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1.
Front Cardiovasc Med ; 11: 1397422, 2024.
Article in English | MEDLINE | ID: mdl-39087072

ABSTRACT

Background: The associations of neutrophil-percentage-to-albumin ratio (NPAR) level with all-cause and cardiovascular disease (CVD)-cause mortality among patients with hypertension remain unclear. This study aims to investigate the associations of NPAR level with all-cause and CVD-cause mortality among patients with hypertension. Methods: This prospective cohort study included 8,990 patients with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs for the associations of NPAR level with all-cause mortality and CVD-cause mortality. Restricted cubic spline analyses were used to examine the nonlinear association of NPAR level with all-cause mortality and CVD-cause mortality. Results: This cohort study included data from 8,990 participants in analysis. During 104,474 person-years of follow-up, 3,069 all-cause deaths and 1,449 CVD-cause deaths were documented. Nonlinear associations were observed for NPAR levels with risk of all-cause mortality and CVD-cause mortality among patients with hypertension. Compared with participants in T1 of NPAR, there was a significantly increased risk of all-cause mortality and CVD-cause mortality for participants in both T2 and T3 in the fully adjusted model (model 3). The corresponding HRs for all-cause mortality were 1.10 (95% CI, 0.98-1.22) and 1.63 (95% CI, 1.45-1.82). The corresponding HRs for CVD-cause mortality were 1.10 (95% CI, 0.99-1.23) and 1.63 (95% CI, 1.46-1.81). Conclusions: Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in adults with hypertension. NPAR may be clinically useful for predicting long-term health outcomes and mortality in hypertensive population.

2.
Biochem Biophys Res Commun ; 735: 150487, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39096885

ABSTRACT

Spinal Cord Injury (SCI) is a significant neurological disorder that can result in severe motor and cognitive impairments. Neuronal regeneration and functional recovery are critical aspects of SCI treatment, with calcium signaling being a crucial indicator of neuronal excitability. In this study, we utilized a murine model to investigate the effects of targeted wireless electrical stimulation (ES) on neuronal activity following SCI. After establishing a complete SCI model in normal mice, flexible electrodes were implanted, and targeted wireless ES was administered to the injury site. We employed fiber-optic photometric in vivo calcium imaging to monitor calcium signals in pyramidal neurons within the CA3 region of the hippocampus and the M1 region of the primary motor cortex. The experimental results demonstrated a significant reduction in calcium signals in CA3 and M1 pyramidal neurons following SCI (reduced by 76 % and 59 %, in peak respectively). However, the application of targeted wireless ES led to a marked increase in calcium signals in these neurons (increased by 118 % and 69 %, in peak respectively), indicating a recovery of calcium activity. These observations suggest that wireless ES has a positive modulatory effect on the excitability of pyramidal neurons post-SCI. Understanding these mechanisms is crucial for developing therapeutic strategies aimed at enhancing neuronal recovery and functional restoration following spinal cord injuries.

3.
Article in English | MEDLINE | ID: mdl-39048852

ABSTRACT

BACKGROUND: The aim of this study was to assess homologous recombination deficiency (HRD) status and its correlation with carboplatin treatment response in early triple-negative breast cancer (TNBC) patients. METHODS: Tumor tissues from 225 consecutive TNBC patients were evaluated with an HRD panel and homologous recombination-related (HRR) gene expression data. HRD positivity was defined as a high HRD score and/or BRCA1/2 pathogenic or likely pathogenic mutation. Clinicopathological factors, neoadjuvant treatment response, and prognosis were analyzed with respect to HRD status in these TNBC patients. RESULTS: HRD positivity was found in 53.3% of patients and was significantly related to high Ki67 levels (P = 0.001). In patients who received neoadjuvant chemotherapy, HRD positivity (P = 0.005) or a high HRD score (P = 0.003) was significantly associated with a greater pathological complete response (pCR) rate, especially in those treated with carboplatin-containing neoadjuvant regimens (HRD positivity vs. negativity: 50.00% vs. 17.65%, P = 0.040). HRD positivity was associated with favorable distant metastasis-free survival (hazard ratio HR 0.49, 95% confidence interval CI 0.26-0.90, P = 0.022) and overall survival (HR 0.45, 95% CI 0.20-0.99, P = 0.049), irrespective of carboplatin treatment. CONCLUSION: TNBC patients with high HRDs had high Ki67 levels and BRCA mutations. HRD-positive TNBC patients treated with carboplatin had a higher pCR rate. Patients with HRD positivity had a better prognosis, irrespective of carboplatin treatment, warranting further evaluation.

