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1.
Sci Rep ; 14(1): 10540, 2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719945

RESUMO

Viruses are crucial for regulating deep-sea microbial communities and biogeochemical cycles. However, their roles are still less characterized in deep-sea holobionts. Bathymodioline mussels are endemic species inhabiting cold seeps and harboring endosymbionts in gill epithelial cells for nutrition. This study unveiled a diverse array of viruses in the gill tissues of Gigantidas platifrons mussels and analyzed the viral metagenome and transcriptome from the gill tissues of Gigantidas platifrons mussels collected from a cold seep in the South Sea. The mussel gills contained various viruses including Baculoviridae, Rountreeviridae, Myoviridae and Siphovirdae, but the active viromes were Myoviridae, Siphoviridae, and Podoviridae belonging to the order Caudovirales. The overall viral community structure showed significant variation among environments with different methane concentrations. Transcriptome analysis indicated high expression of viral structural genes, integrase, and restriction endonuclease genes in a high methane concentration environment, suggesting frequent virus infection and replication. Furthermore, two viruses (GP-phage-contig14 and GP-phage-contig72) interacted with Gigantidas platifrons methanotrophic gill symbionts (bathymodiolin mussels host intracellular methanotrophic Gammaproteobacteria in their gills), showing high expression levels, and have huge different expression in different methane concentrations. Additionally, single-stranded DNA viruses may play a potential auxiliary role in the virus-host interaction using indirect bioinformatics methods. Moreover, the Cro and DNA methylase genes had phylogenetic similarity between the virus and Gigantidas platifrons methanotrophic gill symbionts. This study also explored a variety of viruses in the gill tissues of Gigantidas platifrons and revealed that bacteria interacted with the viruses during the symbiosis with Gigantidas platifrons. This study provides fundamental insights into the interplay of microorganisms within Gigantidas platifrons mussels in deep sea.


Assuntos
Bacteriófagos , Bivalves , Brânquias , Metagenômica , Animais , Metagenômica/métodos , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Brânquias/microbiologia , Brânquias/virologia , Brânquias/metabolismo , Bivalves/microbiologia , Bivalves/virologia , Bivalves/genética , Perfilação da Expressão Gênica , Transcriptoma , Viroma/genética , Bactérias/genética , Bactérias/classificação , Simbiose/genética , Metagenoma
2.
BMC Neurol ; 24(1): 158, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730325

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a natural focal disease transmitted mainly by tick bites, and the causative agent is SFTS virus (SFTSV). SFTS can rapidly progress to severe disease, with multiple-organ failure (MOF) manifestations such as shock, respiratory failure, disseminated intravascular coagulation (DIC) and death, but cases of SFTS patients with central nervous system (CNS) symptoms onset and marked persistent involuntary shaking of the perioral area and limbs have rarely been reported. CASE PRESENTATION: A 69-year-old woman with fever and persistent involuntary shaking of the perioral area and limbs was diagnosed with SFTS with CNS symptom onset after metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and peripheral blood identified SFTSV. The patient developed a cytokine storm and MOF during the course of the disease, and after aggressive antiviral, glucocorticoid, and gamma globulin treatments, her clinical symptoms improved, her laboratory indices returned to normal, and she had a good prognosis. CONCLUSION: This case gives us great insight that when patients with CNS symptoms similar to those of viral encephalitis combined with thrombocytopenia and leukopenia are encountered in the clinic, it is necessary to consider the possibility of SFTS involving the CNS. Testing for SFTSV nucleic acid in CSF and blood (mNGS or polymerase chain reaction (PCR)) should be carried out, especially in critically ill patients, and treatment should be given accordingly.


Assuntos
Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Feminino , Idoso , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Phlebovirus/genética , Phlebovirus/isolamento & purificação , Insuficiência de Múltiplos Órgãos/virologia , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia
4.
Biomaterials ; 309: 122603, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38713972

