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1.
Angew Chem Int Ed Engl ; : e202410816, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990712

RESUMO

Covalent organic frameworks (COFs) have emerged as versatile materials with many applications, such as carbon capture, molecular separation, catalysis, and energy storage. Traditionally, flexible building blocks have been avoided due to their potential to disrupt ordered structures. Recent studies have demonstrated intriguing properties and enhanced structural diversity achievable with flexible components by judicious selection of building blocks. This study presents a novel series of ionic COFs (ICOFs) consisting of tetraborate nodes and flexible linkers. These ICOFs use borohydrides to irreversibly deprotonate the alcohol monomers to achieve a high polymerization degree. Structural analysis confirms the dia topologies. Reticulation is explored using various monomers and metal counter-ions. Also, these frameworks exhibit excellent stability in alcohols and coordinating solvents. The materials are tested as single-ion conductive solid-state electrolytes. ICOF-203-Li displays one of the lowest activation energies reported for ion conduction. This tetraborate chemistry is anticipated to facilitate further structural diversity and functionality in crystalline polymers.

2.
Sci Rep ; 14(1): 16081, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38992114

RESUMO

Tumor-associated macrophages play a crucial role in the tumor microenvironment. Tripartite motif 59 (TRIM59), a member of the tripartite motif (TRIM) family, is known to be associated with immunological diseases and macrophage activation. The functional and molecular mechanisms by which TRIM59 affects the occurrence and development of colorectal cancer (CRC) through macrophages are still not well understood. To address this, we generated macrophage-specific TRIM59 conditional knockout mice and utilized these mice to establish colitis-associated cancer and MC38 transplanted CRC models for further investigation. We found that the deficiency of TRIM59 in macrophages inhibited colorectal tumorigenesis in mice. This tumor-suppressive effect was achieved by promoting the activation of M1 macrophages via STAT1 signaling pathway. Further mechanistic studies revealed that TRIM59 could regulate macrophage polarization by ubiquitinating and degrading STAT1. These findings provide evidence that TRIM59 deficiency promotes M1 macrophage activation and inhibits CRC through the STAT1 signaling pathway, suggesting that the TRIM59/STAT1 signaling pathway may be a promising target for CRC.


Assuntos
Neoplasias Colorretais , Peptídeos e Proteínas de Sinalização Intracelular , Ativação de Macrófagos , Macrófagos , Camundongos Knockout , Fator de Transcrição STAT1 , Transdução de Sinais , Proteínas com Motivo Tripartido , Animais , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT1/genética , Ativação de Macrófagos/genética , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Camundongos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Macrófagos/metabolismo , Humanos , Camundongos Endogâmicos C57BL
3.
Nat Med ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992123

RESUMO

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607 .

4.
J Ethnopharmacol ; : 118538, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992399

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Weifuchun (WFC) is a Traditional Chinese Medicine commonly used for treating atrophic gastritis and intestinal metaplasia. Till date, its antitumor effect on gastric cancer (GC) and the underlying mechanisms of the effect remains unelucidated. AIM OF THE STUDY: We aim to investigate if WFC can suppress the malignancy of stomach cancer cells and dissect the molecular basis and the associated molecular and cellular features. MATERIALS AND METHODS: Stomach cancer cell lines and normal gastric epithelial cells were treated with WFC. CCK8 assay, caspase-3 activity assay, adhesion assay, microRNA database analysis, transfection, RT-PCR, Western Blotting, signaling pathway analysis, and in vivo GC model were employed to examine the changes in the features of the gastric cancer cells and the molecular mechanisms of the effect of WFC. RESULTS: Here we present data demonstrating that WFC suppresses the malignant cellular phenotypes of GC and this inhibitory effect is mediated by downregulating the expression of oncogenic KPNA2. Furthermore, WFC downregulates KPNA2 through miR-26a-5p-mediated gene silencing and the deactivated phosphorylation dynamics of mitogen-activated protein kinase (MAPK). The suppressive effect of WFC on stomach cancer cell behavior was further confirmed in animal model. CONCLUSION: Therefore, WFC can exert inhibitory effect on the malignancy of GC cells by reducing the levels of KPNA2. Moreover, the miR-26a-5p rescue and the deactivation MAPK pathway induced by WFC result in the downregulation of KPNA2 expression. Thus, our findings suggest WFC as a potential treatment option against GC.

