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1.
China CDC Wkly ; 6(15): 312-317, 2024 Apr 12.
Article En | MEDLINE | ID: mdl-38736993

What is already known about this topic?: Mucosal IgA plays a crucial role in host immunity against respiratory viruses. Recent studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. However, a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019 (COVID-19) pandemic is yet to be conducted. What is added by this report?: In our study involving 3,421 participants, we documented IgA responses subsequent to SARS-CoV-2 infection. A significant proportion of individuals sustained increased levels of IgA for over six months. These levels were also observed in individuals with prior infections who underwent asymptomatic reinfections, indicating an active production of IgA antibodies. Further, individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after recovery. What are the implications for public health practice?: IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 infection. These insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

2.
CNS Neurosci Ther ; 30(5): e14720, 2024 05.
Article En | MEDLINE | ID: mdl-38715344

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive malignant tumor with a high mortality rate and is the most prevalent primary intracranial tumor that remains incurable. The current standard treatment, which involves surgery along with concurrent radiotherapy and chemotherapy, only yields a survival time of 14-16 months. However, the introduction of tumor electric fields therapy (TEFT) has provided a glimmer of hope for patients with newly diagnosed and recurrent GBM, as it has been shown to extend the median survival time to 20 months. The combination of TEFT and other advanced therapies is a promising trend in the field of GBM, facilitated by advancements in medical technology. AIMS: In this review, we provide a concise overview of the mechanism and efficacy of TEFT. In addition, we mainly discussed the innovation of TEFT and our proposed blueprint for TEFT implementation. CONCLUSION: Tumor electric fields therapy is an effective and highly promising treatment modality for GBM. The full therapeutic potential of TEFT can be exploited by combined with other innovative technologies and treatments.


Brain Neoplasms , Electric Stimulation Therapy , Glioblastoma , Humans , Glioblastoma/therapy , Brain Neoplasms/therapy , Electric Stimulation Therapy/methods , Electric Stimulation Therapy/trends , Animals
3.
PeerJ ; 12: e17382, 2024.
Article En | MEDLINE | ID: mdl-38766483

Background: Preoperative inflammatory factors and nutritional status are strongly associated with the prognosis of a variety of cancers. We explored the relationship between preoperative lymphocytes, neutrophils and albumin (LANR) and progression-free survival in breast cancer patients. Methods: The clinical and follow-up data of 200 breast cancer patients were retrospectively analyzed in this study, and the value of LANR was determined as follows: LANR, lymphocytes × albumin/neutrophils. ROC curves, COX proportional risk regression analysis and subgroup analysis were used to assess the prognostic value of LANR in progression-free survival of breast cancer patients. Results: The median age of the patients was 55.5 years (range 50-62 years). The median follow-up time was 46 months (range 33-55 months). In progression-free survival, the area under the LANR curve was 0.748 and the HR (95% CI) was 0.035 (0.679-0.817). LANR was associated with age (p = 0.02), positive axillary lymph nodes (p < 0.001), TNM stage (p < 0.001) and human epidermal growth factor receptor 2(p = 0.004). The results indicated that preoperative LANR may be a reliable predictor of progression-free survival in patients with operable breast cancer. Conclusion: LANR may be an essential predictor for breast cancer patients and provides a therapeutic basis for clinicians and patients.


Breast Neoplasms , Lymphocytes , Neutrophils , Humans , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Breast Neoplasms/mortality , Female , Middle Aged , Retrospective Studies , Neutrophils/metabolism , Neutrophils/pathology , Prognosis , Lymphocytes/pathology , Lymphocytes/metabolism , Preoperative Period , Progression-Free Survival , Serum Albumin/analysis , Serum Albumin/metabolism , ROC Curve
4.
Int J Med Sci ; 21(6): 1176-1186, 2024.
Article En | MEDLINE | ID: mdl-38774752

