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1.
Cell ; 154(5): 1060-1073, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23993096

RESUMO

How organ-specific metastatic traits arise in primary tumors remains unknown. Here, we show a role of the breast tumor stroma in selecting cancer cells that are primed for metastasis in bone. Cancer-associated fibroblasts (CAFs) in triple-negative (TN) breast tumors skew heterogeneous cancer cell populations toward a predominance of clones that thrive on the CAF-derived factors CXCL12 and IGF1. Limiting concentrations of these factors select for cancer cells with high Src activity, a known clinical predictor of bone relapse and an enhancer of PI3K-Akt pathway activation by CXCL12 and IGF1. Carcinoma clones selected in this manner are primed for metastasis in the CXCL12-rich microenvironment of the bone marrow. The evidence suggests that stromal signals resembling those of a distant organ select for cancer cells that are primed for metastasis in that organ, thus illuminating the evolution of metastatic traits in a primary tumor and its distant metastases.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Metástase Neoplásica , Transdução de Sinais , Animais , Medula Óssea/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Quimiocina CXCL12/metabolismo , Fibroblastos/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Transplante de Neoplasias , Transcrição Gênica , Transplante Heterólogo , Quinases da Família src/genética , Quinases da Família src/metabolismo
2.
Proc Natl Acad Sci U S A ; 119(25): e2026733119, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35709320

RESUMO

Safeguarding Earth's tree diversity is a conservation priority due to the importance of trees for biodiversity and ecosystem functions and services such as carbon sequestration. Here, we improve the foundation for effective conservation of global tree diversity by analyzing a recently developed database of tree species covering 46,752 species. We quantify range protection and anthropogenic pressures for each species and develop conservation priorities across taxonomic, phylogenetic, and functional diversity dimensions. We also assess the effectiveness of several influential proposed conservation prioritization frameworks to protect the top 17% and top 50% of tree priority areas. We find that an average of 50.2% of a tree species' range occurs in 110-km grid cells without any protected areas (PAs), with 6,377 small-range tree species fully unprotected, and that 83% of tree species experience nonnegligible human pressure across their range on average. Protecting high-priority areas for the top 17% and 50% priority thresholds would increase the average protected proportion of each tree species' range to 65.5% and 82.6%, respectively, leaving many fewer species (2,151 and 2,010) completely unprotected. The priority areas identified for trees match well to the Global 200 Ecoregions framework, revealing that priority areas for trees would in large part also optimize protection for terrestrial biodiversity overall. Based on range estimates for >46,000 tree species, our findings show that a large proportion of tree species receive limited protection by current PAs and are under substantial human pressure. Improved protection of biodiversity overall would also strongly benefit global tree diversity.


Assuntos
Efeitos Antropogênicos , Biodiversidade , Conservação dos Recursos Naturais , Ecossistema , Árvores , Conservação dos Recursos Naturais/métodos , Humanos , Filogenia , Árvores/classificação
3.
Ecol Lett ; 27(6): e14446, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38814284

RESUMO

Grime's competitive, stress-tolerant, ruderal (CSR) theory predicts a shift in plant communities from ruderal to stress-tolerant strategies during secondary succession. However, this fundamental tenet lacks empirical validation using long-term continuous successional data. Utilizing a 60-year longitudinal data of old-field succession, we investigated the community-level dynamics of plant strategies over time. Our findings reveal that while plant communities generally transitioned from ruderal to stress-tolerant strategies during succession, initial abandonment conditions crucially shaped early successional strategies, leading to varied strategy trajectories across different fields. Furthermore, we found a notable divergence in the CSR strategies of alien and native species over succession. Initially, alien and native species exhibited similar ruderal strategies, but in later stages, alien species exhibited higher ruderal and lower stress tolerance compared to native species. Overall, our findings underscore the applicability of Grime's predictions regarding temporal shifts in CSR strategies depending on both initial community conditions and species origin.


