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1.
Clin Chim Acta ; 564: 119917, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39181292

RESUMEN

Hemolysis is the most prevalent pre-analytical interfering factor and a major source of error in laboratory analysis. The examination of samples post-centrifugation can provide valuable information regarding pre-analytical interferences. In this unusual case, a patient's plasma specimen was cherry-red after centrifugation, which is most usually indicative of hemolysis. However, subsequent investigations ruled out common hemolysis causes. We eventually determined that the patient's cherry-red plasma was most likely caused by other factors in the patient's medical history, including cancer treatment with PV-10 (rose bengal disodium 10%). We then conducted an interference study to comprehensively assess the effects of PV-10 on various biochemical tests, especially liver function tests and bilirubin levels. The findings indicate that PV-10 has varying effects on different biochemical assays and test results should be examined individually. This report underlines the need for awareness of potential drug interference on laboratory tests for better result interpretation and making clinical decisions.


Asunto(s)
Hemólisis , Humanos , Masculino , Plasma/química , Plasma/metabolismo
2.
Zookeys ; 1215: 209-234, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39444952

RESUMEN

In this paper, four species of Omphale Haliday, O.longigena Li & Li, sp. nov., O.longitarsus Li & Li, sp. nov., O.rectisulcus Li & Li, sp. nov., and O.xanthosoma Li & Li, sp. nov., are described as new to science; four species, O.brevibuccata Szelényi, O.connectens Graham, O.melina Yefremova & Kriskovich, and O.obscura (Förster) are reported from China for the first time; and the male of O.melina is reported for the first time in the world. A key to all known species of the genus Omphale in China is provided.

3.
Clin Cancer Res ; 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39453770

RESUMEN

PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively indolent but can be more aggressive. The current recommendations for the use of serum CgA for GEP-NET patients are equivocal. This study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in GEP-NET patients. PATIENTS AND METHODS: A prospective, multi-center blinded observational study was designed to validate an automated chromogranin A (CgA) immunofluorescence assay for monitoring disease progression in GEP-NET patients. Tumor progression was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by CT/MRI. An increase ≥ 50% above the prior CgA concentration to a value > 100 ng/mL in the following CgA concentration was considered positive. RESULTS: 153 GEP-NET patients were enrolled. Using the pre-specified cut-off of CgA change for tumor progression, specificity was 93·4% (95%-CI: 90·4%-95·5%, p < 0·001), sensitivity 34·4% (25·6%-44·3%), positive predictive value 57·9% (45·0-69·8), negative predictive value (NPV) 84·3% (80·5-87·6), and area under the curve 0·73 (0·67-0·79). CONCLUSIONS: Changes in serial measurements of serum CgA had a favorable specificity and NPV, making this test a useful adjunct to routine radiographic monitoring.

4.
Br J Nutr ; : 1-11, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39402756

RESUMEN

Depression is highly prevalent in haemodialysis patients, and diet might play an important role. Therefore, we conducted this cross-sectional study to determine the association between dietary fatty acids (FA) consumption and the prevalence of depression in maintenance haemodialysis (MHD) patients. Dietary intake was assessed using a validated FFQ between December 2021 and January 2022. The daily intake of dietary FA was categorised into three groups, and the lowest tertile was used as the reference category. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between dietary FA intake and the prevalence of depression. As a result, after adjustment for potential confounders, a higher intake of total FA [odds ratio (OR)T3 vs. T1 = 1·59, 95 % confidence interval (CI) = 1·04, 2·46] and saturated fatty acids (SFA) (ORT3 vs. T1 = 1·83, 95 % CI = 1·19, 2·84) was associated with a higher prevalence of depressive symptoms. Significant positive linear trends were also observed (P < 0·05) except for SFA intake. Similarly, the prevalence of depression in MHD patients increased by 20% (OR = 1.20, 95% CI = 1.01-1.43) for each standard deviation increment in SFA intake. RCS analysis indicated an inverse U-shaped correlation between SFA and depression (P nonlinear > 0·05). Additionally, the sensitivity analysis produced similar results. Furthermore, no statistically significant association was observed in the subgroup analysis with significant interaction. In conclusion, higher total dietary FA and SFA were positively associated with depressive symptoms among MHD patients. These findings inform future research exploring potential mechanism underlying the association between dietary FA and depressive symptoms in MHD patients.