5.
Chemosphere ; : 142807, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992445

RESUMO

As trace levels of thallium (Tl) in water are lethal to humans and ecosystems, it is essential to exploit advanced technologies for efficient Tl removal. In response to this concern, an innovative composite membrane was developed, incorporating polytetrafluoroethylene (PTFE) and featuring a dual-support system with polydopamine (PDA) and polyethyleneimine (PEI), along with bimetallic Prussian blue analogues (Co@Fe-PBAs) as co-supports. The composite membrane exhibited an exceptional Tl+-adsorption capacity (qm) of 186.1 mg·g-1 when utilized for the treatment of water containing low concentration of Tl+ (0.5 mg⋅L-1). Transmission electron microscopy displayed the obvious Tl+ mapping inside the special hollow Co@Fe-PBAs crystals, demonstrating the deep intercalation of Tl+ via ion exchange and diffusion. The Tl+-adsorption capability of the composite membrane was not greatly affected by coexisting Na+, Ca2+ and Mg2+ as well as the tricky K+, indicating the excellent anti-interference. Co-doped PBAs enhanced ion exchange and intercalation of the composite membrane with Tl+ leading to excellent Tl+ removal efficiency. The composite membrane could efficiently remove Tl+ from thallium- contaminated river water to meet the USEPA standard. This study provides a cost-effective membrane-based solution for efficient Tl+ removal from Tl+-containing wastewater.

6.
J Control Release ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992622

RESUMO

Nanomedicines hold promise for the treatment of various diseases. However, treating cancer metastasis remains highly challenging. In this study, we synthesized gold nanorods (AuNRs) containing (α-GC), an immune stimulator, for the treatment of primary cancer, metastasis, and recurrence of the cancer. Therefore, the AuNR were coated with lipid bilayers loaded with α-GC (α-LA). Upon irradiation with 808 nm light, α-LA showed a temperature increase. Intra-tumoral injection of α-LA in mice and local irradiation of the 4 T1 breast cancer tumor effectively eliminated tumor growth. We found that the presence of α-GC in α-LA activated dendritic cells and T cells in the spleen, which completely blocked the development of lung metastasis. In mice injected with α-LA for primary breast cancer treatment, we observed antigen-specific T cell responses and increased cytotoxicity against 4 T1 cells. We conclude that α-LA is promising for the treatment of both primary breast cancer and its metastasis.

7.
J Food Sci ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992868

RESUMO

Lycium ruthenicum Murray (LR) is a medicine and edible plant in Northwest China, and L. ruthenicum Murray anthocyanins (LRA) are green antioxidants with various pharmacological activities, such as antioxidant and anti-inflammatory activities. However, the protective effect and mechanism of LRA against retinal damage induced by blue light exposure are poorly understood. This study explored the protective effects and potential mechanisms of LRA on retinal damage induced by blue light exposure in vitro and in vivo. The results showed that LRA could ameliorate oxidative stress injury by activating the antioxidant stress nuclear factor-related factor 2 pathway, promoting the expression of phase II detoxification enzymes (HO-1, NQO1) and endogenous antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and reducing reactive oxygen species and malondialdehyde levels. Additionally, LRA could inhibit inflammatory response by decreasing the expression of blue light exposure-induced nuclear factor-κB (NF-κB) pathway-related proteins (NF-κB and p-IκBα), as well as interleukin (IL)-6, tumor necrosis factor-α, IL-1ß pro-inflammatory factors and pro-inflammatory chemokine VEGF, and increasing the expression of anti-inflammatory factor IL-10. Furthermore, LRA could ameliorate oxidative stress-induced apoptosis by upregulating Bcl-2 and downregulating Bax and Caspase-3 protein expression. All these results indicate that LRA can be used as an antioxidant dietary supplement for the treatment or prevention of retinal diseases.

