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1.
Eur J Surg Oncol ; 50(9): 108481, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38959845

ABSTRACT

INTRODUCTION: We aimed to compare early postoperative patient-reported outcomes between multiportal robotic-assisted thoracoscopic surgery (M-RATS) and uniportal video-assisted thoracoscopic surgery (U-VATS) for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Symptom severity and functional status were measured using the Perioperative Symptom Assessment for Lung Surgery at pre-surgery, during postoperative hospitalisation, and within 4 weeks of discharge. A propensity score-matched (PSM) analysis of patients with NSCLC who were treated with M-RATS and U-VATS was performed. The symptom severity and daily functional status presented as proportion of moderate-to-severe scores on a 0-10-point scale, were compared using a generalised estimation equation model. RESULTS: We enrolled 762 patients with NSCLC from a prospective cohort (CN-PRO-Lung 3), including 151 and 611 who underwent M-RATS and U-VATS, respectively, before PSM analysis. After 1:1 PSM, two groups of 148 patients each were created. Pain severity (P = 0.019) and activity limitation (P = 0.001) during hospitalisation were higher in the M-RATS group. However, no significant differences existed post-discharge in pain (P = 0.383), cough (P = 0.677), shortness of breath (P = 0.526), disturbed sleep (P = 0.525), drowsiness (P = 0.304), fatigue (P = 0.153), distress (P = 0.893), walking difficulty (P = 0.242), or activity limitation (P = 0.513). M-RATS caused less intraoperative blood loss (P = 0.013), more stations of dissected lymph nodes (P = 0.001), more numbers of dissected lymph nodes (P = 0.001), and less tube drainage on the first postoperative day (P = 0.003) than U-VATS. CONCLUSION: M-RATS and U-VATS achieved comparable symptom burden and functional impairment after discharge. However, compared to U-VATS, M-RATS was associated with more severe pain and activity limitation in the short postoperative period. TRIAL REGISTRATION NUMBER: ChiCTR2000033016.

2.
NPJ Parkinsons Dis ; 10(1): 129, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38961119

ABSTRACT

The seeding amplification assay (SAA) has recently emerged as a valuable tool for detecting α-synuclein (αSyn) aggregates in various clinically accessible biospecimens. Despite its efficiency and specificity, optimal tissue-specific conditions for distinguishing Parkinson's disease (PD) from non-PD outside the brain remain underexplored. This study systematically evaluated 150 reaction conditions to identify the one with the highest discriminatory potential between PD and non-synucleinopathy controls using skin samples, resulting in a modified SAA. The streamlined SAA achieved an overall sensitivity of 92.46% and specificity of 93.33% on biopsy skin samples from 332 PD patients and 285 controls within 24 h. Inter-laboratory reproducibility demonstrated a Cohen's kappa value of 0.87 (95% CI 0.69-1.00), indicating nearly perfect agreement. Additionally, αSyn seeds in the skin were stable at -80 °C but were vulnerable to short-term exposure to non-ultra-low temperatures and grinding. This study thoroughly investigated procedures for sample preprocessing, seed amplification, and storage, introducing a well-structured experimental framework for PD diagnosis using skin samples.

4.
Chin J Traumatol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38981821

ABSTRACT

PURPOSE: Vibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. METHODS: An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. RESULTS: In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival (p = 0.014), reduced the serum creatinine (p = 0.002), urea nitrogen (p = 0.030), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1ß: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1ß, IL-6, TNF-α in liver (IL-1ß: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1ß: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid (p = 0.225), liver (p = 0.186), or kidney (p = 0.637). CONCLUSION: Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