Background: To uncover the potential significance of JAK-STAT-SOCS1 axis in penile cancer, our study was the pioneer in exploring the altered expression processes of JAK-STAT-SOCS1 axis in tumorigenesis, malignant progression and lymphatic metastasis of penile cancer. Methods: In current study, the comprehensive analysis of JAK-STAT-SOCS1 axis in penile cancer was analyzed via multiple analysis approaches based on GSE196978 data, single-cell data (6 cancer samples) and bulk RNA data (7 cancer samples and 7 metastasis lymph nodes). Results: Our study observed an altered molecular expression of JAK-STAT-SOCS1 axis during three different stages of penile cancer, from tumorigenesis to malignant progression to lymphatic metastasis. STAT4 was an important dominant molecule in penile cancer, which mediated the immunosuppressive tumor microenvironment by driving the apoptosis of cytotoxic T cell and was also a valuable biomarker of immune checkpoint inhibitor treatment response. Conclusions: Our findings revealed that the complexity of JAK-STAT-SOCS1 axis and the predominant role of STAT4 in penile cancer, which can mediate tumorigenesis, malignant progression, and lymphatic metastasis. This insight provided valuable information for developing precise treatment strategies for patients with penile cancer.


Disease Progression , Janus Kinases , Lymphatic Metastasis , Penile Neoplasms , STAT4 Transcription Factor , Suppressor of Cytokine Signaling 1 Protein , Humans , Male , Penile Neoplasms/pathology , Penile Neoplasms/genetics , Penile Neoplasms/metabolism , Suppressor of Cytokine Signaling 1 Protein/genetics , Suppressor of Cytokine Signaling 1 Protein/metabolism , Lymphatic Metastasis/pathology , Lymphatic Metastasis/genetics , Janus Kinases/metabolism , STAT4 Transcription Factor/metabolism , STAT4 Transcription Factor/genetics , Gene Expression Regulation, Neoplastic , Carcinogenesis/genetics , Carcinogenesis/pathology , Signal Transduction , Tumor Microenvironment/immunology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology
5.
J Agric Food Chem ; 72(20): 11759-11772, 2024 May 22.
Article En | MEDLINE | ID: mdl-38738668

This study aimed to investigate alterations in gut microbiota and metabolites mediated by wheat-resistant starch and its repair of gut barrier dysfunction induced by a high-fat diet (HFD). Structural data revealed that chlorogenic acid (CA)/linoleic acid (LA) functioned through noncovalent interactions to form a more ordered structure and fortify antidigestibility in wheat starch (WS)-CA/LA complexes; the resistant starch (RS) contents of WS-CA, WS-LA, and WS-CA-LA complexes were 23.40 ± 1.56%, 21.25 ± 1.87%, and 35.47 ± 2.16%, respectively. Dietary intervention with WS-CA/LA complexes effectively suppressed detrimental alterations in colon tissue morphology induced by HFD and repaired the gut barrier in ZO-1 and MUC-2 levels. WS-CA/LA complexes could augment gut barrier-promoting microbes including Parabacteroides, Bacteroides, and Muribaculum, accompanied by an increase in short-chain fatty acids (SCFAs) and elevated expression of SCFA receptors. Moreover, WS-CA/LA complexes modulated secondary bile acid metabolism by decreasing taurochenodeoxycholic, cholic, and deoxycholic acids, leading to the activation of bile acid receptors. Collectively, this study offered guiding significance in the manufacture of functional diets for a weak gut barrier.


Chlorogenic Acid , Diet, High-Fat , Gastrointestinal Microbiome , Linoleic Acid , Mice, Inbred C57BL , Starch , Triticum , Chlorogenic Acid/metabolism , Chlorogenic Acid/pharmacology , Chlorogenic Acid/administration & dosage , Chlorogenic Acid/chemistry , Diet, High-Fat/adverse effects , Triticum/chemistry , Triticum/metabolism , Gastrointestinal Microbiome/drug effects , Animals , Male , Mice , Starch/metabolism , Starch/chemistry , Linoleic Acid/metabolism , Linoleic Acid/chemistry , Bacteria/classification , Bacteria/metabolism , Bacteria/genetics , Bacteria/drug effects , Bacteria/isolation & purification , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Humans , Fatty Acids, Volatile/metabolism , Resistant Starch/metabolism
6.
Kidney Dis (Basel) ; 10(2): 89-96, 2024 Apr.
Article En | MEDLINE | ID: mdl-38751797

