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1.
Cancer Med ; 13(19): e70202, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39377592

RESUMEN

INTRODUCTION: An increasing body of evidence suggests a close association between COVID-19 infection and the safety of PD-1/PD-L1 inhibitor therapy in cancer patients. However, the available data concerning these impacts remain limited and occasionally contradictory. MATERIAL AND METHODS: We conducted a retrospective analysis of cancer patients who received PD-1/PD-L1 inhibitor therapy at the same institution from November 2022 to May 2023. After excluding patients with missing information, a total of 224 cases were included. In our study, immune-related adverse events (irAEs) that occurred during the hospitalization of patients were included in the analysis. Further analysis of inter-subgroup differences was conducted following a 1:2 propensity score matching. Statistical analyses were performed using the Fisher's exact, chi-squared, and Mann-Whitney U-tests. RESULT: The results showed that no statistically significant differences between the two subgroups in the incidence of irAEs, changes in immune function before and after using PD-1/PD-L1 inhibitors, and alterations in hepatic and renal function (p > 0.05). CONCLUSION: Our findings suggest that infection with COVID-19 does not significantly impact the safety of PD-1/PD-L1 inhibitors in cancer patients. Most cancer patients used PD-1/PD-L1 inhibitors during COVID-19 infection (asymptomatic or mild infection) did not experience exacerbation of their underlying condition, nor did they exhibit a substantial increase in toxic side effects.


Asunto(s)
COVID-19 , Inhibidores de Puntos de Control Inmunológico , Neoplasias , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Neoplasias/terapia , Masculino , Femenino , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Antígeno B7-H1/antagonistas & inhibidores , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Anciano de 80 o más Años
2.
J Int Med Res ; 52(10): 3000605241281907, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39387199

RESUMEN

OBJECTIVE: We examined the factors influencing hospitalization and prognosis among patients with non-small cell lung cancer receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted therapy during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In total, 267 patients diagnosed with NSCLC who were receiving treatment with third-generation EGFR-TKIs were included in our retrospective study. Data on patients' demographics, clinical characteristics, and survival were collected and analyzed. RESULTS: Over a mean follow-up of 18 months, 80.5% (215/267) of the patients contracted COVID-19, and 12.6% (27/215) of these patients were hospitalized for COVID-19 treatment. Vaccinated patients, those with body mass index (BMI) ≥22.3 kg/m2, and those with no comorbidities had lower rates of infection and hospitalization than unvaccinated patients, those with BMI <22.3 kg/m2, and those with comorbidities, respectively. Continued NSCLC treatment in patients with COVID-19 was identified as a risk factor for patient survival. CONCLUSIONS: NSCLC treatment can be continued for patients who received COVID-19 vaccines, those with higher BMI, and those without comorbidities during the COVID-19 epidemic, but treatment interruption might be required for patients during the active phase of infection.


Asunto(s)
COVID-19 , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , SARS-CoV-2 , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/virología , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , China/epidemiología , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , Factores de Riesgo , Hospitalización/estadística & datos numéricos , Índice de Masa Corporal , Pronóstico , Adulto , Anciano de 80 o más Años
3.
J Orthop Surg Res ; 19(1): 626, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39367405

