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2.
Pak J Med Sci ; 38(1): 248-253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035434

RESUMO

Objectives: To investigate the effect and clinical value of the application of vacuum assisted closure (VAC) combined with multiple flaps in the treatment of severe hand trauma. Methods: A total of 100 patients with severe hand trauma admitted to Harrison International Peace Hospital from September 2015 to September 2020 were selected and randomly divided into two groups according to the randomized block method: the single flap repair group and the combined repair group, with 50 patients in each group. Patients in the single flap repair group underwent flap repair according to their condition, while those in the combined repair group were treated with VAC prior to flap repair. The range of motion and hand sensation scores were compared between the two groups, and their levels of interleukin-8 (IL-8), tumor necrosis factor (TNF) and lipopolysaccharide (LPS) were tested by enzyme-linked immunosorbent assay (ELIS). Moreover, the flap survival rate and the incidence of adverse events were recorded and compared between the two groups. Results: Compared with the single flap repair group, the combined repair group had higher range of motion and hand sensation score (p<0.05), lower levels of IL-8, TNF and LPS (p<0.05), higher flap survival rate (p<0.05), and lower incidence of adverse events (p<0.05). Conclusion: VAC combined with multiple flaps boasts significant trauma repair effect and preferable clinical application value in the treatment of patients with severe hand trauma, which is principally reflected in significantly improving the hand function of patients and remarkably alleviating the inflammatory response of patients.

3.
PeerJ ; 10: e12723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35036099

RESUMO

Background: Dental unit waterlines (DUWLs) provide water for handpieces, air/water syringes, and mouth-rinse water outlets. DUWL contamination can negatively affect the operating environment and public health. Therefore, it is important to elucidate the bacterial concentrations and microbial composition in the DUWLs from different dental specialties. Methods: We collected 350 5-mL dental water samples (from high-speed handpieces, air/water syringes, and mouth-rinse water outlets) from 60 dental chair units (DCUs) at a dental hospital to determine the bacterial concentrations by culture methods. Meanwhile, to investigate the diversity and community structure of microbe in the DUWLs, 17 high-quality DNA from 60 250-mL air/water syringe water samples, which were collected from the same 60 DCUs, were analyzed using 16S rDNA high-throughput sequencing. Results: The median bacterial concentration was 166 (31.5, 672.5) CFU/mL and the range was 0-3,816,000 CFU/mL. Only 42.6% of the water samples had bacterial concentrations below 100 CFU/mL. The Kruskal-Wallis H-test revealed that the water samples from three dental specialties had significantly different bacterial concentrations (H = 27.441, P < 0.01). High-throughput sequencing results showed significant differences in bacterial community structure between periodontics and the other two dental specialties. In the samples from three dental specialties, 508 OTUs were detected, with 160, 182 and 176 OTUs unique to the periodontics, endodontics and prosthodontics specialties, respectively. Linear discriminant analysis (LDA) effect size (LEfSe) suggested that Hydrocarboniphaga, Zoogloea, Aquabacterium, and Hydrogenophaga were enriched in the periodontics specialty; Acinetobacter, Geothrix, and Desulfovibrio were enriched in the prosthodontics specialty; and Alistipes, Clostridium XIVa, and Serratia were enriched in the endodontics specialty. Seven potentially human-pathogenic genera (Pseudomonas, Acinetobacter, Sphingomonas, Ochrobactrum, Rhizobium, Brevundimonas, and Methylobacterium) with relative abundance exceeding 1% were also detected in the DUWLs. Conclusions: The bacterial concentrations and microbial composition were influenced by different dental specialties, so a validated disinfection protocol should be used to control DUWL contamination in different dental specialties.