Introduction: Venous valve-related stenosis (VVRS) is an uncommon type of failure of arteriovenous fistula among patients with end-stage renal disease (ESRD). There is a paucity of data on the long-term efficacy of ultrasound-guided percutaneous transluminal angioplasty (PTA) for VVRS. Methods: ESRD patients who underwent PTA because of VVRS between January 2017 and December 2021 at the First Affiliated Hospital of Chongqing Medical University were enrolled. Patients were classified into three cohorts (cohort1, VVRS located within 3 cm of the vein adjacent to the anastomosis; cohort2, VVRS located over 3 cm away from the anastomosis; cohort3, multiple stenoses). The patency rates were assessed by the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox analyses were performed to identify the risk factors. Results: A total of 292 patients were enrolled, including 125 (42.8%), 111 (38.0%), and 56 (19.2%) patients in cohort1, cohort2, and cohort3, respectively. The median follow-up was 34.8 months. The 6-month, 1-year, 2-year, and 3-year primary patency rates were 86.0%, 69.4%, 47.5%, and 35.3%, respectively. The secondary patency rates were 94.5%, 89.4%, 75.5%, and 65.3%, respectively. Cohort1 showed a relatively better primary patency compared to cohort2 and cohort3. The secondary patency rates were comparable in the three cohorts. Duration of dialysis and VVRS type were potential factors associated with primary patency. Conclusions: This study showed acceptable long-term primary and secondary patency rates after PTA for VVRS in ESRD patients, especially for those with VVRS located within 3 cm of the vein adjacent to the anastomosis.

7.
ACS Nano ; 18(20): 13428-13436, 2024 May 21.
Article En | MEDLINE | ID: mdl-38725103

The Co-free Ni-rich layered cathodes become pivotal to reduce cost and increase benefit toward next-generation Li-ion batteries yet raise a major challenge for their extremely fragile cathode-electrolyte interface (CEI) film. Herein, we report the in situ construction of the Si/B-enriched organic-inorganic hybrid CEI films on LiNi0.9Mn0.1O2 (NM91) with the assistance of tris(trimethylsilyl) borate (TMSB) additive. The hybrid film exhibits superior Young's modulus, mechanical strength, and ductility, which greatly dissipate the microstrain of Co-free Ni-rich cathodes under various states of charge with high structural integrity. Furthermore, the surface oxygen anions have been significantly stabilized by bonding with the Si and B ions of TMSB with high safety. These merits enable a durable Co-free Ni-rich layered cathode with 96.9% and 87.7% capacity retentions (versus 72.7% and 70.2% of NM91) at a high rate of 5C and a high-temperature of 55 °C after 100 cycles. In a pouch-type full cell, 88.8% of initial capacity is still maintained after cycling at 1C for 500 times, greatly expediting the development and application of Co-free Ni-rich layered cathodes.

8.
Int J Biol Macromol ; 269(Pt 1): 131978, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38692537

Multiscale structure and digestive characteristic of starch during kernel development of Castanea henryi ('Jinzhui' (YS) and 'Baiyan No.1' (WS)) were investigated in this study. Structural analysis revealed that the surface of starch granules became smooth, the amylopectin content decreased (from 71.32 % to 70.47 %, from 71.44 % to 68.37 %, respectively), the chain length distribution of amylopectin reduced (the proportion of B1 chain decreased from 52.35 % to 50.60 %, from 52.22 % to 50.59 %, respectively) while the amorphous and semi-crystalline lamellae of starch increased during development, which was consistent with the decreasing relative crystallinity (from 28.79 % to 24.11 %, from 29.57 % to 23.66 %, respectively) and short-range ordering degree. The degradation of ordered structure further resulted in the increase of digestibility, especially in the late developmental stage, supported by a significant decrease of resistant starch content (from 70.21 % to 61.70 % and from 73.58 % to 58.86 %, respectively). Transcriptome analysis and RT-qPCR were performed to explore the possible molecular mechanisms affecting starch structure. The high expression of several key genes including AGPase, GBSS, SBE, SSS, ISA and PUL in late development stage might be the reason of structural changes during development. The results provided valuable information for starch accumulation during kernel development of Castanea henryi.