RESUMEN

OBJECTIVE: The aim of this study was to investigate the effect of patellar denervation (PD) on pain, function and ability to kneel after unicompartmental knee arthroplasty (UKA). METHODS: Patients with medial knee osteoarthritis who underwent UKA were prospectively selected. Patients were randomly divided into PD and non-PD groups based on whether patellar denervation was performed. Clinical assessment was performed using the Hospital for Special Surgery (HSS) knee score, Kujiala score, visual analogue scale (VAS) and forgotten joint score (FJS-12), as well as postoperative complications were recorded. The patients' postoperative self-perception and actual ability to perform different kneeling positions were assessed in the two groups. RESULTS: UKA patients treated with PD achieved better Kujiala scores and FJS-12 scores, reduced anterior knee pain and improved kneeling ability postoperatively, validating the effectiveness of PD in UKA. Perception and actual performance of kneeling remained mismatched in PD patients, but performance during different kneeling activities was generally better than in non-PD patients. TRIAL REGISTRATION: Clinical Trial Registration: ChiCTR1900025669. CONCLUSION: Patellar denervation can safely and effectively improve patellofemoral joint function, pain and kneeling ability in the early postoperative period after UKA.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Desnervación , Osteoartritis de la Rodilla , Rótula , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Femenino , Masculino , Desnervación/métodos , Persona de Mediana Edad , Anciano , Osteoartritis de la Rodilla/cirugía , Rótula/inervación , Rótula/cirugía , Pronóstico , Resultado del Tratamiento , Estudios Prospectivos , Articulación de la Rodilla/inervación , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/fisiopatología
4.
Proc Natl Acad Sci U S A ; 121(42): e2406936121, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39388269

RESUMEN

Kirsten rat sarcoma virus (KRAS) mutation is associated with malignant tumor transformation and drug resistance. However, the development of clinically effective targeted therapies for KRAS-mutant cancer has proven to be a formidable challenge. Here, we report that tripartite motif-containing protein 21 (TRIM21) functions as a target of extracellular signal-regulated kinase 2 (ERK2) in KRAS-mutant colorectal cancer (CRC), contributing to regorafenib therapy resistance. Mechanistically, TRIM21 directly interacts with and ubiquitinates v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) at lysine 148 (K148) via K63-linkage, enabling c-Myc to be targeted to the autophagy machinery for degradation, ultimately resulting in the downregulation of enolase 2 expression and inhibition of glycolysis. However, mutant KRAS (KRAS/MT)-driven mitogen-activated protein kinase (MAPK) signaling leads to the phosphorylation of TRIM21 (p-TRIM21) at Threonine 396 (T396) by ERK2, disrupting the interaction between TRIM21 and c-Myc and thereby preventing c-Myc from targeting autophagy for degradation. This enhances glycolysis and contributes to regorafenib resistance. Clinically, high p-TRIM21 (T396) is associated with an unfavorable prognosis. Targeting TRIM21 to disrupt KRAS/MT-driven phosphorylation using the antidepressant vilazodone shows potential for enhancing the efficacy of regorafenib in treating KRAS-mutant CRC in preclinical models. These findings are instrumental for KRAS-mutant CRC treatment aiming at activating TRIM21-mediated selective autophagic degradation of c-Myc.


Asunto(s)
Autofagia , Neoplasias Colorrectales , Compuestos de Fenilurea , Proteínas Proto-Oncogénicas c-myc , Proteínas Proto-Oncogénicas p21(ras) , Piridinas , Ribonucleoproteínas , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , Autofagia/efectos de los fármacos , Compuestos de Fenilurea/farmacología , Animales , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Piridinas/farmacología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Ratones , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Línea Celular Tumoral , Resistencia a Antineoplásicos , Ensayos Antitumor por Modelo de Xenoinjerto , Proteolisis/efectos de los fármacos , Mutación , Ratones Desnudos
5.
Int Orthop ; 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39340642

