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IV-V two-dimensional materials have emerged as key contenders for polarization-sensitive and angle-resolved devices, given their inherent anisotropic physical properties. While these materials exhibit intriguing high-pressure quasi-particle behavior and phase transition, the evolution of quasi-particles and their interactions under external pressure remain elusive. Here, employing a diamond anvil cell and spectroscopic measurements coupled with first-principles calculations, we unveil rarely observed pressure-induced phonon-phonon coupling in layered SiP flakes. This coupling manifests as an anomalous phonon hardening behavior for the A1 mode within a broad wavenumber phonon softening region. Furthermore, we demonstrate the effective tuning of exciton emissions in SiP flakes under pressure, revealing a remarkable 63% enhancement in the degree of polarization (DOP) within the pressure range of 0-3.5 GPa. These findings contribute to our understanding of high-pressure phonon evolution in SiP materials and offer a strategic approach to manipulate the anisotropic performance of in-plane anisotropic 2D materials.
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The interaction between light and moiré superlattices presents a platform for exploring unique light-matter phenomena. Tailoring these optical properties holds immense potential for advancing the utilization of moiré superlattices in photonics, optoelectronics, and valleytronics. However, the control of the optical polarization state in moiré superlattices, particularly in the presence of moiré effects, remains elusive. Here, we unveil the emergence of optical anisotropy in moiré superlattices by constructing twisted WSe2/WSe2/SiP heterostructures. We report a linear polarization degree of â¼70% for moiré excitons, attributed to the spatially nonuniform charge distribution, corroborated by first-principles calculations. Furthermore, we demonstrate the modulation of this linear polarization state via the application of a magnetic field, resulting in polarization angle rotation and a magnetic-field-dependent linear polarization degree, influenced by valley coherence and moiré potential effects. Our findings demonstrate an efficient strategy for tuning the optical polarization state of moiré superlattices using heterointerface engineering.
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BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.
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Antígeno B7-H1 , Biomarcadores Tumorais , Quimioterapia de Manutenção , Neoplasias Ovarianas , Ftalazinas , Piperazinas , Humanos , Feminino , Ftalazinas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Piperazinas/uso terapêutico , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Quimioterapia de Manutenção/métodos , Idoso , Adulto , Estudos Prospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Proteína BRCA2/genética , Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Recombinação HomólogaRESUMO
Efficient drinking water disinfection methods are critical for public health. Locally enhanced electric field treatment (LEEFT) is an antimicrobial method that uses sharp structures, like metallic nanowires, to enhance the electric field at tips and cause bacteria inactivation. Electroporation is the originally designed mechanism of LEEFT. Although oxidation is typically undesired due to byproduct generation and electrode corrosion, it can enhance the overall disinfection efficiency. In this work, we conduct an operando investigation of LEEFT, in which we change the electrical parameters to tune the mechanisms between electrophysical electroporation and electrochemical oxidation. Pure electroporation (i.e., without detectable oxidation) could be achieved under a duty cycle of ≤0.1% and a pulse width of ≤2 µs. Applying 2 µs pulses at 7-8 kV/cm and 0.1% duty cycle results in 80-100% bacteria inactivation with pure electroporation. A higher chance of oxidation is found with a higher duty cycle and a longer pulse width, where the antimicrobial efficiency could also be enhanced. For water with a higher conductivity, a higher antimicrobial efficiency can be achieved under the same treatment conditions, and electrochemical reactions could be induced more easily. The findings shown in this work improve the fundamental understanding of LEEFT and help optimize the performance of LEEFT in real applications.