9.
BMC Oral Health ; 24(1): 514, 2024 May 02.
Article En | MEDLINE | ID: mdl-38698364

BACKGROUND: Studies have shown that visfatin is an inflammatory factor closely related to periodontitis. We examined the levels of visfatin in gingival crevicular fluid (GCF) and gingival tissues under different periodontal conditions, in order to provide more theoretical basis for exploring the role of visfatin in the pathogenesis of periodontitis. METHODS: We enrolled 87 subjects, with 43 in the chronic periodontitis (CP) group, 21 in the chronic gingivitis (CG) group, and 23 in the periodontal health (PH) group. Periodontal indexes (PD, AL, PLI, and BI) were recorded. GCF samples were collected for visfatin quantification, and gingival tissues were assessed via immunohistochemical staining. RESULTS: Visfatin levels in GCF decreased sequentially from CP to CG and PH groups, with statistically significant differences (P < 0.05). The CP group exhibited the highest visfatin levels, while the PH group had the lowest. Gingival tissues showed a similar trend, with significant differences between groups (P < 0.001). Periodontal indexes were positively correlated with visfatin levels in both GCF and gingival tissues (P < 0.001). A strong positive correlation was observed between visfatin levels in GCF and gingival tissues (rs = 0.772, P < 0.001). CONCLUSION: Greater periodontal destruction corresponded to higher visfatin levels in GCF and gingival tissues, indicating their potential collaboration in damaging periodontal tissues. Visfatin emerges as a promising biomarker for periodontitis and may play a role in its pathogenesis.


Chronic Periodontitis , Gingiva , Gingival Crevicular Fluid , Gingivitis , Nicotinamide Phosphoribosyltransferase , Periodontal Index , Humans , Gingival Crevicular Fluid/chemistry , Nicotinamide Phosphoribosyltransferase/metabolism , Nicotinamide Phosphoribosyltransferase/analysis , Male , Female , Cross-Sectional Studies , Gingiva/metabolism , Adult , Chronic Periodontitis/metabolism , Gingivitis/metabolism , Middle Aged , Cytokines/metabolism , Cytokines/analysis
10.
FASEB J ; 38(9): e23643, 2024 May 15.
Article En | MEDLINE | ID: mdl-38703030

Secreted phospholipase A2s are involved in the development of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease, which have become serious and growing health concerns worldwide. Integration of genome-wide association study and gene co-expression networks analysis showed that the secreted phospholipase A2 group XIIA (PLA2G12A) may participate in hepatic lipids metabolism. Nevertheless, the role of PLA2G12A in lipid metabolism and its potential mechanism remain elusive. Here, we used AAV9 vector carrying human PLA2G12A gene to exogenously express hPLA2G12A in the liver of mice. We demonstrated that the overexpression of hPLA2G12A resulted in a significant decrease in serum lipid levels in wild-type mice fed with chow diet or high-fat diet (HFD). Moreover, hPLA2G12A treatment protected against diet-induced obesity and insulin resistance in mice fed a HFD. Notably, we found that hPLA2G12A treatment confers protection against obesity and hyperlipidemia independent of its enzymatic activity, but rather by increasing physical activity and energy expenditure. Furthermore, we demonstrated that hPLA2G12A treatment induced upregulation of ApoC2 and Cd36 and downregulation of Angptl8, which contributed to the increase in clearance of circulating triglycerides and hepatic uptake of fatty acids without affecting hepatic de novo lipogenesis, very low-density lipoprotein secretion, or intestinal lipid absorption. Our study highlights the potential of PLA2G12A gene therapy as a promising approach for treating obesity, insulin resistance and T2DM.


Diet, High-Fat , Energy Metabolism , Insulin Resistance , Mice, Inbred C57BL , Obesity , Triglycerides , Animals , Obesity/metabolism , Obesity/etiology , Mice , Triglycerides/metabolism , Triglycerides/blood , Male , Diet, High-Fat/adverse effects , Humans , Liver/metabolism , Lipid Metabolism
11.
Cell Stem Cell ; 31(5): 583-585, 2024 May 02.
Article En | MEDLINE | ID: mdl-38701751

How nuclear RNA homeostasis impacts cellular functions remains elusive. In this issue of Cell Stem Cell, Han et al.1 utilized a controllable protein degradation system targeting EXOSC2 to perturb RNA homeostasis in mouse pluripotent embryonic stem cells, revealing its vital role in orchestrating crucial nuclear events for cellular fitness.