RESUMO

Sympathetic nerves play a pivotal role in promoting tumor growth through crosstalk with tumor and stromal cells. Chemotherapy exacerbates the infiltration of sympathetic nerves into tumors, thereby providing a rationale for inhibiting sympathetic innervation to enhance chemotherapy. Here, we discovered that doxorubicin increases the density and activity of sympathetic nerves in breast cancer mainly by upregulating the expression of nerve growth factors (NGFs) in cancer cells. To address this, we developed a combination therapy by co-encapsulating small interfering RNA (siRNA) and doxorubicin within breast cancer-targeted poly (lactic-co-glycolic acid) (PLGA) nanoparticles, aiming to suppress NGF expression post-chemotherapy. Incorporating NGF blockade into the nanoplatform for chemotherapy effectively mitigated the chemotherapy-induced proliferation of sympathetic nerves. This not only bolstered the tumoricidal activity of chemotherapy, but also amplified its stimulatory impact on the antitumor immune response by increasing the infiltration of immunostimulatory cells into tumors while concurrently reducing the frequency of immunosuppressive cells. Consequently, the combined nanodrug approach, when coupled with anti-PD-L1 treatment, exhibited a remarkable suppression of primary and deeply metastatic tumors with minimal systematic toxicity. Importantly, the nanoplatform relieved chemotherapy-induced peripheral neuropathic pain (CIPNP) by diminishing the expression of pain mediator NGFs. In summary, this research underscores the significant potential of NGF knockdown in enhancing immunochemotherapy outcomes and presents a nanoplatform for the highly efficient and low-toxicity treatment of breast cancer.

5.
Plant Physiol Biochem ; 211: 108708, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38733938

RESUMO

S-Adenosyl-L-methionine (SAM) is widely involved in plant growth, development, and abiotic stress response. SAM synthetase (SAMS) is the key enzyme that catalyzes the synthesis of SAM from methionine and ATP. However, the SAMS gene family has not been identified and their functions have not been characterized in most Cucurbitaceae plants. Here, a total of 30 SAMS genes were identified in nine Cucurbitaceae species and they were categorized into 3 subfamilies. Physicochemical properties and gene structure analysis showed that the SAMS protein members are tightly conserved. Further analysis of the cis-regulatory elements (CREs) of SAMS genes' promoter implied their potential roles in stress tolerance. To further understand the molecular functions of SAMS genes, watermelon SAMSs (ClSAMSs) were chosen to analyze the expression patterns in different tissues and under various abiotic stress and hormone responses. Among the investigated genes, ClSAMS1 expression was observed in all tissues and found to be up-regulated by abiotic stresses including salt, cold and drought treatments as well as exogenous hormone treatments including ETH, SA, MeJA and ABA. Furthermore, knockdown of ClSAMS1 via virus-induced gene silencing (VIGS) decreased SAM contents in watermelon seedings. The pTRSV2-ClSAMS1 plants showed reduced susceptibility to drought, cold and NaCl stress, indicating a positive role of ClSAMS1 in abiotic stresses tolerance. Those results provided candidate SAMS genes to regulate plant resistance against abiotic stresses in Cucurbitaceae plants.

6.
J Proteomics ; : 105195, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734407

RESUMO

Different populations exhibit varying pathophysiological responses to plateau environments. Therefore, it is crucial to identify molecular markers in body fluids with high specificity and sensitivity to aid in determination. Proteomics offers a fresh perspective for investigating protein changes linked to diseases. We utilize urine as a specific biomarker for early chronic mountain sickness (CMS) detection, as it is a simple-to-collect biological fluid. We collected urine samples from three groups: plains health, plateau health and CMS. Using DIA's proteomic approach, we found differentially expressed proteins between these groups, which will be used as a basis for future studies to identify protein markers. Compared with the healthy plain population, 660 altering proteins were identified in plateau health, which performed the resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Compared to the healthy plateau population, the CMS group had 140 different proteins identified, out of which 8 were potential biomarkers for CMS. Our study has suggested that CMS may be closely related to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity. SIGNIFICANCE: Our team has compiled a comprehensive dataset of urine proteomics for AMS disease. We successfully identified differentially expressed proteins between healthy and AMS groups using the DIA proteomic approach. We discovered that 660 proteins were altered in plateau health compared to the healthy plain population, resulting in a heightened resistance to altitude response function by boosting substance metabolism and reducing immune stress function. Additionally, we pinpointed 140 different proteins in the AMS group compared to the healthy plateau population, with 8 showing potential as biomarkers for AMS. Our findings suggest that the onset of AMS may be closely linked to increased thyroid hormone levels, oxidative damage to the mitochondria, impaired cell detoxification function and inhibited hydrolase activity.

