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1.
Chem Commun (Camb) ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36722871

RESUMO

Sequential azide/diyne cycloadditions proved highly effective for the macrocyclization of a bis-azido aza-dipyrrin. Macrocyclic aza-dipyrrin could be produced in 30 min at rt in water with changes in fluorescence intensity and lifetimes measurable upon reaction. Live cell microscopy showed that aza-dipyrrins were suitable for confocal and STED super-resolution imaging and a bioorthogonal response to macrocyclization could be detected in cellular compartments. These results will encourage a broader examination of the sensing and imaging uses of aza-dipyrrins.

2.
Mikrochim Acta ; 190(2): 76, 2023 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-36708389

RESUMO

The development of a novel colorimetric method is reported, using vB_YepM_ZN18 phages along with AuPt nanozyme for the sensitive detection of Y. pseudotuberculosis. The phage used in this work has been extracted from hospital sewer water and is highly specific toward Y. pseudotuberculosis. The synthesized AuPt NPs possess peroxidase-like activity, which is suitable in the development of nanozyme based detection system. Furthermore, phages@MB and AuPt@phages are added into the bacterial samples for co-incubation, forming an intercalated complex. The magnetic separation and absorbance analysis of enzymatic reaction are carried out for the detection of targeted bacteria. The proposed method has a limit of detection of 14 CFU/mL, a wide linear range from 2.50 × 101 ~ 2.50 × 107 CFU/mL and the assay completion time is 40 min. Benefitting from the outperformance of this sensor, we have successfully employed the developed sensing platform for the detection of Y. pseudotuberculosis in food industry and hospital specimens.


Assuntos
Bacteriófagos , Yersinia pseudotuberculosis , Colorimetria/métodos
3.
BMC Public Health ; 23(1): 48, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609267

RESUMO

BACKGROUND: Human papillomavirus (HPV) vaccination could prevent cervical and other HPV-associated cancers attributable to vaccine-associated HPV types. However, HPV vaccination coverage among women aged 9-18 years old is low in China. Common barriers include poor financial affordability, minimal public engagement, and low confidence in domestically produced HPV vaccines. Pay-it-forward offers an individual a free or subsidized service then an opportunity to voluntarily donate and/or create a postcard message to support future people. This study aims to assess the effectiveness of pay-it-forward as compared to standard-of-care self-paid vaccination to improve HPV vaccine uptake among adolescent girls aged 15-18 years, who are left out in the current pilot free HPV vaccination task force in some parts of China. METHODS: This is a two-arm randomized controlled trial in Chengdu, China. Eligible adolescent girls (via caregivers) will be randomly selected and recruited through four community health centers (one in the most developed urban areas, one in higher middle-income and one in lower middle-income suburban areas, and one in the least developed rural areas) using the resident registration list. A total of 320 participants will be randomized into two study arms (user-paid versus pay-it-forward vaccination) in a 1:1 ratio. The intervention assignment will be blinded to recruiters and participants using envelop concealment until the research assistants open the envelop to determine which treatment to deliver to each individual. The primary outcome of the study will be HPV vaccine uptake by administrative data. Secondary outcomes include costs, vaccine hesitancy, and the completion rates of the 3-dose HPV vaccination series. DISCUSSION: This study will investigate an innovative pay-it-forward strategy's effectiveness and economic costs to improve HPV vaccination among 15-18-year-old adolescent girls. Study findings will have implications for increasing HPV vaccine uptake in places where HPV vaccines are provided for a fee. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2200055542. Registered on 11 January 2022.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Adolescente , Criança , Infecções por Papillomavirus/prevenção & controle , Hesitação Vacinal , Vacinação/métodos , China , Neoplasias do Colo do Útero/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Cancer Sci ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36601865

RESUMO

Mycoplasma is widespread in various hosts and may cause various diseases in animals. Interestingly, the occurrence of mycoplasma infection was observed in many tumor types. However, the mechanism regulating its infection is far from clear. We unexpectedly found that the knockdown of mitochondrial transcription factor A (TFAM) remarkably enhanced mycoplasma infection in HCC cells. More importantly, we found that mycoplasma infection facilitated by TFAM knockdown significantly promoted HCC cell metastasis. Mycoplasma infection was further found to be positively correlated with poor prognosis in patients with HCC. Mechanistically, the decreased TFAM expression upregulated the transcription factor Sp1 to increase the expression level of Annexin A2 (ANXA2), which was reported to interact with membrane protein of mycoplasma. Moreover, we found that mycoplasma infection enhanced by the TFAM downregulation promoted HCC migration and invasion by activating the NF-κB signaling pathway. The downregulation of TFAM enhanced mycoplasma infection in HCC cells and promoted HCC cell metastasis. Our study contributes to the understanding of the pathological role of mycoplasma infection and provides supporting evidence that targeting TFAM may be a potential strategy for the treatment of HCC with mycoplasma infection.