Assuntos
Espécies Introduzidas , Plantas , Fenômenos Fisiológicos Vegetais , Estresse Fisiológico , Ecossistema , Modelos Biológicos , Desenvolvimento Vegetal
4.
BMC Cancer ; 24(1): 88, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38229045

RESUMO

BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Exenteração Pélvica , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/etiologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/etiologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/etiologia
5.
FASEB J ; 37(6): e22965, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37171272

RESUMO

Chronic alcohol consumption is a major risk factor for alcoholic steatohepatitis (ASH). Previous studies have shown that direct injury of hepatocytes is the key factor in its occurrence and development. However, our study shows that the role of Kupffer cells in ASH cannot be ignored. We isolated Kupffer cells from the livers of ASH mice and found that alcohol consumption induced Kupffer cell pyroptosis and increased the release of interleukin-1ß (IL-1ß). Furthermore, we screened the related m6A enzyme methyltransferase-like 3 (METTL3) from liver Kupffer cells, and found that silencing METTL3 alleviated inflammatory cytokine eruption by Kupffer cell pyroptosis in ASH mice. In vitro, we silenced METTL3 with lentivirus in BMDMs and RAW264.7 cells and confirmed that METTL3 could reduce pyroptosis by influencing the splicing of pri-miR-34A. Together, our results revealed a critical role of KC pyroptosis in ASH and highlighted the mechanism by which METLL3 relieves cell pyroptosis, which could be a promising therapeutic strategy for ASH.


Assuntos
Fígado Gorduroso Alcoólico , MicroRNAs , Animais , Camundongos , Células de Kupffer , Piroptose , Hepatócitos , Metiltransferases
6.
Nutr Cancer ; 76(1): 89-97, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37979150

RESUMO

We aimed to explore the association between the serum 25-hydroxyvitamin D concentration and all-cause and cancer-specific mortality in 2,463 adult patients with cancer from the National Health and Nutrition Examination Survey 2007-2018. We linked mortality data from the survey to the National Death Index records up to December 31, 2019. During a median follow-up period of 70 months, 567 patients died, of whom 194 died due to cancer. Multivariate adjustment was performed for demographic characteristics, lifestyle, dietary factors, 25-hydroxyvitamin D testing period, and cancer site. Higher serum 25-hydroxyvitamin D concentrations up to 75 nmol/L significantly reduced the risk of all-cause and cancer-specific mortality. When 25-hydroxyvitamin D quartiles were compared, the multivariable-adjusted hazard ratios were 0.59 (95% confidence interval: 0.42, 0.84) for all-cause mortality (P for trend <0.001) and 0.48 (95% confidence interval: 0.29, 0.79) for cancer-specific mortality (P for trend = 0.037) in quartile 3 (79.3-99.2 nmol/L). A threshold of 75 nmol/L for serum 25-hydroxyvitamin D may represent an intervention target to reduce mortalities in patients with cancer, and maintaining 25(OH)D concentrations within range (79.3-99.2 nmol/L) is beneficial for reducing all-cause and cancer-specific mortality.


Assuntos
Doenças Cardiovasculares , Neoplasias , Deficiência de Vitamina D , Adulto , Humanos , Inquéritos Nutricionais , Vitamina D , Vitaminas , Calcifediol , Fatores de Risco
7.
Infection ; 52(2): 403-412, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37651077

RESUMO

PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.


Assuntos
Carbapenêmicos , Transplante de Pulmão , Humanos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Transplantados , Pulmão , Programas de Rastreamento , Transplante de Pulmão/efeitos adversos
8.
Org Biomol Chem ; 22(16): 3204-3208, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38563260

RESUMO

An efficient palladium-catalyzed [2 + 2 + 1] annulation of 3-iodochromones, bridged olefins, and iodomethane is described, affording a range of chromone-containing polycyclic compounds. Additionally, the corresponding deuterated products were smoothly obtained with iodomethane-d3 instead of iodomethane. Moreover, the synthetic utility of this method is further substantiated by gram scale preparation and application to late-stage modification of estrone.