7.
Water Res ; 257: 121693, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38728785

RESUMO

Cyanobacterial harmful algal blooms (cyanoHABs) are becoming increasingly common in aquatic ecosystems worldwide. However, their heterogeneous distributions make it difficult to accurately estimate the total algae biomass and forecast the occurrence of surface cyanoHABs by using traditional monitoring methods. Although various optical instruments and remote sensing methods have been employed to monitor the dynamics of cyanoHABs at the water surface (i.e., bloom area, chlorophyll a), there is no effective in-situ methodology to monitor the dynamic change of cell density and integrated biovolume of algae throughout the water column. In this study, we propose a quantitative protocol for simultaneously measurements of multiple indicators (i.e., biovolume concentration, size distribution, cell density, and column-integrated biovolume) of cyanoHABs in water bodies by using the laser in-situ scattering and transmissometry (LISST) instrument. The accuracy of measurements of the biovolume and colony size of algae was evaluated and exceeded 95% when the water bloom was dominated by cyanobacteria. Furthermore, the cell density of cyanobacteria was well estimated based on total biovolume and mean cell volume measured by the instrument. Therefore, this methodology has the potential to be used for broader applications, not only to monitor the spatial and temporal distribution of algal biovolume concentration but also monitor the vertical distribution of cell density, biomass and their relationship with size distribution patterns. This provides new technical means for the monitoring and analysis of algae migration and early warning of the formation of cyanoHABs in lakes and reservoirs.

8.
Prev Med ; : 107978, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38697227

RESUMO

OBJECTIVE: Insufficient sleep and skipping breakfast are increasingly prevalent among children and adolescents. Both behaviors are associated with the onset of depression. This study aims to examine the independent and joint associations of these two behaviors with depressive symptoms, and investigate whether these associations varied by age or sex. METHODS: The Center for Epidemiological Studies Depression Scale (CESD) was used to evaluate the depressive symptoms. This cross-sectional study including 11,887 students aged 11-19 years using a stratified cluster, multistage sampling method in Ningbo, China. Multiple logistic regressions were conducted to evaluate the independent and joint association between insufficient sleep, skipping breakfast and depressive symptoms. Sensitivity analyses and stratified analyses by age and sex were performed using the same modelling strategies. RESULTS: The overall prevalence of depressive symptoms was 15.27%. Skipping breakfast (Odds Ratio (OR) = 2.557, 95% Confidence Interval (CI) = 2.236-2.925) and insufficient sleep (OR = 1.547, 95%CI = 1.390-1.723) was independently associated with depressive symptoms. Compared to students with "sufficient sleep and breakfast every day", the OR was 4.385 (95%CI = 3.649-5.271) for those with "insufficient sleep and skipping breakfast". Meanwhile, the joint association was moderated by age group, with a more apparent association observed in the 11-15-year-old group compared to the 16-19-year-old group. CONCLUSIONS: These findings indicated that insufficient sleep and skipping breakfast were independently and jointly associated with depressive symptoms. Insufficient sleep and skipping breakfast could be considered as two of the predictors of depression.

9.
Acta Pharmacol Sin ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698214

RESUMO

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

10.
J Hypertens ; 42(6): 1066-1074, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690905

RESUMO

OBJECTIVE: The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension. METHODS: We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). RESULTS: During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24-1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66-0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence. CONCLUSION: Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.


Assuntos
Bancos de Espécimes Biológicos , Biomarcadores , Hipertensão , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Biomarcadores/sangue , Masculino , Feminino , Adulto , Fatores de Risco , Idoso , Biobanco do Reino Unido
11.
PLoS One ; 19(5): e0301484, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696398

RESUMO

BACKGROUND AND STUDY AIM: The klotho protein, a multifunctional protein, has been shown to be associated with a wide range of endocrine diseases and has been linked to thyroid tumourigenesis. However, the relationship between serum klotho levels and thyroid hormones remains poorly understood. This study aimed to explore the correlation between serum klotho levels and thyroid hormones. METHODS: Data was obtained from the NHANES cycles 2007-2008, 2009-2010, and 2011-2012. A total of 4674 participants were recruited for this study. Statistical analysis was using multiple linear regression analyses, and restricted cubic spline plots (RCS) to investigate the association between serum klotho levels and serum levels of thyroid hormones. RESULTS: In the unadjusted covariate model, ln(klotho) significantly positively correlated with tT3, tT4, fT3, tT4/fT4, and tT3/fT3 (all P<0.01) and negatively correlated with TSH, tT4/tT3, and fT4/fT3 (all P<0.05). Furthermore, tT3, tT4, fT3and tT3/fT3 (P < 0.05) were still significant in the adjusted model. And it is worth noting that there is an approximately L-shaped nonlinear relationship between ln(klotho) and fT3,tT3 with a cut-off point of 6.697 (P-non-linear < 0.05). The stratification analysis showed gender and iodine level differences in the relationship between serum Klotho levels and thyroid hormones. CONCLUSION: There is an L-shaped nonlinear relationship between ln(klotho) and fT3, tT3, suggesting that klotho could be involved in the physiological regulation of thyroid function.


