RESUMO
Objective: This research aimed to investigate the association between the blood urea nitrogen-to-creatinine (BUN/Cr) ratio and the rate of in-hospital mortality in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF), who are also receiving care in intensive care unit (ICU). Methods: A retrospective study was conducted using the MIMIC-IV database. We collected data on BUN/Cr levels at admission for patients with AIS and concurrent AF. To assess the association between BUN/Cr and in-hospital mortality rate, statistical analysis was conducted employing multivariable logistic regression models and restricted cubic spline models. These models were utilized to investigate the potential relationship and provide insights into the impact of BUN/Cr on the likelihood of in-hospital mortality. Interaction and subgroup analyses were performed to evaluate the consistency of the correlation. Results: There were a total of 856 patients (age ≥ 18 years) with a median age of 78.0 years, of which 466 (54.4%) were female. Out of 856 patients, 182 (21.26%) died in the hospital. Upon controlling for confounding factors, the multivariable logistic regression analysis elucidated that patients falling within the third trisection (Q3 > 22.41 mg/dL) exhibited a noticeably increased susceptibility to in-hospital mortality when contrasted with their counterparts positioned in the second trisection (Q2: 17.2-22.41 mg/dL) (OR = 2.02, 95% CI: 1.26-3.26, p = 0.004). A non-linear J-shaped relationship was observed between BUN/Cr at ICU admission and in-hospital mortality rate (p = 0.027), with a turning point at 19.63 mg/dL. In the threshold analysis, there was a 4% rise in in-hospital mortality for each 1 mg/dL increase in BUN/Cr (OR: 1.04, 95% CI: 1.01-1.06, p = 0.012). Conclusion: In patients with AIS complicated by AF, BUN/Cr at admission shows a J-shaped correlation with in-hospital mortality rate. When BUN/Cr exceeds 19.63 mg/dL, the in-hospital mortality rate increases.
RESUMO
In large-scale radiation exposure events, the ability to triage potential victims by the received radiation dosage is crucial. This can be evaluated by radiation-induced biological changes. Radiation-responsive mRNA is a class of biomarkers that has been explored for dose-dependency with methods such as RT-qPCR. However, these methods are challenging to implement for point-of-care devices. We have designed and used molecular beacons as probes for the measurement of radiation-induced changes of intracellular mRNA in a microfluidic device towards determining radiation dosage. Our experiments, in which fixed TK6 cells labeled with a molecular beacon specific to BAX mRNA exhibited dose-dependent fluorescence in a manner consistent with RT-qPCR analysis, demonstrate that such intracellular molecular probes can potentially be used in point-of-care radiation biodosimetry. This proof of concept could readily be extended to any RNA-based test to provide direct measurements at the bedside.
RESUMO
Objective:To explore the clinical characteristics of sarcoidosis of head and neck symptoms, and to summarize the diagnosis and treatment experience. Methods:A retrospective study was conducted on patients with nodular disease with main symptoms in the head and neck who visited Henan Provincial People's Hospital from January 2020 to August 2023. The clinical data including symptom characteristics, pathological characteristics, treatment methods, and prognosis were analyzed. Results:A total of 14 patients were included, with 4 malesï¼28.6%ï¼ and 10 femalesï¼71.4%ï¼, age ranged from 11 to 71 years, with an average age ofï¼52.0±15.8ï¼ years. The lesions were located in the parotid gland in 2 cases and the neck in 12 cases. Twelve cases underwent neck mass resection surgery, and 2 cases underwent ultrasound-guided core biopsy of parotid gland tumor and postoperative pathological diagnosis was confirmed in all cases. Four cases received steroid treatment postoperatively, and showed good prognosis with reduced lesion size after 3 months. Three cases did not take medication and the lesions continued to persist, causing discomfort. Seven cases did not take medication postoperatively, and the lesions expanded with multi-organ progression. Conclusion:Patients with head and neck sarcoidosis are rare in clinical practice, and it is prone to misdiagnosis and missed diagnosis. Steroid therapy can achieve good therapeutic effects.