4.
Nat Prod Res ; : 1-9, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35038938

RESUMO

Five new triterpenoids, including four ursane types (1-4) and one oleanane type (5), together with 15 known ursane types pentacyclic triterpenoids (6-20) were isolated from the fruit spikes of Prunella vulgaris L., a traditional Chinese herbal medicine. Their structures were elucidated based on IR, HR-ESI-MS, and NMR spectroscopic data. The SW579 cell line was used to evaluate anti-thyroid cancer activities of (1-20). The results indicated that (7-9), (16), and (19) exhibited apparent inhibitory activity with IC50 values of 25.73-71.41 µM (cisplatin as positive control, IC50 14.49 ± 0.97 µM). Network pharmacology and molecular docking were also used for the prediction of the synergistic actions and the underlying mechanisms. Accordingly, four potential targets have been characterized.

5.
Acta Neurol Taiwan ; 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040111

RESUMO

Purpose Alzheimer disease (AD) is an irreversible neurodegenerative disease that causes progressive cognitive decline. Co-existing thymoma should be considered when rapid deterioration of cognition was noted in AD patients and removal of thymoma may improve cognition in AD. Case report We report a 72-year-old woman with initial complaints of memory impairment for 2 years. After detailed history taking, neuropsychological tests, brain magnetic resonance imaging, and positive amyloid positron emission tomography, she was diagnosed as having dementia of the Alzheimer type. At the time of diagnosis, her dementia condition was mild (clinical dementia rating [CDR] is equal to 1, CDR sum of boxes [CDR-sb] = 4.5, Mini-Mental State Examination (MMSE) is equal to 21 divided by 30). She needed moderate assistance in performing daily life activities. One year after AD diagnosis, her condition deteriorated drastically, and she experienced frequent falls and severe weakness apart from cognitive symptoms. Concurrent myasthenia gravis (MG) with thymoma was found later, and thymectomy was performed. Her symptoms related to MG alleviated after the operation. Notably, her cognitive symptoms also improved 4 months after the operation, and her dementia reversed to mild cognitive impairment. Conclusion Although the role of neuroinflammation in AD has been widely discussed, it remains elusive. Removal of the co-existing thymoma not only alleviated the patient's MG symptoms but also improved her cognitive performance. We supposed that this effect may have been a direct result of the decrease in acetylcholine receptor antibody or reduction in the degree of neuroinflammation. Keywords Alzheimer disease, thymoma, neuroinflammation, central cholinergic effects, acetylcholine receptor antibody.

6.
ACS Nano ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985244

RESUMO

The development of flexible electronic skins with high performance and multifunctional sensing capabilities is of great significance for applications ranging from healthcare monitoring to artificial intelligence. To mimic and surpass the high-gauge-factor sensing properties of human skin, structure design and appropriate material selection of sensors are both essentially required. Here, we present an efficient, low-cost fabrication strategy to construct an ultra-highly sensitive, flexible pressure sensor by embedding the aligned nickel-coated carbon fibers (NICFs) in a polydimethylsiloxane (PDMS) substrate. Our design substantially contributes to ultrahigh sensitivity through the parallel circuit formed by aligned NICFs as well as surface spinosum microstructure molded by sandpaper. As a result, the sensor exhibits excellent sensitivity (15 525 kPa-1), a fast response time (30 ms), and good stability over 3000 loading-unloading cycles. Furthermore, these superior sensing properties trigger applications in water quality and wave monitoring in conjunction with mechanical flexibility and robustness. As a precedent for adjusting the sensitivities of the sensor, the NICFs/PDMS sensor provides a promising method for multiscenario healthcare monitoring, multiscale pressure spatial distribution, and human-machine interfacing.

7.
Curr Med Sci ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34985612

RESUMO

OBJECTIVE: The eukaryotic release factor 3a (eRF3a), a member of the eukaryotic peptide chain release factor family, is overexpressed in several types of cancer. This study aims to investigate the biological role and mechanism of eRF3a in the progression of liver cancer. METHODS: Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer. Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer. RESULTS: eRF3a was significantly highly expressed in liver cancer cells, and its expression level was negatively correlated with the clinical prognosis of patients. In addition, in vitro experiments showed that eRF3a could promote the proliferation and migration of liver cancer cells through the ERK and JNK signaling pathways. CONCLUSION: This study suggests that eRF3a may be a potential prognostic marker for liver cancer and act as an oncogene by activating JNK and ERK signaling; therefore, eRF3a may be a new target for the treatment of liver cancer.

