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1.
Glob Chang Biol ; 30(8): e17454, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39132898

RESUMO

Tropical and subtropical evergreen broadleaved forests (TEFs) contribute more than one-third of terrestrial gross primary productivity (GPP). However, the continental-scale leaf phenology-photosynthesis nexus over TEFs is still poorly understood to date. This knowledge gap hinders most light use efficiency (LUE) models from accurately simulating the GPP seasonality in TEFs. Leaf age is the crucial plant trait to link the dynamics of leaf phenology with GPP seasonality. Thus, here we incorporated the seasonal leaf area index of different leaf age cohorts into a widely used LUE model (i.e., EC-LUE) and proposed a novel leaf age-dependent LUE model (denoted as LA-LUE model). At the site level, the LA-LUE model (average R2 = .59, average root-mean-square error [RMSE] = 1.23 gC m-2 day-1) performs better than the EC-LUE model in simulating the GPP seasonality across the nine TEFs sites (average R2 = .18; average RMSE = 1.87 gC m-2 day-1). At the continental scale, the monthly GPP estimates from the LA-LUE model are consistent with FLUXCOM GPP data (R2 = .80; average RMSE = 1.74 gC m-2 day-1), and satellite-based GPP data retrieved from the global Orbiting Carbon Observatory-2 (OCO-2) based solar-induced chlorophyll fluorescence (SIF) product (GOSIF) (R2 = .64; average RMSE = 1.90 gC m-2 day-1) and the reconstructed TROPOspheric Monitoring Instrument SIF dataset using machine learning algorithms (RTSIF) (R2 = .78; average RMSE = 1.88 gC m-2 day-1). Typically, the estimated monthly GPP not only successfully represents the unimodal GPP seasonality near the Tropics of Cancer and Capricorn, but also captures well the bimodal GPP seasonality near the Equator. Overall, this study for the first time integrates the leaf age information into the satellite-based LUE model and provides a feasible implementation for mapping the continental-scale GPP seasonality over the entire TEFs.


Assuntos
Florestas , Folhas de Planta , Tecnologia de Sensoriamento Remoto , Estações do Ano , Folhas de Planta/crescimento & desenvolvimento , Fotossíntese , Modelos Teóricos , Luz , Árvores/crescimento & desenvolvimento , Modelos Biológicos , Clima Tropical
2.
iScience ; 27(7): 110286, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39055952

RESUMO

NME1 is a metastatic suppressor inconsistently reported to have multiple roles as both a promoter and inhibitor of cancer metastasis. Nevertheless, the specific mechanism behind these results is still unclear. We observed that A549 cells with stable transfer of NME1 into the nucleus (A549-nNm23-H1) exhibited significantly increased migration and invasion activity compared to vector control cells, which was further enhanced by over-expressing CYP24A1 (p < 0.001). NME1 demonstrated the ability to safely attach to and amplify the transcription activation of JUN, consequently leading to the up-regulation of CYP24A1. Analysis of clinical data showed a positive relationship between nuclear NME1 levels and CYP24A1 expression. Furthermore, they were positively associated with postoperative distant metastasis and negatively correlated with prognosis in those with early stage lung adenocarcinoma. In conclusion, the data presented provides a new understanding of the probable pathways by which nuclear NME1 facilitates tumor metastasis, establishing the groundwork for future prediction and treatment of tumor metastasis.