9.
Appl Microbiol Biotechnol ; 108(1): 22, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38159121

RESUMO

Three new strains of dissimilatory perchlorate-reducing bacteria (DPRB), QD19-16, QD1-5, and P3-1, were isolated from an active sludge. Phylogenetic trees based on 16S rRNA genes indicated that QD19-16, QD1-5, and P3-1 belonged to Brucella, Acidovorax, and Citrobacter, respectively, expanding the distribution of DPRB in the Proteobacteria. The three strains were gram-negative and facultative anaerobes with rod-shaped cells without flagella, which were 1.0-1.6 µm long and 0.5-0.6 µm wide. The three DPRB strains utilized similar broad spectrum of electron donors and acceptors and demonstrated a similar capability to reduce perchlorate within 6 days. The enzyme activity of perchlorate reductase in QD19-16 toward chlorate was higher than that toward perchlorate. The high sequence similarity of the perchlorate reductase operon and chlorite dismutase genes in the perchlorate reduction genomic islands (PRI) of the three strains implied that they were monophyletic origin from a common ancestral PRI. Two transposase genes (tnp1 and tnp2) were found in the PRIs of strain QD19-16 and QD1-5, but were absent in the strain P3-1 PRI. The presence of fragments of IR sequences in the P3-1 PRI suggested that P3-1 PRI had previously contained these two tnp genes. Therefore, it is plausible to suggest that a common ancestral PRI transferred across the strains Brucella sp. QD19-16, Acidovorax sp. QD1-5, and Citrobacter sp. P3-1 through horizontal gene transfer, facilitated by transposases. These results provided a direct evidence of horizontal gene transfer of PRI that could jump across phylogenetically unrelated bacteria through transposase. KEY POINTS: • Three new DPRB strains can effectively remove high concentration of perchlorate. • The PRIs of three DPRB strains are acquired from a single ancestral PRI. • PRIs are incorporated into different bacteria genome through HGT by transposase.


Assuntos
Ilhas Genômicas , Percloratos , Filogenia , Oxirredução , Transferência Genética Horizontal , RNA Ribossômico 16S/genética , Bactérias/genética , Oxirredutases/genética , Ecossistema , Transposases/genética
10.
BMC Oral Health ; 24(1): 733, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926705

RESUMO

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are important candidate seed cells for periodontal tissue engineering, but the presence of lipopolysaccharide(LPS) in periodontal tissues inhibits the self-renewal and osteogenic differentiation of hPDLSCs. Our previous studies demonstrated that TAZ is a positive regulator of osteogenic differentiation of hPDLSCs, but whether TAZ can protect hPDLSCs from LPS is still unknown. The present study aimed to explore the regulatory effect of TAZ on the osteogenic differentiation of hPDLSCs in an LPS-induced inflammatory model, and to preliminarily reveal the molecular mechanisms related to the NF-κB signaling pathway. METHODS: LPS was added to the culture medium of hPDLSCs. The influence of LPS on hPDLSC proliferation was analyzed by CCK-8 assays. The effects of LPS on hPDLSC osteogenic differentiation were detected by Alizarin Red staining, ALP staining, Western Blot and qRT-PCR analysis of osteogenesis-related genes. The effects of LPS on the osteogenic differentiation of hPDLSCs with TAZ overexpressed or knocked down via lentivirus were analyzed. NF-κB signaling in hPDLSCs was analyzed by Western Blot and immunofluorescence. RESULTS: LPS inhibited the osteogenic differentiation of hPDLSCs, inhibited TAZ expression, and activated the NF-κB signaling pathway. Overexpressing TAZ in hPDLSCs partly reversed the negative effects of LPS on osteogenic differentiation and inhibited the activation of the NF-κB pathway by LPS. TAZ knockdown enhanced the inhibitory effects of LPS on osteogenesis. CONCLUSION: Overexpressing TAZ could partly reverse the inhibitory effects of LPS on the osteogenic differentiation of hPDLSCs, possibly through inhibiting the NF-κB signaling pathway. TAZ is a potential target for improving hPDLSC-based periodontal tissue regeneration in inflammatory environments.


Assuntos
Diferenciação Celular , Lipopolissacarídeos , NF-kappa B , Osteogênese , Ligamento Periodontal , Transdução de Sinais , Células-Tronco , Humanos , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Osteogênese/efeitos dos fármacos , NF-kappa B/metabolismo , Diferenciação Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Células Cultivadas , Proliferação de Células/efeitos dos fármacos , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Western Blotting
11.
Angew Chem Int Ed Engl ; 63(13): e202318887, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38237082

RESUMO

Trifluoromethyl cationic carbyne (CF3 C+ :) possessing dual carbene-carbocation behavior emulated as trifluoromethyl metal-carbynoid (CF3 C+ =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α-diazotrifluoroethyl sulfonium salt was prepared and used in Rh-catalyzed three-component [2+1+2] cycloadditions for the first time with commercially available N-fused heteroarenes and nitriles, yielding a series of imidazo[1,5-a] N-heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh-carbynoid (CF3 C+ =Rh) into C=N bonds of N-fused heteroarenes was involved. This strategy demonstrates synthetic applications in late-stage modification of pharmaceuticals, construction of CD3 -containing N-heterocycles, gram-scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5-a] N-heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.