8.
Chemosphere ; 293: 133555, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34999102

RESUMO

A better understanding how to modulate alkaline soil-plant systems with lead (Pb) toxicity with by vinegar residue biochar is important for the remediation of Pb-contaminated soil. Leaching column and pot experiments were conducted to investigate the effect of vinegar residue biochar on Pb speciation, soil properties, and plant growth under Pb stress. The results indicate that biochar could effectively decrease the exchangeable and carbonated-bound Pb but increase the Fe-Mn oxide and residue fractions in the soil with Pb at 500 mg kg-1. Biochar did not effectively immobilize Pb in the soil with Pb at 1000 mg kg-1. After leaching, biochar evidently increased the organic carbon and dissolved organic carbon content of the soil, but slightly affected the pH, cation exchange capacity and carbonate content. The biochar addition at 0.5% had no significant effect on soil aggregates, and biochar at 2.0% and 5.0% significantly decreased soil aggregate stability. The dry weight and soluble protein content of pak choi (Brassica chinensis L.) increased with biochar treatment. Lead assimilation by plants was inhibited by the decreased availability of Pb in biochar-treated soils. Soil enzymes activities also significantly increased, then facilitated biochemical reactions in the soil environment. The applied biochar has shown an important role in mitigating Pb toxicity by increasing the soil organic carbon, dissolved organic carbon content, enzyme activities, and plant growth. The low dose biochar (0.5-2.0%) are recommended as references for subsequent experiments, especially in alkaline loam soil.

9.
BMC Cardiovasc Disord ; 22(1): 9, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35016632

RESUMO

BACKGROUND: Aortic stiffness and coronary heart disease (CHD) share a similar spectrum of risk factors; previous studies have identified the association between aortic stiffness and CHD. Recent studies have demonstrated estimated pulse wave velocity (ePWV) as a simple and easy-acquired indicator of aortic stiffness. Our work aims to evaluate the association between ePWV and the prevalence of CHD and assess the value of ePWV for the identification of prevalent CHD. METHODS: The current cross-sectional work included 7012 subjects from rural areas of southeastern China between September 2020 and February 2021. ePWV was calculated from age and mean blood pressure by specific algorithm. RESULTS: The prevalence of CHD in our population was 3.58% (251 patients among 7012 subjects). After adjusting for age, sex, education, income and exercise level, current smoking and drinking status, body mass index, waist circumference, fasting plasma glucose, total cholesterol, high density lipoprotein, estimated glomerular filtration rate and cerebrovascular diseases, each standard deviation increment of ePWV would produce an additional 37.8% risk of prevalent CHD. Moreover, after dividing ePWV into quartiles, the 4th quartile of ePWV showed a significant risk of prevalent CHD (OR (95% CI): 3.567 (1.963-6.479)) when compared with the 1st quartile. Additionally, the subgroup analysis showed the association between ePWV and prevalent CHD was robust to several common risk factors of CHD, including age, sex, body mass index, hypertension, diabetes and reduced estimated glomerular filtration rate. Finally, the area under curve (AUC) displayed an improvement when adding ePWV into common CHD risk factors (0.705 vs. 0.718. P = 0.044). Consistently, net reclassification index (0.436, 95% CI: 0.301-0.571, P < 0.001) and integrated discrimination index (0.004, 95% CI: 0.001-0.006, P = 0.002) demonstrated the value of ePWV to optimize the identification of prevalent CHD in the general population. CONCLUSION: The present analysis implicates the robust association between ePWV, a simple, rapid, and practical marker of aortic stiffness, and prevalent CHD in the general Chinese population. More importantly, the results suggest the value of ePWV as a potential marker to improve the identification of prevalent CHD.