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Desinfecção , Eletroporação , Eletroporação/métodos , Desinfecção/métodos , Purificação da Água/métodos , Eletricidade , BactériasRESUMO
BACKGROUND: Premenstrual syndrome (PMS) is a pathological condition characterized by a series of abnormal physical, psychological, and behavioral symptoms. We evaluated the effectiveness of laparoscopic sleeve gastrectomy (LSG) in the treatment of patients with obesity and PMS. METHODS: In this case-control study, 131 patients with obesity (BMI ≥ 27.5 kg/cm2) diagnosed with moderate-to-severe PMS from March 2018 to March 2022 were prospectively selected to undergo LSG or not at their own discretion. Participants self-reported their PMS severity using the Premenstrual Syndrome Screening Tool. Among them, 68 patients chose LSG surgery, and 63 control group patients were followed up without surgery. Data were recorded at baseline and at 3 months post-treatment. We used a multivariate analysis to assess the improvement in PMS symptoms and associated factors. RESULTS: Of the 131 patients with obesity and PMS, the improvement rate of PMS in the LSG group was 57.35% (n = 39), while the improvement rate of PMS in the control group was 25.40% (n = 16). Furthermore, our study revealed that surgery is an independent factor affecting the improvement of patients with PMS. Additionally, there was a correlation between alcohol use, T2DM and obesity-related metabolic diseases, and BMI with PMS. The changes in BMI, testosterone, and estradiol(E2) levels may also contribute to the improvement of patients with obesity and PMS. CONCLUSION: LSG can improve the management of obesity in patients with PMS to some extent. Changes in BMI, testosterone, and E2 may be indicative of improvement in patients with obesity and PMS.
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Gastrectomia , Laparoscopia , Obesidade , Síndrome Pré-Menstrual , Humanos , Feminino , Adulto , Laparoscopia/métodos , Gastrectomia/métodos , Estudos de Casos e Controles , Síndrome Pré-Menstrual/cirurgia , Obesidade/complicações , Obesidade/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Cirurgia Bariátrica/métodos , Adulto Jovem , Pessoa de Meia-Idade , Índice de Massa CorporalRESUMO
BACKGROUND: The presence of gallstones in both the gallbladder and bile ducts is referred to as cholelithiasis. The prevalence of cholecystolithiasis and bile duct stones differs. Observational and Mendelian randomization (MR) studies have elucidated the significant contributing role of numerous fatty acids (FAs) in the development of cholelithiasis. Despite numerous studies about cholelithiasis, evidence on the relationship between serum FA levels and cholecystolithiasis, as well as bile duct stones with or without inflammation, remains insufficient. METHODS: A two-sample MR study was designed to clarify the impact of serum FA levels on various bile duct inflammatory diseases. The summary statistics of single nucleotide polymorphisms (SNPs) associated with fatty acids were obtained from the UK Biobank (UKB) and included data from 114,999 participants. The researchers obtained GWAS summary statistics for cholecystolithiasis and bile duct stones in 463,010 and 361,194 European participants, including cases with and without inflammation. No sample overlap between the exposure and outcome was verified through the "mr-lap" package. The SNPs were screened to identify instrumental variables (IVs). Cochran's Q test was applied for heterogeneity assessment. Inverse variance weighting (IVW) (fixed effects or random effects), MR-Egger regression and weighted median methods were used for MR. Multivariable MR was applied to determine the direct effect of each exposure on the outcome. A false discovery rate (FDR) was applied to adjust for multiple testing correction based on the Benjamini-Hochberg method. Finally, the FinnGen Consortium was used to validate some results. RESULTS: The overall concentration of polyunsaturated fatty acids (PUFAs) in the serum was negatively associated with the risk of calculus of the gallbladder with acute cholecystitis (IVW, OR = 0.996, P = 0.038, CI 0.992-0.999; weighted median, OR = 0.995, P = 0.025, CI 0.991-0.999). The percentage of PUFAs to total monounsaturated fatty acids(MUFAs) (IVW, OR = 0.998, P = 0.045, CI 0.997-0.999) and the percentage of PUFAs to total FAs (IVW, OR = 0.997, P = 0.025, CI 0.995-0.999) had a protective role against cholecystitis. The percentage of PUFAs to total FAs had a protective role against calculus of the gallbladder without cholecystitis (IVW, OR = 0.995, P = 0.026, CI 0.990-0.999; MR Egger, OR = 0.99, P = 0.03, CI 0.982-0.998; weighted median, OR = 0.991, P = 5.41e-06, CI 0.988-0.995). Conversely, the percentage of MUFAs to total FAs increased the risk for cholecystitis (IVW, OR = 1.001, P = 0.034, CI 1.0001-1.002). However, there were no causal effects of the above exposures on the outcomes through multivariable MR and multiple testing correction. Finally, the causal effects of the above exposures on cholecystitis were validated in the FinnGen Consortium, which suggested that the percentage of PUFAs to total FAs (IVW, OR = 0.744, P = 0.021, CI 0.579-0.957) had a protective role against cholecystitis. CONCLUSION: These Mendelian randomization findings suggested that more attention should be focused on people who have low serum PUFA levels, which may have a potential role in the occurrence of calculus of the gallbladder or cholecystitis rather than calculus of the bile duct without cholangitis or cholecystitis.
