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1.
bioRxiv ; 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39463927

RESUMO

Frizzled (FZD) proteins are the principal receptors of the Wnt signaling pathway. However, whether Wnt ligands induce FZD endocytosis and degradation remains elusive. The transmembrane E3 ubiquitin ligases ZNRF3 and RNF43 promote the endocytosis and degradation of FZD receptors to inhibit Wnt signaling, and their function is antagonized by R-spondin (RSPO) proteins. However, the dependency of RSPO-ZNRF3/RNF43-mediated FZD endocytosis and degradation on Wnt stimulation, as well as the specificity of this degradation for different FZD, remains unclear. Here, we demonstrated that Wnt specifically induces FZD5/8 endocytosis and degradation in a ZNRF3/RNF43-dependent manner. ZNRF3/RNF43 selectively targets FZD5/8 for degradation upon Wnt stimulation. RSPO1 enhances Wnt signaling by specifically stabilizing FZD5/8. Wnt promotes the interaction between FZD5 and RNF43. We further demonstrated that DVL proteins promote ligand-independent endocytosis of FZD but are dispensable for Wnt-induced FZD5/8 endocytosis and degradation. Our results reveal a novel negative regulatory mechanism of Wnt signaling at the receptor level and illuminate the mechanism by which RSPO-ZNRF3/RNF43 regulates Wnt signaling, which may provide new insights into regenerative medicine and cancer therapy.

2.
J Fungi (Basel) ; 10(9)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39330370

RESUMO

Three new meroterpenoids, asperinsuterpenes A-C (1-3), and eight previously reported natural products, namely asnovolin I (4), (2'E,4'E,6'E)-6-(1'-carboxyocta-2',4',6'-triene)-9-hydroxydrim-7-ene-11,12-olide (5), (2'E,4'E,6'E)-6-(1'-carboxyocta-2',4',6'-triene)-11,12-epoxy-9,11-dihydroxydrim-7-ene (6), cinereain (7), carnequinazolines A and B (8 and 9), carnemycin B (10), and stromemycin (11) were isolated from the fungus Aspergillus insuetus, strain BTBU20220155. The structures of the compounds were determined based on spectroscopic techniques, including 1D and 2D NMR, HRESIMS, and ECD experiments. The in vitro antimicrobial evaluation revealed that compounds 5 and 11 exhibited inhibitory activity against Candida albicans, with minimum inhibitory concentration (MIC) values of 12.5 and 25 µg/mL, respectively. These findings suggest that A. insuetus is a promising source of bioactive natural products with potential applications in antifungal therapy.

3.
Sci Rep ; 14(1): 20672, 2024 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237645

RESUMO

PANoptosis induces programmed cell death (PCD) through extensive crosstalk and is associated with development of cancer. However, the functional mechanisms, clinical significance, and potential applications of PANoptosis-related genes (PRGs) in colorectal cancer (CRC) have not been fully elucidated. Functional enrichment of key PRGs was analyzed based on databases, and relationships between key PRGs and the immune microenvironment, immune cell infiltration, chemotherapy drug sensitivity, tumor progression genes, single-cell cellular subgroups, signal transduction pathways, transcription factor regulation, and miRNA regulatory networks were systematically explored. This study identified 5 key PRGs associated with CRC: BCL10, CDKN2A, DAPK1, PYGM and TIMP1. Then, RT-PCR was used to verify expression of these genes in CRC cells and tissues. Clinical significance and prognostic value of key genes were further verified by multiple datasets. Analyses of the immune microenvironment, immune cell infiltration, chemotherapy drug sensitivity, tumor progression genes, single-cell cellular subgroups, and signal transduction pathways suggest a close relationship between these key genes and development of CRC. In addition, a novel prognostic nomogram model for CRC was successfully constructed by combining important clinical indicators and the key genes. In conclusion, our findings offer new insights for understanding the pathogenesis of CRC, predicting CRC prognosis, and identifying multiple therapeutic targets for future CRC therapy.