4.
Adv Sci (Weinh) ; : e2405474, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39049687

ABSTRACT

Conventional strategies for highly selective and active hydrogen peroxide (H2O2) electrosynthesis primarily focus on catalyst design. Electrocatalytic reactions take place at the electrified electrode-electrolyte interface. Well-designed electrolytes, when combined with commercial catalysts, can be directly applied to high-efficiency H2O2 electrosynthesis. However, the role of electrolyte components is equally crucial but is significantly under-researched. In this study, anionic surfactant n-tetradecylphosphonic acid (TDPA) and its analogs are used as electrolyte additives to enhance the selectivity of the two-electron oxygen reduction reaction. Mechanistic studies reveal that TDPA assembled over the electrode-electrolyte interface modulates the electrical double-layer structure, which repels interfacial water and weakens the hydrogen-bond network for proton transfer. Additionally, the hydrophilic phosphonate moiety affects the coordination of water molecules in the solvation shell, thereby directly influencing the proton-coupled kinetics at the interface. The TDPA-containing catalytic system achieves a Faradaic efficiency of H2O2 production close to 100% at a current density of 200 mA cm-2 using commercial carbon black catalysts. This research provides a simple strategy to enhance H2O2 electrosynthesis by adjusting the interfacial microenvironment through electrolyte design.

5.
J Cell Mol Med ; 28(14): e18559, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39044269

ABSTRACT

Sepsis is one of the major challenges in intensive care units, characterized by the complexity of the host immune status. To gain a deeper understanding of the pathogenesis of sepsis, it is crucial to study the phenotypic changes in immune cells and their underlying molecular mechanisms. We conducted Summary data-based Mendelian randomization analysis by integrating genome-wide association studies data for sepsis with expression quantitative trait locus data, revealing a significant decrease in the expression levels of 17 biomarkers in sepsis patients. Furthermore, based on single-cell RNA sequencing data, we elucidated potential molecular mechanisms at single-cell resolution and identified that LGALS9 inhibition in sepsis patients leads to the activation and differentiation of monocyte and T-cell subtypes. These findings are expected to assist researchers in gaining a more in-depth understanding of the immune dysregulation in sepsis.


Subject(s)
Galectins , Genome-Wide Association Study , Mendelian Randomization Analysis , Quantitative Trait Loci , Sepsis , Sequence Analysis, RNA , Single-Cell Analysis , Humans , Sepsis/genetics , Sepsis/immunology , Sepsis/blood , Single-Cell Analysis/methods , Galectins/genetics , Sequence Analysis, RNA/methods , Biomarkers , Polymorphism, Single Nucleotide , Monocytes/metabolism , Monocytes/immunology , Genetic Predisposition to Disease
6.
Antonie Van Leeuwenhoek ; 117(1): 98, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981868