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Sistema Biliar , Colecistite , Cálculos Biliares , Humanos , Cálculos Biliares/genética , Ácidos Graxos , Análise da Randomização Mendeliana , Inflamação/genética , Colecistite/genéticaRESUMO
BACKGROUND/PURPOSE: Patients with gout are at risk for increased serum uric acid (SUA) levels and gout attacks in the short term after undergoing bariatric surgery, and the purpose of this study was to evaluate the benefits of short-term treatment with uric acid-lowering medication after bariatric surgery for the control of gout attacks and SUA levels in patients with gout. METHODS: 71 patients who underwent SG from January 2020 to December 2022 were prospectively included. These patients were diagnosed with hyperuricemia before surgery and had a history of gout attacks. Patients were classified into a drug-treatment group (DTG, n = 32) and a non-drug-treatment group (NDTG, n = 39) according to whether they took uric acid-lowering medication after surgery. Changes in the number of gout attacks, body mass index (BMI), and SUA levels at 1 week, 1 month, 3 months, and 6 months after bariatric surgery were measured in both groups. RESULTS: In the DTG, 22 patients (68.8%) experienced an increase in SUA within 1 week, 3 patients (9.4%) had an acute attack of gout within the first month, and no patients had a gout attack thereafter. In the NDTG, 35 patients (89.7%) experienced an increase in SUA within 1 week, 7 patients (17.9%) had an acute gout attack within the first month, and 4 patients (10.3%) experienced gout attacks between month 1 and month 3 postoperatively. Both groups were free of gout attacks between the 3rd and 6th postoperative month and showed a significant decrease in SUA and BMI by the sixth month. CONCLUSION: In patients with gout, continued use of uric acid-lowering medication after bariatric surgery is beneficial in reducing the number of gout attacks and the risk of rising SUA.
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Cirurgia Bariátrica , Supressores da Gota , Gota , Ácido Úrico , Humanos , Gota/sangue , Cirurgia Bariátrica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Ácido Úrico/sangue , Supressores da Gota/uso terapêutico , Adulto , Estudos Prospectivos , Hiperuricemia/sangue , Hiperuricemia/etiologia , Índice de Massa Corporal , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
A method utilizing high-performance liquid chromatography-fluorescence detection (HPLC-FLD) has been developed and refined for the simultaneous detection of florfenicol (FF) and its metabolite florfenicol amine (FFA) along with three fluoroquinolone (ciprofloxacin (CIP), enrofloxacin (ENR), and sarafloxacin (SAR)) residues in different parts of eggs (whole egg, egg yolk, and egg albumen). The QuEChERS ("Quick, easy, cheap, effective, rugged, and safe") procedure utilized 0.1 M disodium EDTA solution, water, and acetonitrile as extractants; sodium sulfate, sodium chloride, and trisodium citrate as dehydrating salts; and N-propylethylenediamine and C18 as adsorbents. A dual-channel FLD method was utilized to analyze the target compounds using an XBridge BEH C18 chromatographic column (4.6 mm × 150 mm, 5 µm). The mobile phase was employed isocratically using a solution of 0.01 M sodium dihydrogen phosphate, 0.005 M sodium dodecyl sulfate, and 0.1% triethylamine (pH 4.8) in combination with acetonitrile at a ratio of 65:35 (V/V). The limits of detection (LOD) and quantification (LOQ) of the analytes ranged from 0.03 to 1.5 µg/kg and from 0.1 to 5.0 µg/kg, respectively. The recoveries of the analytes in the blank egg samples ranged from 71.9% to 94.8% when reference standard concentrations of the LOQ, half of the maximum residual limit (MRL), MRL, and twice the MRL were added. The parameters of the presented protocol were validated and subsequently applied to the analysis of real samples, demonstrating the applicability and reliability of the method.
