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2.
iScience ; 27(7): 110219, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39021795

ABSTRACT

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

3.
Arch Gynecol Obstet ; 310(2): 713-718, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38871965

ABSTRACT

BACKGROUND: Acute abdominal conditions during pregnancy are significant risks to maternal and fetal health, necessitating timely diagnosis and intervention. The choice of surgical approach is a major concern for obstetricians. OBJECTIVE: To evaluate the safety and efficacy of the TU-LESS procedure for acute abdomen in late pregnancy. METHODS: We retrospectively analyzed 12 patients who underwent TU-LESS for acute abdominal conditions in the third trimester from 2020 to 2023. We reviewed medical records for clinical characteristics, surgical interventions, postoperative complications, and pregnancy outcomes. RESULTS: The study included patients with a median age of 27 (range 20-35) and a BMI of 24.33 kg/m2 (range 21.34-31.96). The median gestational age at surgery was 30 weeks (range, 28 + 3-32 + 4 weeks), with surgeries lasting an average of 60 min (range, 30-163 min). Blood loss was 2-20 mL, and the median hospital stay post-surgery was 6 days (range, 2-16 days). There were no significant complications. The median time to delivery after TU-LESS was 56 days (range, 26-66 days), resulting in 8 full-term deliveries, 2 preterm cesareans, and 2 preterm vaginal deliveries. All newborns were healthy, with no fetal losses or neonatal deaths. CONCLUSION: TU-LESS, performed by experienced obstetricians and gynecologists with proper preoperative preparation, is safe and effective for managing acute abdomen in late pregnancy, without the need to delay surgery due to gestational age.


Subject(s)
Abdomen, Acute , Pregnancy Complications , Pregnancy Trimester, Third , Humans , Female , Pregnancy , Retrospective Studies , Abdomen, Acute/surgery , Abdomen, Acute/etiology , Adult , Pregnancy Complications/surgery , Young Adult , Pregnancy Outcome , Gestational Age , Postoperative Complications/epidemiology , Length of Stay/statistics & numerical data
4.
J Stomatol Oral Maxillofac Surg ; : 101937, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38844022

ABSTRACT

BACKGROUND: Accumulating evidence has suggested that RNA binding protein (RBP) dysregulation plays an essential role during tumorigenesis. Here, we sought to explore the potential biological functions and clinical significance of RBP and develop diagnostic and prognostic signatures based on RBP in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: The differently expressed RBPs between HNSCC samples and their normal counterparts were identified using the Limma package. The immunohistochemistry (IHC) images of several RBPs were collected from the Human Protein Atlas database. The diagnostic signature based on RBP was built by LASSO-logistic regression and random forest. The prognostic signature based on RBP was constructed by LASSO and stepwise Cox regression analysis in the training cohort and validated in the validation cohort. RESULTS: Eighty-four aberrantly expressed RBPs were obtained, comprising 41 up-regulated and 43 down-regulated RBPs. Seven RBP genes (CPEB3, PDCD4, ENDOU, PARP12, DNMT3B, IGF2BP1, EXO1) were identified as diagnostic-related hub genes. They were used to establish a diagnostic RBP signature risk score (DRBPS) model by the coefficients in least absolute shrinkage and selection operator (LASSO)-logistic regression analysis and showed high specificity and sensitivity in the training (area under the receiver operating characteristic curve (AUC) = 0.998), and in all validation cohorts (AUC > 0.95 for all). Similarly, seven RBP genes (MKRN3, ZC3H12D, EIF5A2, AFF3, SIDT1, RBM24, and NR0B1) were identified as prognosis-associated hub genes by LASSO and stepwise multiple Cox regression analyses and were used to construct the prognostic model named as PRBPS. The AUC of the time-dependent receiver operator characteristic curve of the prognostic model was 0.664 at 3 years and 0.635 at 5 years in the training cohort and 0.720, 0.777 in the validation cohort, showing a favorable predictive efficacy for prognosis in HNSCC. CONCLUSIONS: Our results demonstrate the value of consideration of RBP in the diagnosis and prognosis for HNSCC and provide a novel insight into understanding the potential role of dysregulated RBP in HNSCC.