RESUMEN

PURPOSE: To evaluate the influence of patellar morphology on functional outcomes and patellofemoral joint alignment after unicompartmental knee arthroplasty (UKA). METHODS: This study retrospectively analyzed the clinical and imaging data of 207 patients with osteoarthritis of the unicompartment of the knee who underwent UKA between September 2020 and April 2023. Patients were divided into three groups according to the Wiberg classification: group W1 (I, n = 47), group W2 (II, n = 117), and group W3 (III, n = 43). Knee function was assessed using the Hospital for Specialty Surgery (HSS) knee score and Feller patellar score, and the incidence of anterior knee pain after surgery was recorded and compared. Imaging parameters such as patellar tilt angle (PTA), lateral patellofemoral angle (LPA) and Insall-Salvati ratio (ISR) were measured to assess patellofemoral joint alignment. RESULTS: The HSS scores of the three groups were not statistically different; the postoperative Feller scores of the group W3 differed significantly from those of the other two groups. The incidence of early postoperative anterior knee pain was higher in the group W3 than in the other two groups. The difference between preoperative PTA, postoperative PTA and preoperative LPA in the group W3 and the other two groups was statistically significant. CONCLUSION: Patients with Wiberg III patellae exhibited worse patellar scores, as well as more anterior knee pain and patellar tilt postoperatively. This finding highlights the need for individualized treatment to the Wiberg III patella during UKA to enhance surgical outcomes.

6.
Sci Rep ; 14(1): 22255, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333346

RESUMEN

It is crucial to precisely calculate temperature utilizing thermal models, which require the determination of thermal parameters that optimally align model outcomes with experimental data. In many instances, the refinement of these models is undertaken within space instruments. This paper introduces an optimization methodology for thermal network models, with the objective of enhancing the accuracy of temperature predictions for aerial cameras. The investigation of internal convective heat transfer coefficients for both cylindrical and planar structures provides an estimation of convective thermal parameters. Based on the identification of thermally sensitive parameters and the reliability evaluation of transient temperature data through the Monte-Carlo simulation, the genetic algorithm is employed to search for global optimal parameter values that minimize the root mean square error (RMSE) between calculated and measured node temperatures. As a result, the optimized model shows significantly improved accuracy in temperature prediction, attaining an RMSE of 1.07 ℃ and reducing the maximum relative error between predicted and experimental results from 33.8 to 3.1%. Furthermore, the flight simulation and thermal control experiments validate the robustness of the optimized model, demonstrating that discrepancies between the observed and predicted temperatures are within 2 °C after re-correcting the external convection heat transfer coefficient value.

7.
Clin Res Hepatol Gastroenterol ; 48(9): 102464, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276854

RESUMEN

INTRODUCTION: The prognostic value of baseline variant allele frequency (VAF) in circulating tumor DNA (ctDNA) of colorectal cancer liver metastases (CRLM) patients after curative resection was rarely investigated. METHODS: A single-center prospective study was performed to investigate the prognostic impact of baseline VAF in ctDNA and matched tumor tissues of CRLM patients after curative resection between May 2019 and May 2021 by the Illumina NovoSeq 6000 platform. The relationship of the tumor burden score (TBS) and the VAF in ctDNA and matched tumor tissues was evaluated by the Pearson correlation method. The survival curves of recurrence-free survival (RFS) and overall survival (OS) were plotted. Factors associated with RFS were calculated using Cox regression analysis, and an integrated prognostic model using significant baseline variables was proposed. RESULTS: There were 121 patients with baseline ctDNA and matched tumor tissues enrolled in the study. A total of 417 mutations spanning 20 genes were identified in baseline tumor tissues of 119/121 (98.3 %) cases. The overall mutations in tumor tissues were completely covered by ctDNA in 52 of 121(43.0 %) patients. Baseline VAF in ctDNA but not in tumor tissues was significantly correlated to TBS of CRLM (R = 0.36, p < 0.001). Significantly longer RFS but not OS was observed in patients with lower VAF in ctDNA compared to those with higher one (p < 0.001 and p = 0.33 respectively). Multivariate Cox regression analysis showed higher VAF in baseline ctDNA was an independent risk factor for RFS. An integrated prognostic model including baseline metastasis location and VAF in ctDNA outperformed the traditional CRS model in predicting RFS. CONCLUSION: Baseline VAF in ctDNA but not in tumor tissues influenced RFS of CRLM patients after curative resection.

