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1.
Int J Biol Macromol ; 231: 123307, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36652984

RESUMO

Hyaluronic acid (HA) is an important type of naturally derived carbohydrate polymer with specific polysaccharide macromolecular structures and multifaceted biological functions, including biocompatibility, low immunogenicity, biodegradability, and bioactivity. Specifically, HA hydrogels in a microscopic scale have been widely used for biomedical applications, such as drug delivery, tissue engineering, and medical cosmetology, considering their superior properties outperforming the more conventional monolithic hydrogels in network homogeneity, degradation profile, permeability, and injectability. Herein, we reviewed the recent progress in the preparation and applications of HA microgels in biomedical fields. We first summarized the fabrication of HA microgels by focusing on the different crosslinking/polymerization schemes for HA gelation and the miniaturized fabrication techniques for producing HA-based microparticles. We then highlighted the use of HA-based microgels for different applications in regenerative medicine, including cartilage repair, bioactive delivery, diagnostic imaging, modular tissue engineering. Finally, we discussed the challenges and future perspectives in bridging the translational gap in the utilization of HA-based microgels in regenerative medicine.

2.
J Biomed Inform ; 138: 104292, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36641030

RESUMO

Learning latent representations of patients with a target disease is a core problem in a broad range of downstream applications, such as clinical endpoint prediction. The suffering of patients may have multiple subtypes with certain similarities and differences, which need to be addressed for learning effective patient representation to facilitate the downstream tasks. However, existing studies either ignore the distinction of disease subtypes to learn disease-level representations, or neglect the correlations between subtypes and only learn disease subtype-level representations, which affects the performance of patient representation learning. To alleviate this problem, we studied how to effectively integrate data from all disease subtypes to improve the representation of each subtype. Specifically, we proposed a knowledge-aware shared-private neural network model to explicitly use disease-oriented knowledge and learn shared and specific representations from the disease and its subtype perspectives. To evaluate the feasibility of the proposed model, we conducted a particular downstream task, i.e., clinical endpoint prediction, on the basis of the learned patient presentations. The results on the real-world clinical datasets demonstrated that our model could yield a significant improvement over state-of-the-art models.

3.
J Chromatogr A ; 1690: 463782, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36638689

RESUMO

Terphenyls are important building blocks for a wide range of functional molecules. Among the three isomers, p-terphenyl (C18H14) is particularly useful for the construction of optical devices on account of its unique structure. Herein, two rigid stationary phases bearing p-terphenyl as an external moiety and variable embedded carbamate groups (p-TerC with one embedded carbamate group and p-TerC2 with two embedded carbamate group) were presented. The proposed stationary phases were characterized by various means and evaluated in reversed-phase (RP) mode, using different classes of analytes, including polycyclic aromatic hydrocarbons (PAHs), alkylbenzenes, 4-alkylbiphenyls, substituted ureas, sulfonylureas, substituted sulfanilamides and aromatic acids. The comparison with conventional C18, several other polar-embedded aromatic and C18 equivalents indicated p-terphenyl-based stationary phases were featured by multiple retention mechanisms, involving π-π interaction, charge-transfer interaction, hydrogen-bonding and hydrophobic interaction in RP mode. A unusually high specificity to the analytes with linear structures was observed, as exemplified by an irreversible adsorption of tetracene and a readily separation of tetraphene and chrysene. The aliphatic linker used in the proposed stationary phases was an influential factor for retentivity, selectivity and column efficiency. Interestingly, p-TerC2 was operable in normal-phase mode for the separation of certain PAHs through polar-related interactions. The linear, rigid polyphenyl structure of p-terphenyl endowed the new stationary phase with distinctive chromatographic properties, in contrast to those of the preceding counterparts bonded with alkyl and/or polynuclear aromatic moieties.

4.
Pest Manag Sci ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627758

RESUMO

BACKGROUND: Pesticide resistance is a long-standing and growing problem in the chemical control of invertebrate pests. Molecular diagnostic methods can facilitate pesticide resistance management by accurately and efficiently detecting resistant mutations and their frequency. In this study, the kompetitive allele specific PCR (KASP) approach, a technology for high-throughput single nucleotide polymorphism (SNP) genotyping, is validated as a useful method for characterizing genotypes at a pesticide-resistance locus for the first time. We focus on the spinetoram resistance mutation of G275E in the nicotinic acetylcholine receptor alpha 6 (nAChR α6) subunit gene of Thrips palmi. RESULTS: Of the 341 individuals of Thrips palmi tested, 98.24% were successfully genotyped, with 100% concordance with Sanger sequencing results. We then quantitatively mixed genomic DNA of known genotypes to establish 21 DNA mixtures with a resistant allele frequency ranging from 0 to 100% at steps of 5%. The linear discriminant analysis (LDA) showed that 75.8% of original grouped cases were correctly classified; six groups had no overlap in membership (resistant allele frequency: 0%, 5%, 10-75%, 80-85%, 90-95%, and 100%). When we chose 11 pooled samples with 10% steps for LDA, 84.4% of original grouped cases were correctly classified; seven groups had no overlap in membership (0%, 10%, 20-30%, 40-70%, 80%, 90%, 100%). The results indicated that KASP applied to pooled samples may provide a semi-quantitative estimate of resistance. CONCLUSIONS: Our study points to the suitability of KASP for high-throughput genotyping of genotypes affecting pesticide resistance and semi-quantitative assessments of resistance allele frequencies in populations. © 2023 Society of Chemical Industry.