5.
Hum Genomics ; 18(1): 55, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822443

ABSTRACT

BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/immunology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Male , Female , Immune Checkpoint Inhibitors/therapeutic use , Middle Aged , Biomarkers, Tumor/genetics , Aged , Prognosis , DNA Copy Number Variations/genetics , Mutation/genetics , Microsatellite Instability
6.
Medicine (Baltimore) ; 103(23): e38317, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847662

ABSTRACT

Accumulating evidence has indicated an increased risk of acute pancreatitis in individuals with inflammatory bowel disease (IBD); however, the establishment of a clear and direct causal connection between IBD and acute pancreatitis remains uncertain. Utilizing genetic data from publicly accessible genome-wide association studies (GWAS), we conducted a 2-sample MR analysis to identify the associations between IBD, ulcerative colitis (UC), Crohn disease (CD), and acute pancreatitis risk. Rigorous quality control steps ensured the selection of eligible single nucleotide polymorphisms (SNPs) with strong associations to IBD. The primary estimation used the inverse-variance weighted method. We also assessed heterogeneity, potential pleiotropy, and conducted sensitivity analyses. The direction of causality was confirmed using the Steiger test. The MR analysis showed that IBD increased the risk of acute pancreatitis (IVW: OR = 1.032, 95% CI: 1.006-1.06, P = .015). Among the subgroup of IBD, CD (IVW: OR = 1.034, 95% CI: 1.008-1.06, P = .007) indicates a significant increase in the risk of acute pancreatitis compared to UC (IVW: OR = 1.02, 95% CI: 0.99-1.051, P = .189). The MR analysis assessing the association between CD and acute pancreatitis showed no evidence of heterogeneity or horizontal pleiotropy. Likewise, the leave-one-out (LOO) method indicated no significant influence of any individual SNP on the overall findings. In addition, the Steiger direction test revealed that CD was the cause for increased risk of acute pancreatitis, but not vice versa. In summary, this research pioneers in proposing a causal relationship between CD and acute pancreatitis among the European population.


Subject(s)
Colitis, Ulcerative , Crohn Disease , Genome-Wide Association Study , Mendelian Randomization Analysis , Pancreatitis , Polymorphism, Single Nucleotide , Humans , Colitis, Ulcerative/genetics , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/complications , Crohn Disease/genetics , Crohn Disease/epidemiology , Pancreatitis/genetics , Pancreatitis/epidemiology , Pancreatitis/etiology , Genetic Predisposition to Disease , Risk Factors , Acute Disease
7.
J Environ Manage ; 362: 121299, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38830283

ABSTRACT

Hydrological forecasting is of great importance for water resources management and planning, especially given the increasing occurrence of extreme events such as floods and droughts. The physics-informed machine learning (PIML) models effectively integrate conceptual hydrologic models with machine learning (ML) models. In this process, the intermediate variables of PIML models serve as bridges between inputs and outputs, while the impact of intermediate variables on the performance of PIML models remains unclear. To fill this knowledge gap, this study aims to encompass the construction of PIML models based on various hydrologic models, conduct comparative analyses of different intermediate variables based on a case study of 205 CAMELS basins, and further explore the relationship between the performance of PIML models and catchment characteristics. The optimal ML model for constructing PIML is first selected among four ML models within the 205 basins. The PIML models are then developed based on five monthly water balance models, namely TM, XM, MEP, SLM, and TVGM. To quantify the potential impact of difference in intermediate variables, two sets of experiments are further designed and performed, namely S1 with actual evapotranspiration as the intermediate variable and S2 with soil moisture as the intermediate variable. Results show that five PIML models generally outperformed the optimal standalone ML models, i.e., the Lasso model. Specifically, regardless of the choice of intermediate variables, the PIML-XM model consistently outperformed the other models within the same basins. Almost all constructed PIML models are affected by the intermediate variables in monthly runoff simulations. Typically, S1 exhibited better performance compared to S2. A greater impact of aridity index, forest fraction, and catchment area on model performance is observed in S2. These findings improve our understanding of constructing PIML models in hydrology by emphasizing their excellent performance in runoff simulations and highlighting the importance of intermediate variables.