5.
Arch Sex Behav ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626071

RESUMO

Syphilis testing uptake is low among men who have sex with men (MSM) around the world. Syphilis self-testing (SST) may complement facility-based testing; the distribution model is yet to be explored. This study aimed to investigate the effectiveness of peer distribution of syphilis self-testing on promoting syphilis testing. We conducted a three-arm, unblinded, parallel individually randomized controlled trial among MSM in three cities in Guangdong, China. Inclusion criteria were: men who were born biologically male, aged 18 or above, have ever had sex with a man, will refer the interventions to peers, and will take the three-month follow-up survey. Enrolled indexes were randomly assigned in a 1:1:1 ratio into standard-of-care arm (SOC arm), standard SST delivery arm (S-SST arm), and a web-based referral link SST delivery arm (RL-SST arm). The primary outcome was the number of returned photograph-verified syphilis testing results per index. A total number of 300 indexes were enrolled, with 100 indexes in each arm. The number of verified syphilis tests per index conducted by alters was 0.05 in the control arm, 0.51 in the S-SST arm, and 0.31 in the RL-SST arm. The cost per alter tested was $760.60 for SOC, $83.78 for S-SST, and $93.10 for RL-SST. Minimal adverse event was reported among both indexes and alters during the study. This study showed that peer distribution of SST could improve syphilis testing uptake among MSM in China compared to facility-based testing. This approach warrants further consideration as part of expanding syphilis self-testing.

6.
Protein Pept Lett ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698226

RESUMO

BACKGROUND: The CRISPR-Cas system is an adaptive immune mechanism for bacteria and archaea to resist foreign invasion. Currently, Cas9 and Cpf1 have been widely studied and applied in gene editing. C2c1 is a newly discovered CRISPR-Cas system endonuclease. It has broad application prospects due to its small molecular weight and high substrate recognition specificity. OBJECTIVES: Bacillus thermoamylovorans C2c1(BthC2c1) was expressed in E. coli C43 (DE3) competent cells, purified, and the BthC2c1-sgRNA-dsDNA complex was assembled. The effect of temperature on the cleavage ability of the BthC2c1 system was investigated. METHODS: The cDNA of BthC2c1 was cloned into the vector pGEX-6P-1. BthC2c1 was expressed in E. coli C43(DE3) cells and purified using a GST affinity column and FPLC. The sgRNAs were transcribed and purified in vitro, and the complexes were assembled by gel filtration chromatography. The enzyme cleavage activity of BthC2c1 at different temperatures was investigated using an in vitro cleavage assay. Microscale Thermophoresis detected the affinity of the BthC2c1-sgRNA complexes to substrate DNA. RESULTS: BthC2c1 proteins were prokaryotically expressed and purified. The complex of BthC2c1 with sgRNA and dsDNA was assembled. In vitro cleavage assay results showed that BthC2c1 cleaved the target DNA at temperatures ranging from 37°C to 67°C. The cleavage ability of BthC2c1 at 42℃ was stronger than that at 37℃. The results of affinity detection showed that the affinity between the BthC2c1-sgRNA complex and ds36/36 at 42℃ was stronger than that at 37℃. CONCLUSION: In this study, BthC2c1 was expressed, purified, and assembled into a complex with sgRNA and dsDNA. BthC2c1 cleaved DNA within the temperature range of 37℃ to 67℃. The affinity of BthC2c1-sgRNA to DNA at 42°C was significantly enhanced than that at 37°C. It may be related to its stringent substrate recognition pattern, which differs from Cas9 and Cpf1. The temperature-dependent affinity changes of substrate binding may be part of the reason for the stronger cleavage activity of BthC2c1 at 42℃. This study may provide an experimental basis for optimizing and modifying the C2c1 gene editing system.