5.
J Clin Invest ; 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39436710

RESUMEN

BRAFV600E-mutant metastatic colorectal cancer (mCRC) is associated with poor prognosis. The combination of anti-BRAF/EGFR (encorafenib/cetuximab) treatment for patients with BRAFV600E-mutant mCRC improved clinical benefits; unfortunately, inevitable acquired resistance limits the treatment outcome, and the mechanism has not been validated. Here, we discovered that monoacylglycerol O-Acyltransferase 3 (MOGAT3) mediated diacylglycerol (DAG) accumulation contributed to acquired resistance to encorafenib/cetuximab by dissecting BRAFV600E-mutant mCRC patient-derived xenograft (PDX) model exposed to encorafenib/cetuximab administration. Mechanistically, upregulated MOGAT3 promotes DAG synthesis and reduces fatty acid oxidation (FAO)-promoting DAG accumulation and activating PKCα-CRAF-MEK-ERK, driving acquired resistance. Resistance-induced hypoxia promotes MOGAT3 transcriptional elevation; simultaneously, MOGAT3-mediated DAG accumulation increases HIF1A expression in translation level through PKCα-CRAF-eIF4E activation, strengthening the resistance status. Intriguingly, reducing intratumoral DAG by fenofibrate or Pf-06471553 restores the antitumor efficacy of encorafenib/cetuximab on resistant BRAFV600E-mutant mCRC, interrupted PKCα-CRAF-MEK-ERK signaling. These findings reveal the critical metabolite DAG as a modulator of encorafenib/cetuximab efficacy in BRAFV600E-mutant mCRC, suggesting that fenofibrate may prove beneficial for resistant BRAFV600E-mutant mCRC patients.

6.
Neurochem Int ; 180: 105884, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39419179

RESUMEN

Methamphetamine (METH) is a highly addictive and widely abused drug that causes complex adaptive changes in the brain's reward system, such as the nucleus accumbens (NAc). LASP1 (LIM and SH 3 domain protein 1) as an actin-binding protein, regulates synaptic plasticity. However, the role and mechanism by which NAc LASP1 contributes to METH addiction remains unclear. In this study, adult male C57BL/6J mice underwent repeated METH exposure or METH-induced conditioned place preference (CPP). Western blotting and immunohistochemistry were used to determine LASP1 expression in the NAc. Furthermore, LASP1 knockdown or overexpression using adeno-associated virus (AAV) administration via stereotactic injection into the NAc was used to observe the corresponding effects on CPP. We found that repeated METH exposure and METH-induced CPP upregulated LASP1 expression in the NAc. LASP1 silencing in the NAc reversed METH-induced CPP and reduced PSD95, NR2A, and NR2B expression, whereas LASP1 overexpression in the NAc enhanced CPP acquisition, accompanied by increased PSD95, NR2A, and NR2B expression. Our findings demonstrate an important role of NAc LASP1 in modulating METH induced drug-seeking behavior and the underlying mechanism may be related to regulate the expression of synapse-associated proteins in the NAc. These results reveal a novel molecular regulator of the actions of METH on the NAc and provide a new strategy for treating METH addiction.