3.
Neoplasia ; 53: 101006, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38761505

RESUMO

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced non-small-cell lung cancer (NSCLC) with driver gene mutations. The Response Evaluation Criteria in Solid Tumors (RECIST) are limited in predicting long-term patient benefits. A tumour marker-based evaluation criteria, RecistTM, was used to investigate the potential for assessing targeted-therapy efficacy in lung cancer treatment. METHODS: We retrospectively analysed patients with stage IIIA-IV NSCLC and driver gene mutations, whose baseline tumour marker levels exceeded the pre-treatment cut-off value three-fold and who received TKI-targeted therapy as a first-line treatment. We compared efficacy, progression-free survival (PFS), and overall survival (OS) between RecistTM and RECIST. FINDINGS: The median PFS and OS differed significantly among treatment-response subgroups based on RecistTM but not RECIST. The predicted 1-, 2-, and 3-year disease-progression risk, according to area under the receiver operating characteristic curve, as well as the 1-, 3-, and 5-year mortality risk, differed significantly between RecistTM and RECIST. The median PFS and OS of tmCR according to RecistTM, was significantly longer than (CR+PR) according to RECIST. Imaging analysis revealed that the ΔPFS was 11.27 and 6.17 months in the intervention and non-intervention groups, respectively, suggesting that earlier intervention could extend patients' PFS. INTERPRETATION: RecistTM can assess targeted-therapy efficacy in patients with advanced NSCLC and driver gene mutations, along with tumour marker abnormalities. RecistTM surpasses RECIST in predicting short- and long-term patient benefits, and allows the early identification of patients resistant to targeted drugs, enabling prompt intervention and extending the imaging-demonstrated time to progression.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Mutação , Estadiamento de Neoplasias , Critérios de Avaliação de Resposta em Tumores Sólidos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Feminino , Biomarcadores Tumorais/genética , Masculino , Pessoa de Meia-Idade , Idoso , Terapia de Alvo Molecular/métodos , Estudos Retrospectivos , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Idoso de 80 Anos ou mais , Resultado do Tratamento , Prognóstico
4.
Medicine (Baltimore) ; 103(21): e38155, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787974

RESUMO

BACKGROUND: Numerous studies have demonstrated that psychological interventions are effective in alleviating anxiety and depression in patients with cancer. However, the optimal psychological intervention to alleviate anxiety and depression in patients with cancer remains unknown. This study was carried out to compare and rank the comparative effectiveness of various psychological interventions on anxiety and depression in patients with cancer. METHODS: Databases, namely PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CNKI, WanFang, VIP and CBM were systematically searched from their inception dates to December 2023 for randomized controlled trials of psychological interventions for anxiety and depression in patients with cancer. Utilizing the Cochrane Review Manager 5.4, we evaluated the risk of bias in the studies included in the current study based on the Cochrane Handbook 5.1.0 Methodological Quality Evaluation Criteria. The NMA was conducted using STATA 15.0. This study did not involve human participants and therefore did not require ethical approval. RESULTS: Thirty-one randomized controlled trials involving 3471 participants were included. MT [SMD = 1.35, 95% CI (0.76, 1.93)] and cognitive behavioral therapy (CBT) [SMD = 0.97, 95% CI (0.53, 1.42)] were superior to usual care in alleviating anxiety. Besides, interpersonal psychotherapy (IPT) [SMD = 1.17, 95% CI (0.06, 2.28)], CBT [SMD = 0.97, 95 % CI (0.63, 1.30)], and MT [SMD = 0.93, 95% CI (0.35, 1.50)] were superior to usual care in alleviating depression. In addition, CBT was superior to family therapy in alleviating depression [SMD = 0.73, 95% CI (0.08, 1.38)]. The MT, CBT, and IPT ranked in the top three in alleviating anxiety, while IPT, CBT, and MT ranked in the top three in alleviating depression. CONCLUSION: MT and IPT would be a more appropriate option in alleviating anxiety and depression in patients with cancer, respectively. This study also suggested that CBT had a significant effect in alleviating negative emotions in patients with cancer. However, the results need to be validated by high-quality and large-sample studies.


Assuntos
Ansiedade , Depressão , Neoplasias , Metanálise em Rede , Humanos , Neoplasias/psicologia , Neoplasias/complicações , Neoplasias/terapia , Depressão/terapia , Depressão/etiologia , Depressão/psicologia , Ansiedade/terapia , Ansiedade/etiologia , Terapia Cognitivo-Comportamental/métodos , Psicoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervenção Psicossocial/métodos , Resultado do Tratamento
5.
Angew Chem Int Ed Engl ; 63(29): e202404142, 2024 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-38715431

RESUMO

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.


Assuntos
Corantes Fluorescentes , Raios Infravermelhos , Imagem Óptica , Eletricidade Estática , Corantes Fluorescentes/química , Humanos , Nanopartículas/química , Tiofenos/química , Animais , Camundongos , Estrutura Molecular
6.
Adv Mater ; 36(28): e2402182, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38663035

RESUMO

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.


