV exposure among young people with ASD reported by their parents and teachers. However, SBV is a personal experience, the predictive patterns of cumulative risk on SBV reported by themselves and its psychological mechanism remain unclear. This study aims to explore the relationship between cumulative risk and SBV based on self-report, and to test whether internalizing problems mediates this relationship among adolescents with ASD placed in regular classes. METHODS: This study used data from the Taiwan Special Needs Education Longitudinal Study (SNELS) in 2011. The analysis included 508 adolescents with ASD who were in regular classes across Taiwan. The primary variables under study were the quality of friendship interactions, teacher-student relationship, school connection, perceived stigma, the impact caused by the disabilities, internalizing problem, and whether the participants had experienced SBV over the past semester, while control variables were adaptability and social-emotional skills. Established risk factors were summed to form a cumulative risk score. RESULTS: The cumulative risk was positively associated with SBV. The relationship was characterized by the nonlinear pattern of the quadratic function (negative acceleration model) between cumulative risk and SBV. Internalizing problem played a partial mediating role in the effect of cumulative risk on SBV. CONCLUSIONS: Intervention measures to reduce SBV should include the strategies to reduce the number of risks to which adolescents with ASD in regular classes are exposed, comprehensive prevention targeting each risk factor is needed specially when the number of risks is one or two, and more attention needs to be given to their internalizing problem in various ways.

15.
Discov Med ; 36(180): 113-120, 2024 Jan.
Article En | MEDLINE | ID: mdl-38273751

BACKGROUND: Circular RNA is a type of non-coding RNA that is commonly found in eukaryotic genomes. They play an essential role in the biological processes of cell proliferation and cell apoptosis involved in normal development and abnormal tumorigenesis. In this study, we examined whether that the circular RNA GENE hsa_circ_0120175 is substantially expressed in epithelial ovarian cancer, and then explored whether hsa_circ_0120175 plays an important role in the occurrence and development of ovarian cancer. METHODS: A total of 40 patients with ovarian cancer were included in this study, and tissue samples were collected from both ovarian cancer tissues and paracancer tissues. The levels of hsa_circ_0120175 expression were determined using qRT-PCR in both varian cancer cells and tissues. This study assessed the impact of hsa_circ_0120175 on cellular proliferation, migration, and invasion using various in vitro assays with cultured ovarian carcinoma cells. RESULTS: Hsa_circ_0120175 was highly expressed in both human tissues and ovarian cancer cells. In ovarian cancer patients, the expression level of hsa_circ_0120175 was significantly different among The International Federation of Gynecology and Obstetrics (FIGO) stages (p = 0.03), and the difference was statistically significant. Multivariate Cox regression analysis showed that lymph node metastasis was independently related to Overall Survival (OS), and the difference was statistically significant (p = 0.033). In vitro, decreasing hsa_circ_0120175 significantly reduced ovarian carcinoma cell proliferation, migration, and invasion (p < 0.05). CONCLUSIONS: Hsa_circ_0120175 has the potential to serve as a biomarker for diagnosing and treating ovarian carcinoma. This is because it promotes cellular proliferation, migration, and invasion in epithelial ovarian carcinoma.


MicroRNAs , Ovarian Neoplasms , Humans , Female , RNA, Circular/genetics , RNA, Circular/metabolism , Ovarian Neoplasms/genetics , Carcinogenesis/genetics , Cell Transformation, Neoplastic/genetics , Prognosis , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Cell Line, Tumor , Cell Movement/genetics
16.
Cell Death Dis ; 15(1): 66, 2024 01 18.
Article En | MEDLINE | ID: mdl-38238307

Gasdermin-E (GSDME), the executioner of pyroptosis when cleaved by caspase 3, plays a crucial role in tumor defense and the response to chemotherapy drugs in cells. So far, there are poorly known mechanisms for the expression regulation of GSDME during cell death. Here, we identify the transcription factor Sp1 (Specificity protein 1) as a positive regulator of GSDME-mediated pyroptosis. Sp1 directly interacts with the GSDME promoter at -36 ~ -28 site and promotes GSDME gene transcription. Further, Sp1 knockdown or inhibition suppresses GSDME expression, thus reducing chemotherapy drugs (topotecan, etoposide, doxorubicin, sorafinib and cisplatin) induced cell pyroptosis. The regulation process synergizes with STAT3 (Signal transducer and activator of transcription 3) activity and antagonizes with DNA methylation but barely affects GSDMD-mediated pyroptosis or TNF-induced necroptosis. Our current finding reveals a new regulating mechanism of GSDME expression, which may be a viable target for the intervention of GSDME-dependent inflammatory diseases and cancer therapy.