Assuntos
Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Microambiente Tumoral/genética , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Quinases Associadas com Morte Celular/metabolismo , Prognóstico , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Carcinogênese/genética , Redes Reguladoras de Genes , Transdução de Sinais , Biomarcadores Tumorais/genética , MicroRNAs/genética , Nomogramas
4.
Ann Hematol ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320471

RESUMO

Although the incidence and outcomes of rituximab-induced interstitial lung disease (RILD) have been partially reported, there are no systematic studies on the characteristics and types of RILD. This study aimed to investigate the clinical characteristics, bronchoalveolar lavage (BAL) findings, and treatment course of RILD in patients with non-Hodgkin lymphoma. We retrospectively analyzed the data from 321 patients with non-Hodgkin lymphoma who developed RILD between 2020 and 2022. The extent, distribution, and radiologic patterns of interstitial lung disease were determined using high-resolution computed tomography of the chest. BAL was performed in 299 (93.1%) patients to determine cellular distribution patterns and identify pathogenic microorganisms using metagenomic next-generation sequencing. All patients received combination therapy, with cyclophosphamide, doxorubicin, vincristine, and prednisone being the most commonly administered regimens. The median time from treatment to RILD development was 1.7 months. In the 217 patients who underwent metagenomic next-generation sequencing, 179 pathogenic microorganisms were detected, including 77 (43.0%) bacteria, 45 (25.1%) viruses, 28 (15.6%) Pneumocystis jirovecii strains, 17 (9.5%) fungi, 6 (3.5%) Mycobacterium tuberculosis, and 6 (3.5%) atypical pathogens. All RILD diagnoses were based on multidisciplinary team discussions and compliance with international standards. In conclusion, RILD exhibits a range of radiological and BAL patterns, reflecting different interstitial lung disease types. The most common patterns of RILD are infectious lung disease, organizing pneumonia, and nonspecific interstitial pneumonia. These findings enhance the understanding of RILD in patients with non-Hodgkin lymphoma and serve as a reference for best management guidelines in these patients.

5.
Ultrason Sonochem ; 110: 107031, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39173448

RESUMO

In recent years, ultrasound has emerged as a widely used technology for modifying proteins/peptides. In this study, we focused on the intrinsic mechanism of ultrasound-induced modification of bovine liver peptides, which were treated with ultrasound power of 0, 100, 200, 300, 400, and 500 W, and their physicochemical and functional properties, as well as ultrastructures, were investigated. The results show that ultrasound mainly affects hydrogen bonding and hydrophobic interactions to change the conformation of proteins and unfolds proteins through a cavitation effect, leading to an increase in biological activity. Fourier infrared spectroscopy showed that ultrasound inhibited the formation of hydrogen bonds and reduced intermolecular cross-linking. Molecular weight distribution showed that the antioxidant components of bovine liver polypeptides were mainly concentrated in fractions of 500-1,000 Da. Maximum values of ABTS (82.66 %), DPPH (76.02 %), chelated iron (62.18 %), and reducing power (1.2447) were obtained by treating bovine liver polypeptides with 500 W ultrasound. Combined with the scanning electron microscopy results, with the intervention of ultrasound, the impact force generated by ultrasonication may lead to the loosening of the protein structure, which further promotes the release of antioxidant peptides, and these findings provide new insights into the application of ultrasound in the release of antioxidant peptides from bovine liver.


Assuntos
Fígado , Peptídeos , Ondas Ultrassônicas , Animais , Bovinos , Peptídeos/química , Antioxidantes/química , Antioxidantes/farmacologia , Fenômenos Químicos
6.
Clin Exp Pharmacol Physiol ; 51(10): e13914, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39139001