5.
BMC Genom Data ; 25(1): 70, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009995

ABSTRACT

OBJECTIVES: Ants are ecologically dominant insects in most terrestrial ecosystems, with more than 14,000 extant species in about 340 genera recorded to date. However, genomic resources are still scarce for most species, especially for species endemic in East or Southeast Asia, limiting the study of phylogeny, speciation and adaptation of this evolutionarily successful animal lineage. Here, we assemble and annotate the genomes of Odontoponera transversa and Camponotus friedae, two ant species with a natural distribution in China, to facilitate future study of ant evolution. DATA DESCRIPTION: We obtained a total of 16 Gb and 51 Gb PacBio HiFi data for O. transversa and C. friedae, respectively, which were assembled into the draft genomes of 339 Mb for O. transversa and 233 Mb for C. friedae. Genome assessments by multiple metrics showed good completeness and high accuracy of the two assemblies. Gene annotations assisted by RNA-seq data yielded a comparable number of protein-coding genes in the two genomes (10,892 for O. transversa and 11,296 for C. friedae), while repeat annotations revealed a remarkable difference of repeat content between these two ant species (149.4 Mb for O. transversa versus 49.7 Mb for C. friedae). Besides, complete mitochondrial genomes for the two species were assembled and annotated.


Subject(s)
Ants , Genome, Insect , Animals , Ants/genetics , Ants/classification , Genome, Insect/genetics , Molecular Sequence Annotation , Phylogeny , Genomics/methods
6.
J Orthop Surg Res ; 19(1): 396, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982418

ABSTRACT

BACKGROUND: The progression of osteoporosis (OP) can dramatically increase the risk of fractures, which seriously disturb the life of elderly individuals. Specific protein 1 (SP1) is involved in OP progression. However, the mechanism by which SP1 regulates OP progression remains unclear. OBJECTIVE: This study investigated the mechanism underlying the function of SP1 in OP. METHODS: SAMP6 mice were used to establish an in vivo model of age-dependent OP, and BALB/c mice were used as controls. BMSCs were extracted from two subtypes of mice. Hematoxylin and eosin staining were performed to mark the intramedullary trabecular bone structure to evaluate histological changes. ChIP assay was used to assess the targeted regulation between SP1 and miR-133a-3p. The binding sites between MAPK3 and miR-133a-3p were verified using a dual-luciferase reporter assay. The mRNA levels of miR-133a-3p and MAPK3 were detected using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The protein expression of SP1, MAPK3, Colla1, OCN, and Runx2 was examined using Western blotting. Alkaline phosphatase (ALP) kit and Alizarin Red S staining were used to investigate ALP activity and mineralized nodules, respectively. RESULTS: The levels of SP1 and miR-133a-3p were upregulated, whereas the expression of MAPK3 was downregulated in BMSCs from SAMP6 mice, and miR-133a-3p inhibitor accelerated osteogenic differentiation in BMSCs. SP1 directly targeted miR-133a-3p, and MAPK3 was the downstream mRNA of miR-133a-3p. Mechanically, SP1 accelerated osteogenic differentiation in BMSCs via transcriptional mediation of the miR-133a-3p/MAPK3 axis. CONCLUSION: SP1 regulates osteogenic differentiation by mediating the miR-133a-3p/MAPK3 axis, which would shed new light on strategies for treating senile OP.


Subject(s)
Cell Differentiation , Mesenchymal Stem Cells , MicroRNAs , Mitogen-Activated Protein Kinase 3 , Osteogenesis , Osteoporosis , Sp1 Transcription Factor , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Osteogenesis/genetics , Osteogenesis/physiology , Cell Differentiation/genetics , Cell Differentiation/physiology , Sp1 Transcription Factor/genetics , Sp1 Transcription Factor/metabolism , Mesenchymal Stem Cells/metabolism , Mice , Osteoporosis/genetics , Osteoporosis/pathology , Osteoporosis/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinase 3/genetics , Mice, Inbred BALB C , Cells, Cultured , Disease Models, Animal , Male
7.
Int J Surg ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39028114