ABSTRACT

An aerobic, Gram-stain-negative bacterium, designated as SYSU D00382T, was sourced from soil of Gurbantunggut Desert, PR China. The strain was short-rod-shaped, oxidase-positive and catalase-negative, with yellow-colored, convex, round, and smooth colonies on TSA plate. Growth and proliferation occurred at 4-37 °C (optimal: 28-30 °C), pH 5.0-8.0 (optimal: pH 6.0-7.0) and NaCl concentration of 0-2.5% (optimal: 0-0.5%). The 16S rRNA gene based phylogenetic assessment showed that SYSU D00382T belonged to the genus Pedobacter, and was most closely related to Pedobacter ginsengisoli Gsoil 104T with similarity of 97.7%. The genomic DNA G+C content of SYSU D00382T was 46.4%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between SYSU D00382T and P. ginsengisoli Gsoil 104T were 75.7% and 17.5%, respectively. The main polar lipid was phosphatidylethanolamine. The major fatty acids (> 5%) were iso-C15:0, iso-C17:0 3-OH, summed features 3 and 9. The sole respiratory quinone identified was MK-7. The phylogeny based on 16S rRNA gene and whole-genome sequences revealed that SYSU D00382T formed a robust lineage with P. ginsengisoli Gsoil 104T. Based on phenotypic, phylogenetic and genotypic data, a novel specie named Pedobacter deserti sp. nov. is proposed. The type strain is SYSU D00382T (= CGMCC 1.18627T = MCCC 1K04972T = KCTC 82279T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Pedobacter , Phylogeny , RNA, Ribosomal, 16S , Soil Microbiology , Pedobacter/genetics , Pedobacter/classification , Pedobacter/isolation & purification , Pedobacter/physiology , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Fatty Acids/analysis , China , Nucleic Acid Hybridization , Sequence Analysis, DNA
7.
Int J Mol Sci ; 25(13)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39000331

ABSTRACT

Arsenic-containing hydrocarbons (AsHCs) are common in marine organisms. However, there is little research on their effects on the central nervous system's advanced activities, such as cognition. Bidirectional synaptic plasticity dynamically regulates cognition through the balance of long-term potentiation (LTP) and long-term depression (LTD). However, the effects of AsHCs on bidirectional synaptic plasticity and the underlying molecular mechanisms remain unexplored. This study provides the first evidence that 15 µg As L-1 AsHC 360 enhances bidirectional synaptic plasticity, occurring during the maintenance phase rather than the baseline phase. Further calcium gradient experiments hypothesize that AsHC 360 may enhance bidirectional synaptic plasticity by affecting calcium ion levels. The enhancement of bidirectional synaptic plasticity by 15 µg As L-1 AsHC 360 holds significant implications in improving cognitive function, treating neuro-psychiatric disorders, promoting neural recovery, and enhancing brain adaptability.


Subject(s)
Arsenic , Hippocampus , Neuronal Plasticity , Animals , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/physiology , Arsenic/pharmacology , Arsenic/toxicity , Neuronal Plasticity/drug effects , Long-Term Potentiation/drug effects , Hydrocarbons/pharmacology , Calcium/metabolism , Rats , Male , Long-Term Synaptic Depression/drug effects
8.
Article in English | MEDLINE | ID: mdl-39037442

ABSTRACT

Two Gram-stain-negative, aerobic, milk-white coloured, non-motile, short rod-shaped bacteria, designated as strains SYSU D60010T and SYSU D60012T, were isolated from sand samples collected from the Taklimakan Desert of Xinjiang Province in China. Both strains were positive for oxidase, catalase and nitrate reduction, but negative for amylase, H2S production, hydrolysis of gelatin and cellulase. Strains SYSU D60010T and SYSU D60012T grew well at 28 °C, at pH 7 and had the same NaCl tolerance range of 0-1 % (w/v). The major fatty acids (>5 %) of strains SYSU D60010T and SYSU D60012T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), iso-C19 : 0 cyclo ω8c, C16 : 0 and iso-C18 : 1 2-OH. Q-10 was the only respiratory ubiquinone. Strains SYSU D60010T and SYSU D60012T showed high 16S rRNA gene sequence similarities to Aestuariivirga litoralis SYSU M10001T (94.2 and 94.1 %), Rhodoligotrophos jinshengii BUT-3T (92.0 and 91.9 %) and Rhodoligotrophos appendicifer 120-1T (91.8 and 91.7 %), and the genomes were 7.4 and 5.8 Mbp in size with DNA G+C contents of 62.8 and 63.0 mol%, respectively. Phylogenetic, phenotypic and chemotaxonomic characteristics indicated that these two strains represent a novel genus and two novel species within the family Aestuariivirgaceae. We propose the name Taklimakanibacter deserti gen. nov., sp. nov. for strain SYSU D60010T, representing the type strain of this species (=KCTC 52783T =NBRC 113344T) and Taklimakanibacter lacteus gen. nov., sp. nov. for strain SYSU D60012T, representing the type strain of this species (=KCTC 52785T=NBRC 113128T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Soil Microbiology , RNA, Ribosomal, 16S/genetics , Fatty Acids/chemistry , DNA, Bacterial/genetics , China , Ubiquinone/analogs & derivatives , Sand/microbiology
9.
Natl Sci Rev ; 11(8): nwae218, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39034947