7.
J Neurosci ; 43(4): 559-570, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36639904

RESUMO

Thalamus is a critical component of the limbic system that is extensively involved in both basic and high-order brain functions. However, how the thalamic structure and function develops at macroscopic and microscopic scales during the perinatal period development is not yet well characterized. Here, we used multishell high-angular resolution diffusion MRI of 144 preterm-born and full-term infants in both sexes scanned at 32-44 postmenstrual weeks (PMWs) from the Developing Human Connectome Project database to investigate the thalamic development in morphology, microstructure, associated connectivity, and subnucleus division. We found evident anatomic expansion and linear increases of fiber integrity in the lateral side of thalamus compared with the medial part. The tractography results indicated that thalamic connection to the frontal cortex developed later than the other thalamocortical connections (parieto-occipital, motor, somatosensory, and temporal). Using a connectivity-based segmentation strategy, we revealed that functional partitions of thalamic subdivisions were formed at 32 PMWs or earlier, and the partition developed toward the adult pattern in a lateral-to-medial pattern. Collectively, these findings revealed faster development of the lateral thalamus than the central part as well as a posterior-to-anterior developmental gradient of thalamocortical connectivity from the third trimester to early infancy.SIGNIFICANCE STATEMENT This is the first study that characterizes the spatiotemporal developmental pattern of thalamus during the third trimester to early infancy. We found that thalamus develops in a lateral-to-medial pattern for both thalamic microstructures and subdivisions; and thalamocortical connectivity develops in a posterior-to-anterior gradient that thalamofrontal connectivity appears later than the other thalamocortical connections. These findings may enrich our understanding of the developmental principles of thalamus and provide references for the atypical brain growth in neurodevelopmental disorders.


Assuntos
Conectoma , Imageamento por Ressonância Magnética , Masculino , Adulto , Recém-Nascido , Feminino , Gravidez , Humanos , Lactente , Terceiro Trimestre da Gravidez , Imagem de Difusão por Ressonância Magnética , Conectoma/métodos , Tálamo , Vias Neurais/diagnóstico por imagem , Córtex Cerebral
8.
Clin Transl Med ; 13(1): e1170, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36629024

RESUMO

Sepsis is a persistent systemic inflammatory condition involving multiple organ failures resulting from a dysregulated immune response to infection, and one of the hallmarks of sepsis is endothelial dysfunction. During its progression, neutrophils are the first line of innate immune defence against infection. Aside from traditional mechanisms, such as phagocytosis or the release of inflammatory cytokines, reactive oxygen species and other antibacterial substances, activated neutrophils also release web-like structures composed of tangled decondensed DNA, histone, myeloperoxidase and other granules called neutrophil extracellular traps (NETs), which can efficiently ensnare bacteria in the circulation. In contrast, excessive neutrophil activation and NET release may induce endothelial cells to shift toward a pro-inflammatory and pro-coagulant phenotype. Furthermore, neutrophils and NETs can degrade glycocalyx on the endothelial cell surface and increase endothelium permeability. Consequently, the endothelial barrier collapses, contributing to impaired microcirculatory blood flow, tissue hypoperfusion and life-threatening organ failure in the late phase of sepsis.


Assuntos
Armadilhas Extracelulares , Sepse , Humanos , Neutrófilos/metabolismo , Armadilhas Extracelulares/metabolismo , Células Endoteliais , Microcirculação , Sepse/metabolismo
9.
Mikrochim Acta ; 190(2): 59, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36656362

RESUMO

Based on the resonance energy transfer between CdS@CeO2 and Cu2O@PdAg, a quenching immunosensor for sensitive detection of prostate specific antigen (PSA) was constructed. The CdS@CeO2 heterostructure was obtained by in situ growth of CeO2 particles on the surface of CdS nanorods, and stable cathodic ECL emission was achieved using K2S2O8 as coreactant. Cu2O@PdAg was composed of Cu2O with tetradecahedral structure and bimetallic PdAg nanospheres and has a UV-V is absorption range between 600 and 800 nm. It overlaps with the ECL emission spectrum of CdS@CeO2, realizing the effective quenching of the ECL signal, which provides feasibility for subsequent practical application. The immunosensor exhibited good linearity in the concentration range 10 fg·mL-1 ~ 100 ng·mL-1, with a detection limit of 5.6 fg·mL-1. In sample analysis, the recoveries were 99.8-101%, and the relative standard deviation (RSD) was 0.85-1.6% showing great potential and development value for the sensitive detection of prostate cancer.