ABSTRACT

BACKGROUND: Patient-reported outcome measures (PROMs) have become important tools for evaluating health-related quality of life (HRQOL) in patients with differentiated thyroid cancer (DTC). While there are many PROMs available to measure HRQOL, there is a lack of a comprehensive overview of these PROMs. Therefore, we aimed to systematically review and categorize all PROMs that have been used to measure HRQOL in patients with DTC. MATERIALS AND METHODS: After determining the search strategy and identifying inclusion and exclusion criteria, articles were searched in PubMed and EMBASE from January 1900 to September 2023. Information on PROMs from the included studies, such as development language, target population, (sub)scales name, number of items per (sub)scale, completion time, and validation, was extracted and synthesized. The frequency with which PROMs were utilized in the included studies was also graphed. After innovatively classifying PROMs as five categories, all of the included PROMs were allocated to their respective categories. RESULTS: A total of 330 articles fulfilled all of the criteria, and they utilized 96 different PROMs to measure HRQOL in DTC patients. The 96 PROMs were classified into five categories, namely universal PROMs (16/96), DTC-related PROMs (11/96), radioiodine-related PROMs (4/96), operation-related PROMs (37/96), and psychology-related PROMs (28/96). Among them, some PROMs were the frequently employed PROMs to assess diverse aspects of HRQOL in patients with DTC. CONCLUSION: A large number of PROMs are available for patients with DTC, which evaluate all aspects of HRQOL. Combining the relevant information and frequency of PROMs utilization, it can provide convenience and reference for researchers to select PROMs across different categories. However, a more detailed critical appraisal of the PROMs used in various clinical scenarios is required. Additionally, PROMs usage frequency in previous studies can indirectly indicate the comprehensiveness or gaps in HRQOL aspects studied, guiding further review or research.

8.
Curr Microbiol ; 81(9): 275, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020143

ABSTRACT

In this study, the toxigenic characteristics of 14 strains of Microcystis were analyzed, and single nucleotide polymorphism (SNP) and insertion/deletion (InDel) loci in microcystin synthetase (mcy) gene clusters were screened. Based on SNP and InDel loci associated with the toxigenic characteristics, primers and TaqMan or Cycling fluorescent probes were designed to develop duplex real-time fluorescent quantitative PCR (FQ-PCR) assays. After evaluating specificity and sensitivity, these assays were applied to detect the toxigenic Microcystis genotypes in a shrimp pond where Microcystis blooms occurred. The results showed a total of 2155 SNP loci and 66 InDel loci were obtained, of which 12 SNP loci and 5 InDel loci were associated with the toxigenic characteristics. Three duplex real-time FQ-PCR assays were developed, each of which could quantify two genotypes of toxigenic Microcystis. These FQ-PCR assays were highly specific, and two Cycling assays were more sensitive than TaqMan assay. In the shrimp pond, six genotypes of toxigenic Microcystis were detected using the developed FQ-PCR assays, indicating that above genotyping assays have the potential for quantitative analysis of the toxigenic Microcystis genotypes in natural water.


Subject(s)
Genotype , Microcystis , Multigene Family , Polymorphism, Single Nucleotide , Real-Time Polymerase Chain Reaction , Microcystis/genetics , Microcystis/classification , Real-Time Polymerase Chain Reaction/methods , Microcystins/genetics , INDEL Mutation , Bacterial Proteins/genetics , Sensitivity and Specificity , Ponds/microbiology , Peptide Synthases/genetics
9.
Exploration (Beijing) ; 4(3): 20230085, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38939859

ABSTRACT

To overcome the overheating phenomena of electronic devices and energy components, developing advanced energy-free cooling coatings with promising radiative property seem an effective and energy-saving way. However, the further application of these coatings is greatly limited by their sustainability because of their fragile and easy contamination. Herein, it is reported that a bioinspired radiative cooling coating (BRCC) displayed sustainably efficient heat dissipation by the combination of high emittance and robust self-cleaning property. With the hierarchical porous structure constructed by multiwalled carbon nanotubes (MWCNTs), modified SiO2 and fluorosilicone (FSi) resin, the involvement of the BRCC improves the cooling performance by increasing ≈25% total heat transfer coefficient. During the abrasion and soiling tests, the BRCC-coated Al alloy heat sink always displays stable radiative cooling performance. Moreover, the simulation and experimental results both revealed that reducing surface coverage of BRCC (≈80.9%) can still keep highly cooling efficiency, leading to a cost-effective avenue. Therefore, this study may guide the design and fabrication of advanced radiative cooling coating.