7.
Nano Lett ; 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39432100

RESUMEN

Solvent-free oxidative desulfurization can avoid environmental pollution caused by organic solvents as well as prevent loss of fuel during the oil-water separation process. In this work, first, hydrophilic ionic liquid gel microspheres with [BMIM]BF4 and PHEMA as the dispersion medium and gel network, respectively, were successfully prepared by using mesoporous silica microspheres as a supporting skeleton capable of stabilizing the gel through an anchoring effect, and then the catalyst [BMIM]PW and oxidant H2O2 were incorporated into the gel microspheres to construct a liquid compartment microreactor for deep desulfurization. The prepared microreactor (SiO2@[BMIM]PW/ILG-microspheres) has excellent extraction-catalytic capacity and exhibited ∼100% desulfurization ratio for a model oil of n-heptane with 500 ppm of DBT at 60 °C for 3 h without solvents. Additionally, the prepared microreactor can absorb hydrophilic desulfurization products after the reaction and has advantages of reusability and simple recovery without polluting the fuel oil, which is beneficial for potential petroleum industrial application.

8.
PLoS One ; 19(10): e0306152, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39413105

RESUMEN

Previous studies have shown sleep deprivation is increasingly reported as one of the causes of female infertility. However, how and by what relevant mechanisms it affects female fertility remains unclear. In this study, female mice underwent 72 hours of total sleep deprivation (TSD) caused by rotating wheel or 2 different controls: a stationary wheel, or forced movement at night. Even though, there was no significant difference in the number of eggs ovulated by the TSD mice compared to the control groups. Overall levels of estrogen and FSH were lower throughout the estrus cycle. A total of 42 genes showed significant differential expression in GV oocytes after TSD by RNA sequencing (RNA-Seq). These included genes were enriched in gene ontology terms of mitochondrial protein complex, oxidoreductase activity, cell division, cell cycle G1/S phase transition, as well as others. The increased concentrations of reactive oxygen species (ROS) in germinal vesicle (GV) and metaphase II (MII) oocytes from TSD mice were observed, which might be induced by impaired mitochondrial function caused by TSD. The GV oocytes displayed increased mitochondrial DNA (mtDNA) copy number and a significant transient increase in inner mitochondrial membrane potential (Δψm) from the TSD mice probably due to compensatory effect. In contrast, MII oocytes in the TSD group showed a decrease in the mtDNA copy number and a lower Δψm compared with the controls. Furthermore, abnormal distribution of mitochondria in the GV and MII oocytes was also observed in TSD mice, suggesting mitochondrial dysfunction. In addition, abnormal spindle and abnormal arrangement of chromosomes in MII oocytes were markedly increased in the TSD mice compared with the control mice. In conclusion, our results suggest that TSD significantly alters the oocyte transcriptome, contributing to oxidative stress and disrupted mitochondrial function, which then resulted in oocyte defects and impaired early embryo development in female mice.


Asunto(s)
ADN Mitocondrial , Potencial de la Membrana Mitocondrial , Mitocondrias , Oocitos , Estrés Oxidativo , Especies Reactivas de Oxígeno , Privación de Sueño , Animales , Femenino , Oocitos/metabolismo , Ratones , Privación de Sueño/metabolismo , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Fertilidad , Infertilidad Femenina/metabolismo , Infertilidad Femenina/genética , Infertilidad Femenina/etiología , Infertilidad Femenina/patología
9.
Sci Adv ; 10(39): eado8658, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39321297

RESUMEN

Advancing membranes with enhanced solute-solute selectivity is essential for expanding membrane technology applications, yet it presents a notable challenge. Drawing inspiration from the unparalleled selectivity of biological systems, which benefit from the sophisticated spatial organization of functionalities, we posit that manipulating the arrangement of the membrane's building blocks, an aspect previously given limited attention, can address this challenge. We demonstrate that optimizing the face-to-face orientation of building blocks during the assembly of covalent-organic-framework (COF) membranes improves ion-π interactions with multivalent ions. This optimization leads to extraordinary selectivity in differentiating between monovalent cations and anions from their multivalent counterparts, achieving selectivity factors of 214 for K+/Al3+ and 451 for NO3-/PO43-. Leveraging this attribute, the COF membrane facilitates the direct extraction of NaCl from seawater with a purity of 99.57%. These findings offer an alternative approach for designing highly selective membrane materials, offering promising prospects for advancing membrane-based technologies.