Subject(s)
Hydrology , Machine Learning , Models, Theoretical
8.
Bioinformatics ; 40(Supplement_1): i511-i520, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940121

ABSTRACT

MOTIVATION: Identifying cancer genes remains a significant challenge in cancer genomics research. Annotated gene sets encode functional associations among multiple genes, and cancer genes have been shown to cluster in hallmark signaling pathways and biological processes. The knowledge of annotated gene sets is critical for discovering cancer genes but remains to be fully exploited. RESULTS: Here, we present the DIsease-Specific Hypergraph neural network (DISHyper), a hypergraph-based computational method that integrates the knowledge from multiple types of annotated gene sets to predict cancer genes. First, our benchmark results demonstrate that DISHyper outperforms the existing state-of-the-art methods and highlight the advantages of employing hypergraphs for representing annotated gene sets. Second, we validate the accuracy of DISHyper-predicted cancer genes using functional validation results and multiple independent functional genomics data. Third, our model predicts 44 novel cancer genes, and subsequent analysis shows their significant associations with multiple types of cancers. Overall, our study provides a new perspective for discovering cancer genes and reveals previously undiscovered cancer genes. AVAILABILITY AND IMPLEMENTATION: DISHyper is freely available for download at https://github.com/genemine/DISHyper.


Subject(s)
Neoplasms , Neural Networks, Computer , Humans , Neoplasms/genetics , Computational Biology/methods , Genomics/methods , Genes, Neoplasm , Molecular Sequence Annotation/methods , Databases, Genetic
9.
Int J Biol Macromol ; 273(Pt 2): 132945, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38851614

ABSTRACT

The extensive utilization of non-biodegradable plastic agricultural mulch in the past few decades has resulted in severe environmental pollution and a decline in soil fertility. The present study involves the fabrication of environmentally friendly paper-based mulch with dual functionality, incorporating agrochemicals and heavy metal ligands, through a sustainable papermaking/coating technique. The functional paper-based mulch consists of a cellulose fiber web incorporated with Emamectin Benzoate (EB)@ Aminated sodium lignosulfonate (ASL). The spherical microcapsules loaded with the pesticide EB exhibited an optimal core-shell structure for enhanced protection and controlled release of the photosensitizer EB (Sustained release >75 % in 50 h). Meanwhile, the ASL, enriched with metal chelating groups (-COOH, -OH, and -NH2, etc.), served as a stabilizing agent for heavy metal ions, enhancing soil remediation efficiency. The performance of paper-based mulch was enhanced by the application of a hydrophobic layer composed of natural chitosan/carnauba wax, resulting in exceptional characteristics such as superior tensile strength, hydrophobicity, heat insulation, moisture retention, as well as compostability and biodegradability (biodegradation >80 % after 70 days). This study developed a revolutionary lignocellulosic eco-friendly mulch that enables controlled agrochemical release and soil heavy metal remediation, leading to a superior substitute to conventional and non-biodegradable plastic mulch used in agriculture.