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Fluoroquinolonas , Tianfenicol/análogos & derivados , Cromatografia Líquida de Alta Pressão , Reprodutibilidade dos Testes , AcetonitrilasRESUMO
Diabetic nephropathy (DN) is a crucial metabolic health problem. The renin-angiotensin system (RAS) is well known to play an important role in DN. Abnormal RAS activity can cause the over-accumulation of angiotensin II (Ang II). Angiotensin-converting enzyme inhibitor (ACEI) administration has been proposed as a therapy, but previous studies have also indicated that chymase, the enzyme that hydrolyzes angiotensin I to Ang II in an ACE-independent pathway, may play an important role in the progression of DN. Therefore, this study established a model of severe DN progression in a db/db and ACE2 KO mouse model (db and ACE2 double-gene-knockout mice) to explore the roles of RAS factors in DNA and changes in their activity after short-term (only 4 weeks) feeding of a high-fat diet (HFD) to 8-week-old mice. The results indicate that FD-fed db/db and ACE2 KO mice fed an HFD represent a good model for investigating the role of RAS in DN. An HFD promotes the activation of MAPK, including p-JNK and p-p38, as well as the RAS signaling pathway, leading to renal damage in mice. Blocking Ang II/AT1R could alleviate the progression of DN after administration of ACEI or chymase inhibitor (CI). Both ACE and chymase are highly involved in Ang II generation in HFD-induced DN; therefore, ACEI and CI are potential treatments for DN.
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Diabetes Mellitus , Nefropatias Diabéticas , Hormônios Peptídicos , Animais , Camundongos , Angiotensina II , Enzima de Conversão de Angiotensina 2/genética , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antivirais , Quimases/genética , Nefropatias Diabéticas/genética , Dieta Hiperlipídica , Modelos Animais de Doenças , Camundongos Knockout , Sistema Renina-Angiotensina , Serina ProteasesRESUMO
As the overuse of chemicals in our disinfection processes becomes an ever-growing concern, alternative approaches to reduce and replace the usage of chemicals is warranted. Electric field treatment has shown promising potential to have synergistic effects with standard chemical-based methods as they both target the cell membrane specifically. In this study, we use a lab-on-a-chip device to understand, observe, and quantify the synergistic effect between electric field treatment and copper inactivation. Observations in situ, and at a single cell level, ensure us that the combined approach has an enhancement effect leading more bacteria to be weakened by electric field treatment and susceptible to inactivation by copper ion permeation. The synergistic effects of electric field treatment and copper can be visually concluded here, enabling the further study of this technology to optimally develop, mature, and scale for its various applications in the future.
