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1.
Cancer Lett ; 591: 216892, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38621459

RESUMO

Non-small cell lung cancer (NSCLC) is a leading cause of mortality worldwide and requires effective treatment strategies. Recently, the development of a novel multiple-target tyrosine kinase inhibitor, anlotinib, has drawn increasing attention, especially it shows advantages when combined with PD-1/PD-L1 blockade. However, the mechanism by which anlotinib improves immunotherapy and remodeling of the tumor microenvironment remains unclear. In this study, we found that anlotinib combined with PD-1 blockade significantly inhibited tumor growth and reduced tumor weight in a lung cancer xenograft model compared to any single treatment. Both immunofluorescence and flow cytometry analyses revealed that anlotinib induced a CD8+ T cell dominated tumor microenvironment, which might account for its improved role in immunotherapy. Further investigations showed that CCL5-mediated CD8+ T cell recruitment plays a critical role in anlotinib and PD-1 blockade strategies. The depletion of CD8+ T cells abrogated this process. In conclusion, our findings showed that the combination of anlotinib and PD-1 blockade produced promising effects in the treatment of lung cancer, and that the induction of CCL5-mediced CD8+ T cell recruitment by anlotinib provided a novel mechanism of action.


Assuntos
Antígeno B7-H1 , Linfócitos T CD8-Positivos , Quimiocina CCL5 , Indóis , Neoplasias Pulmonares , Receptor de Morte Celular Programada 1 , Quinolinas , Microambiente Tumoral , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Quinolinas/farmacologia , Quinolinas/administração & dosagem , Indóis/farmacologia , Indóis/administração & dosagem , Camundongos , Humanos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Quimiocina CCL5/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/metabolismo , Feminino
2.
Mycopathologia ; 189(3): 35, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637433

RESUMO

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.


Assuntos
Antifúngicos , Candidíase , Humanos , Antifúngicos/farmacologia , Candidíase/microbiologia , Candida auris , Candida , Anfotericina B/farmacologia , Farmacorresistência Fúngica/genética , Testes de Sensibilidade Microbiana
3.
Biol Psychiatry ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38432522

RESUMO

BACKGROUND: Growing evidence indicates that dynamic changes in gut microbiome can affect intelligence; however, whether these relationships are causal remains elusive. We aimed to disentangle the poorly understood causal relationship between gut microbiota and intelligence. METHODS: We performed a 2-sample Mendelian randomization (MR) analysis using genetic variants from the largest available genome-wide association studies of gut microbiota (N = 18,340) and intelligence (N = 269,867). The inverse-variance weighted method was used to conduct the MR analyses complemented by a range of sensitivity analyses to validate the robustness of the results. Considering the close relationship between brain volume and intelligence, we applied 2-step MR to evaluate whether the identified effect was mediated by regulating brain volume (N = 47,316). RESULTS: We found a risk effect of the genus Oxalobacter on intelligence (odds ratio = 0.968 change in intelligence per standard deviation increase in taxa; 95% CI, 0.952-0.985; p = 1.88 × 10-4) and a protective effect of the genus Fusicatenibacter on intelligence (odds ratio = 1.053; 95% CI, 1.024-1.082; p = 3.03 × 10-4). The 2-step MR analysis further showed that the effect of genus Fusicatenibacter on intelligence was partially mediated by regulating brain volume, with a mediated proportion of 33.6% (95% CI, 6.8%-60.4%; p = .014). CONCLUSIONS: Our results provide causal evidence indicating the role of the microbiome in intelligence. Our findings may help reshape our understanding of the microbiota-gut-brain axis and development of novel intervention approaches for preventing cognitive impairment.

4.
Angew Chem Int Ed Engl ; 63(19): e202400511, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38488202

RESUMO

As ferroelectrics hold significance and application prospects in wearable devices, the elastification of ferroelectrics becomes more and more important. Nevertheless, achieving elastic ferroelectrics requires stringent synthesis conditions, while the elastification of relaxor ferroelectric materials remains unexplored, presenting an untapped potential for utilization in energy storage and actuation for wearable electronics. The thiol-ene click reaction offers a mild and rapid reaction platform to prepare functional polymers. Therefore, we employed this approach to obtain an elastic relaxor ferroelectric by crosslinking an intramolecular carbon-carbon double bonds (CF=CH) polymer matrix with multiple thiol groups via a thiol-ene click reaction. The resulting elastic relaxor ferroelectric demonstrates pronounced relaxor-type ferroelectric behaviour. This material exhibits low modulus, excellent resilience, and fatigue resistance, maintaining a stable ferroelectric response even under strains up to 70 %. This study introduces a straightforward and efficient approach for the construction of elastic relaxor ferroelectrics, thereby expanding the application possibilities in wearable electronics.