Assuntos
Raios Infravermelhos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Animais , Camundongos , Linhagem Celular Tumoral , Humanos , Indóis/química , Indóis/farmacologia , Nanopartículas/química , Pirróis/química , Pirróis/farmacologia
7.
Expert Opin Drug Saf ; 23(4): 513-525, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38533933

RESUMO

OBJECTIVE: The purpose of this study aimed to explore the new and serious adverse events(AEs) of Tacrolimus(FK506), cyclosporine(CsA), azathioprine(AZA), mycophenolate mofetil(MMF), cyclophosphamide(CTX) and methotrexate(MTX), which have not been concerned. METHODS: The FAERS data from January 2016 and December 2022 were selected for disproportionality analysis to discover the potential risks of traditional immunosuppressive drugs. RESULTS: Compared with CsA, FK506 has more frequent transplant rejection, and is more related to renal impairment, COVID-19, cytomegalovirus infection and aspergillus infection. However, CsA has a high infection-related fatality rate. In addition, we also found some serious and rare AE in other drugs which were rarely reported in previous studies. For example, AZA is closely related to hepatosplenic T-cell lymphoma with high fatality rate and MTX is strongly related to hypofibrinogenemia. CONCLUSION: The AEs report on this study confirmed that the results were basically consistent with the previous studies, but there were also some important safety signals that were inconsistent with or not mentioned in previous published studies. EXPERT OPINION: The opinion section discusses some of the limitations and shortcomings, proposing the areas where more effort should be invested in order to improve the safety of immunosuppressive drugs.


Assuntos
Transplante de Rim , Tacrolimo , Humanos , Tacrolimo/efeitos adversos , Farmacovigilância , Imunossupressores/efeitos adversos , Ciclosporina/efeitos adversos , Ácido Micofenólico , Metotrexato , Mineração de Dados , Rejeição de Enxerto
8.
Nurs Open ; 11(1): e2051, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268281

RESUMO

AIM: To systematically review and synthesize the findings of qualitative research on the unmet rehabilitation needs of colorectal cancer survivors (CRC) after surgery. DESIGN: A qualitative meta-synthesis registered with PROSPERO (CRD42022368837). METHODS: CNKI, Wanfang Data, PubMed, Scopus, Embase, Cochrane, Medline, PsychINFO and CINAHL were systematically searched for qualitative studies on the rehabilitation needs of CRC survivors after surgery from the inception of each database to September 2022. RESULTS: A total of 917 relevant reports were initially collected and 14 studies were finally included. A total of 49 needs were extracted and divided into 15 categories in 6 integrated findings: (1) the need to adopt healthy eating habits; (2) the need for exercise motivation and exercise guidance; (3) the conflicting needs to return to work; (4) unaddressed physiological needs; (5) spiritual needs; (6) the need for multi-dimensional social support. PATIENT OR PUBLIC CONTRIBUTION: Not applicable.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/cirurgia
9.
Ecotoxicol Environ Saf ; 270: 115878, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150748

RESUMO

Aluminum (Al) exposure has been linked to the development of a variety of neurodegenerative diseases. However, whether m6A RNA methylation participated in Al-induced neurotoxicity remain to be defined. In this study, mice were administrated with aluminum-lactate at dose of 220 mg/kg. bw by gavage for 3 months. Meanwhile, the primary hippocampal neurons were isolated and treated with 0, 50, 100, 150 µM aluminum-lactate, respectively for 7 days. Al exposure caused neuronal shrinkage, decreased Nissl bodies, and increased apoptosis. In accordance, in vitro studies also showed that Al exposure led to neuronal apoptosis in a dose-dependent manner, together with the decline in m6A RNA methylation levels. Moreover, the mRNA expression of Mettl3, Mettl14, Fto, and Ythdf2 were decreased upon Al exposure. Notably, the protein expression of METTL3 was dramatically down-regulated by 42% and 35% in Al-treated mice and neurons, suggesting METTL3 might exert a crucial role in Al-induced neurotoxicity. We next established a mouse model with hippocampus-specific overexpressing of Mettl3 gene to confirm the regulatory role of RNA methylation and found that METTL3 overexpression relieved the neurological injury induced by Al. The integrated MeRIP-seq and RNA-seq analysis elucidated that 631 genes were differentially expressed at both m6A RNA methylation and mRNA expression. Notably, EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, protein digestion and absorption might be involved in Al-induced neurotoxicity. Moreover, VEGFA, Thbs1, and PDGFB might be the central molecules. Collectively, our findings provide the novel sight into the role of m6A RNA methylation in neurodegenerative disease induced by Al.