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Bactérias , Cobre , Desinfecção/métodos , Eletricidade , Dispositivos Lab-On-A-ChipRESUMO
OBJECTIVE: To explore the effectiveness of multidisciplinary management based on a clinical nursing pathway model for the treatment of hypertensive intracerebral hemorrhage (HICH). METHODS: A total of 124 patients with HICH admitted to our hospital between February 2021 and June 2023 were selected as research subjects in this randomized, controlled, unblinded study. They were divided into Control-group and Study-group using a random number table method, with 62 cases in each group. The Control-group received routine care and the Study-group adopted a multidisciplinary management approach based on the clinical nursing pathway model. A multidisciplinary intervention group including 1 attending physician, 1 psychotherapist, 1 nutritionist, 1 rehabilitation specialist, and 4 responsible nurses was constructed. From preoperative to postoperative day, patients were provided with psychological intervention, health education, respiratory tract management, and specific care for patients who were restless. One to 3 days after operation, the patients and their family members were guided in basic postoperative care and nutrition care. From the 4th day after surgery to the 1st day before discharge, patients were guided for rehabilitation exercises. Patients also received discharge advices upon discharge. Activities of daily living, neurological function, stress response indicators, incidence of complications, and nursing satisfaction before and after the intervention were compared between the 2 groups. RESULTS: After the intervention, the activities of daily living and neurological function of the 2 groups were significantly improved compared to before the intervention, and the Study-group was significantly higher than the Control-group (Pâ <â .05). After intervention, the levels of stress response indicators in both groups significantly decreased compared to before the intervention, and the Study-group was significantly lower than the Control-group (Pâ <â .05). The incidence of complications in the Study-group (3.23%) was lower than that in the Control-group (15.00%) (Pâ <â .05). Nursing satisfaction in the Study-group (95.16%) was higher than that in the Control-group (83.33%) (Pâ <â .05). CONCLUSIONS: Our findings indicate that adopting a multidisciplinary management approach based on clinical nursing pathways to intervene in patients with HICH can reduce stress response levels, reduce the risk of complications, and facilitate the recovery of neurological function and activities of daily living with high patient satisfaction.
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Atividades Cotidianas , Hemorragia Intracraniana Hipertensiva , Humanos , Hemorragia Intracraniana Hipertensiva/cirurgia , Hospitalização , Satisfação do Paciente , Cuidados Pós-OperatóriosRESUMO
[This corrects the article DOI: 10.3389/fnut.2022.933193.].
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Purpose: This study aims to investigate the status of family functioning and dissatisfaction of family function from the perception of adolescents with affective disorders and explore associated factors. Methods: This was a multicentric cross-sectional study conducted from April 2022 to February 2023. Adolescents with affective disorders were surveyed in representative samples drawn from three hospitals in Sichuan province, China. Data were obtained from 235 participants regarding their demographic characteristics, family characteristics, disease-related characteristics, and family functioning. Results: The study found family functioning and its' dissatisfaction both lower than national norms from the perspectives of adolescents. Younger age, single-parent family, and reconstituted family were predictors of not close of cohesion. Younger age, lower educational level of father, and reconstituted family were associated with less change of flexibility. Less times of hospitalizations, higher educational level of father, stem family were more satisfy with cohesion. Higher educational level of father, and stem family were also associated with greater satisfaction with flexibility. Conclusion: The study demonstrated that the family function of adolescents of affective disorders was poor, more attention should be paid to it. Age, family structure, number of hospitalizations and the educational level of father were influencing factors of family functioning. Therefore, it is important for medical worker to assess demographic and family characteristics of adolescents with affective disorders. Younger children, children of reconstituted family and single-parent family, children with repeated hospitalizations and fathers of lower level of education should be given emphasized in implementation of interventions. Based on the evaluation results, personalized family therapy has been proved to be an affective measure and could be used in clinical work.