Pyroptosis , Receptors, Estrogen , Receptors, Estrogen/metabolism , Cell Death , Cisplatin/pharmacology , Doxorubicin/pharmacology , Caspase 3/metabolism
17.
Neural Netw ; 171: 159-170, 2024 Mar.
Article En | MEDLINE | ID: mdl-38091760

Nuclei detection is one of the most fundamental and challenging problems in histopathological image analysis, which can localize nuclei to provide effective computer-aided cancer diagnosis, treatment decision, and prognosis. The fully-supervised nuclei detector requires a large number of nuclei annotations on high-resolution digital images, which is time-consuming and needs human annotators with professional knowledge. In recent years, weakly-supervised learning has attracted significant attention in reducing the labeling burden. However, detecting dense nuclei of complex crowded distribution and diverse appearances remains a challenge. To solve this problem, we propose a novel point-supervised dense nuclei detection framework that introduces position-based anchor optimization to complete morphology-based pseudo-label supervision. Specifically, we first generate cellular-level pseudo labels (CPL) for the detection head via a morphology-based mechanism, which can help to build a baseline point-supervised detection network. Then, considering the crowded distribution of the dense nuclei, we propose a mechanism called Position-based Anchor-quality Estimation (PAE), which utilizes the positional deviation between an anchor and its corresponding point label to suppress low-quality detections far from each nucleus. Finally, to better handle the diverse appearances of nuclei, an Adaptive Anchor Selector (AAS) operation is proposed to automatically select positive and negative anchors according to morphological and positional statistical characteristics of nuclei. We conduct comprehensive experiments on two widely used benchmarks, MO and Lizard, using ResNet50 and PVTv2 as backbones. The results demonstrate that the proposed approach has superior capacity compared with other state-of-the-art methods. In particularly, in dense nuclei scenarios, our method can achieve 95.1% performance of the fully-supervised approach. The code is available at https://github.com/NucleiDet/DenseNucleiDet.


Benchmarking , Diagnosis, Computer-Assisted , Humans , Image Processing, Computer-Assisted , Knowledge , Supervised Machine Learning
18.
Acta Pharmacol Sin ; 45(2): 436-448, 2024 Feb.
Article En | MEDLINE | ID: mdl-37749238

Extracellular matrix metalloproteinase inducer CD147 is a glycoprotein on the cell surface. There is minimal expression of CD147 in normal epithelial and fetal tissues, but it is highly expressed in a number of aggressive tumors. CD147 has been implicated in pan-cancer immunity and progression. With the development of CD147-targeting therapeutic strategy, accurate detection of CD147 expression in tumors and its changes during the therapy is necessary. In this study we constructed a novel radiotracer by labeling the anti-CD147 mAb with radionuclide 124/125I (124/125I-anti-CD147) for noninvasive detection of CD147 expression in pan-cancers, and characterized its physicochemical properties, affinity, metabolic characteristics, biodistribution and immunoPET imaging with 124I-IgG and 18F-FDG as controls. By examining the expression of CD147 in cancer cell lines, we found high CD147 expression in colon cancer cells LS174T, FADU human pharyngeal squamous cancer cells and 22RV1 human prostate cancer cells, and low expression of CD147 in human pancreatic cancer cells ASPC1 and human gastric cancer cells BGC823. 124/125I-anti-CD147 was prepared using N-bromine succinimide (NBS) as oxidant and purified by PD-10 column. Its radiochemical purity (RCP) was over 99% and maintained over 85% in saline or 5% human serum albumin (HSA) for more than 7 d; the RCP of 125I-anti-CD147 in blood was over 90% at 3 h post injection (p.i.) in healthy mice. The Kd value of 125I-anti-CD147 to CD147 protein was 6.344 nM, while that of 125I-IgG was over 100 nM. 125I-anti-CD147 showed much greater uptake in CD147 high-expression cancer cells compared to CD147 low-expression cancer cells. After intravenous injection in healthy mice, 125I-anti-CD147 showed high initial uptake in blood pool and liver, the uptake was decreased with time. The biological half-life of distribution and clearance phases in healthy mice were 0.63 h and 19.60 h, respectively. The effective dose of 124I-anti-CD147 was estimated as 0.104 mSv/MBq. We conducted immunoPET imaging in tumor-bearing mice, and demonstrated a significantly higher tumor-to-muscle ratio of 124I-anti-CD147 compared to that of 124I-IgG and 18F-FDG in CD147 (+) tumors. The expression levels of CD147 in cells and tumors were positively correlated with the maximum standardized uptake value (SUVmax) (P < 0.01). In conclusion, 124/125I-anti-CD147 displays high affinity to CD147, and represents potential for the imaging of CD147-positive tumors. The development of 124I-anti-CD147 may provide new insights into the regulation of tumor microenvironment and formulation of precision diagnosis and treatment programs for tumors.