Assuntos
Alumínio , Doenças Neurodegenerativas , Camundongos , Animais , Alumínio/toxicidade , Alumínio/metabolismo , Metilação de RNA , Metiltransferases/genética , Metiltransferases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Lactatos , RNA/metabolismo
10.
PLoS Biol ; 21(12): e3002439, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38060626

RESUMO

Assimilation of sulfur is vital to all organisms. In S. cerevisiae, inorganic sulfate is first reduced to sulfide, which is then affixed to an organic carbon backbone by the Met17 enzyme. The resulting homocysteine can then be converted to all other essential organosulfurs such as methionine, cysteine, and glutathione. This pathway has been known for nearly half a century, and met17 mutants have long been classified as organosulfur auxotrophs, which are unable to grow on sulfate as their sole sulfur source. Surprisingly, we found that met17Δ could grow on sulfate, albeit only at sufficiently high cell densities. We show that the accumulation of hydrogen sulfide gas underpins this density-dependent growth of met17Δ on sulfate and that the locus YLL058W (HSU1) enables met17Δ cells to assimilate hydrogen sulfide. Hsu1 protein is induced during sulfur starvation and under exposure to high sulfide concentrations in wild-type cells, and the gene has a pleiotropic role in sulfur assimilation. In a mathematical model, the low efficiency of sulfide assimilation in met17Δ can explain the observed density-dependent growth of met17Δ on sulfate. Thus, having uncovered and explained the paradoxical growth of a commonly used "auxotroph," our findings may impact the design of future studies in yeast genetics, metabolism, and volatile-mediated microbial interactions.


Assuntos
Cisteína Sintase , Sulfeto de Hidrogênio , Proteínas de Saccharomyces cerevisiae , Sulfeto de Hidrogênio/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Cisteína Sintase/genética , Cisteína Sintase/metabolismo , Deleção de Genes , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Sulfatos/metabolismo , Modelos Biológicos
11.
Nanoscale ; 15(8): 3940-3951, 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36723206

RESUMO

Hydroxyapatite (HA) is a biomimetic biomaterial that has been widely used in bone repair for many years. However, the increased risk of infection after surgery and long-time tracing for the material distribution and degradation during bone reconstruction remain challenges in the clinic. Zinc (Zn) is considered as an indispensable microelement for humans and is characterized with antibacterial action and osteogenic activity. Terbium (Tb), a rare-earth element, emits stable fluorescence under ultraviolet light. Here, Tb3+/Zn2+ co-doped hydroxyapatite (HA:Tb/Zn) was prepared to synchronously realize the antibacterial effect, osteogenic activity, and long-time tracing property. We found that HA:Tb/Zn had a strong antibacterial effect on both Gram-positive and Gram-negative clinical infectious bacteria, as well as improved osteogenic activity. HA:Tb/Zn also displayed stable green fluorescence in vitro and in vivo, which indicated great potential for recognizing the material changes during the bone reconstruction process. The combination of the ternary functions is of great significance to control the overuse of antibiotics and realize long-time tracing, and provide a versatile design on biomaterials in bone repair.


Assuntos
Durapatita , Térbio , Humanos , Materiais Biocompatíveis , Zinco , Antibacterianos
12.
Wei Sheng Yan Jiu ; 51(5): 787-790, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36222041

RESUMO

OBJECTIVE: To investigate the regulation of PARP-1 deficiency on epidermal growth factor receptor(EGFR) during lung injury of mice induced by benzo[a]pyrene(B[a]P) inhalation exposure. METHODS: PARP-1 knockout mice(PARP-1~(-/-)) and WT mice were selected as the object, and which were randomly assigned into either an intervention or a control group(n=40, half male and half female). The intervention group were individually treated with 10.0 µg/m~(3 )B[a]P for 180 days by dynamic inhalation exposure(6 h per day and 5 days per week), and the control group was given the solvent dimethyl sulfoxide(DMSO) during the same period. The expression of EGFR in lung tissues of animals were examined by RT-PCR, Western blot and immunofluorescence. RESULTS: In WT mice, the intervention manifested significant increase expression of EGFR in lung tissue, but no changes were found in the control. In PARP-1~(-/-) mice, the intervention manifested significant inhibition expression of EGFR, but the control group exhibited no changes. CONCLUSION: PARP-1 deficiency suppresses the abnormal activation of EGFR during lung injury of mice induced by B[a]P inhalation exposure.