Homeostasis , RNA, Nuclear , Animals , Mice , RNA, Nuclear/metabolism , RNA, Nuclear/genetics , Exosome Multienzyme Ribonuclease Complex/metabolism , Exosome Multienzyme Ribonuclease Complex/genetics , Cell Nucleus/metabolism , Mouse Embryonic Stem Cells/metabolism , Mouse Embryonic Stem Cells/cytology , Humans , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , RNA/metabolism , Pluripotent Stem Cells/metabolism , Pluripotent Stem Cells/cytology
12.
Gynecol Oncol ; 187: 37-45, 2024 May 06.
Article En | MEDLINE | ID: mdl-38713997

OBJECTIVE: To assess the prognostic performance of the 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema. METHODS: This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. Study population was 129,146 patients with stage I-IV endometrial cancer per the 2009 FIGO staging schema. Stage-shifting and overall survival (OS) were assessed according to the 2023 FIGO staging schema. RESULTS: Upstage (IA → II, 21.4 %; IB → II, 53.0 %) and downstage (IIIA→IA3, 22.2 %) occurred in both early and advanced diseases. Inter-stage prognostic performance improved in the 2023 schema with widened 5-year OS rate difference between the earliest and highest stages (68.2 % to 76.9 %). Stage IA1-IIB and IIC had distinct 5-year OS rate differences (85.8-96.1 % vs 75.4 %). The 5-year OS rate of the 2009 stage IIIA disease was 63.9 %; this was greater segregated in the 2023 schema: 88.0 %, 62.4 %, and 55.7 % for IIIA→IA3, IIIA1, and IIIA2, respectively (inter-substage rate-difference, 32.3 %). This 5-year OS rate of stage IA3 disease was comparable to the 2023 stage IB-IIB diseases (88.0 % vs 85.8-89.5 %). In the 2023 stage IIIC schema (micrometastasis rates: 29.6 % in IIIC1 and 15.6 % in IIIC2), micrometastasis and macrometastasis had the distinct 3-year OS rates in both pelvic (IIIC1-i vs IIIC1-ii, 84.9 % vs 71.1 %; rate-difference 13.8 %) and para-aortic (IIIC2-i vs IIIC2-ii, 82.9 % vs 65.2 %; rate-difference 17.7 %) nodal metastasis cases. The 5-year OS rate of the 2009 stage IVB disease was 23.4 %; this was segregated to 25.4 % for stage IVB and 19.2 % for stage IVC in the 2023 staging schema (rate-difference, 6.2 %). CONCLUSION: The 2023 FIGO endometrial cancer staging schema is a major revision from the 2009 FIGO schema. Almost doubled enriched sub-stages based on detailed anatomical metastatic site and incorporation of histological information enable more robust prognostication.

13.
Cell Death Dis ; 15(5): 319, 2024 May 06.
Article En | MEDLINE | ID: mdl-38710705

Argininosuccinate synthase (ASS1), a critical enzyme in the urea cycle, acts as a tumor suppressor in many cancers. To date, the anticancer mechanism of ASS1 has not been fully elucidated. Here, we found that phosphoglycerate dehydrogenase (PHGDH), a key rate-limiting enzyme in serine synthesis, is a pivotal protein that interacts with ASS1. Our results showed that ASS1 directly binds to PHGDH and promotes its ubiquitination-mediated degradation to inhibit serine synthesis, consequently suppressing tumorigenesis. Importantly, the tumor suppressive effects of ASS1 were strongly abrogated by PHGDH knockout. In addition, ASS1 knockout and knockdown partially rescued cell proliferation when serine and glycine were depleted, while the inhibitory effect of ASS1 overexpression on cell proliferation was restored by the addition of serine and glycine. These findings unveil a novel role of ASS1 and suggest that the ASS1/PHGDH serine synthesis pathway is a promising target for cancer therapy.