Subject(s)
Lignin , Metals, Heavy , Pesticides , Metals, Heavy/chemistry , Lignin/chemistry , Lignin/analogs & derivatives , Pesticides/chemistry , Delayed-Action Preparations , Plastics/chemistry , Soil Pollutants/chemistry , Agriculture/methods , Chitosan/chemistry , Photosensitizing Agents/chemistry , Biodegradation, Environmental , Soil/chemistry
10.
Biomacromolecules ; 25(7): 4569-4580, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38869359

ABSTRACT

Acute myeloid leukemia (AML) is often associated with poor prognosis and survival. Small molecule inhibitors, though widening the treatment landscape, have limited monotherapy efficacy. The combination therapy, however, shows suboptimal clinical outcomes due to low bioavailability, overlapping systemic toxicity and drug resistance. Here, we report that CXCR4-mediated codelivery of the BCL-2 inhibitor venetoclax (VEN) and the FLT3 inhibitor sorafenib (SOR) via T22 peptide-tagged disulfide cross-linked polymeric micelles (TM) achieves synergistic treatment of FLT3-ITD AML. TM-VS with a VEN/SOR weight ratio of 1/4 and T22 peptide density of 20% exhibited an extraordinary inhibitory effect on CXCR4-overexpressing MV4-11 AML cells. TM-VS at a VEN/SOR dosage of 2.5/10 mg/kg remarkably reduced leukemia burden, prolonged mouse survival, and impeded bone loss in orthotopic MV4-11-bearing mice, outperforming the nontargeted M-VS and oral administration of free VEN/SOR. CXCR4-mediated codelivery of BCL-2 and FLT3 inhibitors has emerged as a prospective clinical treatment for FLT3-ITD AML.


Subject(s)
Leukemia, Myeloid, Acute , Proto-Oncogene Proteins c-bcl-2 , Receptors, CXCR4 , Sorafenib , Sulfonamides , fms-Like Tyrosine Kinase 3 , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , fms-Like Tyrosine Kinase 3/genetics , fms-Like Tyrosine Kinase 3/metabolism , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/genetics , Animals , Receptors, CXCR4/antagonists & inhibitors , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolism , Humans , Mice , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Sulfonamides/pharmacology , Sulfonamides/administration & dosage , Sorafenib/pharmacology , Sorafenib/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cell Line, Tumor , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Micelles
11.
Endocrine ; 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38850440

ABSTRACT

AIM: Tirzepatide, a newly developed dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has received approval for treating type 2 diabetes (T2D) and is currently being studied for its potential in long-term weight control. We aim to explore the safety and efficacy of once-weekly subcutaneous tirzepatide for weight loss in T2D or obese patients. METHODS: A comprehensive search was performed on various databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception up to April 29, 2024, to identify randomized controlled trials (RCTs) that assessed the efficacy of once-weekly tirzepatide compared to a placebo in adults with or without T2D. The mean difference (MD) and risk ratio (RR) were calculated for continuous and dichotomous outcomes, respectively. The risk of bias was evaluated using the RoB-2 tool (Cochrane), while the statistical analysis was conducted utilizing RevMan 5.4.1 software. RESULTS: Seven RCTs comprising 4795 individuals ranging from 12 to 72 weeks were identified. Compared to the placebo group, tirzepatide at doses of 5, 10, and 15 mg demonstrated significant dose-dependent weight loss. The mean difference (MD) in the percentage change in body weight (BW) was -8.07% (95% CI -11.01, -5.13; p < 0.00001), -10.79% (95% CI -13.86, -7.71; p < 0.00001), and -11.83% (95% CI -14.52, -9.14; p < 0.00001), respectively. Additionally, the MD in the absolute change in BW was -7.5 kg (95% CI -10.9, -4.1; p < 0.0001), -11.0 kg (95% CI -16.9, -5.2; p = 0.0002), and -11.5 kg (95% CI -16.2, -6.7; p < 0.00001), for the 5, 10, and 15 mg doses, respectively. All three doses of tirzepatide also significantly reduced body mass index and waist circumference. Furthermore, it led to a greater percentage of patients experiencing weight loss exceeding 5, 10, 15, 20, and 25%. Moreover, tirzepatide showed great success in reducing blood pressure, blood sugar levels, and lipid profiles. In terms of safety, gastrointestinal side effects were the most frequently reported adverse events in all three doses of tirzepatide groups, which were generally mild-to-moderate and transient. CONCLUSION: Tirzepatide treatment could lead to remarkable and sustained weight loss that is well-tolerated and safe, representing a novel and valuable therapeutic strategy for long-term weight management.