RESUMO

The pleiotropic effect of cancer-associated fibroblasts (CAFs) on tumour progression depends on the environment. circFARP1 is critical for CAFs-induced gemcitabine (GEM) resistance in pancreatic cancer. Its specific role and mechanism in non-small cell lung cancer (NSCLC) have not been reported yet. We prepared a cancer-associated fibroblasts-conditioned medium (CAF-CM) to incubate the A549 cells. Quantitative real-time polymerase chain reaction was used to detect RNA levels. We detected protein expression by immunohistochemistry, immunocytochemistry, western blot and immunofluorescence. We also detected the targeting impact between circFARP1, miR-338-3p and SRY-box transcription factor 4 (SOX4) by using dual-luciferase reporter and RNA pull-down assays. We determined cell proliferation, migration and invasion capabilities through Cell Counting Kit-8 and transwell assays. In addition, we measured tumour volume and weight in vivo by establishing a xenograft tumour model. CircFARP1 levels were remarkably high in the CAFs. The transfection experiments found that circFARP1 downregulation in CAFs caused migration, proliferation and invasion inhibition of CAFs and A549 cells, whereas inhibiting miR-38-3p or overexpressing SOX4 in CAFs could significantly reverse the inhibition. In vivo study in nude mice confirmed that CAFs could promote NSCLC tumour growth and knockdown of circFARP1 could inhibit tumour growth of NSCLC, whereas miR-38-3p downregulation or SOX4 overexpression could significantly reverse the inhibition. circFARP1 promotes NSCLC development by stimulating miR-338-3p/SOX4 signalling axis to regulate CAFs.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Invasividade Neoplásica , RNA Circular , Fatores de Transcrição SOXC , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Animais , RNA Circular/genética , RNA Circular/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Proliferação de Células/genética , Camundongos , Células A549 , Metástase Neoplásica , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Masculino
7.
Physiol Plant ; 176(4): e14422, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962815

RESUMO

Low temperatures pose a common challenge in the production of cucumbers and tomatoes, hindering plant growth and, in severe cases, leading to plant death. In our investigation, we observed a substantial improvement in the growth of cucumber and tomato seedlings through the application of corn steep liquor (CSL), myo-inositol (MI), and their combinations. When subjected to low-temperature stress, these treatments resulted in heightened levels of photosynthetic pigments, thereby fostering enhanced photosynthesis in both tomato and cucumber plants. Furthermore, it contributed to a decrease in malondialdehyde (MDA) levels and electrolyte leakage (REP). The effectiveness of the treatment was further validated through the analysis of key gene expressions (CBF1, COR, MIOX4, and MIPS1) in cucumber. Particularly, noteworthy positive outcomes were noted in the treatment involving 0.6 mL L-1 CSL combined with 72 mg L-1 MI. This study provides valuable technical insights into leveraging the synergistic effects of inositol and maize leachate to promote early crop growth and bolster resistance to low temperatures.


Assuntos
Temperatura Baixa , Cucumis sativus , Inositol , Plântula , Solanum lycopersicum , Zea mays , Inositol/metabolismo , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Zea mays/genética , Zea mays/fisiologia , Plântula/crescimento & desenvolvimento , Plântula/genética , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Solanum lycopersicum/fisiologia , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/metabolismo , Cucumis sativus/genética , Cucumis sativus/fisiologia , Fotossíntese/efeitos dos fármacos , Malondialdeído/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos
8.
Rev Sci Instrum ; 95(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38722213

RESUMO

In the experimental advanced superconducting tokamak (EAST), a novel ion cyclotron range of frequency (ICRF) antenna-based diagnostic system is designed to measure ion cyclotron emission (ICE) driven by high-energy ions. The diagnostic system includes ICRF antenna straps, a three-tune impedance matching system, a coaxial switching system, a direct current block, and a data acquisition and storage system. Using the coaxial switching system, the ICRF antenna can be switched from the heating mode to the coupling mode between two discharges. In the 2023 EAST experiment campaign, core ICE was observed using the ICRF antenna-based diagnostic system during neutron beam injection heating, and the obtained results agreed well with the signal detected by the previous high-frequency B-dot probe-based diagnostic system.