10.
Int J Biol Macromol ; 273(Pt 2): 133045, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38942666

ABSTRACT

This work was to investigate the effect of four prebiotic saccharides gum arabic (GA), fructooligosaccharide (FOS), konjac glucomannan (KGM), and inulin (INU) incorporation on the encapsulation efficiency (EE), physicochemical stability, and in vitro digestion of urolithin A-loaded liposomes (UroA-LPs). The regulation of liposomes on gut microbiota was also investigated by in vitro colonic fermentation. Results indicated that liposomes coated with GA showed the best EE, bioaccessibility, storage and thermal stability, the bioaccessibility was 1.67 times of that of UroA-LPs. The UroA-LPs coated with FOS showed the best freeze-thaw stability and transformation. Meanwhile, saccharides addition remarkably improved the relative abundance of Bacteroidota, reduced the abundances of Proteobacteria and Actinobacteria. The UroA-LPs coated with FOS, INU, and GA exhibited the highest beneficial bacteria abundance of Parabacteroides, Monoglobus, and Phascolarctobacterium, respectively. FOS could also decrease the abundance of harmful bacteria Collinsella and Enterococcus, and increase the levels of acetic acid, butyric acid and iso-butyric acid. Consequently, prebiotic saccharides can improve the EE, physicochemical stability, gut microbiota regulation of UroA-LPs, and promote the bioaccessibility of UroA, but the efficiency varied based on saccharides types, which can lay a foundation for the application of UroA in foods industry and for the enhancement of its bio-activities.


Subject(s)
Gastrointestinal Microbiome , Liposomes , Prebiotics , Gastrointestinal Microbiome/drug effects , Liposomes/chemistry , Polymerization , Coumarins/chemistry , Coumarins/metabolism , Fermentation
11.
J Cardiothorac Surg ; 19(1): 398, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937786

ABSTRACT

PURPOSE: Symptom assessment based on patient-reported outcome (PRO) can correlate with disease severity, making it a potential tool for threshold alerts of postoperative complications. This study aimed to determine whether shortness of breath (SOB) scores on the day of discharge could predict the development of post-discharge complications in patients who underwent lung cancer surgery. METHODS: Patients were from a study of a dynamic perioperative rehabilitation cohort of lung cancer patients focusing on patient-reported outcomes. Patients were assessed using the Perioperative Symptom Assessment Scale for Lung surgery (PSA-Lung). Logistic regression model was used to examine the potential association between SOB on the day of discharge and complications within 3 months after discharge. The post-discharge complications were taken as the anchor variable to determine the optimal cutpoint for SOB on the day of discharge. RESULTS: Complications within 3 months post-discharge occurred in 71 (10.84%) of 655 patients. Logistic regression analysis revealed that being female (OR 1.764, 95% CI 1.006-3.092, P < 0.05) and having two chest tubes (OR 2.026, 95% CI 1.107-3.710, P < 0.05) were significantly associated with post-discharge complications. Additionally, the SOB score on the day of discharge (OR 1.125, 95% CI 1.012-1.250, P < 0.05) was a significant predictor. The optimal SOB cutpoint was 5 (on a scale of 0-10). Patients with an SOB score ≥ 5 at discharge experienced a lower quality of life 1 month later compared to those with SOB score<5 at discharge (73 [50-86] vs. 81 [65-91], P < 0.05). CONCLUSION: SOB on the day of discharge may serve as an early warning sign for the timely detection of 3 month post-discharge complications.