Argininosuccinate Synthase , Cell Proliferation , Phosphoglycerate Dehydrogenase , Serine , Triple Negative Breast Neoplasms , Phosphoglycerate Dehydrogenase/metabolism , Phosphoglycerate Dehydrogenase/genetics , Serine/metabolism , Serine/biosynthesis , Humans , Female , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/genetics , Animals , Argininosuccinate Synthase/metabolism , Argininosuccinate Synthase/genetics , Cell Line, Tumor , Mice, Nude , Ubiquitination , Mice , Glycine/metabolism
14.
Life Sci ; 347: 122682, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38702025

Thyroid cancer is one of the most common primary endocrine malignancies worldwide, and papillary thyroid carcinoma (PTC) is the predominant histological type observed therein. Although PTC has been studied extensively, our understanding of the altered metabolism and metabolic profile of PTC tumors is limited. We identified that the content of metabolite homogentisic acid (HGA) in PTC tissues was lower than that in adjacent non-cancerous tissues. We evaluated the potential of HGA as a novel molecular marker in the diagnosis of PTC tumors, as well as its ability to indicate the degree of malignancy. Studies have further shown that HGA contributes to reactive oxygen species (ROS) associated oxidative stress, leading to toxicity and inhibition of proliferation. In addition, HGA caused an increase in p21 expression levels in PTC cells and induced G1 arrest. Moreover, we found that the low HGA content in PTC tumors was due to the low expression levels of tyrosine aminotransferase (TAT) and p-hydroxyphenylpyruvate hydroxylase (HPD), which catalyze the conversion of tyrosine to HGA. The low expression levels of TAT and HPD are strongly associated with a higher probability of PTC tumor invasion and metastasis. Our study demonstrates that HGA could be used to diagnose PTC and provides mechanisms linking altered HGA levels to the biological behavior of PTC tumors.


Cell Cycle Checkpoints , Cell Proliferation , Cyclin-Dependent Kinase Inhibitor p21 , Homogentisic Acid , Reactive Oxygen Species , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Reactive Oxygen Species/metabolism , Thyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/metabolism , Homogentisic Acid/metabolism , Female , Male , Middle Aged , Cell Line, Tumor , Oxidative Stress , Carcinoma, Papillary/pathology , Carcinoma, Papillary/metabolism , Adult
15.
World J Stem Cells ; 16(4): 444-458, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38690512

BACKGROUND: Leukemia stem cells (LSCs) are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia (AML), as they are protected by the bone marrow microenvironment (BMM) against conventional therapies. Gossypol acetic acid (GAA), which is extracted from the seeds of cotton plants, exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2. AIM: To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism. METHODS: In this study, LSCs were magnetically sorted from AML cell lines and the CD34+CD38- population was obtained. The expression of leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) and forkhead box M1 (FOXM1) was evaluated in LSCs, and the effects of GAA on malignancies and mitochondrial function were measured. RESULTS: LRPPRC was found to be upregulated, and GAA inhibited cell proliferation by degrading LRPPRC. GAA induced LRPPRC degradation and inhibited the activation of interleukin 6 (IL-6)/janus kinase (JAK) 1/signal transducer and activator of transcription (STAT) 3 signaling, enhancing chemosensitivity in LSCs against conventional chemotherapies, including L-Asparaginase, Dexamethasone, and cytarabine. GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC. Furthermore, GAA induced reactive oxygen species accumulation, disturbed mitochondrial homeostasis, and caused mitochondrial dysfunction. By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC, GAA resulted in the elimination of LSCs. Meanwhile, GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage. CONCLUSION: Taken together, the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

16.
Front Surg ; 11: 1252131, 2024.
Article En | MEDLINE | ID: mdl-38562586

Introduction: Accessory breast cancer (ABC) is an extremely rare condition, particularly the presence of triple-negative ABC with ipsilateral invasive in situ breast cancer. Binary breast tumors are controversial in terms of surgical methods and comprehensive treatment. Case presentation: We share the case of a 64-year-old postmenopausal woman who presented with an underarm mass for 3 months. Ultrasonography and computed tomography suggested possible breast cancer with axillary lymph node metastasis. The patient underwent a left modified radical mastectomy combined with axillary lymph node dissection. The postoperative pathology confirmed a binary tumor, prompting us to initiate comprehensive treatment. Conclusion: We present the treatment approach for a rare case of triple-negative para-breast cancer complicated with carcinoma in situ of the breast, hoping to contribute new therapeutic ideas for the treatment of this disease.