10.
Biosens Bioelectron ; 202: 113974, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35032920

RESUMO

Rapid and reliable detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody can provide immunological evidence in addition to nucleic acid test for the early diagnosis and on-site screening of coronavirus disease 2019 (COVID-19). All-solid-state biosensor capable of rapid, quantitative SARS-CoV-2 antibody testing is still lacking. Herein, we propose an electronic labelling strategy of protein molecules and demonstrate SARS-CoV-2 protein biosensor employing colloidal quantum dots (CQDs)-modified electrode. The feature current peak corresponding to the specific binding reaction of SARS-CoV-2 antigen and antibody proteins was observed for the first time. The unique charging and discharging effect depending on the alternating voltage applied was ascribed to the quantum confinement, Coulomb blockade and quantum tunneling effects of quantum dots. CQDs-modified electrode could recognize the specific binding reaction between antigen and antibody and then transduce it into significant electrical current. In the case of serum specimens from COVID-19 patient samples, the all-solid-state protein biosensor provides quantitative analysis of SARS-CoV-2 antibody with correlation coefficient of 93.8% compared to enzyme-linked immunosorbent assay (ELISA) results. It discriminates patient and normal samples with accuracy of about 90%. The results could be read within 1 min by handheld testing system prototype. The sensitive and specific protein biosensor combines the advantages of rapidity, accuracy, and convenience, facilitating the implement of low-cost, high-throughput immunological diagnostic technique for clinical lab, point-of-care testing (POCT) as well as home-use test.

11.
BMC Public Health ; 22(1): 127, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042501

RESUMO

BACKGROUND: Subjective cognitive decline (SCD) may be the first symptomatic manifestation of Alzheimer's disease, but information on its health correlates is still sparse in Chinese older adults. This study aimed to estimate SCD symptoms and its association with socio-demographic characteristics, common chronic diseases among southern Chinese older adults. METHODS: Participants aged 60 years and older from 7 communities and 2 nursing homes in Guangzhou were recruited and interviewed with standardized assessment tools. Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure poor sleep quality, depression symptoms and anxiety symptoms. The SCD symptoms were measured by SCD questionnaire 9 (SCD-Q9) which ranged from 0 to 9 points, with a higher score indicating increased severity of the SCD. Participants were divided into low score group (SCD-Q9 score ≤ 3) and higher score group (SCD-Q9 score > 3). Chi-square tests and multivariate logistic regression analysis were used for exploring the influences of different characteristics of socio-demographic and lifestyle factors on SCD symptoms. Univariate and multivariate logistic regression analysis were applied to explore the association between SCD symptoms with common chronic diseases. RESULTS: A total of 688 participants were included in our analysis with a mean age of 73.79 (SD = 8.28, range: 60-101), while 62.4% of the participants were females. The mean score of the SCD-Q9 was 3.81 ± 2.42 in the whole sample. A total of 286 participants (41.6%) were defined as the low score group (≤3 points), while 402 participants (58.4%) were the high score group (> 3 points). Multivariate logistic regression analysis revealed that female (OR = 1.99, 95%CI: 1.35-2.93), primary or lower education level (OR = 2.58, 95%CI: 1.38-4.83), nursing home (OR = 1.90, 95%CI: 1.18-3.05), napping habits (OR = 1.59, 95%CI: 1.06-2.40), urolithiasis (OR = 2.72, 95%CI: 1.15-6.40), gout (OR = 2.12, 95%CI: 1.14-3.93), poor sleep quality (OR = 1.93, 95%CI: 1.38-2.71), depression symptoms (OR = 3.01, 95%CI: 1.70-5.34) and anxiety symptoms (OR = 3.11, 95%CI: 1.29-7.46) were independent positive related to high SCD-Q9 score. On the other hand, tea-drinking habits (OR = 0.64, 95%CI: 0.45-0.92), current smoking (OR = 0.46, 95%CI: 0.24-0.90) were independent negative related to high SCD-Q9 score. CONCLUSIONS: Worse SCD symptoms were closely related to common chronic diseases and socio-demographic characteristics. Disease managers should pay more attention to those factors to early intervention and management for SCD symptoms among southern Chinese older adults.