8.
Inorg Chem ; 63(38): 17478-17487, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39229693

RESUMEN

Metalo hydrogen-bonded organic frameworks (MHOFs) have received growing interest in designing crystalline functional materials. However, reports on bifunctional MHOFs showing magnetic and proton-conductive properties are extremely limited and their design is challenging. Herein, we investigated the magnetic and proton-conductive properties of two sulfonated CoHOF and MnHOF, {M(H2O)2(abs)2}n (M = Co2+ and Mn2+, Habs = 4-aminoazobenzene-4'-sulfonic anion), constructed by coordination chains. The supramolecular frameworks sustained by H bonds between -SO3- and coordinated water show directional ladder-type H bonds with hydrophilic nanochannels, leading to high proton conduction with exceptionally high conductivity around 10-2 S cm-1 at 100 °C under 97% relative humidity. In particular, the maximum σ value of CoHOF, 2.11 × 10-2 S cm-1, recorded the highest value among the reported proton-conducting materials showing slow magnetic relaxation. Meanwhile, the molecular structure of organosulfonate enables the magnetic isolation of high-spin Co2+ and Mn2+ centers in the frameworks. Magnetic measurements indicated that the MHOFs show field-induced single-ion magnet (SIM) properties, making these compounds rare magnetic-proton-conductive MHOFs. The work provides not only two unique MHOFs with SIM behavior and high proton conduction performance but also avenues for designing stable bifunctional MHOFs via a coordination chain approach.

9.
Heliyon ; 10(17): e36218, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281616

RESUMEN

Background: Low-density neutrophils are heterogeneous immune cells with immunosuppressive (such as polymorphonuclear myeloid-derived suppressor cells [PMN-MDSC]) or pro-inflammatory (such as low-density granulocytes [LDG]) properties that have been well described in multiple cancers and immune diseases. However, its role in allergic rhinitis (AR) is still unclear. Methods: In the present study, we defined low-density neutrophils as CD14-CD11B+CD15+LOX-1+ (LOX-1+ neutrophils), and their levels in the peripheral blood (PB) were evaluated and compared between patients with AR and healthy donors using flow cytometric analysis. LOX-1 expression on polymorphonuclear neutrophils was identified. Carboxyfluorescein succinimidyl ester (CFSE)-stained CD3+ T cells were cultured alone or with LOX-1+ neutrophils, T cell proliferation was assessed using flow cytometry, and pro-inflammatory cytokines in the supernatants were detected using enzyme-linked immunosorbent assay (ELISA). Clinicopathological analyses were performed to gain a thorough understanding of LOX-1+ neutrophils. Results: We determined that LOX-1+ neutrophils were significantly increased in the PB of patients with AR, and LOX-1 expression in neutrophils from patients with AR was elevated. Interestingly, LOX-1+ neutrophils derived from patients with AR, unlike PMN-MDSC, promoted T cell proliferation and pro-inflammatory cytokine production. Moreover, clinicopathological analysis revealed that there was no any relation between circulating LOX-1+ neutrophil levels and the levels of IgE, age and sex. Conclusion: These findings indicate that elevated circulating LOX-1+ neutrophils play a pro-inflammatory role in AR.

10.
Food Chem ; 463(Pt 1): 141059, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39243618

RESUMEN

Heterocyclic aromatic amines (HAAs) are harmful byproducts in food heating. Therefore, exploring the prediction and generation patterns of HAAs is of great significance. In this study, genetic algorithm (GA) and support vector regression (SVR) are used to establish a prediction model of HAAs based on heating conditions, reveal the influence of heating temperature and time on the precursor and formation of HAAs in roast beef, and study the formation rules of HAAs under different processing conditions. Principal component analysis (PCA) showed that the effect on HAAs generation increases with the increase of heating temperature and time. The GA-SVR model exhibited near-zero absolute errors and regression correlation coefficients (R) close to 1 when predicting HAAs contents. The GA-SVR model can be applied for real-time monitoring of HAAs in grilled beef, providing technical support for controlling hazardous substances and intelligent processing of heat-processed meat products.