Assuntos
Benzo(a)pireno , Lesão Pulmonar , Animais , Benzo(a)pireno/toxicidade , Dimetil Sulfóxido , Receptores ErbB/genética , Feminino , Exposição por Inalação/efeitos adversos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/genética , Masculino , Camundongos , Camundongos Knockout , Poli(ADP-Ribose) Polimerase-1/genética , Inibidores de Poli(ADP-Ribose) Polimerases , Solventes
13.
Medicine (Baltimore) ; 101(36): e30363, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086673

RESUMO

Haemophilus influenzae is a common commensal organism of the human upper respiratory tract and an important cause of human disease. No data on H influenzae carriage rate has been carried out on the Qinghai-Tibet Plateau of China. This study aims to present the H influenzae carriage rate and influencing factors of H influenzae in healthy children <15 years of age in Qinghai Province, an area located on the Qinghai-Tibet Plateau in China. Oropharyngeal swabs for the detection of H influenzae DNA were collected between September and October 2019. Taqman real-time polymerase chain reaction was used to detect the nucleic acids from the oropharyngeal swabs. Self-designed questionnaires were used to investigate the related information among this group of children. A number of 284 children were enrolled in this study. The carriage rate of H influenzae was 44.7%. The carriage rate in cities was 47.5%, in rural areas was 21.9%, and in pastoral areas was 52.8%. The carriage rate was found to be higher among children of minority ethnic groups than those of Han ethnicity (55.6% vs 38.1%). H influenzae carriage rate was influenced by tobacco smoke exposure (adjusted odds ratio [aOR] = 2.31, 95% CI [confidence interval]: 1.14-4.70), having siblings <5 years of age (aOR = 2.36, 95% CI: 1.21-4.59), respiratory infections during the last 30 days (aOR = 2.37, 95% CI: 1.11-5.06), and parent/guardian education level (aOR = 0.08, 95% CI: 0.02-0.27). H influenzae was highly prevalent in healthy children in Qinghai Province, especially among children of minority ethnicities and those living in pastoral areas. Tobacco smoke exposure, having siblings <5 years of age, and respiratory infections during the last 30 days were risk factors for H influenzae carriage. Parents or guardians having education levels of college or higher was a protective factor for H influenzae carriage. It is of critical importance that the government take effective measures to reduce the carriage rate and the occurrence of H influenzae related diseases in susceptible populations.


Assuntos
Infecções por Haemophilus , Infecções Respiratórias , Poluição por Fumaça de Tabaco , Altitude , Portador Sadio/epidemiologia , Criança , China/epidemiologia , Estudos Transversais , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae , Humanos , Prevalência , Infecções Respiratórias/epidemiologia
14.
EClinicalMedicine ; 46: 101381, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35434583