9.
BMC Geriatr ; 24(1): 478, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822230

RESUMO

BACKGROUND: Evidence of the optimal blood pressure (BP) target for older adults with disability in long-term care is limited. We aim to analyze the associations of BP with mortality in older adults in long-term care setting with different levels of disability. METHODS: This prospective cohort study was based on the government-led long-term care programme in Chengdu, China, including 41,004 consecutive disabled adults aged ≥ 60 years. BP was measured during the baseline survey by trained medical personnel using electronic sphygmomanometers. Disability profile was assessed using the Barthel index. The association between blood pressure and mortality was analyzed with doubly robust estimation, which combined exposure model by inverse probability weighting and outcome model fitted with Cox regression. The non-linearity was examined by restricted cubic spline. The primary endpoint was all-cause mortality, and the secondary endpoints were cardiovascular and non-cardiovascular mortality. RESULTS: The associations between systolic blood pressure (SBP) and all-cause mortality were close to a U-shaped curve in mild-moderate disability group (Barthel index ≥ 40), and a reversed J-shaped in severe disability group (Barthel index < 40). In mild-moderate disability group, SBP < 135 mmHg was associated with elevated all-cause mortality risks (HR 1.21, 95% CI, 1.10-1.33), compared to SBP between 135 and 150 mmHg. In severe disability group, SBP < 150 mmHg increased all-cause mortality risks (HR 1.21, 95% CI, 1.16-1.27), compared to SBP between 150 and 170 mmHg. The associations were robust in subgroup analyses in terms of age, gender, cardiovascular comorbidity and antihypertensive treatment. Diastolic blood pressure (DBP) < 67 mmHg (HR 1.29, 95% CI, 1.18-1.42) in mild-moderate disability group and < 79 mmHg (HR 1.15, 95% CI, 1.11-1.20) in severe disability group both demonstrated an increased all-cause mortality risk. CONCLUSION: The optimal SBP range was found to be higher in older individuals in long-term care with severe disability (150-170mmHg) compared to those with mild to moderate disability (135-150mmHg). This study provides new evidence that antihypertensive treatment should be administered cautiously in severe disability group in long-term care setting. Additionally, assessment of disability using the Barthel index can serve as a valuable tool in customizing the optimal BP management strategy. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2100049973).


Assuntos
Pressão Sanguínea , Pessoas com Deficiência , Assistência de Longa Duração , Humanos , Masculino , Feminino , Idoso , China/epidemiologia , Estudos Prospectivos , Assistência de Longa Duração/métodos , Assistência de Longa Duração/tendências , Pressão Sanguínea/fisiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos de Coortes , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Hipertensão/epidemiologia , Mortalidade/tendências , População do Leste Asiático
10.
Thromb Haemost ; 124(10): 897-911, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38744425

RESUMO

The consensus guidelines of the Geriatric Society of Chinese Medical Association on the management of atrial fibrillation (AF) in the elderly was first published in 2011 and updated in 2016, with endorsement by Chinese Society of Geriatric Health Medicine. Since then, many important studies regarding the screening and treatment in the elderly population have been reported, necessitating this updated expert consensus guideline. The writing committee members comprehensively reviewed updated evidence pertaining to elderly patients with AF, and formulated this 2024 update. The highlighted issues focused on the following: screening for AF, geriatric comprehensive assessment, use of the Atrial fibrillation Better Care (ABC) pathway for the elderly patients, and special clinical settings related to elderly patients with AF. New recommendations addressing smart technology facilitated AF screening, ABC pathway based management, and optimal anticoagulation were developed, with a focus on the elderly.