11.
Nat Commun ; 15(1): 7796, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39242635

RESUMEN

Epigenetic modifications are crucial for plant development. EFD (Exine Formation Defect) encodes a SAM-dependent methyltransferase that is essential for the pollen wall pattern formation and male fertility in Arabidopsis. In this study, we find that the expression of DRM2, a de novo DNA methyltransferase in plants, complements for the defects in efd, suggesting its potential de novo DNA methyltransferase activity. Genetic analysis indicates that EFD functions through HB21, as the knockout of HB21 fully restores fertility in efd mutants. DNA methylation and histone modification analyses reveal that EFD represses the transcription of HB21 through epigenetic mechanisms. Additionally, we demonstrate that HB21 directly represses the expression of genes crucial for pollen formation and anther dehiscence, including CalS5, RPG1/SWEET8, CYP703A2 and NST2. Collectively, our findings unveil a double negative regulatory cascade mediated by epigenetic modifications that coordinates anther development, offering insights into the epigenetic regulation of this process.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Metilación de ADN , Epigénesis Genética , Flores , Regulación de la Expresión Génica de las Plantas , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Polen/crecimiento & desarrollo , Polen/genética , Polen/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Mutación , Plantas Modificadas Genéticamente
12.
Chem Sci ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39184303

RESUMEN

The advent of dual-atom nanozymes (DAzymes) featuring distinctive bimetallic active sites garnered significant attention, representing enhanced iterations of conventional single-atom nanozymes. The quest for an effective and universal strategy to modulate the catalytic activity of DAzymes posed a formidable challenge, yet few published reports addressed this. Herein, we designed and synthesized S-doped Fe/Co DAzymes (S-FeCo-NC) under theoretical guidance and revealed their excellent oxidase-like activity. Experimental and theoretical calculations indicated that the superior oxidase-like activity exhibited by S-FeCo-NC was attributed to the S-doping, which modulated the local electronic structure of the dual-atom active site. This modulation of the local electronic structure significantly optimizes oxygen adsorption energy, thereby accelerating the rate of enzyme-catalyzed reactions. As a proof-of-concept, this study integrated S-FeCo-NC with the cascade inhibition reaction of acetylcholinesterase (AChE) to devise a sensitive analytical platform for detecting organophosphorus pesticides. This study paved the way for elucidating the correlation between the local electronic structure of the active site and enzyme activity, offering novel methodologies and insights for the rational design of DAzymes.

13.
Cancer ; 130(S17): 3054-3066, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39092590

RESUMEN

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.


Asunto(s)
Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Receptor ErbB-2 , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , China , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Neumonía/tratamiento farmacológico , Femenino , Consenso , Trastuzumab/uso terapéutico , Trastuzumab/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Camptotecina/análogos & derivados
14.
Int J Biol Macromol ; 278(Pt 1): 134597, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39127286

RESUMEN

The considerable challenge of wound healing remains. In this study, we fabricated a novel multifunctional core-shell nanofibrous scaffold named EGF@BSP-CeO2/PLGA (EBCP), which is composed of Bletilla striata polysaccharide (BSP), Ceria nanozyme (CeO2) and epidermal growth factor (EGF) as the core and poly(lactic-co-glycolic acid) (PLGA) as the shell via an emulsion electrospinning technique. An increase in the BSP content within the scaffolds corresponded to improved wound healing performance. These scaffolds exhibited increased hydrophilicity and porosity and improved mechanical properties and anti-UV properties. EBCP exhibited sustained release, and the degradation rate was <4 % in PBS for 30 days. The superior biocompatibility was confirmed by the MTT assay, hemolysis, and H&E staining. In addition, the in vitro results revealed that, compared with the other groups, the EBCP group presented excellent antioxidant and antibacterial effects. More importantly, the in vivo results indicated that the wound closure rate of the EBCP group reached 94.0 % on day 10 in the presence of H2O2. The results demonstrated that EBCP could comprehensively regulate the wound microenvironment, possess hemostatic abilities, and significantly promote wound healing. In conclusion, the EBCP is promising for facilitating the treatment of infected wounds and represents a potential material for clinical applications.