Assuntos
Técnicas Biossensoriais , Antígeno Prostático Específico , Neoplasias da Próstata , Humanos , Masculino , Técnicas Eletroquímicas , Imunoensaio , Limite de Detecção , Medições Luminescentes , Neoplasias da Próstata/diagnóstico
10.
PLoS Med ; 20(1): e1004091, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36595536

RESUMO

BACKGROUND: To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. METHODS AND FINDINGS: In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). CONCLUSIONS: Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.


Assuntos
Tuberculose , Humanos , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Aconselhamento , Motivação
11.
Environ Res ; 220: 115240, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36621544

RESUMO

In order to solve nitrogen pollution in environmental water, two heterotrophic nitrifying and aerobic denitrifying strains isolated from acid paddy soil were identified as Achromobacter sp. strain HNDS-1 and Enterobacter sp. strain HNDS-6 respectively. Strain HNDS-1 and strain HNDS-6 exhibited amazing ability to nitrogen removal. When (NH4)2SO4, KNO3, NaNO2 were used as nitrogen resource respectively, the NH4+-N, NO3--N, NO2--N removal efficiencies of strain HNDS-1 were 93.31%, 89.47%, and 100% respectively, while those of strain HNDS-6 were 82.39%, 96.92%, and 100%. And both of them could remove mixed nitrogen effectively in low C/N (C/N = 5). Strain HNDS-1 could remove 76.86% NH4+-N and 75.13% NO3--N. And strain HNDS-6 can remove 65.07% NH4+-N and 78.21% NO3--N. A putative ammonia monooxygenase, nitrite reductase, nitrate reductase, assimilatory nitrate reductase, nitrate/nitrite transport protein and nitric oxide reductase of strain HNDS-1, while hydroxylamine reductase, nitrite reductase, nitrate reductase, assimilatory nitrate reductase, nitrate/nitrite transport protein, and nitric oxide reductase of strain HNDS-6 were identified by genomic analysis. DNA-SIP analysis showed that genes Nxr, narG, nirK, norB, nosZ were involved in nitrogen removal pathway, which indicates that the denitrification pathway of strain HNDS-1 and strain HNDS-6 was NO3-→NO2-→NO→N2O→N2 during NH4+-N removal process. And the nitrification pathway of strain HNDS-1 and strain HNDS-6 was NO2-→NO3-, but the nitrification pathway of NH4+→ NO2- needs further studies.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36673677

RESUMO

Urban construction land (UCL) change is a significant cause of changes in urban carbon emissions. However, as the extent of this effect is currently unclear, cities cannot easily formulate reasonable carbon reduction policies in terms of land use. Taking the city of Wuhan, China, as an example, this paper combines data on land use and carbon emissions from 1995 to 2019 and uses spatial analysis, curve estimation, and correlation evaluation to explore the direct and indirect effects of the UCL changes on carbon emissions. The results show that: (1) Between 1995 and 2019, the UCL area in Wuhan increased by 193.44%, and carbon emissions increased by 78.63%; moreover, both changes showed a gradually increasing spatial correlation, and the quantitative relationship could be better fitted with a composite function model; (2) The UCL change had mainly an indirect impact on carbon emissions via factors such as population and energy use intensity per unit of carbon emissions; (3) The maximum value of carbon emissions inside a unit area decreased during the study period, with an average annual decrease of about 2.02%. Therefore, the city of Wuhan can promote the achievement of its carbon emissions reduction targets by improving the existing land use policies, for example, by dividing the city into multiple functional zones.