12.
Small ; 19(50): e2304677, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37632318

RESUMO

To achieve high-performance solid-state lithium-metal batteries (SSLMBs), solid electrolytes with high ionic conductivity, high oxidative stability, and high mechanical strength are necessary. However, balancing these characteristics remains dramatically challenging and is still not well addressed. Herein, a simple yet effective design strategy is presented for the development of high-performance polymer electrolytes (PEs) by exploring the synergistic effect between dynamic H-bonded networks and conductive zwitterionic nanochannels. Multiple weak intermolecular interactions along with ample nanochannels lead to high oxidative stability (over 5 V), improved mechanical properties (strain of 1320%), and fast ion transport (ionic conductivity of 10-4 S cm-1 ) of PEs. The amphoteric ionic functional units also effectively regulate the lithium ion distribution and confine the anion transport to achieve uniform lithium ion deposition. As a result, the assembled SSLMBs exhibit excellent capacity retention and long-term cycle stability (average Coulombic efficiency: 99.5%, >1000 cycles with LiFePO4 cathode; initial capacity: 202 mAh g-1 , average Coulombic efficiency: 96%, >230 cycles with LiNi0.8 Co0.1 Mn0.1 O2 cathode). It is exciting to note that the corresponding flexible cells can be cycled stably and can withstand severe deformation. The resulting polyzwitterion-mediated PE therefore offers great promise for the next-generation safe and high-energy-density flexible energy storage devices.

13.
New Phytol ; 239(6): 2389-2403, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37438886

RESUMO

Karyological characteristics are among the traits underpinning the invasion success of vascular plants. Using 11 049 species, we tested the effects of genome size and ploidy levels on plant naturalization (species forming self-sustaining populations where they are not native) and invasion (naturalized species spreading rapidly and having environmental impact). The probability that a species naturalized anywhere in the world decreased with increasing monoploid genome size (DNA content of a single chromosome set). Naturalized or invasive species with intermediate monoploid genomes were reported from many regions, but those with either small or large genomes occurred in fewer regions. By contrast, large holoploid genome sizes (DNA content of the unreplicated gametic nucleus) constrained naturalization but favoured invasion. We suggest that a small genome is an advantage during naturalization, being linked to traits favouring adaptation to local conditions, but for invasive spread, traits associated with a large holoploid genome, where the impact of polyploidy may act, facilitate long-distance dispersal and competition with other species.


Assuntos
Ecossistema , Traqueófitas , Tamanho do Genoma , Cidadania , Ploidias , Espécies Introduzidas , DNA
14.
Virol J ; 20(1): 98, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37221518

RESUMO

BACKGROUND: Pseudorabies (PR) (also called Aujeszky's disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections. METHODS: The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines. RESULTS: Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90-100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits. CONCLUSIONS: The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.


Assuntos
Vírus GB C , Herpesvirus Suídeo 1 , Pseudorraiva , Coelhos , Animais , Suínos , Vacinas Atenuadas , Vacinas de Subunidades Antigênicas , Adjuvantes Imunológicos
15.
Nutr Cancer ; 75(5): 1340-1348, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36988095

RESUMO

Vitamin D (VD) plays a regulatory role in tumor occurrence and development, although the factors influencing serum 25-hydroxyvitamin D3 (25(OH)D3) levels in patients with cancer have not been studied. Therefore, we aimed to evaluate circulating levels of 25(OH)D3 and factors influencing the VD status in patients with malignant tumors. Adult patients with malignant tumors who had undergone assessments of serum 25(OH)D3 at Beijing Cancer Hospital from January 2019 to July 2022 were included. A multiple logistic regression model was applied to explore the associations of patient characteristics, environment, and disease characteristics with 25(OH)D3 levels. Among the 1,076 included patients, the median 25(OH)D3 serum concentration was 16.25 ng/mL. VD deficiency and the combined VD insufficiency and sufficiency were observed in 811 (75.37%) and 265 (24.63%) patients, respectively. Latitude, season, sex, body mass index, and type of cancer were associated with VD concentration/status in patients with malignant tumors. 25(OH)D3 concentrations were significantly higher in patients with thyroid cancer and significantly lower in patients receiving tumor-related treatment than in untreated patients. Surprisingly, we observed 25(OH)D3 serum concentration was lower in patients receiving nutritional supplementation than in those receiving no nutritional supplements. Patients with malignant tumors are at high risk of VD deficiency.