Assuntos
Pescoço , Sarcoidose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Sarcoidose/diagnóstico , Idoso , Criança , Adolescente , Cabeça , Adulto Jovem , Prognóstico , Glândula Parótida/patologiaRESUMO
Melanoma is a common malignant tumor, with a five-year mortality rate as high as 62% in cases of metastatic melanoma according to cancer statistics (2024). In recent years, the focus of melanoma research has predominantly centered on immunotherapy and targeted therapy, grappling with challenges such as resistance and immunogenicity. The discovery of nanoparticles (NPs) has brought nano-delivery systems to the forefront of melanoma diagnosis and treatment. Although certain NPs, like liposomes, have gained clinical approval, utilizing most nano-delivery systems for melanoma diagnosis and treatment remains largely exploratory. The inherent limitations of NPs present a major obstacle to their clinical translation. By selecting suitable nanocarriers and functionalizing NPs to optimize nano-delivery systems, and combining these systems with other therapies, it is possible to reduce the systemic toxicity and resistance associated with conventional therapies and the NPs themselves. This optimization could significantly improve the effectiveness of nano-delivery systems in the early detection and timely treatment of melanoma. However, there have been few reviews on the optimization of NPs and the combined application of other therapies in the treatment and diagnostic application of melanoma in the past three years. This review summarizes the latest applications of nano-delivery systems in the diagnosis and treatment of melanoma over the past three years, including innovations and achievements in both preclinical and clinical studies, offering new perspectives on their potential and future application prospects. It integrates clinical data and patent information, highlights trends in nano-delivery system development, and offers new insights into their clinical translation. Additionally, it discusses the challenges and opportunities of nano-delivery systems in melanoma treatment, providing a foundation for advancing their application in diagnosis, treatment, and clinical translation.
Assuntos
Sistemas de Liberação de Medicamentos , Melanoma , Nanopartículas , Humanos , Melanoma/tratamento farmacológico , Melanoma/diagnóstico , Nanopartículas/química , Animais , Imunoterapia/métodos , Lipossomos/química , Antineoplásicos , Portadores de Fármacos/químicaRESUMO
Patrinia punctiflora is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the isolation of six iridoids, which were previously unreported compounds, patriscabioins PU (1-6). Their structures were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Among them, compound 5 was screened to evaluate its insulin resistance activity on an IR-HepG-2 cell model. Compound 5 had no cytotoxicity compared with the control group and could promote glucose uptake in IR-HepG-2 cells. Through further mechanism studies, the undescribed compound 5 could increase the expression levels of PI-3 K, p-AKT, GLUT4 and p-GSK3ß proteins. Moreover, the expression of PEPCK and G6Pase proteins, which are key gluconeogenic enzymes, was also inhibited. Thus, compound 5 promotes the transfer of GLUT4 to the plasma membrane by activating the PI-3 K/AKT signaling pathway, at the same time, promotes glycogen synthesis and inhibits the onset of gluconeogenesis, which in turn ameliorates insulin resistance.
RESUMO
BACKGROUND: Impaired hospitalizations for heart failure (HHF) and mortality are associated with tricuspid regurgitation (TR). OBJECTIVES: The objective of this study was to investigate the benefit of transcatheter tricuspid valve replacement (TTVR) over guideline-directed medical therapy (GDMT) in patients with symptomatic severe TR. METHODS: Between May 2020 and April 2023, 88 patients with symptomatic severe TR were treated in our center. Of these, 57 patients received GDMT alone, and 31 patients underwent combined TTVR and GDMT. We collected and analyzed baseline data, and follow-up information for both groups. The primary endpoints were all-cause mortality and the combined endpoint (including all-cause mortality and HHF). RESULTS: At a median follow-up of 20 (IQR 10-29) months, significant improvements were shown in TR severity, right ventricular function, and dimensions in TTVR group (all P < 0.001). It also resulted in superior survival rates (75.8% vs. 48.4%, P = 0.019), improved freedom from combined endpoint (61.5% vs. 45.9%, P = 0.007) and fewer major adverse events. After stratification by TRI-SCORE, the subgroup with < 6 points in the TTVR group exhibited a significant difference in the combined endpoint compared to the other subgroups (all P < 0.05), while no significant differences were observed in the GDMT subgroups (P = 0.680). CONCLUSIONS: The utilization of LuX-Valve in TTVR effectively improves TR and is associated with lower rates of major adverse events, HHF and all-cause mortality. The TRI-SCORE may help identify higher-benefit patients with TR from TTVR. Clinical trial registration ClinicalTrials.gov Protocol Registration System (NCT02917980).
Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Tricúspide , Humanos , Insuficiência da Valva Tricúspide/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Implante de Prótese de Valva Cardíaca/métodos , Valva Tricúspide/cirurgia , Pessoa de Meia-Idade , Resultado do Tratamento , Índice de Gravidade de Doença , Cateterismo Cardíaco/métodosRESUMO
BACKGROUND: Endoscopic resection has been reported for vascular anomalies (VA) previously. However, there is no study comparing endoscopic resection surgery (ERS) with open resection surgery (ORS) in children. We aimed to compare clinical and cosmetic outcomes between two approaches in pediatric VA. METHODS: Between June 2018 and June 2023, 138 pediatric VA patients undergoing ERS or ORS were retrospectively reviewed. Propensity score matching (PSM) was performed to minimize selection bias. The Scar Cosmesis Assessment and Rating (SCAR) Scale and numerical rating scale (NRS) based on patient satisfaction were used for cosmetic assessment. RESULTS: After PSM for age, depth of lesion, size of lesion, and site of surgery, 72 patients (ERS = 24, ORS = 48) were analyzed. Patients undergoing ERS had longer operative time (164.25 ± 18.46 vs. 112.85 ± 14.26 min; P < 0.001), less estimated blood loss (5.42 ± 2.15 vs. 18.04 ± 1.62 ml; P < 0.001), and shorter median hospital stay (4.50 [3.00-5.00] vs. 6.00 [5.00-6.00] days; P < 0.001). The follow-up time was 8.04 ± 1.23 month for ERS group and 8.56 ± 1.57 month for ORS group. For aesthetic results, the median overall SCAR score in ERS was lower than that in ORS (2 [1-3] vs. 5 [4-5]; P < 0.001), and the subscales of "scar spread," "dyspigmentation," "track marks or suture marks," and "overall impression" were better. The median NRS score was higher (8 [7-8] vs. 6 [5-6]; P < 0.001) and length of scars was shorter (2.18 ± 0.30 vs. 8.75 ± 1.98 cm; P < 0.001) in ERS group than those in ORS group. The incidences of total complications and recurrence showed no significant difference between two groups. CONCLUSIONS: Endoscopic surgery can be a safe and effective option for pediatric VA in the limbs and trunk. It offers the advantages of improving aesthetic outcomes and reducing postoperative wound healing time.
RESUMO
Photocatalytic overall splitting of pure water (H2O) without sacrificial reagent to hydrogen (H2) and oxygen (O2) holds a great potential for achieving carbon neutrality. Herein, by anchoring cobalt sulfide (Co9S8) as cocatalyst and cadmium sulfide (CdS) as light absorber to channel wall of a porous polymer microreactor (PP12), continuous violent H2 and O2 bubbling productions from photocatalytic overall splitting of pure H2O without sacrificial reagent is achieved, with H2 and O2 production rates as high as 4.41 and 2.20 mmol h-1 gcat.-1 respectively. These are significantly enhanced than those in the widely used stirred tank-type reactor in which no O2 is produced and H2 production rate is only 0.004 mmol h-1 gcat.-1. Besides improved charge separation and interaction of H2O with photocatalyst in PP12, bonding interaction of Co9S8 with PP12 creates abundant catalytic active sites for simultaneous productions of H2 and O2, thus leading to the significantly enhanced H2 and O2 bubbling productions in PP12. This offers a new strategy to enhance photocatalytic overall splitting of pure H2O without sacrificial reagent.