5.
J Virol ; 98(3): e0150223, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38315015

RESUMO

Capsid assembly is critical in the hepatitis B virus (HBV) life cycle, mediated by the viral core protein. Capsid assembly is the target for new anti-viral therapeutics known as capsid assembly modulators (CAMs) of which the CAM-aberrant (CAM-A) class induces aberrant shaped core protein structures and leads to hepatocyte cell death. This study aimed to identify the mechanism of action of CAM-A modulators leading to HBV-infected hepatocyte elimination where CAM-A-mediated hepatitis B surface antigen (HBsAg) reduction was evaluated in a stable HBV replicating cell line and in AAV-HBV-transduced C57BL/6, C57BL/6 SCID, and HBV-infected chimeric mice with humanized livers. Results showed that in vivo treatment with CAM-A modulators induced pronounced reductions in hepatitis B e antigen (HBeAg) and HBsAg, associated with a transient alanine amino transferase (ALT) increase. Both HBsAg and HBeAg reductions and ALT increase were delayed in C57BL/6 SCID and chimeric mice, suggesting that adaptive immune responses may indirectly contribute. However, CD8+ T cell depletion in transduced wild-type mice did not impact antigen reduction, indicating that CD8+ T cell responses are not essential. Transient ALT elevation in AAV-HBV-transduced mice coincided with a transient increase in endoplasmic reticulum stress and apoptosis markers, followed by detection of a proliferation marker. Microarray data revealed antigen presentation pathway (major histocompatibility complex class I molecules) upregulation, overlapping with the apoptosis. Combination treatment with HBV-specific siRNA demonstrated that CAM-A-mediated HBsAg reduction is dependent on de novo core protein translation. To conclude, CAM-A treatment eradicates HBV-infected hepatocytes with high core protein levels through the induction of apoptosis, which can be a promising approach as part of a regimen to achieve functional cure. IMPORTANCE: Treatment with hepatitis B virus (HBV) capsid assembly modulators that induce the formation of aberrant HBV core protein structures (CAM-A) leads to programmed cell death, apoptosis, of HBV-infected hepatocytes and subsequent reduction of HBV antigens, which differentiates CAM-A from other CAMs. The effect is dependent on the de novo synthesis and high levels of core protein.


Assuntos
Antivirais , Apoptose , Regulação Viral da Expressão Gênica , Antígenos do Núcleo do Vírus da Hepatite B , Vírus da Hepatite B , Hepatócitos , Biossíntese de Proteínas , Animais , Camundongos , Antivirais/farmacologia , Antivirais/uso terapêutico , Apoptose/efeitos dos fármacos , Capsídeo/química , Capsídeo/classificação , Capsídeo/efeitos dos fármacos , Capsídeo/metabolismo , Proteínas do Capsídeo/metabolismo , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/metabolismo , Hepatite B/virologia , Antígenos do Núcleo do Vírus da Hepatite B/biossíntese , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/metabolismo , Vírus da Hepatite B/crescimento & desenvolvimento , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/metabolismo , Vírus da Hepatite B/patogenicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/virologia , Camundongos Endogâmicos C57BL , Camundongos SCID , Replicação Viral , Linhagem Celular , Linfócitos T CD8-Positivos/imunologia , Apresentação de Antígeno
6.
Cancers (Basel) ; 16(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38398086