10.
Nat Commun ; 15(1): 8137, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289381

RESUMEN

Efficient energy conversion using ions as carriers necessitates membranes that sustain high permselectivity in high salinity conditions, which presents a significant challenge. This study addresses the issue by manipulating the linkages in covalent-organic-framework membranes, altering the distribution of electrostatic potentials and thereby influencing the short-range interactions between ions and membranes. We show that a charge-neutral covalent-organic-framework membrane with ß-ketoenamine linkages achieves record permselectivity in high salinity environments. Additionally, the membrane retains its permselectivity under temperature gradients, providing a method for converting low-grade waste heat into electrical energy. Experiments reveal that with a 3 M KCl solution and a 50 K temperature difference, the membrane generates an output power density of 5.70 W m-2. Furthermore, guided by a short-range ionic screening mechanism, the membrane exhibits adaptable permselectivity, allowing reversible and controllable operations by finely adjusting charge polarity and magnitude on the membrane's channel surfaces via ion adsorption. Notably, treatment with K3PO4 solutions significantly enhances permselectivity, resulting in a giant output power density of 20.22 W m-2, a 3.6-fold increase over the untreated membrane, setting a benchmark for converting low-grade heat into electrical energy.

11.
Adv Mater ; : e2407882, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285807

RESUMEN

Stability-issues of organic light-emitting diodes (OLEDs) employing thermally activated delayed fluorescence (TADF) require further advancements, especially in pure-blue range of CIEy < 0.20, existing a dilemma between color purity and device lifetime. Though improving bond-dissociation-energy (BDE) can effectively improve material intrinsic stability, strategies to simultaneously improve BDE and photophysical performances are still lacking. Herein, it is disclosed that synergistic intramolecular non-covalent interactions (Intra-NI) can achieve not only the highest C─N BDE among blue TADF materials, but enhanced molecular-rigidity, near-unity photoluminescent quantum yields and short delayed lifetime. Pure-blue TADF-OLEDs based on proof-of-concept TADF material realize high external-quantum-efficiency and record-high LT80@500 cd m-2 of 109 h with CIEy = 0.16. Furthermore, deep-blue TADF-sensitized devices exhibit high LT80@500 cd m-2 of 81 h with CIEy = 0.10. The findings provide new insight into the critical role of Intra-NI in OLED materials and open the way to tackling vexing stability issues for developing robust pure-blue organic emitters and other functional materials.

12.
Clin Chem Lab Med ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39299928

RESUMEN

OBJECTIVES: CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples. METHODS: CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020-2021) and KEQAS (2020-2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%). RESULTS: Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from -29.28 to 9.86 %, into -0.09-0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from -23.78 to 2.00 % pre-harmonization to -3.13-1.42 % post-harmonization. CONCLUSIONS: The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs.

13.
World J Clin Cases ; 12(26): 5983-5989, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39286392

RESUMEN

BACKGROUND: A sclerosing epithelioid fibrosarcoma (SEF) is a rare malignant fibroblastic soft tissue tumor that rarely occurs in intra-abdominal organs. A case of a SEF in the pancreatic head is reported herein, including its clinical manifestations, preoperative imaging features, gross specimen and pathological findings. CASE SUMMARY: A 33-year-old male patient was admitted to Peking Union Medical College Hospital in December 2023 due to a one-year history of intermittent upper abdominal pain and the discovery of a pancreatic mass. The patient underwent an enhanced computed tomography scan of the abdomen, which revealed a well-defined, round mass with clear borders and calcifications in the pancreatic head. The mass exhibited progressive, uneven mild enhancement, measuring approximately 6.6 cm × 6.3 cm. The patient underwent laparoscopic pylorus-preserving pancreaticoduodenectomy. Postoperative pathological examination revealed that the lesion was consistent with a SEF. At the 3-month postoperative follow-up, the patient did not report any short-term complications, and there were no signs of tumor recurrence. CONCLUSION: SEFs are rare malignant fibrous soft tissue tumors. SEFs rarely develop in the pancreas, and its preoperative diagnosis depends on imaging findings, with confirmation depending on pathological examination and immunohistochemistry. Currently, only four cases of pancreatic SEF have been reported in studies written in English. This case is the first reported case of a pancreatic SEF by a clinical physician.