ABSTRACT

Both the catalyst and electrolyte strongly impact the performance of CO2 electrolysis. Despite substantial progress in catalysts, it remains highly challenging to tailor electrolyte compositions and understand their functions at the catalyst interface. Here, we report that the ethylenediaminetetraacetic acid (EDTA) and its analogs, featuring strong Lewis acid-base interaction with metal cations, are selected as electrolyte additives to reshape the catalyst-electrolyte interface for promoting CO2 electrolysis. Mechanistic studies reveal that EDTA molecules are dynamically assembled toward interface regions in response to bias potential due to strong Lewis acid-base interaction of EDTA4--K+. As a result, the original hydrogen-bond network among interfacial H2O is disrupted, and a hydrogen-bond gap layer at the electrified interface is established. The EDTA-reshaped K+ solvation structure promotes the protonation of *CO2 to *COOH and suppressing *H2O dissociation to *H, thereby boosting the co-electrolysis of CO2 and H2O toward carbon-based products. In particular, when 5 mM of EDTA is added into the electrolytes, the Faradaic efficiency of CO on the commercial Ag nanoparticle catalyst is increased from 57.0% to 90.0% at an industry-relevant current density of 500 mA cm-2. More importantly, the Lewis-base ligand-reshaped interface allows a range of catalysts (Ag, Zn, Pd, Bi, Sn, and Cu) to deliver substantially increased selectivity of carbon-based products in both H-type and flow-type electrolysis cells.

10.
World J Surg Oncol ; 22(1): 179, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982409

ABSTRACT

BACKGROUND: Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal tumor that mostly involves the pleura and infrequently involves extra-pleural sites. De novo SFT of the kidney is uncommon, and malignant SFT is extremely rare. CASE PRESENTATION: We report a case of a 51-year-old man with a large malignant SFT in the left kidney. Pathological examination confirmed the diagnosis of SFT based on typical morphology, nuclear STAT6 expression, and NAB2-STAT6 gene fusion. The malignant subtype was determined by a large tumor size (≥ 15 cm) and high mitotic counts (8/10 high-power fields). KRAS mutation was identified by DNA sequencing. Insulin-like growth factor 2 (IGF2) was diffusely and strongly expressed in tumor cells, however, hypoglycemia was not observed. Hyperglycemia and high adrenocorticotropic hormone (ACTH) concentration were observed one month after surgery. Hormone measurements revealed normal blood cortisol and aldosterone levels, and increased urinary free cortisol level. A pituitary microadenoma was identified using brain magnetic resonance imaging, which may be responsible for the promotion of hyperglycemia. CONCLUSIONS: We report a case of renal malignant SFT with a KRAS mutation, which was previously unreported in SFT and may be associated with its malignant behavior. Additionally, we emphasize that malignant SFT commonly causes severe hypoglycemia due to the production of IGF2. However, this effect may be masked by the presence of other lesions that promote hyperglycemia. Therefore, when encountering a malignant SFT with diffuse and strong IGF2 expression and without hypoglycemia, other lesions promoting hyperglycemia need to be ruled out.