17.
Front Nutr ; 11: 1352030, 2024.
Article En | MEDLINE | ID: mdl-38571747

Malnutrition is associated with adverse outcomes in patients with diabetic kidney disease (DKD). However, it is uncertain which nutritional assessment tools are most effective in predicting the adverse outcomes of DKD. This retrospective study was conducted at a single center and included 367 patients diagnosed with DKD based on biopsy results between August 2009 and December 2018. Four nutritional assessment indices, namely the Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI), and Controlling Nutritional Status (CONUT) score, were selected and calculated. We aimed to assess the association between these nutritional scores and adverse outcomes, including progression to end-stage kidney disease (ESKD), cardiovascular diseases events (CVD), and all-cause mortality. Univariate and multivariate Cox regression analyses, Kaplan-Meier analysis, along with Restricted cubic spline analysis were used to examine the relationship between nutritional scores and adverse outcomes. Furthermore, the area under the curve (AUC) was calculated using time-dependent receiver operating characteristics to determine the predictive value of the four nutritional scores alone and some combinations. Lastly, ordered logistic regression analysis was conducted to explore the correlation between the four nutritional scores and different renal histologic changes. The incidence of ESKD, CVD, and all-cause mortality was significantly higher in patients with DKD who had a lower PNI, lower GNRI, and higher CONUT score. Additionally, The TCBI performed the worst in terms of grading and risk assessment. The PNI offer the highest predictive value for adverse outcomes and a stronger correlation with renal histologic changes compared to other nutritional scores. Patients diagnosed with DKD who have a worse nutritional status are more likely to experience higher rates of adverse outcomes. The PNI might offer more valuable predictive values and a stronger correlation with different renal histologic changes compared to other nutritional scores.

18.
J Mol Cell Biol ; 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38578631

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

19.
Lifetime Data Anal ; 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38642215

Doubly censored failure time data occur in many areas and for the situation, the failure time of interest usually represents the elapsed time between two related events such as an infection and the resulting disease onset. Although many methods have been proposed for regression analysis of such data, most of them are conditional on the occurrence time of the initial event and ignore the relationship between the two events or the ancillary information contained in the initial event. Corresponding to this, a new sieve maximum likelihood approach is proposed that makes use of the ancillary information, and in the method, the logistic model and Cox proportional hazards model are employed to model the initial event and the failure time of interest, respectively. A simulation study is conducted and suggests that the proposed method works well in practice and is more efficient than the existing methods as expected. The approach is applied to an AIDS study that motivated this investigation.

20.
ACS Appl Mater Interfaces ; 16(15): 18855-18866, 2024 Apr 17.
Article En | MEDLINE | ID: mdl-38577763

Solar-driven interfacial evaporation provides a promising pathway for sustainable freshwater and energy generation. However, developing highly efficient photothermal and photocatalytic nanomaterials is challenging. Herein, substoichiometric molybdenum oxide (MoO3-x) nanoparticles are synthesized via step-by-step reduction treatment of l-cysteine under mild conditions for simultaneous photothermal conversion and photocatalytic reactions. The MoO3-x nanoparticles of low reduction degree are decorated on hydrophilic cotton cloth to prepare a MCML evaporator toward rapid water production, pollutant degradation, as well as electricity generation. The obtained MCML evaporator has a strong local light-to-heat effect, which can be attributed to excellent photothermal conversion via the local surface plasmon resonance effect in MoO3-x nanoparticles and the low heat loss of the evaporator. Meanwhile, the rich surface area of MoO3-x nanoparticles and the localized photothermal effect together effectively accelerate the photocatalytic degradation reaction of the antibiotic tetracycline. With the benefit of these advantages, the MCML evaporator attains a superior evaporation rate of 4.14 kg m-2 h-1, admirable conversion efficiency of 90.7%, and adequate degradation efficiency of 96.2% under 1 sun irradiation. Furthermore, after being rationally assembled with a thermoelectric module, the hybrid device can be employed to generate 1.0 W m-2 of electric power density. This work presents an effective complementary strategy for freshwater production and sewage treatment as well as electricity generation in remote and off-grid regions.

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