Subject(s)
Dyspnea , Lung Neoplasms , Patient Discharge , Postoperative Complications , Humans , Female , Male , Lung Neoplasms/surgery , Dyspnea/etiology , Aged , Middle Aged , Pneumonectomy/adverse effects
12.
Sheng Li Xue Bao ; 76(3): 418-428, 2024 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-38939936

ABSTRACT

Aging refers to a progressive decline in biological functions, leading to age-related diseases and mortality. The transition metals, including iron, copper, and manganese, play important roles in human physiological and pathological processes. Substantial research has demonstrated that senescent cells accumulate higher levels of transition metals, which in turn accelerates the process of cellular senescence and related diseases through mechanisms such as production of excessive reactive oxygen species (ROS), induction of oxidative stress, DNA damage, and mitochondrial dysfunction. This review article provides a comprehensive overview of the causes of transition metal accumulation in senescent cells, as well as the mechanisms by which it further promotes cellular senescence and related diseases. The aim is to provide insights into anti-aging and treatment of aging-related diseases caused by transition metal accumulation.


Subject(s)
Aging , Cellular Senescence , DNA Damage , Oxidative Stress , Reactive Oxygen Species , Cellular Senescence/physiology , Humans , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism , Aging/physiology , Aging/metabolism , Animals , Transition Elements/metabolism , Iron/metabolism , Mitochondria/metabolism , Mitochondria/physiology , Copper/metabolism , Manganese/metabolism
13.
BMC Pulm Med ; 24(1): 297, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918735

ABSTRACT

OBJECTIVE: To understand the prevalence rate of obstructive pulmonary dysfunction in workers exposed to silica dust and analyze its risk factors, so as to provide reference for the formulation of diagnostic criteria for chronic obstructive pulmonary disease caused by occupational dust. METHODS: Data collection and structured questionnaire were used to collect the data of 2064 workers exposed to silica dust who underwent health examination in Hunan Occupational Disease Prevention and Control Hospital and Yuanling Second People's Hospital from January 1, 2021 to June 30, 2022. The prevalence rate of obstructive pulmonary ventilation dysfunction was analyzed and the risk factors were analyzed. RESULTS: The prevalence rate of obstructive pulmonary ventilation dysfunction (FEV1/FVC < 70%) was 2.3% in 2064 silica dust exposed workers. The prevalence of restrictive pulmonary ventilation dysfunction (FVC/Pre < 80%) was 8.1%. The prevalence of obstructive pulmonary ventilation dysfunction in the high level exposure group was higher than that in the low level exposure group, 8.2 vs0.9% (P < 0.05). The rate of obstructive pulmonary ventilation dysfunction in female group was higher than that in male group (5.3% vs. 1.7%, p = 0.00). Workers with obstructive pulmonary dysfunction were older and worked longer than workers without obstructive pulmonary dysfunction, but there was no statistical difference. Multivariate regression analysis showed that high exposure level was a risk factor for obstructive pulmonary ventilation dysfunction in silica dust exposed workers (P < 0.05). Females were the risk factors for obstructive pulmonary ventilation dysfunction (P < 0.05). CONCLUSION: Silica dust exposure can cause obstructive pulmonary ventilation dysfunction and lead to chronic obstructive pulmonary disease. High level of exposure is a risk factor for obstructive pulmonary ventilation dysfunction. Women exposed to dust are more prone to obstructive pulmonary ventilation dysfunction than men. Early diagnosis of chronic obstructive pulmonary disease caused by silica dust and timely intervention measures are very important to delay the decline of lung function and protect the health of workers.


Subject(s)
Dust , Occupational Exposure , Silicon Dioxide , Humans , Female , Male , Silicon Dioxide/adverse effects , Risk Factors , Cross-Sectional Studies , Occupational Exposure/adverse effects , Prevalence , Middle Aged , Adult , China/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Surveys and Questionnaires , Lung Diseases, Obstructive/epidemiology , Lung Diseases, Obstructive/physiopathology , Multivariate Analysis
14.
J Ethnopharmacol ; 333: 118404, 2024 Oct 28.
Article in English | MEDLINE | ID: mdl-38824977