Subject(s)
Hypoglycemia , Insulin-Like Growth Factor II , Kidney Neoplasms , Proto-Oncogene Proteins p21(ras) , Solitary Fibrous Tumors , Humans , Insulin-Like Growth Factor II/metabolism , Insulin-Like Growth Factor II/genetics , Male , Solitary Fibrous Tumors/pathology , Solitary Fibrous Tumors/surgery , Solitary Fibrous Tumors/metabolism , Solitary Fibrous Tumors/genetics , Solitary Fibrous Tumors/diagnosis , Middle Aged , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/metabolism , Kidney Neoplasms/genetics , Kidney Neoplasms/diagnosis , Hypoglycemia/metabolism , Hypoglycemia/etiology , Hypoglycemia/pathology , Hypoglycemia/diagnosis , Proto-Oncogene Proteins p21(ras)/genetics , Prognosis , Mutation
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(4): 497-507, 2024 Apr 28.
Article in English, Chinese | MEDLINE | ID: mdl-39019778

ABSTRACT

OBJECTIVES: The rehabilitation work for patients with motor dysfunction after stroke is crucial. However, there is currently a lack of summarized evidence regarding the rehabilitation management of stroke patients in rehabilitation wards, communities, and at home. This study aims to compile relevant evidence on the rehabilitation management of patients with motor dysfunction after stroke, providing a reference for clinical and community health professionals to carry out rehabilitation interventions. METHODS: A systematic search was conducted in BMJ Best Practice, UpToDate, National Guidebook Clearinghouse, American Heart Association/American Stroke Association, Canadian Medical Association, National Institute for Health and Clinical Excellence, United States Department of Veterans Affairs/ Department of Defense, Registered Nurses Association of Ontario, JBI Evidence-Based Healthcare Center Database, The Cochrane Library, PubMed, Web of Science, Embase, CINAHL, CNKI, Wanfang Database, SinoMed, and other databases for all literature on the rehabilitation management of patients with motor dysfunction after stroke. This included clinical decision-making, guidelines, expert consensuses, recommended practices, systematic reviews, and evidence summaries, with the search period spanning from the establishment of each database to October 2023. Two researchers independently evaluated the quality of the literature. RESULTS: A total of twenty-one documents were included, consisting of 11 guidelines, 2 expert consensus, and 8 systematic reviews. Evidence was extracted and integrated from the included literature, summarizing forty-five pieces of evidence across nine areas: rehabilitation management model, rehabilitation institutions, rehabilitation teams, timing of rehabilitation interventions, rehabilitation assessment, rehabilitation programs, rehabilitation duration and frequency, rehabilitation intensity, and rehabilitation support These covered comprehensive rehabilitation management content for stroke patients in the early, subacute, and chronic phases. CONCLUSIONS: The best evidence summarized in this study for the rehabilitation management of patients with motor dysfunction after stroke is comprehensive and of high quality. It provides important guidance for clinical and community healthcare professionals in carrying out rehabilitation interventions. When applying the evidence, it is recommended to consider the current condition of the stroke patient, the extent of motor dysfunction, environmental factors, and the patient's preferences. Then, select the most appropriate rehabilitation plan, and adjust the type and intensity of training according to each patient's specific needs and preferences.


Subject(s)
Stroke Rehabilitation , Humans , Stroke Rehabilitation/methods , Stroke/complications , China
12.
Photoacoustics ; 38: 100625, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38974142

ABSTRACT

Here we present a computational and experimental fluid dynamics study for the characterization of the flow field within the gas chamber of a Quartz-Enhanced Photoacoustic Spectroscopy (QEPAS) sensor, at different flow rates at the inlet of the chamber. The transition from laminar to turbulent regime is ruled both by the inlet flow conditions and dimension of the gas chamber. The study shows how the distribution of the flow field in the chamber can influence the QEPAS sensor sensitivity, at different operating pressures. When turbulences and eddies are generated within the gas chamber, the efficiency of photoacoustic generation is significantly altered.