12.
Org Lett ; 26(24): 5074-5081, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38857312

ABSTRACT

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp2)-C(sp2) bond and a C(sp3)-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable σ-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the σ-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

13.
J Biomed Inform ; 156: 104662, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880236

ABSTRACT

BACKGROUND: Malnutrition is a prevalent issue in aged care facilities (RACFs), leading to adverse health outcomes. The ability to efficiently extract key clinical information from a large volume of data in electronic health records (EHR) can improve understanding about the extent of the problem and developing effective interventions. This research aimed to test the efficacy of zero-shot prompt engineering applied to generative artificial intelligence (AI) models on their own and in combination with retrieval augmented generation (RAG), for the automating tasks of summarizing both structured and unstructured data in EHR and extracting important malnutrition information. METHODOLOGY: We utilized Llama 2 13B model with zero-shot prompting. The dataset comprises unstructured and structured EHRs related to malnutrition management in 40 Australian RACFs. We employed zero-shot learning to the model alone first, then combined it with RAG to accomplish two tasks: generate structured summaries about the nutritional status of a client and extract key information about malnutrition risk factors. We utilized 25 notes in the first task and 1,399 in the second task. We evaluated the model's output of each task manually against a gold standard dataset. RESULT: The evaluation outcomes indicated that zero-shot learning applied to generative AI model is highly effective in summarizing and extracting information about nutritional status of RACFs' clients. The generated summaries provided concise and accurate representation of the original data with an overall accuracy of 93.25%. The addition of RAG improved the summarization process, leading to a 6% increase and achieving an accuracy of 99.25%. The model also proved its capability in extracting risk factors with an accuracy of 90%. However, adding RAG did not further improve accuracy in this task. Overall, the model has shown a robust performance when information was explicitly stated in the notes; however, it could encounter hallucination limitations, particularly when details were not explicitly provided. CONCLUSION: This study demonstrates the high performance and limitations of applying zero-shot learning to generative AI models to automatic generation of structured summarization of EHRs data and extracting key clinical information. The inclusion of the RAG approach improved the model performance and mitigated the hallucination problem.

14.
J Colloid Interface Sci ; 671: 354-373, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38815372

ABSTRACT

Berberine (Ber), an isoquinoline alkaloid, is a potential drug therapy for ulcerative colitis (UC) because of its anti-inflammatory activity, high biological safety, and few side effects. Nevertheless, its clinical application is hindered by its limited water solubility and low bioavailability. Currently, compared to synthetic nanocarriers, exosomes as carriers possess advantages such as low toxicity, high stability, and high specificity. Human placental mesenchymal stem cell-derived exosomes (HplMSC-Exos) have emerged as a promising drug delivery system, offering intrinsic anti-inflammatory and antioxidant activities. Therefore, we engineered MSC-Exos loaded with Ber (Exos-Ber) to enhance the solubility and bioavailability of Ber and for colon targeting, revealing a novel approach for treating UC with natural compounds. Structurally and functionally, Exos-Ber closely resembled unmodified Exos. Both in vitro and in vivo investigations confirmed the antioxidant and anti-inflammatory properties of Exos-Ber. Notably, Exos-Ber exhibited reparative effects on injured epithelial cells and reduced cellular apoptosis. Furthermore, Exos-Ber concurrently demonstrated anti-inflammatory and antioxidant activities, contributing to the mitigation of UC, possibly through its modulation of the MAPK signaling pathway. Overall, our findings demonstrate the potential of Exos-Ber as a promising therapeutic option for alleviating UC, highlighting its capacity to enhance the clinical applicability of Ber.