9.
Cell ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971151

RESUMO

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

10.
Heliyon ; 10(11): e31775, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38947426

RESUMO

Diabetic nephropathy (DN) has emerged as the foremost cause of end-stage renal disease (ESRD) globally. Endoplasmic reticulum (ER) stress plays a critical role in DN progression. Triterpenoid saponin from Aralia taibaiensis (sAT) has been reported to possess anti-diabetic and anti-oxidant effects. The aim of this study was to examine the influence of sAT on DN treatment and elucidate potential underlying mechanisms. A high-fat diet (HFD) and Streptozotocin (STZ) were employed to induce DN in male Sprague Dawley (SD) rats which were subsequently treated with varying concentrations of sAT for 8 weeks. Our findings reveal that different doses of sAT significantly mitigated hyperglycemia, reduced urinary albumin excretion, and decreased plasma creatinine and blood urea nitrogen levels in DN rats. Moreover, sAT administration improved body weight, alleviated renal fibrosis and histopathological changes in the diabetic kidneys. Notably, sAT treatment partially restored increased Bax expression and decreased Bcl-2 expression. Additionally, sAT inhibited ER stress-related proteins, including GRP78, p-PERK, ATF4 and CHOP in kidneys of DN rats. These results suggest that sAT ameliorated experimental diabetic nephropathy, at least in part, through ER stress pathway. These findings provide a scientific basis for the potential development of sAT as a therapeutic agent for DN treatment.

11.
Diagn Pathol ; 19(1): 90, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956596

RESUMO

BACKGROUND: Cerebral echinococcosis is relatively rare, and it is important to distinguish cerebral cystic echinococcosis (CCE) from cerebral alveolar echinococcosis (CAE) in terms of pathological diagnosis. We aim to describe the different clinicopathological features among patients with CCE and CAE. METHODS: We collected 27 cases of cerebral echinococcosis which were diagnosed in the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University from January 1, 2012, to June 30, 2023. We compared the patients' clinical characteristics, MRI features, and pathologic manifestations of CCE and CAE. RESULTS: Among 27 cases of cerebral echinococcosis, 23 cases were CAE and 4 cases were CCE. The clinical manifestations of both CCE and CAE patients mainly included headache (21 patients, 77.78%), limb movement disorders (6 patients, 22.22%), epileptic seizures (4 patients, 14.81%) and visual disturbances (2 patients, 7.41%). The average onset age of CAE cases was 34.96 ± 11.11 years, which was 9.00 ± 7.26 years in CCE cases. All CAE patients presented with multiple involvements in the brain and extracranial organs while all CCE patients observed a solitary lesion in the brain and 3 CCE cases had no extracranial involvement. Lesions of CCE in MRI showed a single isolated circular, which was well demarcated from the surrounding tissues and with no obvious edema around the lesions, whereas CAE lesions presented as multiple intracranial lesions, with blurred edges and edema around the lesions, and multiple small vesicles could be observed in the lesions. The edge of CAE lesions could be enhanced, while CCE lesions have no obvious enhancement. CCE foci were clear cysts with a wall of about 0.1 cm. Microscopically, the walls of the cysts were characterized by an eosinophilic keratin layer, which was flanked on one side by basophilic germinal lamina cells, which were sometimes visible as protocephalic nodes. While the CAE lesion was a nodular structure with a rough and uneven nodule surface, and the cut section was cystic and solid; microscopically, the CAE lesion had areas of coagulative necrosis, and the proto-cephalic nodes were barely visible. Inflammatory cell areas consisting of macrophages, lymphocytes, epithelioid cells, plasma cells, eosinophils, and fibroblasts can be seen around the lesion. Brain tissues in the vicinity of the inflammatory cell areas may show apoptosis, degeneration, necrosis, and cellular edema, while brain tissues a little farther away from the lesion show a normal morphology. CONCLUSIONS: With the low incidence of brain echinococcosis, the diagnosis of echinococcosis and the differential diagnosis of CAE and CCE are challenging for pathologists. Grasping the different clinical pathology characteristics of CAE and CCE is helpful for pathologists to make accurate diagnoses.


Assuntos
Equinococose , Humanos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Equinococose/patologia , Adulto Jovem , Imageamento por Ressonância Magnética , Diagnóstico Diferencial , Encefalopatias/parasitologia , Encefalopatias/patologia , Adolescente , Encéfalo/patologia , Encéfalo/parasitologia
12.
BMC Womens Health ; 24(1): 381, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956627

RESUMO

BACKGROUND: For women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data. METHODS: A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features. RESULTS: In the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer-Lemeshow test was 7.427, and P = 0.505. CONCLUSIONS: Predicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).