RESUMO

Background: As the immune-related response evaluation criteria in solid tumors (irRECIST) by imaging greatly underestimated the objective response to immunotherapy, we established the response evaluation criteria in solid tumors based on tumor markers (RecistTM) to explore whether RecistTM can compensate for the deficiencies of the irRECIST criteria. Methods: This was an observational study, which consisted of two parts. The first part (Group A) was a retrospective study including the patients with malignant solid tumors. The second part (Group B) was a prospective study, which were EGFR-negative and ALK-negative patients with stage IIIB-IV non-small cell lung cancer receiving first-line treatment. From January 2017 to September 2020, one hundred and ten patients with a three-time increase in tumor markers receiving immunotherapy were recruited. The treatment response to immunotherapy was evaluated by irRECIST and RecistTM. Efficacy, overall survival (OS), first evaluation time and earliest response time under the different evaluation criteria were compared by statistics. Findings: The treatment response evaluated by the RecistTM criteria was not consistent with that evaluated by the irRECIST criteria (Kappa = 0.386, p < 0.001). RecistTM had a higher completed response (CR) rate compared to irRECIST criteria (20.9% vs 1.8%, p < 0.001). The earliest response time under the RecistTM criteria was 3.42 weeks earlier than that under the irRECIST criteria (u = -5.233, p < 0.001). There were significant differences in median OS between tumor marker-related complete response (tmCR) and tumor marker-related partial response (tmPR), as well as between tmPR and tumor marker-related stable disease (tmSD) (χ2 = 15.572, p < 0.001; χ2 = 7.720, p = 0.005), but not between tmSD and tumor marker-related progressive disease (tmPD) (χ2 = 1.596, p = 0.206). When applying both criteria together, for patients with immune-related CR / immune-related PR (irCR/irPR) (n = 54) under irRECIST criteria, there was a significant difference in median OS between achieving tmCR (n = 22) and tmPR (n = 32) (χ2 = 14.011, p < 0.001). RecistTM criteria can predict 1-year and 2-year OS more accurately than irRECIST criteria (AUCs:0.862 vs 0.552, 0.649 vs 0.521, respectively;both p < 0.001). In RecistTM, 4 patients had been observed with pseudoprogression in tumor markers. Interpretation: The RecistTM criteria could effectively distinguish CR, PR, and SD, which may help resolve the shortcomings of the RECIST criteria in evaluating the treatment response to immunotherapy, especially in assessing whether patients can achieve deep or even complete response as soon as possible. Funding: This work was supported by the Key projects of Chongqing Health and Family Planning Commission (to Xueqin Yang, 2019ZDXM011).

15.
J Gastrointest Oncol ; 13(1): 1-12, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35284129

RESUMO

Background: N6-methyladenosine (m6A) mRNA modification is the most prevalent in certain tumors. However, its expression profile and prognostic value in human esophageal squamous cell carcinoma (ESCC) remains unknown. Methods: Herein, we performed an extensive investigation of the m6A-associated gene expression profile and determined its significance in the prognosis of ESCC. We received the RNA expression profiles of 81 ESCC tissues and one normal esophageal tissue from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier (KM) survival analysis was used to assess the predictability of m6A methylation-associated gene expression in ESCC prognosis. In addition, univariate and multivariate Cox regression, as well as least absolute shrinkage and selection operator (LASSO) regression models were employed for the establishment of prognostic signatures. Lastly, KM survival analysis, proportional hazard models, and receiver operating characteristic (ROC) curves were used to verify the prognostic value. Moreover, we also investigated the associations among the m6A prognostic signature, immune cell infiltration, and programmed cell death-ligand 1 (PD-L1) expression. Results: We demonstrated that YTHDF3 [hazard ratio (HR): 0.910; 95% confidence interval (CI): 0.832-0.995; P=0.038], RBM15 (HR: 0.721; 95% CI: 0.549-0.948; P=0.019), KIAA1429 (HR: 0.801; 95% CI: 0.664-0.967; P=0.021), and ALKBH5 (HR: 0.948; 95% CI: 0.895-1.003; P=0.0.064) overexpression predicted better overall survival (OS) of ESCC patients. Furthermore, based on prognostic factors, the high-risk (H-R) cohort was found to have worse survival than the low-risk (L-R) cohort (P<0.001). Conclusions: We revealed three m6A methylation-associated genes that were closely correlated with enhanced survival in ESCC patients. In addition, we generated an independent prognostic signature based on the expression of YTHDF3, RBM15, KIAA1429, and ALKBH5 genes. The results revealed significantly higher proportions of CD8+ T cells and higher expression of PD-L1 in the H-R group.