Subject(s)
Berberine , Colitis, Ulcerative , Exosomes , Mesenchymal Stem Cells , Exosomes/metabolism , Exosomes/chemistry , Colitis, Ulcerative/therapy , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Berberine/pharmacology , Berberine/chemistry , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Humans , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Apoptosis/drug effects , Antioxidants/pharmacology , Antioxidants/chemistry , Cells, Cultured , Female , Particle Size , Cell Survival/drug effects
15.
Nat Med ; 30(6): 1680-1688, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38740994

ABSTRACT

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .


Subject(s)
Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Psychological Distress , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Female , Male , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Middle Aged , Aged , Prospective Studies , Depression/drug therapy , Anxiety/drug therapy , Treatment Outcome , Progression-Free Survival , Adult , Aged, 80 and over
16.
J Biomater Appl ; 39(2): 117-128, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38775351

ABSTRACT

The aim of this study is to explore the therapeutic effects of Mg-Sr-Ca containing bioactive glass nanoparticles sodium alginate hydrogel modified mineralized collagen scaffold (Mg-Sr-Ca-BGNs-SA-MC) on the repair of osteoporotic bone defect. During the study, Mg-Sr-Ca containing bioactive glass nanoparticles (Mg-Sr-Ca-BGNs) were synthesized using the sol-gel method, and the Mg-Sr-Ca-BGNs-SA-MC scaffold was synthesized by a simple method. The Mg-Sr-Ca-BGNs and the Mg-Sr-Ca-BGNs-SA-MC scaffold were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The elements of Mg, Sr, Ca and Si were effectively integrated into Mg-Sr-Ca-BGNs. SEM analysis revealed the presence of Mg-Sr-Ca-BGNs on the scaffold's surface. Furthermore, the cytotoxicity of the scaffolds were assessed using a live/dead assay. The result of the live/dead assay demonstrated that the scaffold materials were non-toxic to cell growth. More importantly, the in vivo study indicated that implanted scaffold promoted tissue regeneration and integration with newly formed bone. Overall, the Mg-Sr-Ca-BGNs-SA-MC scaffold is suitable for guided bone regeneration and beneficial to repair of osteoporotic bone defects.


Subject(s)
Bone Regeneration , Collagen , Glass , Hydrogels , Nanoparticles , Strontium , Tissue Scaffolds , Tissue Scaffolds/chemistry , Animals , Collagen/chemistry , Bone Regeneration/drug effects , Nanoparticles/chemistry , Strontium/chemistry , Strontium/pharmacology , Hydrogels/chemistry , Glass/chemistry , Magnesium/chemistry , Calcium/chemistry , Biocompatible Materials/chemistry , Alginates/chemistry , Tissue Engineering , Rabbits
17.
Ultrason Sonochem ; 107: 106920, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38805885

ABSTRACT

Cavitation erosion is a general phenomenon in the fields of aviation, navigation, hydraulic machinery, and so on, causing great damage to fluid machinery. With the vast requirements in deep ocean applications, it is urgent to study the mechanism of cavitation erosion and the cavitation erosion resistance of different materials under high hydrostatic pressure to predict and avoid the effect of cavitation erosion. In this work, the spatially confined cavitation bubble cloud associated with Gaussian-like intensity distribution sonoluminescence (SL) was produced by a spherically focused ultrasound transducer with two opening ends near metallic plates under different hydrostatic pressures (0.1, 3, 6, and 10 MPa). The cavitation erosion effects on copper, 17-4PH stainless steel and tungsten plates were studied. Through coupling analysis towards the SL intensity distribution, the macro/micro morphology of cavitation erosion, and the physical parameters of different metallic materials (hardness, yield strength, and melting point), it is found that with increasing hydrostatic pressure, the erosion effect is intensified, the depth of cavitation pits increases, the phenomenon of melting can be observed on materials with relatively low melting points, and the cavitation erosion experienced an evolution process from high-temperature creep to fracture. This work has also established a method for the evaluation of materials' cavitation erosion resistance with measurable SL intensity distribution, which is promising to promote the designing and selection of anti-cavitation materials in deep-sea applications.