RESUMO

OBJECTIVE: The diagnosis of lung adenocarcinoma (LUAD) is often delayed due to the typically asymptomatic nature of the early-stage disease, causing advanced-stage LUAD diagnosis in most patients. Hypoxia is widely recognized as a driving force in cancer progression. Exosomes originating from hypoxic tumor cells promote tumorigenesis by influencing glycolysis, migration, invasion, and immune infiltration. Given these insights, our study aimed to explore the role of hypoxia-derived exosomal long non-coding RNA (lncRNA) OIP5-AS1 in LUAD cell lines and mouse models. MATERIALS AND METHODS: Exosomes were meticulously isolated and authenticated based on their morphology and biomarkers. The interaction between heparan sulfate (glucosamine) 3-O-sulfotransferase 1 (HS3ST1) and Glypican 4 (GPC4) was examined using immunoprecipitation. The influence of the hypoxia-derived exosomal lncRNA OIP5-AS1 on glycolysis was assessed in LUAD cell lines. The effect of the hypoxia-derived exosomal lncRNA OIP5-AS1 on cell proliferation and metastasis was evaluated using colony formation, cell viability, cell cycle, and apoptosis analyses. Its effects on tumor size were confirmed in xenograft animal models. RESULTS: Our study revealed the mechanism of the hypoxia-derived exosomal lncRNA OIP5-AS1 in LUAD progression. We discovered that GPC4 promotes HS3ST1-mediated glycolysis and that the hypoxia-derived exosomal lncRNA OIP5-AS1 enhances glycolysis by regulating miR-200c-3p in LUAD cells. Notably, this lncRNA stimulates LUAD cell proliferation and metastasis and fosters LUAD tumor size via miR-200c-3p. Our findings underscore the potential role of the hypoxia-derived exosomal lncRNA OIP5-AS1 in LUAD progression. CONCLUSIONS: The hypoxia-derived exosomal lncRNA OIP5-AS1 promotes LUAD by regulating HS3ST1-GPC4-mediated glycolysis via miR-200c-3p.

7.
J Am Chem Soc ; 146(8): 5614-5621, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38354217

RESUMO

With the emergence of wearable electronics, ferroelectrics are poised to serve as key components for numerous potential applications. Currently, intrinsically elastic ferroelectrics featuring a network structure through a precise "slight cross-linking" approach have been realized. The resulting elastic ferroelectrics demonstrate a combination of stable ferroelectric properties and remarkable resilience under various strains. However, challenges arose as the cross-linking temperature was too high when integrating ferroelectrics with other functional materials, and the Curie temperature of this elastic ferroelectric was comparatively low. Addressing these challenges, we strategically chose a poly(vinylidene fluoride)-based copolymer with high vinylidene fluoride content to obtain a high Curie temperature while synthesizing a cross-linker with carbene intermediate for high reactivity to reduce the cross-linking temperature. At a relatively low temperature, we successfully fabricated elastic ferroelectrics through carbene cross-linking. The resulting elastic polymer ferroelectrics exhibit a higher Curie temperature and show a stable ferroelectric response under strains up to 50%. These materials hold significant potential for integration into wearable electronics.

8.
J Virol Methods ; 325: 114875, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38176614

RESUMO

Chronic Hepatitis B Virus (HBV) infection remains a global burden. To identify small molecule RIG-I agonists as antivirals against HBV, we developed an HBV-pgRNA-based interferon-ß (IFN-ß) luciferase reporter assay with high level of assay sensitivity, specificity and robustness. Through HTS screening, lead compound (JJ#1) was identified to activate RIG-I signaling pathway by inducing TBK1 phosphorylation. Knockdown experiments demonstrated that JJ#1-induced retinoic acid-inducible gene 1 (RIG-I) signaling pathway activation was MAVS-dependent. Furthermore, JJ#1 exhibited HBV antiviral potency in HBV-infected cell models by reducing HBV DNA and antigens (HBsAg and HBeAg).


Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B , Tretinoína , Fosforilação , Antivirais/farmacologia
9.
J Fish Biol ; 104(2): 497-504, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37278092

RESUMO

A total of 40 specimens of the genus Schizothorax (Cyprinidae: Schizothoracinae), including 10 matured males, 19 matured females and 11 juveniles, were captured from the Kirong Tsangpo River in China, which is located in the southern slope of the Central Himalayas. These specimens are identified as Schizothorax richardsonii (Grey, 1832) based on morphological characters and molecular analyses using mitochondrial Cyt b gene sequences. The Kirong population of S. richardsonii is relatively isolated from other populations in the Himalayas and has low genetic diversity. This is the first record of the genus Schizothorax fish in rivers of the Central Himalayas in China. As S. richardsonii is a vulnerable species on the IUCN Red List, a protection plan should be conducted to reduce the impact of anthropogenic disturbance by monitoring the natural population dynamics and assessing the ecological determinants of its distribution.