12.
Mucosal Immunol ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013572

RESUMO

IL-10-expressing regulatory B cells (B10 cells) are dysfunctional in patients with many immune disorders. The underlying mechanism remains to be further elucidated. Glutamine is an essential nutrient for cell metabolism. This study aims to elucidate the role of glutaminolysis in maintaining the immune regulatory capacity in B10 cells. Peripheral blood samples were collected from 50 patients with allergic rhinitis and 50 healthy control subjects. B cells were isolated from blood samples by cell sorting with flow cytometry. The role of glutaminolysis in regulating B10 cell activities was assessed by immunological and biochemical approaches. The results showed that B cells from patients with allergic rhinitis expressed low levels of the transporter of glutamine and neutral amino acid. Glutaminolysis was required in the IL-10 expression in B cells. The glutamine catabolism was required in B10 cell generation. The mTOR activation mediated the glutaminolysis-associated B10 cell induction, and the suppression of the B cell glycogen synthase kinase-3 (GSK3) activation. GSK3 activation suppressed IL-10 expression in B cells. Inhibition of GSK3 enhanced IL-10 expression in B cells and alleviated experimental allergic rhinitis by generating immune competent type 1 regulatory T cells.

13.
Eur J Pharmacol ; 917: 174754, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35007521

RESUMO

Glutamic Oxaloacetic Transaminase 1 (GOT1) is one distinct isoenzyme of glutamic oxaloacetic transaminase in eukaryotic cells, which is located in the cytoplasm. To date, several studies have shown that GOT1 plays a critical role in regulating cell proliferation by participating in amino acid metabolism, especially in glutamine metabolism. In addition, GOT1 is overexpressed in many cancer, so GOT1 has been identified as a potentially therapeutic target. Herein, this review summarizes the structure and function of GOT1 and the important roles of GOT1 in some tumor progress, as well as the characterization of GOT1 inhibitors. It may provide new insight into the discovery of small compounds as potential anti-GOT1 drugs for treatment of cancer.

14.
Diabetol Metab Syndr ; 14(1): 8, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35033170

RESUMO

BACKGROUND: Body composition alterations may participate in the pathophysiological processes of type 2 diabetes (T2D). A sedentary lifestyle may be responsible for alterations of body composition and adverse consequences, but on which body composition of patients with T2D and to what extent the sedentary lifestyle has an effect have been poorly investigated. METHODS: We recruited 402 patients with T2D for this cross-sectional study. All patients received questionnaires to evaluate sedentary time and were further divided into three subgroups: low sedentary time (LST, < 4 h, n = 109), middle sedentary time (MST, 4-8 h, n = 129) and high sedentary time (HST, > 8 h, n = 164). Each patient underwent a dual energy X-ray absorptiometry (DXA) scan to detect body composition, which included body fat percentage (B-FAT), trunk fat percentage (T-FAT), appendicular skeletal muscle index (ASMI), lumbar spine bone mineral density (BMD) (LS-BMD), femoral neck BMD (FN-BMD), hip BMD (H-BMD) and total BMD (T-BMD). Other relevant clinical data were also collected. RESULTS: With increasing sedentary time (from the LST to HST group), B-FAT and T-FAT were notably increased, while ASMI, LS-BMD, FN-BMD, H-BMD and T-BMD were decreased (p for trend < 0.01). After adjustment for other relevant clinical factors and with the LST group as the reference, the adjusted mean changes [B (95% CI)] in B-FAT, T-FAT, ASMI, LS-BMD, FN-BMD, H-BMD and T-BMD in the HST group were 2.011(1.014 to 3.008)%, 1.951(0.705 to 3.197)%, - 0.377(- 0.531 to - 0.223) kg/m2, - 0.083(- 0.124 to - 0.042) g/cm2, - 0.051(- 0.079 to - 0.024) g/cm2, - 0.059(- 0.087 to - 0.031) g/cm2 and - 0.060(- 0.088 to - 0.033) g/cm2, p < 0.01, respectively. CONCLUSIONS: A sedentary lifestyle may independently account for increases in trunk and body fat percentage and decreases in appendicular skeletal muscle mass and BMD of the lumbar spine, femoral neck, hip and total body in patients with T2D.