18.
BMJ Open ; 14(5): e078933, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38719326

ABSTRACT

OBJECTIVES: To determine the association of non-alcoholic fatty liver disease (NAFLD) with the incidence of sarcopenia. DESIGN: Systematic review and meta-analysis of observational clinical studies. SETTING AND PARTICIPANTS: Adults with NAFLD. METHODS: Databases such as PubMed, Embase, Cochrane and Web of Science were searched for eligible studies published from the inception of each database up to 4 April 2023. All cross-sectional studies on the association between NAFLD and sarcopenia were included in this study. The quality of the included studies and risk of bias was assessed using the Agency for Healthcare Research and Quality checklist. STATA V.15.1 software was used for statistical analysis. RESULTS: Of the 1524 retrieved articles, 24 were included in this review, involving 88 609 participants. Our findings showed that the prevalence of sarcopenia was higher in the NAFLD group than in the control group (pooled OR 1.74, 95% CI 1.39 to 2.17). In a subgroup analysis by region, patients with NAFLD showed an increased risk of sarcopenia (pooled OR 1.97, 95% CI 1.54 to 2.51) in the Asian group, whereas patients with NAFLD had no statistically significant association with the risk of sarcopenia in the American and European groups, with a pooled OR of 1.31 (95% CI 0.71 to 2.40) for the American group and a pooled OR of 0.99 (95% CI 0.21 to 4.69) for the European group. Similar results were observed in the sensitivity analysis, and no evidence of publication bias was observed. CONCLUSIONS AND IMPLICATIONS: The current study indicated a significant positive correlation between NAFLD and sarcopenia, which may be affected by regional factors. This study provides the correlation basis for the relationship between NAFLD and sarcopenia and helps to find the quality strategy of sarcopenia targeting NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Sarcopenia , Sarcopenia/epidemiology , Sarcopenia/complications , Humans , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Risk Factors , Prevalence , Incidence
19.
ACS Appl Mater Interfaces ; 16(19): 24601-24611, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38710043

ABSTRACT

The Zn dendrite growth and side reactions are two major issues for the practical use of Zn metal anodes (ZMAs). Herein, an N-doped carbon-based hybrid fiber with the 3D porous skeleton and the zincophilic Cu nanoparticles (denoted as Cu@HLCF) is developed for stable ZMAs. The zincophilic Cu particles in the skeleton work as the active sites to facilitate uniform Zn nucleation. Meanwhile, the abundant pores in the framework of the hybrid fibers provide a large space to relieve the structural stress and suppress the dendrite growth. Moreover, the good mechanical characteristics of the hybrid fiber ensure its high potential applications for flexible electronics. Theoretical analysis results disclose the strong interaction between Zn and Cu sites, and experimental results demonstrate the low voltage hysteresis, high reversibility, and dendrite-free behavior of the Cu@HLCF host for Zn plating/stripping. Moreover, the solid-state Zn-ion battery (ZIB) assembled with a Cu@HLCF/Zn anode shows the prominent flexibility, impressively reliability, and outstanding cycling capability. Therefore, this work not only provides a novel design for the efficient and stable Zn metal anode but also promotes the development of flexible power sources for flexible electronics.

20.
Sci Rep ; 14(1): 10729, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730055

ABSTRACT

Due to the BCS theory, hydrogen, the lightest element, would be the prospect of room-temperature superconductor after metallization, but because of the difficulty of the hydrogen metallization, the theory about hydrogen pre-compression was proposed that the hydrogen-rich compounds could be a great option for the high Tc superconductors. The superior properties of TmH6, YbH6 and LuH6 indicated the magnificent potential of heavy rare earth elements for low-pressure stability. Here, we designed XTmH12 (X = Y, Yb, Lu, and La) to obtain higher Tc while maintaining low pressure stability. Most prominently, YbTmH12 can stabilize at a pressure of 60 GPa. Compared with binary TmH6 hydride, its Tc was increased to 48 K. The results provide an effective method for the rational design of moderate pressure stabilized hydride superconductors.

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