Assuntos
Cyprinidae , Rios , Animais , Himalaia , Filogenia , China , Cyprinidae/genética
10.
Diabetes Obes Metab ; 26(1): 135-147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37779362

RESUMO

AIM: Genome-wide association studies (GWAS) have identified multiple susceptibility loci associated with insulin resistance (IR)-relevant phenotypes. However, the genes responsible for these associations remain largely unknown. We aim to identify susceptibility genes for IR-relevant phenotypes via a transcriptome-wide association study. MATERIALS AND METHODS: We conducted a large-scale multi-tissue transcriptome-wide association study for IR (Insulin Sensitivity Index, homeostasis model assessment-IR, fasting insulin) and lipid-relevant traits (high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol and total cholesterol) using the largest GWAS summary statistics and precomputed gene expression weights of 49 human tissues. Conditional and joint analyses were implemented to identify significantly independent genes. Furthermore, we estimated the causal effects of independent genes by Mendelian randomization causal inference analysis. RESULTS: We identified 1190 susceptibility genes causally associated with IR-relevant phenotypes, including 58 genes that were not implicated in the original GWAS. Among them, 11 genes were further supported in differential expression analyses or a gene knockout mice database, such as KRIT1 showed both significantly differential expression and IR-related phenotypic effects in knockout mice. Meanwhile, seven proteins encoded by susceptibility genes were targeted by clinically approved drugs, and three of these genes (H6PD, CACNB2 and DRD2) have been served as drug targets for IR-related diseases/traits. Moreover, drug repurposing analysis identified four compounds with profiles opposing the expression of genes associated with IR risk. CONCLUSIONS: Our study provided new insights into IR aetiology and avenues for therapeutic development.


Assuntos
Resistência à Insulina , Transcriptoma , Animais , Humanos , Camundongos , LDL-Colesterol , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Resistência à Insulina/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Análise da Randomização Mendeliana
11.
J Med Chem ; 66(16): 11335-11350, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37552639

RESUMO

Artemisinin, a prominent anti-malaria drug, is being investigated for its potential as a repurposed cancer treatment. However, its effectiveness in tumor cell lines remains limited, and its mechanism of action is unclear. To make more progress, the PROteolysis-TArgeting chimera (PROTAC) technique has been applied to design and synthesize novel artemisinin derivatives in this study. Among them, AD4, the most potent compound, exhibited an IC50 value of 50.6 nM in RS4;11 cells, over 12-fold better than that of its parent compound, SM1044. This was supported by prolonged survival of RS4;11-transplanted NOD/SCID mice. Meanwhile, AD4 effectively degraded PCLAF in RS4;11 cells and thus activated the p21/Rb axis to exert antitumor activity by directly targeting PCLAF. The discovery of AD4 highlights the great potential of using PROTACs to improve the efficacy of natural products, identify therapeutic targets, and facilitate drug repurposing. This opens a promising avenue for transforming other natural products into effective therapies.


Assuntos
Artemisininas , Quimera de Direcionamento de Proteólise , Animais , Camundongos , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Reposicionamento de Medicamentos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteólise
12.
Am J Hum Genet ; 110(8): 1266-1288, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37506691

RESUMO

Most of the single-nucleotide polymorphisms (SNPs) associated with insulin resistance (IR)-relevant phenotypes by genome-wide association studies (GWASs) are located in noncoding regions, complicating their functional interpretation. Here, we utilized an adapted STARR-seq to evaluate the regulatory activities of 5,987 noncoding SNPs associated with IR-relevant phenotypes. We identified 876 SNPs with biased allelic enhancer activity effects (baaSNPs) across 133 loci in three IR-relevant cell lines (HepG2, preadipocyte, and A673), which showed pervasive cell specificity and significant enrichment for cell-specific open chromatin regions or enhancer-indicative markers (H3K4me1, H3K27ac). Further functional characterization suggested several transcription factors (TFs) with preferential allelic binding to baaSNPs. We also incorporated multi-omics data to prioritize 102 candidate regulatory target genes for baaSNPs and revealed prevalent long-range regulatory effects and cell-specific IR-relevant biological functional enrichment on them. Specifically, we experimentally verified the distal regulatory mechanism at IRS1 locus, in which rs952227-A reinforces IRS1 expression by long-range chromatin interaction and preferential binding to the transcription factor HOXC6 to augment the enhancer activity. Finally, based on our STARR-seq screening data, we predicted the enhancer activity of 227,343 noncoding SNPs associated with IR-relevant phenotypes (fasting insulin adjusted for BMI, HDL cholesterol, and triglycerides) from the largest available GWAS summary statistics. We further provided an open resource (http://www.bigc.online/fnSNP-IR) for better understanding genetic regulatory mechanisms of IR-relevant phenotypes.