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis presents complex pathophysiological challenges. Taohe Chengqi Decoction (THCQ), a traditional Chinese medicine, offers potential in managing sepsis-related complications, though its exact mechanisms are not fully understood. AIM OF THE STUDY: This research aimed to assess the therapeutic efficacy and underlying mechanisms of THCQ on sepsis-induced lung injury. MATERIALS AND METHODS: The study began with validating THCQ's anti-inflammatory effects through in vitro and in vivo experiments. Network pharmacology was employed for mechanistic exploration, incorporating GO, KEGG, and PPI analyses of targets. Hub gene-immune cell correlations were assessed using CIBERSORT, with further scrutiny at clinical and single-cell levels. Molecular docking explored THCQ's drug-gene interactions, culminating in qPCR and WB validations of hub gene expressions in sepsis and post-THCQ treatment scenarios. RESULTS: THCQ demonstrated efficacy in modulating inflammatory responses in sepsis, identified through network pharmacology. Key genes like MAPK14, MAPK3, MMP9, STAT3, LYN, AKT1, PTPN11, and HSP90AA1 emerged as central targets. Molecular docking revealed interactions between these genes and THCQ components. qPCR results showed significant modulation of these genes, indicating THCQ's potential in reducing inflammation and regulating immune responses in sepsis. CONCLUSION: This study sheds light on THCQ's anti-inflammatory and immune regulatory mechanisms in sepsis, providing a foundation for further research and potential clinical application.


Subject(s)
Anti-Inflammatory Agents , Drugs, Chinese Herbal , Molecular Docking Simulation , Sepsis , Sepsis/drug therapy , Sepsis/complications , Sepsis/immunology , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Male , Mice , Mice, Inbred C57BL , Humans , Lung Injury/drug therapy , Network Pharmacology , Disease Models, Animal
15.
Cancer Lett ; 595: 216999, 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-38823762

ABSTRACT

Tumor protein p63 isoform ΔNp63 plays roles in the squamous epithelium and squamous cell carcinomas (SCCs), including esophageal SCC (ESCC). By integrating data from cell lines and our latest patient-derived organoid cultures, derived xenograft models, and clinical sample transcriptomic analyses, we identified a novel and robust oncogenic role of ΔNp63 in ESCC. We showed that ΔNp63 maintains the repression of cancer cell endogenous retrotransposon expression and cellular double-stranded RNA sensing. These subsequently lead to a restricted cancer cell viral mimicry response and suppressed induction of tumor-suppressive type I interferon (IFN-I) signaling through the regulations of Signal transducer and activator of transcription 1, Interferon regulatory factor 1, and cGAS-STING pathway. The cancer cell ΔNp63/IFN-I signaling axis affects both the cancer cell and tumor-infiltrating immune cell (TIIC) compartments. In cancer cells, depletion of ΔNp63 resulted in reduced cell viability. ΔNp63 expression is negatively associated with the anticancer responses to viral mimicry booster treatments targeting cancer cells. In the tumor microenvironment, cancer cell TP63 expression negatively correlates with multiple TIIC signatures in ESCC clinical samples. ΔNp63 depletion leads to increased cancer cell antigen presentation molecule expression and enhanced recruitment and reprogramming of tumor-infiltrating myeloid cells. Similar IFN-I signaling and TIIC signature association with ΔNp63 were also observed in lung SCC. These results support the potential application of ΔNp63 as a therapeutic target and a biomarker to guide candidate anticancer treatments exploring viral mimicry responses.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Transcription Factors , Tumor Microenvironment , Tumor Suppressor Proteins , Humans , Tumor Microenvironment/immunology , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/immunology , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Squamous Cell Carcinoma/virology , Esophageal Neoplasms/pathology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/immunology , Esophageal Neoplasms/virology , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Cell Line, Tumor , Animals , Cell Survival , Gene Expression Regulation, Neoplastic , Mice , Signal Transduction , Interferon Type I/metabolism
16.
Theor Appl Genet ; 137(7): 159, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872054