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Background: Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are major health burdens, with emerging evidence suggesting NAFLD as a significant risk factor for AF, but the mechanism is remain unclear. Methods: In this study, we analyzed gene expression data from NAFLD (GSE89632) and AF (GSE75092) datasets from the Gene Expression Omnibus. We identified co-upregulated and co-downregulated genes between NAFLD and AF, assessed diagnostic potential of specific genes, conducted immune infiltration analysis, and performed molecular docking studies with sodium glucose co-transporter 2 inhibitors (SGLT2i). Results: We identified eight co-upregulated and 31 co-downregulated genes between NAFLD and AF. Genes such as AMOT, PDE11A, TYMS, TMEM98, and PTGS2 demonstrated substantial diagnostic potential for identifying NAFLD patients at risk of AF. Immune infiltration analysis discovered an elevated presence of CD8 T cells, γδ T cells, and M2 macrophages in NAFLD livers, linking systemic inflammation to NAFLD and AF. Additionally, studies have shown that a connection between mitochondrial dysfunction and several hub genes like DGAT1, TYMS, and PTGS2, suggesting that mitochondrial disturbances may underpin the systemic inflammation in NAFLD, which possibly exacerbating AF. Molecular docking studies indicated that empagliflozin's binding affinity with key genes such as DGAT1, TYMS, and PTGS2 presents a novel therapeutic avenue for NAFLD-associated AF. Conclusion: Our study firstly discovered that AMOT, PDE11A, TYMS, TMEM98, and PTGS2 are associated with NAFLD-related AF and hold strong diagnostic values. Our study also indicates that mitochondrial dysfunction and systemic inflammation may be potential mechanisms bridging NAFLD and AF. Additionally, we identified empagliflozin as a potentially effective therapeutic agent for NAFLD-related AF at the molecular structure level. These novel insights contribute to the further understanding, diagnosis, and intervention of NAFLD-related AF.
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PURPOSE: Pancreatic cancer (PC) is one of the most lethal malignant gastrointestinal tumors (GI) characterized by a poor prognosis. Ferroptosis is an emerging programmed cell death that plays an essential role in the progression of various cancers. Ferroptosis is driven by iron-dependent phospholipid peroxidation and is regulated by mitochondrial activity, lipid peroxidation, and reactive oxygen species (ROS). The function and mechanism of ferroptosis in PC need more research. METHODS: The levels of circRNAs, miRNAs, and mRNAs were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used for protein detection. CCK8 assays were used to detect cell proliferation. Cell death, lipid peroxidation, ROS, and Fe2+ were detected by indicted kits. Dual-luciferase reporter and RNA pull-down assays were conducted to confirm the interaction between circRNAs, miRNAs, and mRNAs. RESULTS: In this research, we found that circular RNA hsa_circ_0000003(circ_WASF2) was upregulated in pancreatic cancer cells. The silence of circ_WASF2 inhibited cancer proliferation and increased cell death by increasing ferroptosis accompanied by up-regulation of lipid peroxidation, ROS, and Fe2+. Further studies showed that circ_WASF2 could attenuate ferroptosis by targeting miR-634 and the downstream glutathione peroxidase 4 (GPX4). GPX4 has been well-reported as a central factor in ferroptosis. Our research revealed a new pathway for regulating ferroptosis in PC. CONCLUSION: In summary, we have determined that circ_WASF2/miR-634/GPX4 contributed to ferroptosis-induced cell death, and provided a possible therapeutic target in PC.
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AIM OF THE STUDY: Cholestasis induces severe liver injury and subsequent liver fibrosis. However, a comprehensive understanding of the relationships between liver fibrosis and cholestasis-induced changes in metabolites in the gut and fibrotic liver tissue and in the gut microbiota is insufficient. METHODS: Common bile duct ligation (BDL) was employed to establish a cholestatic liver fibrosis model in mice for 26 days. Fibrotic liver tissue and the gut contents were collected. Untargeted metabolomics was conducted for the determination of metabolites in the gut contents and liver tissues. Metagenomics was adopted to explore the gut microbiota. RESULTS: The metabolites in the gut contents and liver tissues between normal and cholestatic liver fibrosis mice were highly distinct. Beta-alanine metabolism and glutathione metabolism were downregulated in the gut of the BDL group. Galactose metabolism, biosynthesis of unsaturated fatty acids, and ABC transporters were upregulated in the gut and downregulated in the liver of the BDL group. Arginine biosynthesis, taurine and hypotaurine metabolism, arginine and proline metabolism, and primary bile acid biosynthesis were downregulated in the gut and upregulated in the liver of the BDL group. Metagenomic analysis revealed that the alpha diversity of the microbiota in the BDL group decreased. The altered structure of the gut microbiota in the BDL group led to the hypofunction of important metabolic pathways (such as folate biosynthesis, histidine metabolism, thiamine metabolism, biotin metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis) and enzymes (such as NADH, DNA helicase, and DNA-directed DNA polymerase). Correlation analyses indicated that certain gut microbes were associated with gut and liver metabolites. CONCLUSIONS: Untargeted metabolomics and metagenomics provided comprehensive information on gut and liver metabolism and gut microbiota in mice with cholestatic liver fibrosis. Therefore, significantly altered bacteria and metabolites may help provide some targets against cholestatic liver fibrosis in the future.