Assuntos
Glucuronidase , Proteínas Klotho , Hormônios Tireóideos , Humanos , Masculino , Feminino , Glucuronidase/sangue , Estudos Transversais , Hormônios Tireóideos/sangue , Pessoa de Meia-Idade , Adulto , Idoso
12.
Plants (Basel) ; 13(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38732488

RESUMO

Dioscorea alata, commonly known as "greater yam", is a vital crop in tropical and subtropical regions of the world, yet it faces significant threats from anthracnose disease, mainly caused by Colletotrichum gloeosporioides. However, exploring disease resistance genes in this species has been challenging due to the difficulty of genetic mapping resulting from the loss of the flowering trait in many varieties. The receptor-like kinase (RLK) gene family represents essential immune receptors in plants. In this study, genomic analysis revealed 467 RLK genes in D. alata. The identified RLKs were distributed unevenly across chromosomes, likely due to tandem duplication events. However, a considerable number of ancient whole-genome or segmental duplications dating back over 100 million years contributed to the diversity of RLK genes. Phylogenetic analysis unveiled at least 356 ancient RLK lineages in the common ancestor of Dioscoreaceae, which differentially inherited and expanded to form the current RLK profiles of D. alata and its relatives. The analysis of cis-regulatory elements indicated the involvement of RLK genes in diverse stress responses. Transcriptome analysis identified RLKs that were up-regulated in response to C. gloeosporioides infection, suggesting their potential role in resisting anthracnose disease. These findings provide novel insights into the evolution of RLK genes in D. alata and their potential contribution to disease resistance.

13.
Polymers (Basel) ; 16(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38732732

RESUMO

Nano-hydroxyapatite (n-HA) is the main inorganic component of natural bone, which has been widely used as a reinforcing filler for polymers in bone materials, and it can promote cell adhesion, proliferation, and differentiation. It can also produce interactions between cells and material surfaces through selective protein adsorption and has therefore always been a research hotspot in orthopedic materials. However, n-HA nano-particles are inherently easy to agglomerate and difficult to disperse evenly in the polymer. In addition, there are differences in trace elements between n-HA nano-particles and biological apatite, so the biological activity needs to be improved, and the slow degradation in vivo, which has seriously hindered the application of n-HA in bone fields, is unacceptable. Therefore, the modification of n-HA has been extensively reported in the literature. This article reviewed the physical modification and various chemical modification methods of n-HA in recent years, as well as their modification effects. In particular, various chemical modification methods and their modification effects were reviewed in detail. Finally, a summary and suggestions for the modification of n-HA were proposed, which would provide significant reference for achieving high-performance n-HA in biomedical applications.

14.
Clin Genet ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747114

RESUMO

Type IV collagen is an integral component of basement membranes. Mutations in COL4A1, one of the key genes encoding Type IV collagen, can result in a variety of diseases. It is clear that a significant proportion of mutations that affect splicing can cause disease directly or contribute to the susceptibility or severity of disease. Here, we analyzed exonic mutations and intronic mutations described in the COL4A1 gene using bioinformatics programs and identified candidate mutations that may alter the normal splicing pattern through a minigene system. We identified seven variants that induce splicing alterations by disrupting normal splice sites, creating new ones, or altering splice regulatory elements. These mutations are predicted to impact protein function. Our results help in the correct molecular characterization of variants in COL4A1 and may help develop more personalized treatment options.

15.
J Gen Virol ; 105(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747699

RESUMO

Nasopharyngeal carcinoma (NPC) carcinogenesis and malignant transformation are intimately associated with Epstein-Barr virus (EBV) infection. A zinc-fingered transcription factor known as Krüppel-like factor 5 (KLF5) has been shown to be aberrantly expressed in a number of cancer types. However, little is known about the regulatory pathways and roles of KLF5 in EBV-positive NPC. Our study found that KLF5 expression was significantly lower in EBV-positive NPC than in EBV-negative NPC. Further investigation revealed that EBER1, which is encoded by EBV, down-regulates KLF5 via the extracellular signal-regulated kinase (ERK) signalling pathway. This down-regulation of KLF5 by EBER1 contributes to maintaining latent EBV infection in NPC. Furthermore, we uncovered the biological roles of KLF5 in NPC cells. Specifically, KLF5 may influence the cell cycle, prevent apoptosis, and encourage cell migration and proliferation - all of which have a generally pro-cancer impact. In conclusion, these findings offer novel strategies for EBV-positive NPC patients' antitumour treatment.