Assuntos
Anticoagulantes , Fibrilação Atrial , Consenso , Geriatria , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Idoso , Anticoagulantes/uso terapêutico , China/epidemiologia , Geriatria/normas , Idoso de 80 Anos ou mais , Avaliação Geriátrica , Sociedades Médicas , Fatores Etários , Fatores de Risco
11.
Oncogene ; 43(28): 2160-2171, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38783100

RESUMO

It has been demonstrated that tRNA-derived small RNAs (tsRNAs) perform essential functions in the pathophysiology of cancer. In this study, we focused on the possible mechanisms of tRF-33-P4R8YP9LON4VDP (tRF-33) underlying the development of gastric malignancy. In total, 454 tissue samples with different gastric mucosal lesions were collected. The tRF-33 expression level in different cohorts was determined, and its value for diagnostic efficiency and prognosis evaluation were assessed. Cell proliferation assays, Transwell assay, flow cytometry, and xenotransplantation model were used to evaluate its effect on gastric cancer cells. The molecular mechanism was verified by fluorescence in situ hybridization, dual luciferase assay, Western blot, and RNA binding protein immunoprecipitation. The results showed that the expression of tRF-33 exhibited a gradual modification from normal control samples to gastritis tissues, early and latent stage of gastric cancer tissues. Consequently, tRF-33 holds significant potential as a predictive and diagnostic biomarker for gastric malignancy. Over-expression of tRF-33 inhibited gastric cancer cell progression and metastatic viability, and induced cell apoptosis. Tumorigenicity in nude mice showed the suppressive characteristics of tRF-33. Mechanistic investigation revealed that tRF-33 exerted silencing on STAT3 mRNA via binding to AGO2. In conclusion, tRF-33 exhibited values in diagnosing gastric cancer and evaluating its prognosis, and suppressed tumor cell viability by inhibiting STAT3 signaling pathway. The schematic mechanisms underlying tRF-33 regulating gastric cancer occurrence. tRF-33 binds to AGO2 proteins and then negatively regulates STAT3 expression through targeting its 3'UTR. The downregulated expression of STAT3 results in the decrease of STAT3 and p-STAT3 and further blocks the transcription of the downstream genes and finally inhibits the gastric cancer occurrence. MMP-9, matrix metalloproteinase-9; Bcl-2, B-cell lymphoma-2; STAT3, signal transducer and activator of transcription 3; UTR, untranslated region.


Assuntos
Proteínas Argonautas , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Fator de Transcrição STAT3 , Transdução de Sinais , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Animais , Transdução de Sinais/genética , Camundongos , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Masculino , Apoptose/genética , Feminino , Prognóstico , Camundongos Endogâmicos BALB C
12.
PLoS One ; 19(4): e0298153, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38603661

RESUMO

OBJECTIVE: The Da Vinci Robot is the most advanced micro-control system in endoscopic surgical instruments and has gained a lot of valuable experience today. However, the technical feasibility and oncological safety of the robot over open surgery are still uncertain. This work is to systematically evaluate the efficacy of the unilateral axillary approach for robotic surgery compared to open surgery for differentiated thyroid carcinoma. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were utilized to search for relevant literatures of robotic thyroid surgery using unilateral axillary approach compared to open thyroid surgery, and a meta-analysis was performed using RevMan software version 5.3. Statistical analysis was performed through Mantle-Haenszel and inverse variance methods. RESULTS: Twelve studies with a total of 2660 patients were included in the meta-analysis. The results showed that compared with the open group, the robotic group had a longer total thyroidectomy time, shorter hospital stay, less intraoperative bleeding, more postoperative drainage, fewer retrieved central lymph nodes, and higher cosmetic satisfaction (all P < 0.05). In contrast, temporary and permanent laryngeal recurrent nerve injury, temporary and permanent hypoparathyroidism or hypocalcemia, brachial plexus nerve injury, number of retrieved central lymph nodes, number of retrieved lymph nodes in the lateral cervical region, number of lymph node metastases in the lateral cervical region, hematoma, seroma, lymphatic leak, stimulated thyroglobulin (sTg) and unstimulated thyroglobulin (uTg), and the number and recurrence rate of patients with sTg <1ng/ml were not statistically different between the two groups (P > 0.05). CONCLUSIONS: The unilateral axillary approach for robotic thyroid surgery may achieve outcomes similar to those of open surgery. Further validation is required in a prospective randomized controlled trial.