RESUMO
Estrogens and estrogenic chemicals are endocrine-disrupting chemicals (EDCs). The potential toxicity of EDCs to humans and aquatic organisms has become increasingly concerning. However, at present, the potential toxic mechanisms of EDCs on neural and vascular development are still being fully investigated. During the study, we utilized zebrafish to assess the developmental neural and vascular toxicity of different estrogens. The results indicated that zebrafish treated with different estrogens, especially E2, exhibit developmental malformations, including increased mortality, decreased body length, decreased heart rate, aberrant swimming behavior, and increased developmental malformations, including spinal curvature (SC), yolk edema (YE) and pericaidial edema (PE), in a dose-dependent manner with 72â¯h-treated. Further morphological evaluation revealed that E2 exposure significantly induced motor neural abnormalities in zebrafish embryos. In addition, treated with these three estrogens also impaired the vascular development in the early stage of zebrafish embryos. Mechanistically, the identification of downstream factors revealed that several key neural and vascular development-related genes, including syn2a, gfap, gap43, shha, kdr, flt1 and flt4, were transcriptionally downregulated after estrogen exposure in zebrafish, suggesting that estrogen exposure might cause neural and vascular toxicity by interfering the mRNA levels of genes relevant to neural and vascular development.
RESUMO
Background: Imatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system. Methods: We retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores. Results: The area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778-0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P < 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P<0.05). Conclusion: We constructed a nomogram that can be effectively used to predict the efficacy of imatinib in patients with newly diagnosed CML-CP based on a single center, 10-year retrospective cohort study.
RESUMO
Osmanthus fragrans is an evergreen shrub with a pleasant fragrance and a wide range of applications in many fields. The condensed hydrolat obtained during the drying process of its fresh flowers was collected in a low-temperature vacuum environment and its sensory evaluation and volatile components were studied. The main aroma compounds in Osmanthus fragrans were dihydro-ß-ionone, nonanal, ß-cyclocitral, ß-ionone, benzaldehyde, α-ionone, and 6-methyl-5-hepten-2-one, whose contents were used as the main evaluation criteria, and the hydrolats obtained under different scenting and drying times were compared. This process can effectively collect the aroma components in Osmanthus fragrans and the optimal drying conditions were 50 °C for 5 h. The hydrolat was used to provide the scent of osmanthus black tea, which had a fresher and mellower taste, while the fragrance of osmanthus was abundant. These results show that osmanthus hydrolat can be used to provide the scent of floral black tea. Chemical compounds studied in this article: (-)-Catechin (PubChem CID: 1203); (-)-epigallocatechin gallate (PubChem CID: 65064); (-)-epicatechin gallate (PubChem CID: 367141); (-)-epigallocatechin (PubChem CID: 72277); (-)-epicatechin (PubChem CID: 72276); (-)-gallocatechin gallate (PubChem CID: 199472); (-)-catechin gallate (PubChem CID: 6419835); (-)-gallocatechin (PubChem CID: 9882981).