14.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4148-4157, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39307747

RESUMEN

This study aims to explore the active components and mechanism of Wuhu Decoction in treating respiratory syncytial virus(RSV)-induced asthma. Ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry was used to determine the components of Wuhu Decoction in the blood. By utilizing databases, Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis and Gene Ontology(GO) functional analysis were conducted to investigate the targets of the components of Wuhu Decoction in asthma. Furthermore, the information on target proteins, and metabolite-target-pathway was imported into the STRING database to construct a network interaction diagram to identify the core components and key pathways of Wuhu Decoction. In the in vivo experiment, an asthma model was established using RSV combined with ovalbumin(OVA) in mice. The intervention effect of Wuhu Decoction on RSV-induced asthma in mice was validated through lung function tests, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and immunohistochemistry. The results showed that the main components of Wuhu Decoction in the blood were flavonoids, phenylpropanoids, lignans, and terpenoids. The core components of Wuhu Decoction in treating pediatric asthma included(-)-epigallocatechin, kaempferol, isoliquiritigenin, diosmetin, betulinic acid, ursolic acid, daphnetin, aescin. The main pathways targeted by Wuhu Decoction were calcium signaling pathway, neuroactive ligand-receptor interaction, NOD-like receptor signaling pathway, T cell receptor signaling pathway, and Toll-like receptor signaling pathway. The results of in vivo experiments demonstrated that Wuhu Decoction could improve lung function indicators, down-regulate levels of interleukin-6(IL-6), interleukin-17(IL-17), and tumor necrosis factor-alpha(TNF-α), and reduce the expression of proteins such as NOD-like receptor pyrin domain-containing 3(NLRP3), mitogen-activated protein kinase 1(MAPK1), mitogen-activated protein kinase 14(MAPK14), and nuclear factor kappaB subunit 1(NFKB1) in lung tissue, thereby alleviating neutrophilic inflammation and pulmonary congestion. These findings indicate that Wuhu Decoction intervenes in virus-induced asthma through a synergistic effect on multiple components, targets, and pathways, and it can inhibit the activation of the NOD-like receptor signaling pathway, thereby alleviating airway inflammation and injury in asthmatic mice.


Asunto(s)
Asma , Medicamentos Herbarios Chinos , Ratones Endogámicos BALB C , Farmacología en Red , Infecciones por Virus Sincitial Respiratorio , Virus Sincitiales Respiratorios , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Asma/tratamiento farmacológico , Asma/metabolismo , Ratones , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Virus Sincitiales Respiratorios/efectos de los fármacos , Humanos , Femenino , Pulmón/efectos de los fármacos , Pulmón/metabolismo
15.
Abdom Radiol (NY) ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225717

RESUMEN

BACKGROUND: The expansion of function-preserving surgery became possible due to a more profound understanding of gastric cancer (GC), and T1N + or T2N + gastric cancer patients might be potential beneficiaries. However, ways to evaluate the possibility of function-preserving pylorus surgery are still unknown. METHODS: A total of 288 patients at Renji Hospital and 58 patients at Huadong Hospital, pathologically diagnosed with gastric cancer staging at T1 and T2 with tumors located in the upper two-thirds of the stomach, were retrospectively enrolled from March 2015 to October 2022. Tumor regions of interest (ROIs) were manually delineated on bi-phase CT images, and a nomogram was built and evaluated. RESULTS: The radiomic features distributed differently between positive and negative pLNm groups. Two radiomic signatures (RS1 and RS2) and one clinical signature were constructed. The radiomic signatures exhibited good performance for discriminating pLNm status in the test set. The three signatures were then combined into an integrated nomogram (IN). The IN showed good discrimination of pLNm in the Renji cohort (AUC 0.918) and the Huadong cohort (AUC 0.649). The verification models showed high values. CONCLUSION: For GC patients with T1 and T2 tumors located in the upper two-thirds of the stomach, a nomogram was successfully built for predicting pylorus lymph node metastasis, which would guide the surgical indication extension of conservative gastrectomies.