Assuntos
Neoplasias da Glândula Tireoide , Deficiência de Vitamina D , Adulto , Humanos , Vitamina D , Vitaminas , Calcifediol , Suplementos Nutricionais
16.
Br J Clin Pharmacol ; 89(1): 209-221, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35939394

RESUMO

AIM: Propofol and opioids are commonly used in anaesthesia, but are highly susceptible to haemodynamic instability, thereby threatening the patient's surgical safety and prognosis. The purpose of this study was to investigate the predictors of haemodynamic instability and establish its predictive model. METHODS: A total of 150 Chinese patients undergoing thyroid or breast surgery participated in the study, with target-controlled infusion concentrations of propofol, opioids dosage, heart rate (HR), mean arterial pressure (MAP) and Narcotrend Index recorded at key points throughout the procedure. The Agena MassARRAY system was used to genotype candidate single nucleotide polymorphisms related to pharmacodynamics and pharmacokinetics of propofol and opioids. RESULTS: Among nongenetic factors, baseline HR (R = -.579, P < .001) and baseline MAP (R = -.725, P < .001) had a significant effect on the haemodynamic instability. Among genetic factors, the CT/CC genotype of GABRB1 rs4694846 (95% confidence interval [CI]: -11.309 to -3.155), AA/AG of OPRM1 rs1799971 (95%CI: 0.773 to 10.290), AA of CES2 rs8192925 (95%CI: 1.842 to 9.090) were associated with higher HR instability; the AA/GG genotype of NR1I2 rs6438550 (95%CI: 0.351 to 7.761), AA of BDNF rs2049046 (95%CI: -9.039 to -0.640) and GG of GABBR2 rs1167768 (95%CI: -10.146 to -1.740) were associated with higher MAP instability. The predictive models of HR and MAP fluctuations were developed, accounting for 45.0 and 59.2% of variations, respectively. CONCLUSION: We found that cardiovascular fundamentals and genetic variants of GABRB1, GABBR2, OPRM1, BDNF, CES2 and NR1I2 are associated with cardiovascular susceptibility, which can provide a reference for haemodynamic management in clinical anaesthesia.


Assuntos
Propofol , Humanos , Propofol/farmacocinética , Anestésicos Intravenosos/farmacocinética , Analgésicos Opioides/farmacologia , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Receptor de Pregnano X , Estudos Retrospectivos , Pressão Sanguínea , Hemodinâmica
17.
J Org Chem ; 88(1): 371-383, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36563325

RESUMO

A cooperative tertiary amine/palladium-catalyzed sequential reaction process, proceeding via a [4 + 3] cyclization of isatin-derived Morita-Baylis-Hillman Expansion (MBH) carbonates and tert-butyl 2-(hydroxymethyl)allyl carbonates followed by a [1,3]-rearrangement, has been found and developed. A range of structurally diverse spiro[methylene cyclopentane-1,3'-oxindolines] bearing two adjacent ß,γ-acyl quaternary carbon stereocenters, which are difficult to obtain by conventional strategies, were obtained in good yields. Further synthetic utility of this protocol is highlighted by its excellent regio- and stereocontrol as well as the large-scale synthesis and diverse functional transformations of the synthetic compounds. Moreover, the control experiments probably established the plausible mechanism for this sequential [4 + 3] cyclization/[1,3]-rearrangement process.