Assuntos
Adenocarcinoma , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Glândula Tireoide , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Tireoglobulina , Estudos Prospectivos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Robótica/métodos , Tireoidectomia/efeitos adversos , Adenocarcinoma/cirurgia , Estudos Retrospectivos , Esvaziamento Cervical
13.
Parasit Vectors ; 17(1): 191, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643189

RESUMO

BACKGROUND: Toxoplasma gondii is an obligate intracellular protozoan parasite that causes severe threats to humans and livestock. Macrophages are the cell type preferentially infected by T. gondii in vivo. Protein phosphorylation is an important posttranslational modification involved in diverse cellular functions. A rapidly accelerated fibrosarcoma kinase (A-Raf) is a member of the Raf family of serine/threonine protein kinases that is necessary for MAPK activation. Our previous research found that knockout of A-Raf could reduce T. gondii-induced apoptosis in porcine alveolar macrophages (3D4/21 cells). However, limited information is available on protein phosphorylation variations and the role of A-Raf in macrophages infected with T. gondii. METHODS: We used immobilized metal affinity chromatography (IMAC) in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile changes in phosphorylation in T. gondii-infected 3D4/21 and 3D4/21-ΔAraf cells. RESULTS: A total of 1647 differentially expressed phosphorylated proteins (DEPPs) with 3876 differentially phosphorylated sites (DPSs) were identified in T. gondii-infected 3D4/21 cells (p3T group) when compared with uninfected 3D4/21 cells (pho3 group), and 959 DEPPs with 1540 DPSs were identified in the p3T group compared with infected 3D4/21-ΔAraf cells (p3KT group). Venn analysis revealed 552 DPSs corresponding to 406 DEPPs with the same phosphorylated sites when comparing p3T/pho3 versus p3T/p3KT, which were identified as DPSs and DEPPs that were directly or indirectly related to A-Raf. CONCLUSIONS: Our results revealed distinct responses of macrophages to T. gondii infection and the potential roles of A-Raf in fighting infection via phosphorylation of crucial proteins.


Assuntos
Fibrossarcoma , Toxoplasma , Toxoplasmose , Humanos , Animais , Suínos , Fosforilação , Cromatografia Líquida , Espectrometria de Massas em Tandem , Toxoplasmose/parasitologia , Toxoplasma/fisiologia , Macrófagos/metabolismo
14.
Curr Mol Med ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38310550

RESUMO

BACKGROUND: Radiosensitivity remains an important factor affecting the clinical outcome of radiotherapy for non-small cell lung cancer (NSCLC). Liver kinase B1 (LKB1) as a tumor suppressor, is one of the most commonly mutated genes in NSCLC. However, the role of LKB1 on radiosensitivity and the possible mechanism have not been elucidated in the NSCLC. In this study, we investigated the regulatory function of LKB1 in the radiosensitivity of NSCLC cells and its possible signaling pathways. METHODS: After regulating the expression of LKB1, cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assay. The flow cytometry assay was used to analyse cell cycle distribution. Survival fraction and sensitization enhancement ratio (SER) were generated by clonogenic survival assay. Western blot analysis was used to assess expression levels of LKB1, p53, p21, γ-H2AX and p-Chk2. RESULTS: Our study found that when the NSCLC cells were exposed to ionizing radiation, LKB1 could inhibit NSCLC cell proliferation by promoting DNA double strand break and inducing DNA repair. In addition, LKB1 could induce NSCLC cells G1 and G2/M phase arrest through up-regulating expression of p53 and p21 proteins. CONCLUSION: This current study demonstrates that LKB1 enhances the radiosensitivity of NSCLC cells via inhibiting NSCLC cell proliferation and inducing G2/M phase arrest, and the mechanism of cell cycle arrest associated with signaling pathways of p53 and p21 probably.