Asunto(s)
Nanofibras , Orchidaceae , Polisacáridos , Andamios del Tejido , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Nanofibras/química , Polisacáridos/química , Polisacáridos/farmacología , Animales , Andamios del Tejido/química , Orchidaceae/química , Cerio/química , Cerio/farmacología , Ratones , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Antibacterianos/farmacología , Antibacterianos/química , Antioxidantes/farmacología , Antioxidantes/química , Factor de Crecimiento Epidérmico/farmacología , Ratas , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Masculino , Porosidad , Humanos
15.
Appl Environ Microbiol ; 90(8): e0069324, 2024 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-39058040

RESUMEN

Symbiotic microorganisms that reside on the host skin serve as the primary defense against pathogens in vertebrates. Specifically, the skin microbiome of bats may play a crucial role in providing resistance against Pseudogymnoascus destructans (Pd), the pathogen causing white-nose syndrome. However, the epidermis symbiotic microbiome and its specific role in resisting Pd in highly resistant bats in Asia are still not well understood. In this study, we collected and characterized skin microbiota samples of 19 Myotis pilosus in China and explored the differences between Pd-positive and negative individuals. We identified inhibitory effects of these bacteria through cultivation methods. Our results revealed that the Simpson diversity index of the skin microbiota for positive individuals was significantly lower than that of negative individuals, and the relative abundance of Pseudomonas was significantly higher in positive bats. Regardless of whether individuals were positive or negative for Pd, the relative abundance of potentially antifungal genera in skin microbiota was high. Moreover, we successfully isolated 165 microbes from bat skin and 41 isolates from positive individuals able to inhibit Pd growth compared to only 12 isolates from negative individuals. A total of 10 genera of Pd-inhibiting bacteria were screened, among which the genera Algoriella, Glutamicibacter, and Psychrobacter were newly discovered as Pd-inhibiting genera. These Pd-inhibiting bacteria metabolized a variety of volatile compounds, including dimethyl trisulfide, dimethyl disulfide, propylene sulfide, 2-undecanone, and 2-nonanone, which were able to completely inhibit Pd growth at low concentrations.IMPORTANCERecently, white-nose syndrome has caused the deaths of millions of hibernating bats, even threatening some with regional extinction. Bats in China with high resistance to Pseudogymnoascus destructans can provide a powerful reference for studying the management of white-nose syndrome and understanding the bats against the pathogen's intrinsic mechanisms. This study sheds light on the crucial role of host symbiotic skin microorganisms in resistance to pathogenic fungi and highlights the potential for harnessing natural defense mechanisms for the prevention and treatment of white-nose syndrome. In addition, this may also provide promising candidates for the development of bioinsecticides and fungicides that offer new avenues for addressing fungal diseases in wildlife and agricultural environments.


Asunto(s)
Ascomicetos , Bacterias , Quirópteros , Hibernación , Microbiota , Piel , Quirópteros/microbiología , Animales , Piel/microbiología , Ascomicetos/aislamiento & purificación , Ascomicetos/fisiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , China , Simbiosis
16.
J Synchrotron Radiat ; 31(Pt 5): 1010-1018, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39042579

RESUMEN

The damage threshold of an Au-coated flat mirror, one of the reflective optics installed on the FEL-2 beamline of the Dalian Coherent Light Source, China, upon far-UV free-electron laser irradiation is evaluated. The surface of the coating is characterized by profilometer and optical microscope. A theoretical approach of the phenomenon is also presented, by application of conventional single-pulse damage threshold calculations, a one-dimensional thermal diffusion model, as well as finite-element analysis with ANSYS.