RESUMO
Background: Hyperuricemia (HUA) is a glo\bal public health problem. The etiology of HUA is complex and efficient and accurate assessment metrics are still lacking when conducting large-scale epidemiologic screening. The aim of this study was to evaluate the association of the triglyceride glucose (TyG) index, TyG-body mass index (BMI), TyG-waist-to-height ratio (WHtR) with the risk of HUA. Methods: Based on data collected from the National Health and Nutrition Examination Survey (NHANES) in the United States and the China Health and Aging Longitudinal Study (CHARLS) in China, a total of 14,286 U.S. adults and 4,620 Chinese adults were included in the analysis. The study examined the levels of TyG, TyG-BMI, TyG-WHtR, and TyG-WC. Multivariate logistic regression was utilized to investigate the relationships between these variables and hyperuricemia (HUA), separately. Additionally, the study used restricted cubic splines (RCS) to explore the linear associations of TyG, TyG-BMI, TyG-WHtR, TyG-WC, and HUA, separately. Results: The NHANES results showed that TyG [Q2, 1.58(1.26, 1.98); Q3, 2.36 (1.94, 2.88); Q4, 3.21 (2.61, 3.94)], TyG-BMI [Q2, 2.14 (1.74, 2.65); Q3, 3.38 (2.74, 4.17); Q4, 6.70 (5.55, 8.02)], TyG-WHtR [Q2, 1.92 (1.56, 2.36); Q3, 3.14 (2.56, 3.85); Q4, 6.28 (5.12, 7.69)], TyG-WC [Q2, 2.32 (1.85, 2.90); Q3, 3.51 (2.84, 4.34); Q4, 7.32 (5.95, 9.02)] were identified as risk factors for hyperuricemia (HUA). Similarly, the CHARLS results, when fully adjusted for covariates, indicated that TyG [Q4, 2.36 (1.08, 5.15)], TyG-BMI [Q3, 2.60 (1.05, 6.41); Q4, 3.70 (1.64, 8.32)], TyG-WHtR (Q4, 2.84 (1.23, 6.55), TyG-WC [Q4, 2.85 (1.23, 6.5)] were also risk factors for HUA. The predictive ability of each indicator for the risk of developing HUA was stronger in women than in men. Furthermore, there was an observed nonlinear relationship between TyG, TyG-BMI, TyG-WHtR, TyG-WC, and HUA in both the NHANES and CHARLS datasets (P-nonlinearity < 0.05). Conclusion: These findings suggest that TyG, TyG-BMI, TyG-WHtR and TyG-WC are associated with an increased risk of HUA. They are potential indicators for screening HUA status in the general population in China and the United States.
Assuntos
Glicemia , Índice de Massa Corporal , Hiperuricemia , Inquéritos Nutricionais , Triglicerídeos , Humanos , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Hiperuricemia/diagnóstico , China/epidemiologia , Masculino , Feminino , Triglicerídeos/sangue , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Adulto , Glicemia/análise , Idoso , Estudos Longitudinais , Fatores de RiscoRESUMO
Diabetes mellitus, stemming from either insulin resistance or inadequate insulin secretion, represents a complex ailment that results in prolonged hyperglycemia and severe complications. Patients endure severe ramifications such as kidney disease, vision impairment, cardiovascular disorders, and susceptibility to infections, leading to significant physical suffering and imposing substantial socio-economic burdens. This condition has evolved into an increasingly severe health crisis. There is an urgent need to develop new treatments with improved efficacy and fewer adverse effects to meet clinical demands. However, novel drug development is costly, time-consuming, and often associated with side effects and suboptimal efficacy, making it a major challenge. Artificial Intelligence (AI) and Machine Learning (ML) have revolutionized drug development across its comprehensive lifecycle, spanning drug discovery, preclinical studies, clinical trials, and post-market surveillance. These technologies have significantly accelerated the identification of promising therapeutic candidates, optimized trial designs, and enhanced post-approval safety monitoring. Recent advances in AI, including data augmentation, interpretable AI, and integration of AI with traditional experimental methods, offer promising strategies for overcoming the challenges inherent in AI-based drug discovery. Despite these advancements, there exists a notable gap in comprehensive reviews detailing AI and ML applications throughout the entirety of developing medications for diabetes mellitus. This review aims to fill this gap by evaluating the impact and potential of AI and ML technologies at various stages of diabetes mellitus drug development. It does that by synthesizing current research findings and technological advances so as to effectively control diabetes mellitus and mitigate its far-reaching social and economic impacts. The integration of AI and ML promises to revolutionize diabetes mellitus treatment strategies, offering hope for improved patient outcomes and reduced healthcare burdens worldwide.