ABSTRACT

KEY MESSAGE: Integrated linkage and association analysis revealed genetic basis across multiple environments. The genes Zm00001d003102 and Zm00001d015905 were further verified to influence amylose content using gene-based association study. Maize kernel amylose is an important source of human food and industrial raw material. However, the genetic basis underlying maize amylose content is still obscure. Herein, we used an intermated B73 × Mo17 (IBM) Syn10 doubled haploid population composed of 222 lines and a germplasm set including 305 inbred lines to uncover the genetic control for amylose content under four environments. Linkage mapping detected 16 unique QTL, among which four were individually repeatedly identified across multiple environments. Genome-wide association study revealed 17 significant (P = 2.24E-06) single-nucleotide polymorphisms, of which two (SYN19568 and PZE-105090500) were located in the intervals of the mapped QTL (qAC2 and qAC5-3), respectively. According to the two population co-localized loci, 20 genes were confirmed as the candidate genes for amylose content. Gene-based association analysis indicated that the variants in Zm00001d003102 (Beta-16-galactosyltransferase GALT29A) and Zm00001d015905 (Sugar transporter 4a) affected amylose content across multi-environment. Tissue expression analysis showed that the two genes were specifically highly expressed in the ear and stem, respectively, suggesting that they might participate in sugar transport from source to sink organs. Our study provides valuable genetic information for breeding maize varieties with high amylose.


Subject(s)
Amylose , Chromosome Mapping , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Zea mays , Zea mays/genetics , Amylose/metabolism , Amylose/genetics , Genome-Wide Association Study , Phenotype , Genetic Linkage , Genes, Plant , Genotype , Genetic Association Studies
17.
BMC Public Health ; 24(1): 1550, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853276

ABSTRACT

BACKGROUND: Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. METHODS: Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007-2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. RESULTS: A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (ß=-8.85, P < 0.05) obtained significantly higher LAP reduction as opposed to being weekend warriors (WWs) (ß=-4.70, P = 0.3841). Furthermore, subgroup analyses and interaction tests indicated that the PA-LAP association was more pronounced in individuals with higher education levels (P interaction = 0.0084) and diabetes (P interaction = 0.0062). Additionally, a significant, non-linear, and negative correlation between weekly total PA and LAP in non-inactive individuals was identified by RCS analysis (P for overall < 0.001, P for nonlinearity = 0.009). A threshold of 440 min in weekly total PA was found to arouse favorable LAP reduction. CONCLUSIONS: Being regularly active obtained better LAP reduction as opposed to being WWs. For non-inactive adults, engaging in more than 440 min of PA per week helps to reduce LAP effectively.


Subject(s)
Exercise , Leisure Activities , Nutrition Surveys , Humans , Male , Female , Adult , Middle Aged , Exercise/physiology , United States , Lipid Accumulation Product , Obesity/prevention & control , Young Adult , Waist Circumference
18.
Article in English | MEDLINE | ID: mdl-38900626

ABSTRACT

Microscopic cell detection is a challenging task due to significant inter-cell occlusions in dense clusters and diverse cell morphologies. This paper introduces a novel framework designed to enhance automated cell detection. The proposed approach integrates a deep learning model that produces an inverse distance transform-based detection map from the given image, accompanied by a secondary network designed to regress a cell density map from the same input. The inverse distance transform-based map effectively highlights each cell instance in the densely populated areas, while the density map accurately estimates the total cell count in the image. Then, a custom counting-aided cell center extraction strategy leverages the cell count obtained by integrating over the density map to refine the detection process, significantly reducing false responses and thereby boosting overall accuracy. The proposed framework demonstrated superior performance with F-scores of 96.93%, 91.21%, and 92.00% on the VGG, MBM, and ADI datasets, respectively, surpassing existing state-of-the-art methods. It also achieved the lowest distance error, further validating the effectiveness of the proposed approach. These results demonstrate significant potential for automated cell analysis in biomedical applications.