17.
J Immunother Cancer ; 12(7)2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39067875

RESUMEN

BACKGROUND: This study comprehensively investigates the association between the expression of nicotinamide N-methyltransferase (NNMT) and clinical outcomes of urothelial bladder cancer (UBC), as well as the molecular mechanisms by which NNMT in cancer-associated fibroblast (CAF) modulates tumor progression and immunotherapy resistance in UBC. METHODS: Single-cell transcriptomic analyses, immunohistochemical and immunofluorescence assays were performed on bladder cancer samples to validate the relationship between NNMT expression and clinical outcomes. A series of experiments, including chromatin immunoprecipitation assay, liquid chromatography tandem mass spectrometry assay, and CRISPR‒Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) knockout, together with in vivo models, have been established to determine the molecular functions of NNMT in CAFs in UBC. RESULTS: We demonstrated that elevated expression of the nicotinamide adenine dinucleotide (NAD+) metabolism enzyme NNMT in CAFs (NNMT+ CAFs) was significantly associated with non-response to programmed death-ligand 1 (PD-L1) blockade immunotherapy in patients with UBC and predicted the unfavorable prognosis of UBC in two independent large cohorts. Targeting NNMT using the inhibitor 5-Amino-1-methylquinolinium iodide significantly reduced tumor growth and enhanced the apoptotic effects of the anti-PD-L1 antibody in UBC mouse models. Mechanistically, NNMT+ CAFs recruit tumor-associated macrophages via epigenetic reprogramming of serum amyloid A (SAA) to drive tumor cell proliferation and confer resistance to programmed death-1/PD-L1 blockade immunotherapy. CONCLUSIONS: NNMT+ CAFs were significantly associated with non-response to PD-L1 blockade immunotherapy in patients with UBC. Elevated NNMT, specifically in CAFs, upregulates SAA expression and enhances the recruitment and differentiation of macrophages in the tumor microenvironment, thereby directly or indirectly promoting tumor progression and conferring resistance to immunotherapies in bladder cancer.


Asunto(s)
Fibroblastos Asociados al Cáncer , Inmunoterapia , Macrófagos , Nicotinamida N-Metiltransferasa , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/genética , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Ratones , Animales , Nicotinamida N-Metiltransferasa/metabolismo , Inmunoterapia/métodos , Macrófagos/metabolismo , Macrófagos/inmunología , NAD/metabolismo , Resistencia a Antineoplásicos , Femenino , Progresión de la Enfermedad , Masculino , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología
18.
Acta Psychol (Amst) ; 248: 104380, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38955033

RESUMEN

This study investigated the effects of different types of short video addiction on social adaptation. The aim of this study was to identify the various types of short video addiction among freshmen and the correlations with career adaptability, insomnia, and depressive symptoms. We recruited 931 freshmen and used latent profile analysis to classify participants based on different characteristics of short video addiction. Based on the results of a short video addiction questionnaire, participants were found to exhibit distinct answer patterns, categorized into five types. Class 1 exhibited minimal signs of addiction. Class 2 displayed fluctuations with stronger tendencies towards withdrawal or escape. Class 3 demonstrated a moderate inability to control cravings for short videos. Class 4 showed fluctuations but with less anxiety and feelings of lost. Finally, Class 5 presented the most pronounced symptoms of short video addiction. Freshmen with varying degrees of short video addiction exhibited significant differences in career adaptability, sleep quality, and depressive symptoms. Class 1 students showed strong career adaptability and sound sleep, whereas Class 5 students had the highest depression rates. Overall, our findings suggest that the characteristics of short video addiction in first-year students also indicate poor social adaptation, which is mainly manifested as weak career adaptability, decreased sleep quality, and depressive symptoms. One way to guide first-year students to adapt to campus life is for educators to provide timely interventions for students with severe short video addiction.