Assuntos
Resistência à Insulina , Polimorfismo de Nucleotídeo Único , Humanos , Polimorfismo de Nucleotídeo Único/genética , Estudo de Associação Genômica Ampla , Resistência à Insulina/genética , Fatores de Transcrição/genética , Cromatina/genética , Fenótipo , Elementos Facilitadores Genéticos/genética
13.
J Med Chem ; 66(15): 10458-10472, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37279091

RESUMO

As a novel protein knockdown tool, proteolysis targeting chimeras (PROTACs) can induce potent degradation of target proteins by hijacking E3 ubiquitin ligases. However, the uncontrollable protein disruption of PROTACs is prone to cause "off-target" toxicity after systemic administration. Herein, we designed a photocaged-PROTAC (phoBET1) and loaded it in UCNPs-based mesoporous silica nanoparticles (UMSNs) to construct a NIR light-activatable PROTAC nanocage (UMSNs@phoBET1) for controllable target protein degradation. Upon NIR light (980 nm) irradiation, UMSNs@phoBET1 nanocages could be activated to release active PROTAC via a controlled pattern for degrading bromodomain-containing protein 4 (BRD4) and inducing MV-4-11 cancer cell apoptosis. In vivo experiments demonstrated that UMSNs@phoBET1 nanocages were capable of responding to NIR light in tumor tissues to achieve BRD4 degradation and effectively suppress tumor growth. This NIR light-activatable PROTAC nanoplatform compensates for the current shortcomings of short-wavelength light-controlled PROTACs and presents a paradigm for the precise regulation of PROTACs in living tissues.


Assuntos
Neoplasias , Fatores de Transcrição , Humanos , Proteólise , Fatores de Transcrição/metabolismo , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias/tratamento farmacológico , Proteínas de Ciclo Celular/metabolismo
14.
J Hazard Mater ; 453: 131408, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37080022

RESUMO

Mercury biomagnification in aquatic ecosystems is a global issue. Biomagnification patterns and drivers in alpine regions remain poorly understood. Hg biomagnification in the aquatic food web of the Qinghai-Tibetan Plateau (Q-T Plateau) was investigated. A total of 302 fish and macroinvertebrate tissue samples were analysed for total mercury (THg) and nitrogen (δ15N) stable isotope ratios. Overall, 26.75% of fish individuals exceeded the USFWS consumption guidelines. A total of 52.17% of the sampling sites covering different habitats exhibited a significantly positive THg-δ15N relationship, which confirmed the Hg biomagnification potential of Q-T Plateau aquatic ecosystems. The Q-T Plateau Hg biomagnification rates were generally far higher than global averages regardless of the habitat type. Hg in sediments, elevation and population density were positively related to the Hg biomagnification magnitude on the Q-T Plateau, which could be attributed to the disproportionate response of Hg concentrations in macroinvertebrates and fishes along environmental gradients. Our findings offer empirical evidence that fish consumption on the Q-T Plateau poses a substantial Hg exposure risk to people living along river and lake shores. Higher biomagnification rates could further disproportionately accelerate Hg pollution in Q-T Plateau aquatic ecosystems under future anthropogenic activities and climate warming trajectories.


Assuntos
Mercúrio , Poluentes Químicos da Água , Animais , Mercúrio/análise , Ecossistema , Tibet , Bioacumulação , Cadeia Alimentar , Peixes , Monitoramento Ambiental , Poluentes Químicos da Água/análise
15.
Sci Rep ; 13(1): 6936, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37117396