15.
Cell Mol Life Sci ; 79(1): 22, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34981210

RESUMO

The three-dimensional configuration of the genome ensures cell type-specific gene expression profiles by placing genes and regulatory elements in close spatial proximity. Here, we used in situ high-throughput chromosome conformation (in situ Hi-C), RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to characterize the high-order chromatin structure signature of female germline stem cells (FGSCs) and identify its regulating key factor based on the data-driven of multiple omics data. By comparison with pluripotent stem cells (PSCs), adult stem cells (ASCs), and somatic cells at three major levels of chromatin architecture, A/B compartments, topologically associating domains, and chromatin loops, the chromatin architecture of FGSCs was most similar to that of other ASCs and largely different from that of PSCs and somatic cells. After integrative analysis of the three-dimensional chromatin structure, active compartment-associating loops (aCALs) were identified as a signature of high-order chromatin organization in FGSCs, which revealed that CCCTC-binding factor was a major factor to maintain the properties of FGSCs through regulation of aCALs. We found FGSCs belong to ASCs at chromatin structure level and characterized aCALs as the high-order chromatin structure signature of FGSCs. Furthermore, CTCF was identified to play a key role in regulating aCALS to maintain the biological functions of FGSCs. These data provide a valuable resource for future studies of the features of chromatin organization in mammalian stem cells and further understanding of the fundamental characteristics of FGSCs.


Assuntos
Fator de Ligação a CCCTC/metabolismo , Genoma , Imageamento Tridimensional , Células-Tronco de Oogônios/metabolismo , Células-Tronco Adultas/metabolismo , Animais , Sequência de Bases , Forma Celular , Cromatina/metabolismo , Cromossomos de Mamíferos/metabolismo , Feminino , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Células-Tronco de Oogônios/citologia
16.
Theranostics ; 12(1): 396-409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987652

RESUMO

Photothermal agents (PTAs) based on organic small-molecule dyes emerge as promising theranostic strategy in imaging and photothermal therapy (PTT). However, hydrophobicity, photodegradation, and low signal-to-noise ratio impede their transformation from bench to bedside. In this study, a novel supramolecular PTT formulation by a stimuli-responsive macrocyclic host is prepared to overcome these obstacles of organic small-molecule PTAs. Methods: Sulfonated azocalix[4]arene (SAC4A) was synthesized as a hypoxia-responsive macrocyclic host. Taking IR780 as an example, the supramolecular nanoformulation IR780@SAC4A was constructed by grinding method, and its solubility, photostability, and photothermal conversion were evaluated. The hypoxia tumor-selective imaging and supramolecular PTT of IR780@SAC4A were further evaluated in vitro and in vivo. Results: IR780@SAC4A is capable of enhancing the solubility, photostability, and photothermal conversion of IR780 significantly, which achieve this supramolecular formulation with good imaging-guided PTT efficacy in vitro and in vivo. Conclusions: This study demonstrates that the supramolecular PTT strategy is a promising cancer theranostic method. Moreover, this supramolecular approach is applicative to construct kinds of supramolecular PTAs, opening a general avenue for extending smart PTT formulations.

17.
Adv Sci (Weinh) ; : e2104349, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34994113

RESUMO

Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia-responsive macrocycle with small-molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host-guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A•AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation-mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent-based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.