16.
Adv Sci (Weinh) ; 9(11): e2104997, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35132827

RESUMO

The integration of aggregation-induced emission luminogens (AIEgens) and inorganic constituents to generate multifunctional nanocomposites has attracted much attention because it couples the bright aggregate-state fluorescence of AIEgens with the diverse imaging modalities of inorganic constituents. Herein, a facile and universal strategy to prepare metal-phenolic-network (MPN)-coated AIE dots in a high encapsulation efficiency is reported. Through precise control on the nucleation of AIEgens and deposition of MPNs in tetrahydrofuran/water mixtures, termed as coacervation, core-shell MPN-coated AIE dots with bright emission are assembled in a one-pot fashion. The optical properties of MPN-coated AIE dots can be readily tuned by varying the incorporated AIEgens. Different metal ions, such as Fe3+ , Ti4+ , Cu2+ , Ni2+ , can be introduced to the nanoparticles. The MPN-coated AIE dots with a red-emissive AIEgen core are successfully used to perform magnetic resonance/fluorescence dual-modality imaging in a tumor-bearing mouse model and blood flow visualization in a zebrafish larva. It is believed that the present study provides a tailor-made nanoplatform to meet the individual needs of in vivo bioimaging.


Assuntos
Nanopartículas , Imagem Óptica , Animais , Corantes Fluorescentes , Metais , Camundongos , Imagem Óptica/métodos , Peixe-Zebra
17.
Glob Chang Biol ; 28(4): 1583-1595, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34854168

RESUMO

Our limited understanding of the impacts of drought on tropical forests significantly impedes our ability in accurately predicting the impacts of climate change on this biome. Here, we investigated the impact of drought on the dynamics of forest canopies with different heights using time-series records of remotely sensed Ku-band vegetation optical depth (Ku-VOD), a proxy of top-canopy foliar mass and water content, and separated the signal of Ku-VOD changes into drought-induced reductions and subsequent non-drought gains. Both drought-induced reductions and non-drought increases in Ku-VOD varied significantly with canopy height. Taller tropical forests experienced greater relative Ku-VOD reductions during drought and larger non-drought increases than shorter forests, but the net effect of drought was more negative in the taller forests. Meta-analysis of in situ hydraulic traits supports the hypothesis that taller tropical forests are more vulnerable to drought stress due to smaller xylem-transport safety margins. Additionally, Ku-VOD of taller forests showed larger reductions due to increased atmospheric dryness, as assessed by vapor pressure deficit, and showed larger gains in response to enhanced water supply than shorter forests. Including the height-dependent variation of hydraulic transport in ecosystem models will improve the simulated response of tropical forests to drought.


Assuntos
Secas , Ecossistema , Mudança Climática , Florestas , Árvores , Clima Tropical
19.
Front Microbiol ; 12: 696195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603225

RESUMO

Cadmium (Cd) is carcinogenic to humans and can accumulate in the liver, kidneys, and bones. There is widespread presence of cadmium in the environment as a consequence of anthropogenic activities. It is important to detect cadmium in the environment to prevent further exposure to humans. Previous whole-cell biosensor designs were focused on single-sensing constructs but have had difficulty in distinguishing cadmium from other metal ions such as lead (Pb) and mercury (Hg). We developed a dual-sensing bacterial bioreporter system to detect bioavailable cadmium by employing CadC and CadR as separate metal sensory elements and eGFP and mCherry as fluorescent reporters in one genetic construct. The capability of this dual-sensing biosensor was proved to simultaneously detect bioavailable cadmium and its toxic effects using two sets of sensing systems while still maintaining similar specificity and sensitivity of respective signal-sensing biosensors. The productions of double-color fluorescence were directly proportional to the exposure concentration of cadmium, thereby serving as an effective quantitative biosensor to detect bioavailable cadmium. This novel dual-sensing biosensor was then validated to respond to Cd(II) spiked in environmental water samples. This is the first report of the development of a novel dual-sensing, whole-cell biosensor for simultaneous detection of bioavailable cadmium. The application of two biosensing modules provides versatile biosensing signals and improved performance that can make a significant impact on monitoring high concentration of bioavailable Cd(II) in environmental water to reduce human exposure to the harmful effects of cadmium.

20.
Sci Rep ; 11(1): 19044, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561515

RESUMO

Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94-3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.


Assuntos
Antígeno Carcinoembrionário/sangue , Pneumopatias/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Criança , Comorbidade , Diabetes Mellitus/epidemiologia , Diagnóstico Diferencial , Doenças do Sistema Endócrino/epidemiologia , Feminino , Humanos , Pneumopatias/sangue , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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