RESUMO

To assess the safety and efficacy of endovascular embolization techniques, we compared the short- to medium-term prognosis of coil embolization for symptomatic visceral aneurysms (SVAA) and asymptomatic visceral aneurysms (ASVAA) to identify risk factors associated with 30-day mortality. Explore the symptom profile and intrinsic associations of SVAA. A retrospective study of 66 consecutive patients at two tertiary care hospitals from 2010 to 2020 compared the short- to mid-term outcomes of 22 symptomatic VAAs and 44 asymptomatic VAAs treated with coil embolization. Univariate and log-rank tests were used to analyze the prognostic impact of SVAA and ASVAA. SVAA group had significantly higher 30-day mortality than ASVAA group (2(9.1%) vs 0, P = 0.042), both patients who died had symptomatic pseudoaneurysms. Perioperative complications such as end-organ ischemia (P = 0.293) and reintervention (P = 1) were similar in both groups. No difference in event-free survival was identified between the two groups (P = 0.900), but we found that the majority of pseudoaneurysms were SVAA (4/5) and that they had a much higher event rate than true aneurysms. In addition, dyslipidemia may be an influential factor in the development of VAA (P = 0.010). Coil embolization is a safe and effective method of treatment for VAA. Most pseudoaneurysms have symptoms such as abdominal pain and bleeding, and in view of their risk, more attention should be paid to symptomatic patients and the nature of the aneurysm should be determined as soon as possible to determine the next stage of treatment.


Assuntos
Falso Aneurisma , Aneurisma , Embolização Terapêutica , Procedimentos Endovasculares , Humanos , Falso Aneurisma/terapia , Estudos Retrospectivos , Resultado do Tratamento , Aneurisma/terapia , Aneurisma/diagnóstico , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Artérias/cirurgia , Vísceras/irrigação sanguínea
16.
Mol Ecol ; 32(8): 1955-1971, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36704928

RESUMO

Anthropogenic biological invasions represent major concerns but enable us to investigate rapid evolutionary changes and adaptation to novel environments. The goldfish Carassius auratus with sexual diploids and unisexual triploids coexisting in natural waters is one of the most widespread invasive fishes in Tibet, providing an ideal model to study evolutionary processes during invasion in different reproductive forms from the same vertebrate. Here, using whole-genome resequencing data of 151 C. auratus individuals from invasive and native ranges, we found different patterns of genomic responses between diploid and triploid populations during their invasion of Tibet. For diploids, although invasive individuals derived from two different genetically distinct sources had a relative higher diversity (π) at the population level, their individual genetic diversity (genome-wide observed heterozygosity) was significantly lower (21.4%) than that of source individuals. Population structure analysis revealed that the invasive individuals formed a specific genetic cluster distinct from the source populations. Runs of homozygosity analysis showed low inbreeding only in invasive individuals, and only the invasive population experienced a recent decline in effective population size reflecting founder events. For triploids, however, invasive populations showed no loss of individual genetic diversity and no genetic differentiation relative to source populations. Regions of putative selective sweeps between invasive and source populations of diploids mainly involved genes associated with mannosidase activity and embryo development. Our results suggest that invasive diploids deriving from distinct sources still lost individual genetic diversity resulting from recent inbreeding and founder events and selective sweeps, and invasive triploids experienced no change in genetic diversity owing to their reproduction mode of gynogenesis that precludes inbreeding and founder effects and may make them more powerful invaders.


Assuntos
Diploide , Carpa Dourada , Animais , Carpa Dourada/genética , Triploidia , Altitude , Evolução Biológica , Variação Genética/genética
17.
J Fish Biol ; 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36571395

RESUMO

Phylogeographic congruence among co-distributed taxa is regarded as an inherent inference to vicariance events. Nonetheless, incongruent patterns of contemporary lineage divergence among taxa indicated that species differ in their response to common past events. To investigate the role of past events, ecological traits and lineage diversification time in shaping the contemporary phylogeographic patterns, comparative analyses were conducted for Tibetan stone loaches in the Himalayas using three gene markers and two ecological traits (depth of caudal peduncle in their length and presence/absence of posterior chamber of the air bladder). By a thorough sampling in two flanks of the Himalayas, the authors detected that phylogenetic breaks were spatially discordant and divergences of populations were also temporally asynchronous in co-distributed loaches. Estimated divergence time using fossil-calibrated node dating indicated that the Tibetan stone loaches colonised into the south flank of the Himalayas until the Pleistocene. The demographic expansions were also disconcerted between populations in north and south flanks, or east and west Himalayas. Ongoing gene flows between populations in north and south sides implied that the Himalayas do not strictly impede dispersal of cold-adapted species. The results highlight that the quaternary climatic oscillation, in conjunction with ecological traits and lineage diversification time, shaped contemporary phylogenetic patterns of stone loaches in the Himalayas and provide new insights into the biodiversity and composition of species in the Himalayas and surrounding region.