Assuntos
Regulação para Baixo , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Fatores de Transcrição Kruppel-Like , Sistema de Sinalização das MAP Quinases , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiologia , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Apoptose , Latência Viral
16.
Mol Genet Genomics ; 299(1): 51, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743077

RESUMO

This study examines the prognostic role and immunological relevance of EMP1 (epithelial membrane protein-1) in a pan-cancer analysis, with a focus on ovarian cancer. Utilizing data from TCGA, CCLE, and GTEx databases, we assessed EMP1 mRNA expression and its correlation with tumor progression, prognosis, and immune microenvironment across various cancers. Our results indicate that EMP1 expression is significantly associated with poor prognosis in multiple cancer types, including ovarian, bladder, testicular, pancreatic, breast, brain, and uveal melanoma. Immune-related analyses reveal a positive correlation between EMP1 and immune cell infiltration, particularly neutrophils, macrophages, and dendritic cells, as well as high expression of immune checkpoint such as CD274, HAVCR2, IL10, PDCD1LG2, and TGFB1 in most tumors. In vivo experiments confirm that EMP1 promotes ovarian cancer cell proliferation, metastasis, and invasion. In conclusion, EMP1 emerges as a potential prognostic biomarker and therapeutic target in various cancers, particularly ovarian cancer, due to its influence on tumor progression and immune cell dynamics. Further research is warranted to elucidate the precise mechanisms of EMP1 in cancer biology and to translate these findings into clinical applications.


Assuntos
Biomarcadores Tumorais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Microambiente Tumoral , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Prognóstico , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Biomarcadores Tumorais/genética , Animais , Proliferação de Células/genética , Linhagem Celular Tumoral , Camundongos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Glicoproteínas de Membrana/genética
17.
Mol Neurobiol ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743210

RESUMO

PRNP Q160X is one of the five dominantly inheritable nonsense mutations causing familial prion diseases. Till now, it remains unclear how this type of nonsense mutations causes familial prion diseases with unique clinical and pathological characteristics. Human prion protein (PrP) Q160X mutation is equivalent to Q159X in mouse PrP, which produces the mutant fragment PrP1-158. Through intracerebroventricular injection of recombinant adeno-associated virus in newborn mice, we successfully overexpressed mouse PrP1-158-FLAG in the central nervous system. Interestingly, high level PrP1-158-FLAG expression in the brain caused death in these mice with an average survival time of 60 ± 9.1 days. Toxicity correlated with levels of PrP1-158-FLAG but was independent of endogenous PrP. Histopathological analyses showed microgliosis and astrogliosis in mouse brains expressing PrP1-158-FLAG and most of PrP1-158-FLAG staining appeared intracellular. Biochemical characterization revealed that the majority of PrP1-158-FLAG were insoluble and a significant part of PrP1-158-FLAG appeared to contain an un-cleaved signal peptide that may contribute to its cytoplasmic localization. Importantly, an ~10-kDa proteinase K-resistant PrP fragment was detected, which was the same as those observed in patients suffering from this type of prion diseases. To our knowledge, this is the first animal study of familial prion disease caused by Q159X that recapitulates key features of human disease. It will be a valuable tool for investigating the pathogenic mechanisms underlying familial prion diseases caused by nonsense mutations.

18.
Sci Total Environ ; : 173142, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38744395

RESUMO

Marine fuel combustion from shipping releases SO2 and forms sulfate particles, which may alter low cloud characteristics. A series of strategies were implemented to control the sulfur content of ship fuel oil from 2018 to 2020, offering insights into the effects of the ship fuel oil transition on sulfur-related pollutants and the consequent cloud condensation nuclei (CCN) in the atmosphere. Compared to 2018 in the southeast China waters, shipping SO2 emission decreased by 78 % in 2020, resulting in a 76 % reduction in ship-related total sulfur concentration, and a decrease of 54 % in CCN number concentration under supersaturation 0.2 % (CCN0.2) contributed by shipping. The response of CCN0.2 to ship-related sulfate modification is more pronounced in relatively clean environments than polluted environments, highlighting the uneven changes in coastal CCN along the Eastern China Sea induced by the ship fuel policies. CCN can trigger the formation of cloud droplets, 2020 fuel regulation may have and will reduce the cooling radiative forcing effect with strong spatial heterogeneity. The study provides insights into the variations in coastal atmospheric sulfur-related pollutants and CCN in uneven response to changes in ship fuel oil, prompting the need for further comprehensive assessments of the climate effects resulting from potential shifts in ship fuel use in the future.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38744769