13.
Heliyon ; 10(12): e32920, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38948041

ABSTRACT

The historical sedimentary and evolutionary characteristics of persistent organic pollutants and endocrine disruptors in typical regions of the Three Gorges Reservoir are scarcely studied. Herein, the 96-year data on contaminated sediment history were reconstructed using Caesium 137 isotope dating. Polychlorinated biphenyl concentrations in the involved sediment cores ranged from non-detected (ND) to 11.39 ng/g. The concentrations of polycyclic aromatic hydrocarbons ranged from ND to 2075.20 ng/g and peaked in the 1970s owing to natural, agricultural and human activities. Further, phthalate esters (PAEs) and heavy metals (HMs) were detected at concentrations ranging from ND to 589.2 ng/g and 12.10-93.67 µg/g, respectively, with highest values recorded in the 1980s owing to rapid industrialisation and insufficient management during China's early reform and development stages. PAE and HM concentrations have increased in recent years, suggesting the need to focus on industrial and agricultural activities that have caused this impact. Although current pollutant concentrations in sediments do not pose a risk to the aquatic ecosystem, they should be continuously monitored.

14.
Antonie Van Leeuwenhoek ; 117(1): 108, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080041

ABSTRACT

A novel rod-shaped bacterium, designated as strain SYSU D60015T that formed yellowish colonies was isolated from a sandy soil collected from the Kumtag Desert in Xinjiang, China. Cells were Gram-stain-negative, oxidase-positive, catalase-negative and motile with a single polar flagellum. Growth optimum occurred between 28 and 37 °C, pH 7.0 and with 0-0.5% (W/V) NaCl. The predominant cellular fatty acids (> 5%) were summed feature 8 (C18:1 ω7c and/or C18:1 ω6c), C19:0 cyclo ω8c, C18:1 ω7c 11-methyl and C16:0. The polar lipid profile contained one phosphatidylethanolamine, one diphosphatidylglycerol, one phosphatidylglycerol, one unidentified phospholipid, three unidentified aminolipids, two unidentified aminophospholipids and seven unidentified lipids. The only respiratory quinone was ubiquinone-10. Based on 16S rRNA gene sequence phylogenetic analysis, strain SYSU D60015T was found to form a distinct linage within the family Sneathiellaceae, and had 16S rRNA gene sequence similarities of 90.8% to Taonella mepensis H1T, and 90.2% to Ferrovibrio denitrificans S3T. The genome of SYSU D60015T was 5.66 Mb in size with 68.2% of DNA G + C content. The low digital DNA-DNA hybridization (dDDH, 18.0%), average nucleotide identity (ANI, 77.5%) and amino acid identity (AAI, 56.0%) values between SYSU D60015T and Ferrovibrio terrae K5T indicated that SYSU D60015T might represent a distinct genus. Based on the phylogenetic, phenotypic, chemotaxonomic and genomic data, we propose Desertibaculum subflavum gen. nov., sp. nov. as a novel species of a new genus within the family Sneathiellaceae. The type strain is SYSU D60015T (= NBRC 112952T = CGMCC 1.16256T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Phylogeny , RNA, Ribosomal, 16S , Soil Microbiology , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , China , Fatty Acids/analysis , Fatty Acids/chemistry , Sequence Analysis, DNA , Phospholipids/analysis , Phospholipids/chemistry
15.
Front Immunol ; 15: 1407837, 2024.
Article in English | MEDLINE | ID: mdl-39026672