18.
Biology (Basel) ; 11(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36552317

RESUMO

As one of the most sensitive regions to global climate change, Tibet is subject to remarkable changes in biota over the past decades, including endemic fish species. However, no study has attempted to predict the changes in the distribution of Tibetan fishes, leaving a great blank for aquatic conservation in Tibet. Based on the Maximum Entropy model (MaxEnt), this study predicted the changes in the suitable habitats of three endemic fish species, including two species mainly inhabiting the rivers (Glyptosternon maculatum, Oxygymnocypris stewartii) and one species mainly inhabiting lakes (Gymnocypris selincuoensis) in Tibet under two representative concentration pathways (RCP2.6 and RCP8.5) under two future scenarios (2050 and 2090), and explored the impact of the barrier effects of hydropower projects on the suitable habitats of fish. The results showed that under the four scenarios, the net change in the suitable habitats of the G. maculatum was negative (-2.0--18.8%), while the suitable habitats of the O. stewartii and G. selincuoensis would be expanded, with the net change of 60.0-238.3% and 46.4-56.9%, respectively. Under different scenarios, the suitable habitats of the three species had a tendency to migrate to a higher elevation, and the largest expansion in the range of migration was projected to occur under the 2090-RCP8.5 scenario. In addition, due to the impact of the hydropower projects, the ability of G. maculatum to obtain new suitable habitats from climate change would be reduced by 2.0-8.1%, which was less than the loss induced by climate change (5.5-25.1%), while the suitable habitats of O. stewartii would be reduced by 3.0-9.7%, which was more than the impact of climate change (about 1%). The results of this study have guiding significance for the conservation and management of fish resources diversity in the Yarlung Tsangpo River basin and Siling Co basin of Tibet, and also provide a reference for the coordination and scientific planning of hydropower projects in Tibet.

19.
World J Clin Cases ; 10(33): 12404-12409, 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36483826

RESUMO

BACKGROUND: There are a few cases of lateral lymph node (LLN) metastasis (LLNM) of T1 rectal cancer. Moreover, LLNM is easily missed, especially in patients with early-stage rectal cancer. To our knowledge, the possibility of bilateral LLNM before surgery has not been reported in previous studies. CASE SUMMARY: A 36-year-old woman underwent endoscopic submucosal dissection at a local hospital owing to a clinical diagnosis of a rectal polyp. The pathology report showed a diagnosis of T1 rectal mucinous adenocarcinoma. She was considered to have bilateral LLNM after the examination at our hospital. Laparoscopic total mesorectal excision plus bilateral LLN dissection was performed and the pathological outcomes indicated unilateral LLNM. The patient received long-course adjuvant chemoradiotherapy with no recurrence or metastasis observed during the 1-year follow-up period. CONCLUSION: T1 rectal cancer could lead to LLNM and possibly, bilateral LLNM. Therefore, adequate clinical evaluation is essential for these patients.

20.
ACS Appl Mater Interfaces ; 14(50): 55548-55558, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36472911

RESUMO

Charge carrier transfer efficiency as a crucial factor determines the performance of heterogeneous photocatalysis. Here, we demonstrate a simple nanohybrid structure of BaTiO3-Au (BTO-Au) for the efficient selective oxidization of benzyl alcohol to benzaldehyde upon piezotronic effect boosted plasmonic photocharge carrier transfer. With the aid of ultrasonic mechanical vibration, the reaction rate of the photocatalytic organic conversion would be considerably accelerated, which is about 4.2 and 6.2 times higher than those driven by sole visible light irradiation and sole ultrasonication, respectively. Photoelectrochemical tests under ultrasonic stimuli reveal the BTO-Au catalytic system is independent of the light intensity, showing a consistent photocurrent density, over a wide range of incident light brightness. The largely enhanced photocatalytic activity can be ascribed to the synergetic effect of surface plasmonic resonance (SPR)-piezotronic coupling by which a built-in electric field induced by the piezotronic effect significantly favors the oriented mobilization of energetic charge carriers generated by the SPR effect at the heterojunction. Notably, a decrease of the Schottky barrier height of ∼0.3 eV at the BTO-Au interface is verified experimentally, due to the band bending of BTO induced by the piezotronic effect, which can greatly augment the hot electron transfer efficiency. This work highlights the coupling of the piezotronic effect with SPR within the BTO-Au nanostructure as a versatile and promising route for efficient charge transfer in photocatalytic organic conversion.

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