16.
Clin Chem Lab Med ; 62(12): 2435-2443, 2024 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-39238208

RESUMEN

OBJECTIVES: This study aimed to assess the validity of external quality assessment (EQA) laboratory results across various cultural and environmental contexts and to identify potential improvement areas. METHODS: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a 2-year study (2022 and 2023) in which EQA materials, related software and online training was provided by a commercial vendor to 100 laboratories in ten IFCC member society countries. The results were analysed on a monthly basis by the TF-GLQ, to show the number of submissions per country, tests per lab, acceptability rates, random failures and to get a measure of which analytes performed poorly. RESULTS: The EQA material was dispatched on a quarterly basis. Some countries had problems with customs releasing the material in a timely manner, resulting in laboratories not receiving them on time leading to no submission. We report here the results for the second year of the survey. The number of examinations varied between laboratories, ranging from seven to 84 analytes. Of the ten countries surveyed, six averaged greater than 90 % acceptable results over the whole 12-months cycle, one had unacceptable results for two of the nine months they returned results and the other four were considered to not perform to an acceptable standard. CONCLUSIONS: All 100 participating laboratories indicated satisfaction with the EQA survey and related services, including on-site training, and report handling. However, specimen receiving issues, suggest benefits in dispatching materials for a full 12-month cycle. Significant discrepancies in EQA performance indicate that four countries require long-term assistance, training and guidance. To ensure reliable patient results, promoting EQA in certain countries is essential to achieve the required level of quality.


Asunto(s)
Laboratorios Clínicos , Humanos , Laboratorios Clínicos/normas , Garantía de la Calidad de Atención de Salud/normas , Control de Calidad , Laboratorios/normas
17.
Cancer Res ; 84(20): 3371-3387, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39250301

RESUMEN

Tumor stroma plays a critical role in fostering tumor progression and metastasis. Cancer-associated fibroblasts (CAF) are a major component of the tumor stroma. Identifying the key molecular determinants for the protumor properties of CAFs could enable the development of more effective treatment strategies. In this study, through analyses of single-cell sequencing data, we identified a population of CAFs expressing high levels of sulfatase 1 (SULF1), which was associated with poor prognosis in patients with colorectal cancer. Colorectal cancer models using mice with conditional SULF1 knockout in fibroblasts revealed the tumor-supportive function of SULF1+ CAFs. Mechanistically, SULF1+ CAFs enhanced the release of VEGFA from heparan sulfate proteoglycan. The increased bioavailability of VEGFA initiated the deposition of extracellular matrix and enhanced angiogenesis. In addition, intestinal microbiota-produced butyrate suppressed SULF1 expression in CAFs through its histone deacetylase (HDAC) inhibitory activity. The insufficient butyrate production in patients with colorectal cancer increased the abundance of SULF1+ CAFs, thereby promoting tumor progression. Importantly, tumor growth inhibition by HDAC was dependent on SULF1 expression in CAFs, and patients with colorectal cancer with more SULF1+ CAFs were more responsive to treatment with the HDAC inhibitor chidamide. Collectively, these findings unveil the critical role of SULF1+ CAFs in colorectal cancer and provide a strategy to stratify patients with colorectal cancer for HDAC inhibitor treatment. Significance: SULF1+ cancer-associated fibroblasts play a tumor-promoting role in colorectal cancer by stimulating extracellular matrix deposition and angiogenesis and can serve as a biomarker for the therapeutic response to HDAC inhibitors in patients.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Colorrectales , Sulfotransferasas , Microambiente Tumoral , Factor A de Crecimiento Endotelial Vascular , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Animales , Humanos , Ratones , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Sulfotransferasas/metabolismo , Sulfotransferasas/genética , Ratones Noqueados , Neovascularización Patológica/patología , Neovascularización Patológica/metabolismo , Neovascularización Patológica/genética , Femenino , Microbioma Gastrointestinal , Butiratos/metabolismo , Butiratos/farmacología , Línea Celular Tumoral , Pronóstico , Masculino
18.
Nat Commun ; 15(1): 6837, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39122706