15.
Sci Total Environ ; 921: 171126, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38387574

RESUMO

A growing consensus is reached that microbes contributes to regulating the formation and accumulation of soil organic carbon (SOC). Nevertheless, less is known about the role of soil microbes (necromass, biomass) in SOC accumulation in different habitat conditions in alpine ecosystems. To address this knowledge gap, the composition and distribution of amino sugars (ASs) and phospholipid fatty acids (PLFAs) as biomarkers of microbial necromass and biomass were investigated in forest, meadow and wetland soil profile (0-40 cm) of Mount Segrila, Tibet, China, as well the contribution of bacterial and fungal necromass to SOC. The results revealed that microbial necromass carbon contributed 45.15 %, 72.51 % and 78.08 % on average to SOC in 0-40 cm forest, meadow and wetland soils, respectively, and decreased with microbial biomass. Fungal necromass contributed more to SOC in these habitats than bacterial necromass. Microbial necromass increased with microbial biomass and both of them decreased with soil depth in all habitats. The necromass accumulation coefficient was significantly correlated with microbial necromass and biomass, affected by habitat and soil moisture. Structural equation model indicated that soil abiotic factors indirectly mediated the accumulation of SOC through microbial necromass and biomass. This study revealed that different habitats and soil depths control considerably soil physicochemical properties and microbial community, finally influencing SOC accumulation in alpine ecosystems, which emphasized the influence of abiotic factors on microbial necromass and biomass for SOC accumulation in alpine ecosystems.


Assuntos
Microbiota , Solo , Solo/química , Carbono , Microbiologia do Solo , Biomassa , Bactérias
16.
Food Sci Nutr ; 12(1): 35-47, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268870

RESUMO

As living standards advance, an escalating emphasis is placed on health, particularly in relation to prevalent chronic metabolic disorders. It is necessary to explore safe and effective functional foods or drugs. Fu brick tea (FBT) is a kind of dark tea fermented by fungi. The extracts are rich in compounds that can effectively relieve metabolic diseases such as hyperglycemia and hyperlipidemia, protect the liver, improve human immunity, enhance antioxidant activity, and regulate intestinal flora. This paper summarizes the biological activities and mechanisms of the extracts, polysaccharides, and small molecular compounds of FBT, which provides a certain theoretical basis for the rational, systematic, comprehensive development and utilization of the FBT resources. It is expected to develop and apply these active substances in health care products and natural medicines and provide more beneficial and diversified FBT products for human beings.

17.
J Clin Hypertens (Greenwich) ; 26(1): 71-83, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38126623

RESUMO

Nocturnal hypertension is highly prevalent among Chinese and Asian populations, which is mainly attributed to high salt intake and high salt sensitivity. Nocturnal hypertension increases the risk of cardiovascular and all-cause mortality, independent of daytime blood pressure (BP). However, it can usually be detected by 24-h ambulatory BP monitoring, rather than routine office or home BP measurement, thus is often underdiagnosed in clinical practice. Currently, no specific guidance is available for the management of nocturnal hypertension in China or worldwide. Experts from the Chinese Hypertension League summarized the epidemiologic and pathophysiologic characteristics and clinical phenotype of nocturnal hypertension and provided consensus recommendations on optimal management of nocturnal hypertension, with the goal of maximally reducing the cardiovascular disease risks. In this consensus document, 24-h ABPM is recommended for screening and diagnosis of nocturnal hypertension, especially in the elderly, patients with diabetes, chronic kidney diseases, obstructive sleep apnea and other conditions prone to high nocturnal BP. Lifestyle modifications including salt intake restriction, exercise, weight loss, sleep improvement, and mental stress relief are recommended. Long-acting antihypertensive medications are preferred for nocturnal and 24-h BP control. Some newly developed agents, renal denervation, and other device-based therapy on nocturnal BP reduction are evaluated.