ABSTRACT

The aim of this study was to evaluate the mutation spectrum of homologous recombination repair (HRR) genes and its association with tumor immune infiltration and prognosis in triple-negative breast cancer (TNBC). TNBC patients (434 patients from Ruijin cohort) were evaluated with targeted next-generating sequencing for mutations in HRR genes. The frequencies of mutations were compared with public reference cohorts (320 TNBC patients from METABRIC, 105 from TCGA, and 225 from MSKCC 2018). Associations between mutation status and tumor immune infiltration and prognosis were analyzed. HRR genes mutations were seen in 21.89% patients, with BRCA1/2 mutations significantly enriched in tumors with breast/ovarian cancer family history (P = 0.025) and high Ki-67 levels (P = 0.018). HRR genes mutations were not related with recurrence-free survival (RFS) (adjusted P = 0.070) and overall survival (OS) (adjusted P = 0.318) for TNBC patients, regardless of carboplatin treatment (P > 0.05). Moreover, tumor immune infiltration and PD-L1 expression was positively associated with HRR or BRCA1/2 mutation (all P < 0.001). Patients with both HRR mutation and high CD8+ T cell counts had the best RFS and OS, whereas patients with no HRR mutation and low CD8+ T cell counts had the worst outcomes (RFS P < 0.001, OS P = 0.019). High frequency of HRR gene mutations was found in early TNBC, with no prognostic significance. Immune infiltration and PD-L1 expression was positively associated with HRR mutation, and both HRR mutation and high CD8+ T cell infiltration levels were associated with superior disease outcome.


Subject(s)
Lymphocytes, Tumor-Infiltrating , Mutation , Recombinational DNA Repair , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/mortality , Female , Prognosis , Middle Aged , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Recombinational DNA Repair/genetics , Adult , BRCA1 Protein/genetics , B7-H1 Antigen/genetics , Aged , BRCA2 Protein/genetics , Biomarkers, Tumor/genetics
16.
J Gastrointest Oncol ; 15(3): 1002-1019, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38989407

ABSTRACT

Background: Tumor cell inhibition is a pivotal focus in anti-cancer research, and extensive investigations have been conducted regarding the role of p53. Numerous studies have highlighted its close association with reactive oxygen species (ROS). However, the precise impact of the antioxidant glutathione (GSH) in this context remains inadequately elucidated. Here, we will elucidate the anti-cancer mechanisms mediated by p53 following treatment with GSH. Methods: In this study, we employed a p53 gene knockout approach in SW480 colorectal cells and conducted comprehensive analyses of 20 amino acids and proteomics using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Results: These analyses unveiled profound alterations in amino acids and proteins triggered by GSH treatment, shedding light on novel phenomena and delineating the intricate interplay between GSH and cellular proteins. The deletion of the p53 gene exerts a profound influence on tumor cell proliferation. Moreover, tumor cell proliferation is significantly affected by elevated GSH levels. Importantly, in the absence of the p53 gene, cells exhibit heightened sensitivity to GSH, leading to inhibited cell growth. The combined therapeutic approach involving GSH and p53 gene deletion expedites the demise of tumor cells. It is noteworthy that this treatment leads to a marked decline in amino acid metabolism, particularly affecting the down-regulation of methionine (Met) and phenylalanine (Phe) amino acids. Among the 41 proteins displaying significant changes, 8 exhibit consistent alterations, with 5 experiencing decreased levels and 3 demonstrating increased quantities. These proteins primarily participate in crucial cellular metabolic processes and immune functions. Conclusions: In conclusion, the concurrent administration of GSH treatment and p53 gene deletion triggers substantial modifications in the amino acid and protein metabolism of tumor cells, primarily characterized by down-regulation. This, in turn, compromises cell metabolic activity and immune function, ultimately culminating in the demise of tumor cells. These newfound insights hold promising implications and could pave the way for the development of straightforward and efficacious anti-cancer treatments.