Assuntos
Aborto Habitual , Humanos , Feminino , Gravidez , Adulto , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , China/epidemiologia , Estudos de Coortes , Modelos Logísticos
13.
Heliyon ; 10(11): e32686, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961957

RESUMO

Periodontitis is an inflammatory disease characterized by the destruction of periodontal tissues, and the promotion of bone tissue regeneration is the key to curing periodontitis. Psoralen is the main component of Psoralea corylifolia Linn, and has multiple biological effects, including anti-osteoporosis and osteogenesis. We constructed a novel hydrogel loaded with psoralen (PSO) and stromal cell-derived factor-1 (SDF-1) for direct endogenous cell homing. This study aimed to evaluate the synergistic effects of PSO/SDF-1 on periodontal bone regeneration in patients with periodontitis. The results of CCK8, alkaline phosphatase (ALP) activity assay, and Alizarin Red staining showed that PSO/SDF-1 combination treatment promoted cell proliferation, chemotaxis ability, and ALP activity of PDLSCs. qRT-PCR and western blotting showed that the expression levels of alkaline phosphatase (ALP), dwarf-associated transcription factor 2 (RUNX2), and osteocalcin (OCN) gene were upregulated. Rat periodontal models were established to observe the effect of local application of the composite hydrogel on bone regeneration. These results proved that the PSO/SDF-1 combination treatment significantly promoted new bone formation. The immunohistochemical (IHC) results confirmed the elevated expression of ALP, RUNX2, and OCN osteogenic genes. PSO/SDF-1 composite hydrogel can synergistically regulate the biological function and promote periodontal bone formation. Thus, this study provides a novel strategy for periodontal bone regeneration.

14.
Front Psychiatry ; 15: 1383992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962062

RESUMO

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

15.
Int J Surg ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963751

RESUMO

BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.

16.
World Neurosurg ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964458

RESUMO

OBJECTIVE: We aimed to preliminarily explore the efficacy and safety of unilateral biportal endoscopy (UBE) for the treatment of epidural cement leaks. We report a patient who underwent epidural cement leakage removal and achieved endoscopic spinal decompression. METHODS: A 67-year-old female patient underwent biportal endoscopic paraspinal decompression following percutaneous vertebroplasty for an osteoporotic fracture that resulted in neurologic impairment due to epidural cement leakage. A transforaminal biportal endoscopic surgery was performed to remove the leaked cement, and the left L1 and bilateral L2 nerves were decompressed. RESULTS: The patient's postoperative clinical course was uneventful. CONCLUSIONS: A paraspinal approach that avoids a posterior approach reduces the need to remove stabilizing facet bone, is truly minimally invasive and does not involve an instrumented fusion, maybe a helpful addition in the minimally invasive spine surgeon's armamentarium.

17.
J Transl Med ; 22(1): 628, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970045

RESUMO

BACKGROUND: Bladder cancer is a common malignancy with high recurrence rate. Early diagnosis and recurrence surveillance are pivotal to patients' outcomes, which require novel minimal-invasive diagnostic tools. The urinary microbiome is associated with bladder cancer and can be used as biomarkers, but the underlying mechanism is to be fully illustrated and diagnostic performance to be improved. METHODS: A total of 23 treatment-naïve bladder cancer patients and 9 non-cancerous subjects were enrolled into the Before group and Control group. After surgery, 10 patients from the Before group were further assigned into After group. Void mid-stream urine samples were collected and sent for 16S rDNA sequencing, targeted metabolomic profiling, and flow cytometry. Next, correlations were analyzed between microbiota, metabolites, and cytokines. Finally, receiver operating characteristic (ROC) curves of the urinary biomarkers were plotted and compared. RESULTS: Comparing to the Control group, levels of IL-6 (p < 0.01), IL-8 (p < 0.05), and IL-10 (p < 0.05) were remarkably elevated in the Before group. The α diversity of urine microbiome was also significantly higher, with the feature microbiota positively correlated to the level of IL-6 (r = 0.58, p < 0.01). Significant differences in metabolic composition were also observed between the Before and Control groups, with fatty acids and fatty acylcarnitines enriched in the Before group. After tumor resection, cytokine levels and the overall microbiome structure in the After group remained similar to that of the Before group, but fatty acylcarnitines were significantly reduced (p < 0.05). Pathway enrichment analysis revealed beta-oxidation of fatty acids was significantly involved (p < 0.001). ROC curves showed that the biomarker panel of Actinomycetaceae + arachidonic acid + IL-6 had superior diagnostic performance, with sensitivity of 0.94 and specificity of 1.00. CONCLUSIONS: Microbiome dysbiosis, proinflammatory environment and altered fatty acids metabolism are involved in the pathogenesis of bladder cancer, which may throw light on novel noninvasive diagnostic tool development.