Assuntos
Dióxido de Carbono , Carbono , Cidades , Carbono/análise , Análise Espacial , China , Dióxido de Carbono/análise
13.
Theranostics ; 13(1): 324-338, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593960

RESUMO

Rationale: Mitochondrial dysfunction caused by mitochondrial DNA (mtDNA) mutations and subsequent metabolic defects are closely involved in tumorigenesis and progression in a cancer-type specific manner. To date, the mutational pattern of mtDNA somatic mutations in colorectal cancer (CRC) tissues and its clinical implication are still not completely clear. Methods: In the present study, we generated a large mtDNA somatic mutation dataset from three CRC cohorts (432, 1,015, and 845 patients, respectively) and then most comprehensively characterized the CRC-specific evolutionary pattern and its clinical implication. Results: Our results showed that the mtDNA control region (mtCTR) with a high mutation density exhibited a distinct mutation spectrum characterizing a high enrichment of L-strand C > T mutations, which was contrary to the H-strand C > T mutational bias observed in the mtDNA coding region (mtCDR) (P < 0.001). Further analysis clearly confirmed the relaxed evolutionary selection of mtCTR mutations, which was mainly characterized by the similar distribution of hypervariable region (HVS) and non-HVS mutation density. Moreover, significant negative selection was identified in mutations of mtDNA complex V (ATP6/ATP8) and tRNA loop regions. Although our data showed that oxidative metabolism was commonly increased in CRC cells, mtDNA somatic mutations in CRC tissues were not closely associated with mitochondrial biogenesis, oxidative metabolism, and clinical progression, suggesting a cancer-type specific relationship between mtDNA mutations and mitochondrial metabolic functions in CRC cells. Conclusion: Our study identified the CRC-specific evolutionary mode of mtDNA mutations, which is possibly matched to specific mitochondrial metabolic remodeling and confers new mechanic insight into CRC tumorigenesis.


Assuntos
Neoplasias Colorretais , DNA Mitocondrial , Humanos , DNA Mitocondrial/genética , Mutação/genética , Mitocôndrias/genética , Neoplasias Colorretais/genética , Carcinogênese , Estresse Oxidativo
14.
J Phys Chem Lett ; 14(3): 645-652, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36637141

RESUMO

The rational design of high-efficiency catalysts is hindered by the knowledge of active sites, which always experience dynamic transformations within different time scales. In this regard, tracking these time-dependent processes is essential to building the correlation between the active site and catalytic performance. Achieving this goal requires powerful characterization techniques to overcome the obstacle induced by the time mismatch. By virtue of the local structure sensitivity, synchrotron X-ray absorption spectroscopy (XAS) comprising step-scanning XAS, quick-scanning XAS, and energy-dispersive XAS has been widely applied to record structural evolution events. In this Perspective, we highlight the substantial accomplishments achieved by these time-resolved XAS techniques. Their principles, advantages, and limitations involved in monitoring energy-involving electrocatalysis were also introduced. Meanwhile, the key challenges that we are encountering and the further directions of time-resolved XAS are also provided. We sincerely hope that these insights could offer a reliable guideline for other researchers to design more efficient in situ experiments.

15.
Hypertens Res ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631554

RESUMO

Fatty liver has been suggested to be associated with the development of hypertension. However, whether this association is related to glycemia has not been elucidated. Therefore, we investigated whether the fatty liver index (FLI) predicts the development of hypertension among individuals with and without dysglycemia in a general Japanese population. A total of 3114 participants (1036 males and 2078 females) without hypertension who underwent a Specific Health Checkup in the fiscal year 2013 were followed up until 2018. The participants were divided into six groups based on FLI tertiles (low, moderate, or high) and whether they had dysglycemia. We estimated the hazard ratios (HRs) of each group by sex using the Cox proportional hazard model. Models were adjusted for age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, smoking, and alcohol consumption and further adjusted for systolic blood pressure (SBP). During the mean follow-up period of 2.8 years, 160 of the 3114 participants developed hypertension. Using the low FLI group with normoglycemia as a reference, the HR for incident hypertension was increased in the high FLI group with and without dysglycemia in both sexes after adjusting for confounders, except SBP (HR [95% confidence interval]: male: 1.52 (1.06-2.17) in normoglycemia and 2.05 (1.43-2.92) in dysglycemia, and female: 1.86 (1.43-2.42) in normoglycemia and 2.98 (2.19-4.07) in dysglycemia). Furthermore, in females, this association was observed after adjusting for SBP. We concluded that FLI was independently associated with an increased risk of incident hypertension in individuals with and without dysglycemia.