Asunto(s)
Depresión , Trastornos del Inicio y del Mantenimiento del Sueño , Estudiantes , Humanos , Masculino , Femenino , Adulto Joven , Estudiantes/psicología , Adolescente , Trastorno de Adicción a Internet , Universidades , Adulto , Encuestas y Cuestionarios , Ajuste Social
19.
Sci Total Environ ; 947: 174548, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38972418

RESUMEN

Microbial carbon use efficiency (CUE) and nitrogen use efficiency (NUE) are crucial parameters reflecting soil C and N sequestration. Concerns about how artificial activities disturb alpine meadow ecosystem are increasing, but the knowledge of variances in microbial CUE and NUE in response to turf storage remains scarce. Here, we conducted a turf storage experiment on the Tibetan Plateau with two common storage methods, laying turfs method (LT) and stacking turfs method (ST). Plant litter, aboveground and belowground biomass declined considerably in the LT and ST than those in natural meadow. Soil pH and available phosphorus were significantly lower, but soil organic carbon, total nitrogen, dissolved organic carbon, and available nitrogen were substantially higher in stored turfs (both ST and LT) than in natural meadow. These results led to a differentiation in nutrient status among treatments. Vetor model indicated a stronger C limitation (vector length > 0.61) in ST than that in the LT and a shift from N to P limitation (vector angle >55°) in all stored turfs. Microbial CUE was prominently higher in the LT than those in the ST, signifying that microbes allocated more exogenous C to self-growth in the LT. Microbial NUE declined considerably in stored turfs, indicating a great proportion of N used for catabolic process instead of anabolic process. Microbial CUE and NUE were tightly linked to nutrient content and availability, enzymatic stoichiometry, microbial traits and plant biomass. Our results suggest that variations in microbial CUE and NUE were indirectly regulated by soil physicochemical properties via mediating nutrient imbalance and enzymatic stoichiometry in stored turfs.


Asunto(s)
Carbono , Nitrógeno , Microbiología del Suelo , Suelo , Tibet , Carbono/metabolismo , Suelo/química , Biomasa , Pradera
20.
Surg Endosc ; 38(8): 4731-4744, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39009728

RESUMEN

BACKGROUND: The advancement of laparoscopic technology has broadened the application of laparoscopic pancreaticoduodenectomy (LPD) for treating pancreatic head and ampullary tumors. Despite its benefits, postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH) remain significant complications. Ligamentum teres hepatis wrapping around the gastroduodenal artery (GDA) stump show limitations in reducing POPF and PPH. METHODS: This study retrospectively analyzed patients undergoing LPD from January 2016 to October 2023, We compared the effectiveness of the two-parts wrapping (the ligamentum teres hepatis wrapping of the gastroduodenal artery stump and the omentum flap wrapping of the pancreatojejunal anastomosis) and ligamentum teres hepatis wrapping around the gastroduodenal artery (GDA) in reducing postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH), using propensity score matching for the analysis. RESULTS: A total of 172 patients were analyzed, showing that the two-parts wrapping group significantly reduced the rates of overall and severe complications, POPF, and PPH compared to ligamentum teres hepatis wrapping around the GDA group. Specifically, the study found lower rates of grade B/C POPF and no instances of PPH in the two-parts wrapping group, alongside shorter postoperative hospital stays and drainage removal times. These benefits were particularly notable in patients with soft pancreatic textures and pancreatic duct diameters of < 3 mm. CONCLUSION: The two-parts wrapping technique significantly reduce the risks of POPF and PPH in LPD, offering a promising approach for patients with soft pancreas and pancreatic duct diameter of < 3 mm.


Asunto(s)
Laparoscopía , Fístula Pancreática , Pancreaticoduodenectomía , Complicaciones Posoperatorias , Humanos , Pancreaticoduodenectomía/métodos , Pancreaticoduodenectomía/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Laparoscopía/métodos , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Anciano , Fístula Pancreática/prevención & control , Fístula Pancreática/etiología , Hemorragia Posoperatoria/prevención & control , Hemorragia Posoperatoria/etiología , Neoplasias Pancreáticas/cirugía , Resultado del Tratamiento , Colgajos Quirúrgicos
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