19.
Int J Surg ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38896873

ABSTRACT

BACKGROUND: Electronic symptom monitoring via patient-reported outcome in surgical oncology is limited owing to lengthy instruments and non-specific items in common patient-reported outcome instruments. To establish electronic symptom monitoring through a clinically relevant and fit-for-purpose core set of patient-reported outcome in patients undergoing lung cancer surgery. MATERIALS AND METHODS: One qualitative (Cohort 1) and two prospective studies (Cohorts 2 and 3) were conducted between 2018 and 2023. Patients undergoing lung cancer surgery were recruited. Items of symptoms and daily functioning were generated through extensive interviews in Cohort 1 and incorporated into a smartphone-based platform to establish the electronic Perioperative Symptom Assessment for Lung surgery (ePSA-Lung). This tool was finalized and validated in Cohort 2. Patients in Cohort 3 were longitudinally monitored for the first year post-surgery using the validated ePSA-Lung. RESULTS: In total, 1,037 patients scheduled for lung cancer surgery were recruited. The 11-item draft PSA-Lung was generated based on qualitative interview with 39 patients and input from a Delphi study involving 42 experts. A 9-item ePSA-Lung was finalized by assessing 223 patients in the validation cohort; the results supported the instrument's understandability, reliability, sensitivity, and surgical specificity. In Cohort 3 (n=775), compliance ranged from 63.21% to 84.76% during the one-year follow-up after discharge. Coughing, shortness of breath, and disturbed sleep were the most severe symptoms after discharge. Longitudinally, patients who underwent single-port video-assisted thoracic surgery had a lower symptom burden than those who underwent multi-port video-assisted thoracic surgery or thoracotomy (all symptoms, P<0.001). CONCLUSION: The ePSA-Lung is valid, concise, and clinically applicable as it supports electronic symptom monitoring in surgical oncology care. The need for long-term extensive care was identified for patients after discharge, even in early-stage cancer with potential curative treatment.

20.
Sci Rep ; 14(1): 13389, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38862595

ABSTRACT

While EZH2 enzymatic activity is well-known, emerging evidence suggests that EZH2 can exert functions in a methyltransferase-independent manner. In this study, we have uncovered a novel mechanism by which EZH2 positively regulates the expression of SKP2, a critical protein involved in cell cycle progression. We demonstrate that depletion of EZH2 significantly reduces SKP2 protein levels in several cell types, while treatment with EPZ-6438, an EZH2 enzymatic inhibitor, has no effect on SKP2 protein levels. Consistently, EZH2 depletion leads to cell cycle arrest, accompanied by elevated expression of CIP/KIP family proteins, including p21, p27, and p57, whereas EPZ-6438 treatment does not modulate their levels. We also provide evidence that EZH2 knockdown, but not enzymatic inhibition, suppresses SKP2 mRNA expression, underscoring the transcriptional regulation of SKP2 by EZH2 in a methyltransferase-independent manner. Supporting this, analysis of the Cancer Genome Atlas database reveals a close association between EZH2 and SKP2 expression in human malignancies. Moreover, EZH2 depletion but not enzymatic inhibition positively regulates the expression of major epithelial-mesenchymal transition (EMT) regulators, such as ZEB1 and SNAIL1, in transformed cells. Our findings shed light on a novel mechanism by which EZH2 exerts regulatory effects on cell proliferation and differentiation through its methyltransferase-independent function, specifically by modulating SKP2 expression.


Subject(s)
Enhancer of Zeste Homolog 2 Protein , S-Phase Kinase-Associated Proteins , Enhancer of Zeste Homolog 2 Protein/metabolism , Enhancer of Zeste Homolog 2 Protein/genetics , S-Phase Kinase-Associated Proteins/metabolism , S-Phase Kinase-Associated Proteins/genetics , Humans , Signal Transduction , Cell Cycle/genetics , Epithelial-Mesenchymal Transition/genetics , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cyclin-Dependent Kinase Inhibitor p57/metabolism , Cyclin-Dependent Kinase Inhibitor p57/genetics , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Proliferation
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