Fluorodeoxyglucose F18 , Prostatic Neoplasms , Male , Humans , Mice , Animals , Tissue Distribution , Radiopharmaceuticals , Iodine Radioisotopes , Immunoglobulin G , Cell Line, Tumor , Tumor Microenvironment
19.
J Interpers Violence ; 39(3-4): 499-518, 2024 02.
Article En | MEDLINE | ID: mdl-37705406

Cyber reactive aggression (CRA) among college students is a prevalent and harmful phenomenon. Psychological characteristics, such as trait anger (TA), hostile attribution bias (HAB), and revenge motivation (RM), are known to contribute to reactive aggression. However, the interactions between these factors in the context of cyberspace and their contribution to CRA among college students have not been extensively studied. This cross-sectional study aimed to identify the associations among psychological characteristics, demographic factors, and CRA among Chinese college students through Mixed Graphical Model (MGM) network and mediation effect analyses. A total of 926 participants completed questionnaires assessing TA, HAB, RM, and CRA. The study found both direct and indirect relationships between TA and CRA, with HAB and RM serving as mediating factors. Comparisons indicated that HAB had a more significant impact on the three indirect effects than RM. Furthermore, gender was found to be associated with TA and CRA, while the left-behind experience strongly influenced HAB but had no association with other variables. This study highlights the importance of considering psychological characteristics and demographic factors in understanding CRA among college students, suggesting that effective psychological interventions, such as anger management, and promoting positive attribution training, may help reduce CRA among college students and inform the development of targeted interventions to reduce cyber aggression.


Aggression , Mediation Analysis , Humans , Aggression/psychology , Cross-Sectional Studies , Anger , Students/psychology
20.
J Diabetes Investig ; 15(1): 34-43, 2024 Jan.
Article En | MEDLINE | ID: mdl-38041572

AIMS/INTRODUCTION: Different types of diabetes show distinct genetic characteristics, but the specific genetic susceptibility factors remain unclear. Our study aimed to explore the associations between the ribosomal protein S26 (RPS26) gene rs1131017 polymorphisms and susceptibility to type 1 diabetes mellitus, latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus in the Chinese Han population, and their correlations with clinical features. MATERIALS AND METHODS: Genotyping of the rs1131017 variant was carried out for 1,006 type 1 diabetes mellitus patients, 210 LADA patients, 642 type 2 diabetes mellitus patients and 2,099 control individuals. RESULTS: We found that the rs1131017 C allele was a risk locus for both type 1 diabetes mellitus and LADA (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.33-1.69, P < 0.001; OR 1.31, 95% CI 1.04-1.64, P = 0.021, respectively). Nevertheless, this association was not found for type 2 diabetes mellitus. Carrying the C allele genotype was associated with a lower postprandial C-peptide for type 1 diabetes mellitus (OR 1.41, 95% CI 1.11-1.80, P = 0.006) and lower fasting C-peptide for LADA (OR 1.55, 95% CI 1.01-2.38, P = 0.047). Interestingly, a lower GC frequency was noted for LADA than for type 1 diabetes mellitus, regardless of classification based on age at diagnosis, C-peptide or glutamic acid decarboxylase antibody positivity. CONCLUSIONS: The RPS26 polymorphism was associated with susceptibility and clinical characteristics of type 1 diabetes mellitus and LADA in the Chinese population, but was not related to type 2 diabetes mellitus. Thus, it might serve as a novel biomarker for particular types of diabetes.


Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Latent Autoimmune Diabetes in Adults , Adult , Humans , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , C-Peptide , Polymorphism, Genetic , China/epidemiology , Autoantibodies
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