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Colestase , Microbioma Gastrointestinal , Cirrose Hepática , Fígado , Animais , Colestase/metabolismo , Colestase/patologia , Colestase/microbiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/microbiologia , Cirrose Hepática/patologia , Camundongos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , MetabolômicaRESUMO
Background: Generalized joint laxity (GJL) is a risk factor for inferior outcomes after the modified Broström procedure for chronic lateral ankle instability, while anatomic reconstruction with tendons is more inclined to be recommended. However, whether anatomic reconstruction could achieve better results than the modified Broström procedure in patients with GJL is unknown. Purpose: To compare clinical outcomes and return to sports between anatomic reconstruction and the modified Broström procedure in patients with GJL. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with GJL (Beighton score ≥4) who underwent either the modified Broström procedure or anatomic reconstruction with gracilis autografts between 2017 and 2020 were reviewed. Included were 19 patients who underwent anatomic reconstruction (reconstruction group) and 49 patients who underwent the modified Broström procedure (MBP group). Clinical outcomes were compared using the Foot and Ankle Outcome Score (FAOS) and the Karlsson score. The rates of return to preinjury level in high-demand sports, sprain recurrence, and range of motion between the 2 groups were also compared. Results: The mean follow-up duration was 38.3 months in the reconstruction group and 43.7 months in the MBP group. The FAOS and Karlsson scores improved significantly after surgery in both groups (P < .001 for all), with the reconstruction group having significantly higher postoperative FAOS-Sports scores (87.9 ± 8.9 vs 80.5 ± 11.6; P = .015) and Karlsson scores (86.9 ± 6.1 vs 82 ± 8.4; P = .025) than the MBP group. The rate of return to preinjury high-demand sports was higher in the reconstruction group than in the MBP group (73.3% vs 38.9%; P = .034). The MBP group had a significantly higher rate of sprain recurrence (22.4% vs 0%; P = .027). More patients reported dorsiflexion restriction in the reconstruction group (n = 4; 21.1%) than in the MBP group (n = 1; 2%) (P = .019); nonetheless, there was no noticeable effect on daily life and sports. Conclusion: Better clinical outcomes, less sprain recurrence, and a higher rate of return to preinjury high-demand sports were found after anatomic reconstruction with free tendons compared with the modified Broström procedure in patients with GJL. Anatomic tendon reconstruction can be recommended for such patients, especially those participating in high-demand sports.