16.
Biomacromolecules ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633601

RESUMO

Although traditional nanomedicines have enhanced the therapeutic efficacy and improved the survival quality of cancer patients, random drug release and drug resistance are deep-rooted problems hindering their clinical application. A precise nanoplatform combing chemotherapy and photodynamic therapy (PDT) is developing as a new therapeutic strategy to overcome the above challenges. Herein, a novel supramolecular nanomedicine is ingeniously constructed for in situ self-boosting cancer photochemotherapy. Hydrophilic polyethylene glycol (PEG) chains or ß-cyclodextrin (ß-CD) hosts are first conjugated onto tetraphenyl porphyrin (TCPP) to improve the solubility of TCPP and decrease their π-π stacking interactions, guaranteeing a high-efficiency PDT. Then, two camptothecin (CPT) molecules are linked together via a reactive oxygen species (ROS)-responsive thioketal bond, which averts the premature burst release of CPT and realizes in situ drug release at the tumor site where PDT is performed, resulting in an enhanced chemotherapy. Benefiting from the collaboration of host-guest complexation between ß-CD and CPT, multiple intermolecular hydrogen bonds of ß-CD, π-π stacking interactions among CPT and TCPP as well as PEG shell protection, a prolonged blood circulation time, and a selective tumor accumulation are acquired, which facilitate the synergistic photochemotherapy and bring a pre-eminent antitumor response with a low systemic toxicity.

17.
Toxins (Basel) ; 15(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36668884

RESUMO

Aflatoxin is a potent mycotoxin and a common source of grain contamination that leads to great economic losses and health problems. Although distilled baijiu cannot be contaminated by aflatoxin, its presence in the brewing process affects the physiological activities of micro-organisms and reduces product quality. Bacillus cereus XSWW9 capable of degrading aflatoxin B1 (AFB1) was isolated from daqu using coumarin as the sole carbon source. XSWW9 degraded 86.7% of 1 mg/L AFB1 after incubation at 37 °C for 72 h and tolerated up to 1 mg/L AFB1 with no inhibitory effects. Enzymes in the cell-free supernatant of XSSW9 played a significant role in AFB1 degradation. The AFB1-degradation activity was sensitive to protease K and SDS treatment, which indicated that extracellular proteins were responsible for the degradation of AFB1. In order to investigate the AFB1-degradation ability of XSSW9 during the baijiu brewing process, AFB1 and XSWW9 were added to grain fermentation (FG-T) and normal grain fermentation without AFB1, while normal grain fermentation without AFB1 and XSWW9 was used as a control (FG-C). At the end of the fermentation, 99% AFB1 was degraded in the residue of fermented grains. The differences of microbial communities in the fermented grains showed that there were no significant differences between FG-T and FG-C in the relative abundance of dominant genera. The analysis of volatile compounds of their distillation showed that the contents of skeleton flavor components was similar between FG-T and FG-C. These results offer a basis for the development of effective strategies to reduce the effect of AFB1 on the brewing process and ensure that the production of baijiu is stable.


Assuntos
Aflatoxina B1 , Bacillus cereus , Bacillus cereus/metabolismo , Aflatoxina B1/metabolismo , Fermentação , Endopeptidase K , Biodegradação Ambiental
18.
Sex Health ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36653021

RESUMO

The number of older adults identifying as lesbian, gay, bisexual, transgender and other sexual and gender diverse identities (LGBTQIA+) is growing as populations age and social environments become more accepting. This study uses a global evidence synthesis to understand perceived barriers and facilitators to access to sexual healthcare globally for older LGBTQIA+ adults. We used a scoping review and qualitative evidence synthesis. Embase, PubMed and PsycInfo were searched with terms related to LGBTQIA+ populations, adults aged 45years, and sexual health care. We used the Cochrane Handbook and the review protocol was registered. Primary and secondary textual data were coded and grouped into themes using PRISMA-SCR and the Minority Stress Model. The certainty of review findings was assessed using the GRADE-CERQual approach. We identified 19 studies and 15 were included in the qualitative evidence synthesis. All studies were from high-income countries. Heterocentricity and male-centricity of sexual healthcare services contributed to feelings of exclusion for older LGBTQIA+ adults. Both anticipated and enacted stigma from healthcare providers resulted in older LGBTQIA+ adults, especially those with chronic conditions, avoiding health services (seven studies each, low certainty). Older LGBTQIA+ adults have unique sexual health needs and may feel their age empowers them to access appropriate care (four studies, low certainty). This review highlights the need for additional research and interventions to improve sexual health services for older LGBTQIA+ adults. Practical strategies to make sexual health less heterocentric (e.g. gender neutral signage) may increase uptake of essential sexual health services.