17.
ACS Appl Mater Interfaces ; 16(29): 38083-38091, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-38986045

ABSTRACT

Both the catalyst and electrolyte deeply impact the performance of the carbon dioxide reduction reaction (CO2RR). It remains a challenge to design the electrolyte compositions for promoting the CO2RR. Here, typical anionic surfactants, dodecylphosphonic acid (DDPA) and its analogues, are employed as electrolyte additives to tune the catalysis interface where the CO2RR occurs. Surprisingly, the anionic surfactant-tailored interfacial microenvironment enables a set of typical commercial catalysts for the CO2RR to deliver a significantly enhanced selectivity of carbon products in both neutral and acidic electrolytes. Mechanistic studies disclose that the DDPA addition restructures the interfacial hydrogen-bond environment via increasing the weak H-bonded water, thus promoting the CO2 protonation to CO. Specifically, in an H-type cell, the Faradaic efficiency of CO increases from 70 to 98% at -1.0 V versus the reversible hydrogen electrode. Furthermore, in a flow cell, the DDPA-containing electrolyte maintains over 90% FECO from 50-400 mA cm-2. Additionally, this electrolyte modulation strategy can be extended to acidic CO2RR with a pH of 1.5-3.5.

18.
Cell Rep ; 43(7): 114425, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38970789

ABSTRACT

Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host's energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight.


Subject(s)
Diet, High-Fat , Energy Metabolism , Obesity , Animals , Obesity/metabolism , Obesity/therapy , Mice , Uncoupling Protein 1/metabolism , Tissue Engineering/methods , Male , Mice, Inbred C57BL , Mice, Transgenic , Humans , Body Weight , Mice, Obese
19.
Heliyon ; 10(13): e33915, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39071623

ABSTRACT

Background: Hemihypertrophy (HH) is a rare congenital malformation usually recognized at birth. It is often diagnosed due to impaired aesthetics and mobility caused by asymmetry of the face, body, or limbs. Some patients are diagnosed due to the presence of tumors and mental abnormalities. Case presentation: A 14-year-old boy with hoarseness since infancy and progressively increasing with age. Laryngoscopy and CT of the larynx suggested bilateral asymmetry of the laryngeal structures, and voice analysis suggested severe voice disorders. The boy had no history of trauma or other medical conditions, but had physical asymmetry since birth, which coincided with the laryngeal asymmetry. After a detailed examination and evaluation, we considered that his voice disorders were unexpectedly caused by crossed idiopathic HH. Since the boy in his growth spurts is not a candidate for surgery, we implemented individualized voice correction therapy. After practicing, the boy's voice disorders were significantly relieved. Conclusion: Congenital HH can cause asymmetrical development of the larynx, which leads to voice disorders. Voice correction therapy is an effective treatment for patients unsuitable for surgery.

20.
Sensors (Basel) ; 24(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38894169

ABSTRACT

In order to achieve the remote application of inverse synthetic aperture laser radar for high resolution spatial situational awareness, it is essential to analyze the main factors that restrict its remote application. This study combines the range equation of inverse synthetic aperture lidar with the stimulated Brillouin threshold power equation to investigate the variation of laser transmitting power with distance. Additionally, by utilizing the excited Brillouin threshold power equation, laser linewidth formula, and pulse width characteristics of pulse signal, we examine the variation law of laser coherence that meets corresponding power requirements at different distances. The results indicate that a detection distance of 22 km and below can be achieved using continuous fiber lasers without compensation. Coherence compensation is necessary for distances between 22 km and 57 km. For distances ranging from 57 km to 3000 km, pulsed solid-state lasers are used to analyze coherence and conclude that imaging non-cooperative targets within this range is feasible. It is observed that coherence compensation is required from 57 km to 2179 km, becoming more challenging after 2000 km. Furthermore, pulsed solid-state lasers can still be utilized for imaging cooperative targets within a range of 2179-3273 km; however, coherence compensation remains necessary and becomes increasingly difficult. Finally, several coherent length compensation schemes are proposed in order to extend the imaging range of inverse synthetic aperture LiDAR to approximately 3000 km.

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