RESUMEN

Membrane reactors are known for their efficiency and superior operability compared to traditional batch processes, but their limited diversity poses challenges in meeting various reaction requirements. Herein, we leverage the molecular tunability of covalent organic frameworks (COFs) to broaden their applicability in membrane reactors. Our COF membrane demonstrates an exceptional ability to achieve complete conversion in just 0.63 s at room temperature-a benchmark in efficiency for Knoevenagel condensation. This performance significantly surpasses that of the corresponding homogeneous catalyst and COF powder by factors of 176 and 375 in turnover frequency, respectively. The enhanced concentration of reactants and the rapid removal of generated water within the membrane greatly accelerate the reaction, reducing the apparent activation energy. Consequently, this membrane reactor enables reactions that are unattainable using both COF powders and homogeneous catalysts. Considering the versatility, our findings highlight the substantial promise of COF-based membrane reactors in organic transformations.

19.
Front Med (Lausanne) ; 11: 1438624, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185468

RESUMEN

Streptococcus is one of the common pathogens of suppurative infections. Invasive group A Streptococcus (iGAS) infections often develop from skin or soft tissue infections, and streptococcal toxic shock syndrome is considered the main cause of death in Chinese children with iGAS infectious disease. However, soft tissue infections caused by iGAS infections, especially the formation of abscesses, are relatively rare. A retrospective study was conducted, and pediatric in-patients who were diagnosed with an iGAS infection identified by cultures from normally sterile sites and treated in a tertiary hospital during 2016-2018 were included. A total of 14 patients were identified, which included 10 boys and four girls. The patients had an age range from 3 months to 10 years and were diagnosed with soft tissue infections and a formation of abscesses caused by iGAS infections. The most common sites of infections were the lower limbs. In five patients, the abscess was accompanied by fever, and the local soft tissue showed redness, swelling, tenderness, and an elevated skin temperature. Laboratory findings included an increased white blood cell (WBC) count in 12 patients, an increased C reactive protein (CRP) level in seven patients, and an increased erythrocyte sedimentation rate (ESR) in 10 patients. No patients had an elevated procalcitonin level. For all 14 patients, we performed puncture and drainage of abscesses, and cultured GAS from the drainage fluid. All children also received antibiotic treatment. During 2 months of follow-up, the patients' condition remained stable and no evidence of kidney or heart damage was observed. For pediatric patients with abscesses, early diagnosis, prompt treatment with incision and drainage, and immediate culture of the drainage fluid are important. Upon confirmation of an iGAS infection, ß-lactam antibiotics should be given to provide effective treatment, and in some patients with poor therapeutic outcomes, the use of vancomycin as an alternative can achieve the desired results.

20.
World J Clin Cases ; 12(23): 5416-5421, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39156097

RESUMEN

BACKGROUND: Endobronchial metastases (EBMs) are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi, and are visible under a bronchofibrescope. Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours, such as lung cancer, oesophageal cancer or mediastinum tumours. Renal cell carcinoma (RCC), accounting for 2% to 3% of all tumours, is a common malignant tumour of the urinary system. Renal clear cell carcinoma (RCCC) constitutes the predominant pathological subtype of RCC, comprising approximately 70% to 80% of all RCC cases. RCCC can spread and metastasise through arterial, venous and lymphatic circulation to almost all organs of the body. Moreover, lung, bone, liver, brain and local recurrence are the most common metastatic neoplasms of RCCC. However, EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer. CASE SUMMARY: A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough. The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung, and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe. Therefore, the patient underwent thoracoscopic left superior lobe wedge resection, and pathology confirmed EBM from the RCCC. CONCLUSION: EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage. If a bronchial tumour is found in a patient with RCCC, the possibility of bronchial metastatic cancer should be considered.

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