Assuntos
Carbonatos , Paládio , Ciclização , Estrutura Molecular , Estereoisomerismo , Catálise , Aminas
18.
BMC Gastroenterol ; 23(1): 293, 2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37653473

RESUMO

BACKGROUND: Milligan-Morgan hemorrhoidectomy (MMH) is the most widely used surgical procedure because of its precise curative effect, but it has the disadvantages such as obvious postoperative pain and bleeding. To retrospectively evaluate the efficacy and safety of MMH combined with non-Doppler hemorrhoidal artery ligation (MMH + ND-HAL) for the treatment of grade III/IV hemorrhoids. METHODS: We conducted a retrospective analysis of 115 patients with grade III/IV hemorrhoids, 53 patients had received MMH + ND-HAL, and the remaining 62 patients received MMH. We collected and compared demographic and clinical characteristics of both groups, including intraoperative blood loss, postoperative visual analog scale (VAS) for pain, analgesic consumption, postoperative bleeding, perianal incision edema, urinary retention, anal stenosis, anal incontinence incidence, recurrence rate (prolapse or bleeding), and patient satisfaction. RESULTS: The VAS pain score of the first postoperative defecation and at the postoperative 12 h, 1 day, 2 days, 3 days, and 7 days, as well as the total analgesic consumption within 7 days, for the MMH + ND-HAL group were lower than those for the MMH group (P < 0.05). The intraoperative blood loss, the incidence of postoperative bleeding, perianal incision edema, and urinary retention in the MMH + ND-HAL group was lower than that in the MMH group (P < 0.05). No anal stenosis or anal incontinence occurred in either group. At follow-up by telephone or outpatient 12 months after surgery, the recurrence rate (prolapse or bleeding) was lower in the MMH + ND-HAL group than in the MMH group (P < 0.05), and satisfaction was higher in the MMH + ND-HAL group than in the MMH group (P < 0.05). CONCLUSIONS: MMH + ND-HAL was a satisfactory surgical modality for treating III/IV hemorrhoids.


Assuntos
Malformações Anorretais , Hemorroidectomia , Hemorroidas , Retenção Urinária , Humanos , Estudos Retrospectivos , Hemorroidectomia/efeitos adversos , Hemorroidas/cirurgia , Constrição Patológica , Hemorragia Pós-Operatória , Perda Sanguínea Cirúrgica , Dor Pós-Operatória/etiologia , Artérias/cirurgia
19.
Int J Med Sci ; 20(11): 1460-1468, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37790842

RESUMO

Periodontal ligament stem cells (PDLSCs) are important candidate seed cells for alveolar bone tissue engineering. Dasatinib is a tyrosine kinase inhibitor, and its influence on the osteogenic differentiation of mesenchymal stem cells is a controversial topic. The present study explored the effects of different concentrations of dasatinib on the proliferation and osteogenic differentiation of PDLSCs and tentatively revealed the related mechanism. The results of CCK8 showed that low concentrations of dasatinib (1 nM) did not affect proliferation, while high concentrations of dasatinib significantly inhibited the proliferative activity of PDLSCs. This could be related to the inhibiting effects of dasatinib on Erk signals. ALP staining, alizarin red staining, and western blot proved that low concentrations of dasatinib (1 nM) promoted the osteogenic differentiation of PDLSCs, while high concentrations of dasatinib inhibited it. The negative effects of dasatinib on osteogenic differentiation were reversed when EID3 was knocked down, suggesting that EID3 mediates the regulation of dasatinib on the osteo-differentiation of PDLSCs. Taken together, high concentrations of dasatinib inhibited the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals, while low concentrations of dasatinib could be a potential method to enhance the bone regeneration ability of PDLSCs.


Assuntos
Osteogênese , Ligamento Periodontal , Osteogênese/genética , Dasatinibe/farmacologia , Proliferação de Células , Diferenciação Celular , Células-Tronco , Células Cultivadas
20.
Chem Soc Rev ; 51(8): 3181-3225, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35348147

RESUMO

With the aim of addressing the global warming issue and fossil energy shortage, eco-friendly and sustainable renewable energy technologies are urgently needed. In comparison to energy conversion, studies on energy storage fall behind and remain largely to be explored. By storing energy from electrochemical processes at the electrode surface, supercapacitors (SCs) bridge the performance gap between electrostatic double-layer capacitors and batteries. Organic electrode materials have drawn extensive attention because of their special power density, good round trip efficiency and excellent cycle stability. Porous organic polymers (POPs) have drawn extensive attention as attractive electrode materials in SCs. In this review, we present and discuss recent advancements and design principles of POPs as efficient electrode materials for SCs from the perspectives of synthetic strategies and the structure-performance relationships of POPs. Finally, we put forward the outlook and prospects of POPs for SCs.

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