19.
BMC Med ; 21(1): 31, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36691001

RESUMO

BACKGROUND: Concurrent atherogenic dyslipidemia and elevated inflammation are commonly observed in overt hyperglycemia and have long been proposed to contribute to diabetogenesis. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident type 2 diabetes (T2D) remains unclear. METHODS: Longitudinal analysis of data on 52,224 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between high-sensitivity C-reactive protein (hsCRP) and the atherogenic index of plasma (AIP, calculated as triglyceride/high-density lipoprotein) in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 8824 participants with known diabetes, 43,360 nondiabetic participants were included for further analysis of the T2D outcome. Cox regression models were used to examine the adjusted hazard ratios (aHRs) upon the cumulative hsCRP (CumCRP) and AIP (CumAIP) in the exposure period. RESULTS: In temporal analysis, the adjusted standardized correlation coefficient (ß1) of hsCRP_2006/2007 and AIP_2010/2011 was 0.0740 (95% CI, 0.0659 to 0.0820; P < 0.001), whereas the standardized correlation coefficient (ß2) of AIP_2006/2007 and hsCRP_2010/2011 was - 0.0293 (95% CI, - 0.0385 to - 0.0201; P < 0.001), which was significantly less than ß1 (P < 0.001). During a median follow-up of 7.9 years, 5,118 T2D cases occurred. Isolated exposure to CumAIP or CumCRP was dose-dependently associated with T2D risks, independent of traditional risk factors. Significant interactions were observed between the median CumAIP (- 0.0701) and CumCRP thresholds (1, 3 mg/L) (P = 0.0308). Compared to CumAIP < - 0.0701 and CumCRP < 1 mg/L, those in the same CumAIP stratum but with increasing CumCRP levels had an approximately 1.5-fold higher T2D risk; those in higher CumAIP stratum had significantly higher aHRs (95% CIs): 1.64 (1.45-1.86), 1.87 (1.68-2.09), and 2.04 (1.81-2.30), respectively, in the CumCRP < 1, 1 ≤ CumCRP < 3, CumCRP ≥ 3 mg/L strata. Additionally, the T2D risks in the co-exposure were more prominent in nonhypertensive, nondyslipidemic, nonprediabetic, or female participants. CONCLUSIONS: These findings suggest a stronger association between elevated hsCRP and future AIP changes than vice versa and highlight the urgent need for combined assessment and management of chronic inflammation and atherogenic dyslipidemia in primary prevention, particularly for those with subclinical risks of T2D.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 2 , Dislipidemias , Humanos , Feminino , Proteína C-Reativa/análise , Estudos Longitudinais , Estudos Prospectivos , Inflamação , Fatores de Risco , Estudos de Coortes
20.
J Control Release ; 354: 626-634, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36681280

RESUMO

Two water-soluble supramolecular complexes (CB[10]⊃PSA and CB[10]⊃TPE-cyc) are constructed based on the host-guest interaction between cucurbit[10]uril (CB[10]) and perylene diimide derivative (PSA) or tetracationic cyclophane (TPE-cyc). Attributing to the matched redox potential, both supramolecular complexes can be specifically reduced into corresponding supramolecular radical cations or anions by facultative anaerobic E. coli. Benefiting from the strong near-infrared (NIR) absorption, CB[10]⊃PSA radical anions and CB[10]⊃TPE-cyc radical cations act as efficient NIR photosensitizers and perform an excellent antimicrobial activity (close to 100%) via PTT. In addition, the biocompatibility of TPE-cyc is notably improved under the protection of CB[10], guaranteeing its biosafety for in vivo application. CB[10]⊃PSA radical anions and CB[10]⊃TPE-cyc radical cations are in situ generated in the E. coli-infected abscess of mice and effectively inhibit the bacterial infection without obvious system toxicity. It is anticipated that this supramolecular strategy may pave a new way for the selective bacteria inhibition to regulate the balance of different bacterial flora.

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