18.
J Med Chem ; 65(1): 424-435, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34918930

RESUMO

Nitric oxide (NO) has an important class of endogenous diatomic molecules that play a key regulatory role in many physiological and biochemical processes. However, the type of nitrosamine NO donor stimulated by light has many advantages compared to the conventional NO donors such as diazeniumdiolates and S-nitrosothiols compounds, including easy synthesis, good stability, and controllable release. In addition, NO release can be regulated by light induction with a built-in calibration mechanism fluorescence. Here, we report that the migration and proliferation of human umbilical vein vascular endothelial cells could be accelerated by the light-triggered NO donors, leading to the angiogenesis. Meanwhile, the screened NO donor 3a with Levofloxacin (Lev) showed synergistic effects to eradicate Methicillin-resistant Staphylococcus aureus (MRSA) biofilms in vitro and treat bacteria-infected wound in vivo.

19.
Inorg Chem ; 61(1): 254-264, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34951312

RESUMO

An in-depth study on a stimuli-responsive tetranuclear cuprous luminescent complex is reported and gives new insights into the origin and possible use of the observed stimuli-responsive luminescence. Its crystalline polymorphs with two different shapes are obtained by using different crystallization solvents and show distinct emissions, with one being blue emissive and the other being yellow emissive. Upon grinding, only the blue-emitting polymorph has a marked change in the emission color from blue to yellow, and its ground sample exhibits a yellow emission similar to that of the yellow-emitting polymorph. Interestingly, the yellow-emitting polymorph after exposure to acetone vapor can emit a blue emission and display luminescence mechanochromism similar to that of the blue-emitting polymorph. Single-crystal structural analyses of the two different polymorphs reveal the relationship between the mechanochromic luminescence and the geometrical configuration of the {Cu(µ-dppm)2Cu} unit and intramolecular "pyridyl/phenyl" π···π interactions, supported as well by their PXRD, FT-IR, TGA, and PL studies in various states and by TD-DFT analyses. The results demonstrate the different roles of switchable intramolecular π···π interactions and the geometrical configuration of the {Cu(µ-dppm)2Cu} unit in this stimuli-responsive luminescence and potential applications of such stimuli-responsive luminescence in optical sensing and anticounterfeiting encryption technologies and deepen the understanding of such stimuli-responsive luminescence originating from switchable intramolecular π···π interactions. In addition, it is clearly suggested that the rational utilization of switchable intramolecular π···π interactions is a feasible route for developing stimuli-responsive intelligent luminescent materials and devices.

20.
Appl Microbiol Biotechnol ; 106(2): 563-578, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34939133

RESUMO

ß-1,3-Glucans are well-known biological and health-promoting compounds in edible fungi. Our previous results characterized a glucan synthase gene (GFGLS) of Grifola frondosa for the first time to understand its role in mycelial growth and glucan biosynthesis. In the present study, we identified and functionally reannotated another glucan synthase gene, GFGLS2, based on our previous results. GFGLS2 had a full sequence of 5944 bp including 11 introns and 12 exons and a coding information for 1713 amino acids of a lower molecular weight (195.2 kDa) protein with different conserved domain sites than GFGLS (5927 bp with also 11 introns and a coding information for 1781 aa). Three dual-promoter RNA-silencing vectors, pAN7-iGFGLS-dual, pAN7-iGFGLS2-dual, and pAN7-CiGFGLS-dual, were constructed to downregulate GFGLS, GFGLS2, and GFGLS/GFGLS2 expression by targeting their unique exon sequence or conserved functional sequences. Silencing GFGLS2 resulted in higher downregulation efficiency than silencing GFGLS. Cosilencing GFGLS and GFGLS2 had a synergistic downregulation effect, with slower mycelial growth and glucan production by G. frondosa. These findings indicated that GFGLS2 plays major roles in mycelial growth and polysaccharide synthesis and provides a reference to understand the biosynthesis pathway of mushroom polysaccharides. KEY POINTS: • The 5944-bp glucan synthase gene GFGLS2 of G. frondosa was cloned and reannotated • GFGLS2 showed identity and significant differences with the previously identified GFGLS • GFGLS2 played a major role in fermentation and glucan biosynthesis.

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