Assuntos
Disbiose , Ácidos Graxos , Inflamação , Microbiota , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/microbiologia , Neoplasias da Bexiga Urinária/urina , Inflamação/microbiologia , Masculino , Disbiose/microbiologia , Disbiose/urina , Pessoa de Meia-Idade , Feminino , Ácidos Graxos/metabolismo , Ácidos Graxos/urina , Curva ROC , Citocinas/metabolismo , RNA Ribossômico 16S/genética , Idoso , Estudos de Casos e Controles
18.
Artigo em Inglês | MEDLINE | ID: mdl-38972898

RESUMO

Eugenol possesses anti-inflammatory and antioxidant properties, and may serve as a potential therapeutic agent for hepatic fibrosis. However, the development of solid eugenol formulations is challenging due to its volatility. To address this issue, this study employed porous silica to adsorb solidified eugenol. The solidified powder was characterized using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In addition, the differences in in vitro release and oral bioavailability between eugenol and solidified eugenol powder were investigated. The effectiveness of eugenol and eugenol powder in treating liver fibrosis was investigated using enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and histopathological observations. Our results indicate that porous silica can effectively solidify eugenol into powder at a lower dosage. Furthermore, we observed that porous silica accelerates eugenol release in vitro and in vivo. The pharmacodynamic results indicated that eugenol has a positive therapeutic effect against hepatic fibrosis and that porous silica does not affect its efficacy. In conclusion, porous silica was able to solidify eugenol, which may facilitate the preparation and storage of solid formulations.

19.
Adv Sci (Weinh) ; : e2405050, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973148

RESUMO

Transition metal disulfide compounds (TMDCs) emerges as the promising candidate for new-generation flexible (opto-)electronic device fabrication. However, the harsh growth condition of TMDCs results in the necessity of using hard dielectric substrates, and thus the additional transfer process is essential but still challenging. Here, an efficient strategy for preparation and easy separation-transfer of high-uniform and quality-enhanced MoS2 via the precursor pre-annealing on the designed graphene inserting layer is demonstrated. Based on the novel strategy, it achieves the intact separation and transfer of a 2-inch MoS2 array onto the flexible resin. It reveals that the graphene inserting layer not only enhances MoS2 quality but also decreases interfacial adhesion for easy separation-transfer, which achieves a high yield of ≈99.83%. The theoretical calculations show that the chemical bonding formation at the growth interface has been eliminated by graphene. The separable graphene serves as a photocarrier transportation channel, making a largely enhanced responsivity up to 6.86 mA W-1, and the photodetector array also qualifies for imaging featured with high contrast. The flexible device exhibits high bending stability, which preserves almost 100% of initial performance after 5000 cycles. The proposed novel TMDCs growth and separation-transfer strategy lightens their significance for advances in curved and wearable (opto-)electronic applications.

20.
Hematology ; 29(1): 2366631, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38975808

RESUMO

Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) comprise over half of all Cutaneous T-cell lymphoma diagnoses. Current risk stratification is largely based on TNMB staging, few research investigated the prognostic value of clinical exams. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and HADC inhibitors. Few clinical trials or retrospective research compared the efficacy of different drugs.Method: Here, we performed a retrospective analysis of prognostic factors and treatment outcomes of 92 patients diagnosed with MF/SS at the Peking Union Medical College Hospital from 2013-2023.Results: Cox regression analysis identified that age ≥ 50 years, WBC ≥ 8 × 109/L, serum LDH ≥ 250U/L, ß2-MG ≥ 4.50 mg/L, and stage IV were associated with reduced overall survival, age ≥ 50 years, serum LDH ≥ 250U/L and stage IV were associated with reduced progression free survival. Kaplan-Meier analysis established that immunomodulatory therapy was associated with longer progression free survival.Conclusion: These results suggested new factors in predicting prognosis and selecting appropriate treatments in patients with advanced MF/SS.


Assuntos
Micose Fungoide , Síndrome de Sézary , Humanos , Síndrome de Sézary/terapia , Síndrome de Sézary/mortalidade , Síndrome de Sézary/patologia , Micose Fungoide/terapia , Micose Fungoide/mortalidade , Micose Fungoide/patologia , Micose Fungoide/diagnóstico , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Resultado do Tratamento , Estadiamento de Neoplasias , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/diagnóstico , Idoso de 80 Anos ou mais
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