Assuntos
Hipertensão , Humanos , Idoso , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Consenso , Cloreto de Sódio na Dieta/farmacologia , Ritmo Circadiano/fisiologia , Pressão Sanguínea/fisiologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Monitorização Ambulatorial da Pressão Arterial
18.
Heliyon ; 9(12): e22370, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38076164

RESUMO

The Huajiying Formation (135.4-128.7 Ma) of the northern Hebei represents the early stage of the Early Cretaceous Jehol Biota in China, yielding many kinds of vertebrates. The only known pterosaur specimen was incomplete and assigned to the Ornithocheiroidea. Here we report a more complete pterosaur specimen, assigned to the Ctenochasmatidae. A new taxon is established on two autapomorphies: a large pneumatic foramen present on the ventral surface of the proximal end of the first wing phalanx; and coracoid lacking an expansion at its contact with the scapula, as well as the following combination of characteristics: subsquare sternal plate; coracoid having an extremely concave articulation with a posterior expansion; humerus without a tubercle on the proximal margin between the deltopectoral crest and the head; humerus slightly longer than the wing metacarpal; and the first and third wing phalanges equal in length. The relative thicknesses of bone walls are investigated among pterosaurs in three ways. The overall distribution of R/t ratios shows that most non-pterodactyloids, archaeopterodactyloids, and dsungaripterids have smaller R/t ratios than other groups. Relatively thick bone walls are not unique for the Dsungaripteridae as previously thought, and the humerus and radius of dsungaripterids have thinner walls than other bones. The feature of small R/t ratios is plesiomorphic and the thin-walled humerus and radius of dsungaripterids were evolved to meet the need of the flight, not for frequent take-off and landing as previously thought.

19.
Sci Rep ; 13(1): 22642, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129429

RESUMO

The Chaoyangopteridae is a clade of azhdarchoid pterosaurs that stands out in China, particularly in the Jehol Biota, as a Cretaceous group of medium-sized and high-crested pterosaurs. Herein, we describe a new species, Meilifeilong youhao gen. et sp. nov., based on two specimens, one tentatively referred to this taxon. This new species represents the most complete and well-preserved chaoyangopterid recorded to date. Along with a set of characters (low premaxillary crest above the nasoantorbital fenestra extending posteriorly, posterior premaxillary process arched and curving posteriorly, a slightly convex sternal articulation surface of coracoid, and a fibular shaft close to proximal articulation strongly arched posteriorly), this species also provides new information both on the unknown palatal region of this clade, and on the rarely preserved (in place) ear portion with stapes. Moreover, M. youhao sheds light on paleoecological aspects, while also giving new information about the taxonomic diversity of this peculiar group of Jiufotang pterosaurs.


Assuntos
Dinossauros , Fósseis , Animais , Filogenia , Dinossauros/anatomia & histologia , China , Biota
20.
Plants (Basel) ; 12(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38140437

RESUMO

Salinity poses a significant threat to plant growth through induction of osmotic and ionic stress and disruption of nutrient absorption. Biostimulants derived from agricultural waste offer a sustainable solution to alleviate salt-induced damage to plants and contribute to a circular and sustainable economy. In this study, we applied a combination of myo-inositol and corn steep liquor from waste sources to seedling cabbage (Brassica rapa subsp. pekinensis) and investigated their effects on plant growth under NaCl-simulated salt stress. Different concentrations of myo-inositol and corn steep liquor were applied to the roots, revealing that 150 mM NaCl significantly inhibited the growth and physiological metabolism of cabbage seedlings. Substrate application of myo-inositol, corn steep liquor, and their combination materials increased biomass, photosynthetic pigments, soluble sugars, soluble proteins, and the contents of K+, Ca2+, and Mg2+ in cabbage under salt stress conditions, while reducing malondialdehyde, electrolyte leakage, Na+ content, and the ratios of Na+/K+, Na+/Ca2+, and Na+/Mg2+. Therefore, root application of myo-inositol, corn steep liquor, and myo-inositol-corn steep liquor combination materials enhanced photosynthesis and enhanced cabbage salt stress resistance by maintaining cell osmotic and ion balance. The most pronounced positive effects were observed in the treatment with 0.1 mL L-1 corn steep liquor +288 mg L-1 myo-inositol. This study provides a theoretical basis and technical guidance for the combined utilization of myo-inositol and corn steep liquor to boost early growth and salt resistance in crops.

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