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OBJECTIVE: Investigate the long-term protective effects of gastric bypass surgery on the kidneys of hypertensive obese rats to better understand the role of gastric bypass surgery in preventing renal injury in humans with hypertension and obesity. METHODS: Compare 6-week-old spontaneously hypertensive rats, including 30 Roux-en-Y gastric bypass (RYGB) and 30 sham operations. Body weight and blood pressure were monitored before and up to 12 months after the operation. Blood lipids, blood creatinine, and blood urea nitrogen were measured. Kidney pathology was assessed using HE staining, while renal fibrosis was observed via Masson staining. Inflammatory indicators were examined by ELISA. The expression of the NLRP3 gene in the kidney was measured using immunofluorescence and western blot, and the changes in key pathways including ASC/IL-1ß protein were verified. RESULTS: RYGB reduced the body weight of hypertensive obese rats and had a protective effect on blood pressure. Additionally, the bypass effectively mitigated renal inflammation and fibrosis. Moreover, RYGB modulated the expression of NLRP3 and prevented kidney damage via the ASC/IL-1 pathway. CONCLUSION: This study validates that RYGB effectively attains sustained blood pressure control in hypertensive obese rats and has a potential kidney-protective mechanism via the NLRP3-ASC/IL-1ß pathway.
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Derivação Gástrica , Hipertensão , Obesidade Mórbida , Humanos , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Obesidade Mórbida/cirurgia , Obesidade/cirurgia , RimRESUMO
BACKGROUND: The BCL2 interacting protein 3-like (BNIP3L) protein is involved in multiple myeloma (MM) development and progression. This study aims to explore the connection between BNIP3L single-nucleotide polymorphisms (SNPs) and MM. METHODS: SNaPshot was used to examine six SNP loci of the BNIP3L gene in enrolled subjects. The relationship between these loci and MM susceptibility and prognosis was explored. Survival analysis was used to evaluate the impact of different factors on patient survival. RESULTS: The rs2874670 AA genotype and A allele were associated with increased MM risk (P < 0.05). The CCACAC haplotype had a higher frequency in MM, while CCGCAC had a higher frequency in normal patients (all P < 0.05). Patients with R-ISS stage I and II had higher survival rates than those with stage III (P < 0.05). Patients, who received chemotherapy followed by autologous stem cell transplantation, had longer survival time than those who only received chemotherapy (P < 0.05). Low levels of LDH and ß2-MG were associated with better survival rates (P < 0.05). Cox regression identified that LDH levels, ß2-MG levels, and R-ISS staging were the risk factors for the death of MM. Mann-Whitney U test found a significant difference in survival time between MM patients with different BNIP3L rs2874670 genotypes after BD chemotherapy (P < 0.05). CONCLUSION: To our knowledge, this is the first study to find that BNIP3L rs2874670 could increase MM susceptibility in China. Different BNIP3L rs2874670 genotypes may affect the prognosis of MM patients receiving BD chemotherapy.
Assuntos
Proteínas de Membrana , Mieloma Múltiplo , Polimorfismo de Nucleotídeo Único , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Proteínas de Membrana/genética , Feminino , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Proteínas Proto-Oncogênicas/genética , Predisposição Genética para Doença , Adulto , Idoso , Prognóstico , Genótipo , Proteínas Supressoras de TumorRESUMO
The instability of viral targets including SARS-CoV-2 in sewage is an important challenge in wastewater monitoring projects. The unrecognized interruptions in the 'cold-chain' transport from the sample collection to RNA quantification in the laboratory may undermine the accurate quantification of the virus. In this study, bovine serum albumin (BSA)-modified porous superabsorbent polymer (PSAP) beads were applied to absorb raw sewage samples as a simple method for viral RNA preservation. The preservation efficiency for SARS-CoV-2 and pepper mild mottle virus (PMMoV) RNA were examined during storage for 14 days at 4 °C or room temperature against the control (no beads applied). While a non-significant difference was observed at 4 °C (â¼80 % retention for both control and PSAP-treated sewage), the reduction of SARS-CoV-2 RNA concentrations was significantly lower in sewage retrieved from PSAP beads (25-40 % reduction) compared to control (>60 % reduction) at room temperature. On the other hand, the recovery of PMMoV, known for its high persistence in raw sewage, from PSAP beads or controls were consistently above 85 %, regardless of the storage temperature. Our results demonstrate the applicability of PSAP beads to wastewater-based epidemiology (WBE) projects for preservation of SARS-CoV-2 RNA in sewage, especially in remote settings with no refrigeration capabilities.