RESUMO

Syngas produced from supercritical water gasification typically contain a high amount of CO2 along with H2. In order to improve the quality of syngas, amine-functionalized copper benzene-1,3,5-tricarboxylate (Cu-BTC) was synthesized as an effective adsorbent for selective removal of CO2 from syngas to increase the concentration of H2. The amines used in this study included monoethanolamine (MEA), ethylenediamine (EDA), and polyethyleneimine (PEI). The fundamental physicochemical character of adsorbents, CO2 adsorption capacity, and CO2/H2 selectivity were analyzed. The physicochemical characterization indicated that the structure of amine-functionalized Cu-BTC was partially damaged, which resulted in a decrease in specific surface area and pore volume. On the other hand, the enlarged pore size was beneficial for the mass transfer of gas in the adsorbent. Among these adsorbents, Cu-BTC/PEI exhibited the maximum CO2 adsorption capacity of 3.83 mmol/g and the highest CO2/H2 selectivity of 19.74. It was found that the adsorption pressure is the most significant factor for the CO2 adsorption capacity. Lower temperature and higher pressure were favored for CO2 adsorption capacity and CO2/H2 selectivity, so physical adsorption by Cu-BTC played a dominant role. Moreover, Cu-BTC/PEI can be well-regenerated with stable adsorption efficiency after five consecutive cycles. These findings suggested that Cu-BTC/PEI could be a promising alternative adsorbent for CO2 capture from syngas.

20.
Cancer Control ; 31: 10732748241253959, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736182

RESUMO

OBJECTIVE: To evaluate the effectiveness of oral probiotic supplements in patients undergoing immune checkpoint inhibitors (ICIs) for the treatment of advanced lung cancer. METHODS: This prospective real-world study enrolled patients with advanced lung cancer who were receiving ICIs as part of their treatment. The patients were divided into 2 groups: Group OPS received oral probiotic supplements along with ICIs, while Group C did not. The primary endpoint was progression-free survival (PFS). The secondary outcome measure was the objective response rate (ORR). RESULTS: A total of 253 patients were included in the study, with 71 patients in Group OPS and 182 patients in the control group (Group C). No significant differences were observed in the median PFS between the 2 groups for all patients. However, for small cell lung cancer (SCLC) patients, the median PFS was significantly better in the Group OPS compared to the Group C (11.1 months vs 7.0 months, P = .049). No significant differences were observed in median PFS for the non-small cell lung cancer (NSCLC) cohort between the 2 groups, but a trend towards better median PFS in Group OPS was noticed (16.5 months vs 12.3 months, P = .56). The ORR for the entire cohort was 58.0%. CONCLUSION: Oral probiotics supplements in combination with ICIs included regimen may improve the outcome in patients with advanced SCLC. The above points should be proved by further study.


This study examined whether the addition of oral probiotic supplements to ICIs could enhance the treatment of advanced lung cancer. A total of 253 patients with advanced lung cancer were involved in the study, with some receiving probiotics in combination with ICIs and others not. The findings revealed that patients with SCLC who took probiotics had significantly better PFS compared to those who did not. Additionally, there was a tendency towards enhanced PFS in NSCLC patients who received probiotics. In conclusion, the study indicates that incorporating oral probiotics with ICIs may lead to better outcomes for patients with advanced SCLC, although further research is necessary to validate these results.This real world study explores whether oral probiotic supplements along with immune checkpoint inhibitors (ICIs) can help treat advanced lung cancer. The study included 253 patients with advanced lung cancer receiving ICIs treatment, part of them taking probiotics along with ICIs. The results showed that patients with small cell lung cancer (SCLC) who took probiotics had better progression-free survival (PFS) compared to those who didn't. There was also a trend towards better PFS in non-small cell lung cancer (NSCLC) patients who took probiotics. Overall, the study suggests that taking oral probiotics along with ICIs may improve outcomes for patients with advanced SCLC, but more research is needed to confirm these findings.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Probióticos , Humanos , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/terapia , Carcinoma de Pequenas Células do Pulmão/patologia , Administração Oral , Suplementos Nutricionais , Intervalo Livre de Progressão , Terapias Complementares/métodos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Adulto
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