RESUMO
Extending covalent organic frameworks (COFs) into crystalline carbon-free covalent backbones is an important strategy to endow these materials with more exotic functions. Integrating metal-free inorganic and organic components into one covalent framework is an effective way to address the issue of poor thermal/solvent stability in the field of nonlinear optics (NLO). However, constructing such structures is very challenging. Here, we linked 3-connected nods (BO3) and 2-connected organic building blocks (Te(Ph)2) together to produce colorless single crystals (size up to 400 µm) of a three-dimensional (3D) chiral covalent framework (CityU-22). The single-crystal X-ray diffraction (SCXRD) analysis reveals that CityU-22 has a non-carbon Te-O-B-O bond-based network with the srs topology. The chiral CityU-22 displays good stability under the treatment of different common solvents or heat (the decomposition temperature above 300 °C). Due to its non-π-conjugated backbone (-Te-O-B-O-), CityU-22 shows an ultraviolet NLO behavior with a second-harmonic generation (SHG) response similar to KH2PO4 (KDP).
RESUMO
Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)-bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains.
Assuntos
Antivirais , Soroalbumina Bovina , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Animais , Humanos , Influenza Humana/tratamento farmacológico , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Estrutura Molecular , Cães , Bovinos , Testes de Sensibilidade Microbiana , Neuraminidase/antagonistas & inibidores , Neuraminidase/metabolismo , Internalização do Vírus/efeitos dos fármacos , Células Madin Darby de Rim Canino/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , GlicosídeosRESUMO
Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma, and is closely associated with hepatitis B virus (HBV) infection status and hepatitis B X (HBx) gene integration. This project investigated the cellular biological effects and molecular mechanisms responsible for lymphomagenesis and the progression of HBx integration in DLBCL. The data showed that clinical DLBCL cells demonstrated HBx integration, and the sequencing analysis of integrated sites validated HBx integration in the constructed HBx-transfected cells. Compared with control cells, HBx-transfected cells had a significantly reduced proportion of mitochondrial membrane potential, signals of chromosomal DNA breaks, and proportion of apoptotic cells. Further studies found that this decreased apoptosis level was associated with a significant reduction of cleaved Caspase-3 and downstream poly ADP-ribose polymerase (PARP) proteins, revealing the molecular mechanisms of HBx-associated apoptosis in DLBCL. Animal experiments also demonstrated that the protein expression of cleaved Caspase-3 and PARP was prominently reduced in HBx-transfected cells from subcutaneous tumors in mice. Furthermore, the HBx-integrated cells in clinical tissues had significantly lower cleaved PARP levels than the HBx-negative samples. Therefore, HBx integration inhibits cell apoptosis through the Caspase-3-PARP pathway in DLBCL indicating a potential biomarker and therapeutic target in HBV related DLBCL.
RESUMO
The large molecular weight and high viscosity of natural konjac glucomannan (KGM) limit its industrial application. Microbial degradation of low-molecular-weight KGM has health benefits and various biological functions; however, the available KGM strains used in the industry have microbial contamination and low degradation efficiencies. Therefore, exploring novelly adaptable strains is critical for industrial processes. Here, the Bacillus licheniformis Z7-1 strain isolated from decaying konjac showed high efficiency for KGM degradation. The monosaccharide composition of the degradation products had a reduced molar ratio of mannose to glucose, indicating that Z7-1 preferentially degraded glucose in KGM. The degraded component was further characterized by ESI-MS, Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and it also exhibited good antibacterial activity against various food-spoilage bacteria. Genome sequencing and zymolytic analysis revealed that abundant carbohydrate-active enzymes exist in the Z7-1 genome, with at least five types of extracellular enzymes responsible for KGM degradation, manifesting multi-enzyme synergetic action. The extracellular enzymes had significant thermal stability, indicating their potential application in industry. This study provides an alternative method for obtaining low-molecular-weight KGM with antibacterial functions and supports foundational knowledge for its development as a biocatalyst for the direct conversion of biomass polysaccharides into functional components.