5.
BMC Genomics ; 24(1): 2, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597034

RESUMO

BACKGROUND: Maintaining osmotic equilibrium plays an important role in the survival of cold-water fishes. Heat stress has been proven to reduce the activity of Na+/K+-ATPase in the gill tissue, leading to destruction of the osmotic equilibrium. However, the mechanism of megatemperature affecting gill osmoregulation has not been fully elucidated. RESULTS: In this study, Siberian sturgeon (Acipenser baerii) was used to analyze histopathological change, plasma ion level, and transcriptome of gill tissue subjected to 20℃, 24℃and 28℃. The results showed that ROS level and damage were increased in gill tissue with the increasing of heat stress temperature. Plasma Cl- level at 28℃ was distinctly lower than that at 20℃ and 24℃, while no significant difference was found in Na+ and K+ ion levels among different groups. Transcriptome analysis displayed that osmoregulation-, DNA-repair- and apoptosis-related terms or pathways were enriched in GO and KEGG analysis. Moreover, 194 osmoregulation-related genes were identified. Amongst, the expression of genes limiting ion outflow, occluding (OCLN), and ion absorption, solute carrier family 4, member 2 (AE2) solute carrier family 9, member 3 (NHE3) chloride channel 2 (CLC-2) were increased, while Na+/K+-ATPase alpha (NKA-a) expression was decreased after heat stress. CONCLUSIONS: This study reveals for the first time that the effect of heat stress on damage and osmotic regulation in gill tissue of cold-water fishes. Heat stress increases the permeability of fish's gill tissue, and induces the gill tissue to keep ion balance through active ion absorption and passive ion outflow. Our study will contribute to research of global-warming-caused effects on cold-water fishes.


Assuntos
Perfilação da Expressão Gênica , Brânquias , Animais , Brânquias/metabolismo , Temperatura , Água/metabolismo , Sódio/metabolismo , Adenosina Trifosfatases/metabolismo , Peixes/metabolismo
6.
J Food Sci ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650660

RESUMO

This study investigated the effect of 0.8% (m/v) kojic acid treatment on changes in the microstructure and myofibrillar protein of duck meat covered with oxygen-permeable polyvinylchloride (PVC) film (9 ± 0.5 µM) during superchilled storage (-1.65 ± 0.5°C). The superchilled samples exhibited wider gaps between muscle fibers at 5 weeks storage compared with kojic acid-treated groups. Based on the variation of water status, the water-holding capacity decreased significantly (p < 0.05), and bound water and immobilized water were gradually converted into free water during superchilled storage. For kojic acid-treated samples, however, no major changes were observed with respect to muscle structure, water status, and protein degradation at 6 weeks. The 0.8% (m/v) kojic acid treatment increased the water-holding capacity, reduced carbonyl content and protein degradation, and decreased the α-helix contents loss of myofibrillar proteins. Kojic acid treatment effectively protected myofibrillar protein structure from being destroyed during superchilled storage, suggesting that this method was a good way to reduce protein oxidation and prolonged its shelf life.

7.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614276

RESUMO

Auxin action largely depends on the establishment of auxin concentration gradient within plant organs, where PIN-formed (PIN) auxin transporter-mediated directional auxin movement plays an important role. Accumulating studies have revealed the need of polar plasma membrane (PM) localization of PIN proteins as well as regulation of PIN polarity in response to developmental cues and environmental stimuli, amongst which a typical example is regulation of PIN phosphorylation by AGCVIII protein kinases and type A regulatory subunits of PP2A phosphatases. Recent findings, however, highlight the importance of PIN degradation in reestablishing auxin gradient. Although the underlying mechanism is poorly understood, these findings provide a novel aspect to broaden the current knowledge on regulation of polar auxin transport. In this review, we summarize the current understanding on controlling PIN degradation by endosome-mediated vacuolar targeting, autophagy, ubiquitin modification and the related E3 ubiquitin ligases, cytoskeletons, plant hormones, environmental stimuli, and other regulators, and discuss the possible mechanisms according to recent studies.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Proteólise , Transporte Biológico , Ácidos Indolacéticos/metabolismo , Ubiquitinas/metabolismo , Raízes de Plantas/metabolismo
8.
Pest Manag Sci ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594581

RESUMO

BACKGROUND: The two-spotted spider mite (TSSM), Tetranychus urticae (Acari: Tetranychidae), is a cosmopolitan phytophagous pest in agriculture and horticulture. It has developed resistance to many acaricides by target-site mutations. Understanding the status and evolution of resistant mutations in the field is essential for resistance management. Here, we applied a high-throughput Kompetitive allele-specific polymerase chain reaction (KASP) method for detecting six mutations conferring resistance to four acaricides of the TSSM. We genotyped 3274 female adults of TSSM from 43 populations collected across China in 2017, 2020, and 2021. RESULTS: The KASP genotyping of 24 testing individuals showed 99% agreement with Sanger sequencing results. KASP assays showed that most populations had a high frequency of mutations conferring avermectin (G314D and G326E) and pyridaben (H92R) resistance. The frequency of mutation conferring bifenazate (A269V and G126S) and etoxazole (I1017F) resistance was relatively low. Multiple mutations were common in the TSSM, with 70.2% and 24.6% of individuals having 2-6 and 7-10 of 10 possible resistant alleles, respectively. No loci were linked in most populations among the six mutations, indicating the development of multiple resistance is mainly by independent selection. However, G314D and I1017F on the nuclear genome deviated from Hardy-Weinberg equilibrium in most populations, indicating significant selective pressure on TSSM populations by acaricides or fitness cost of the mutations in the absence of acaricide selection. CONCLUSION: Our study revealed that the high frequency of TSSMs evolved multiple resistant mutations in population and individual levels by independent selection across China, alarming for managing multiple-acaricides resistance. © 2023 Society of Chemical Industry.

9.
Exp Lung Res ; : 1-10, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36636918

RESUMO

Objective: Chronic pulmonary inflammation caused by long-term smoking is the core pathology of COPD. Alveolar macrophages (AMs) are involved in the pulmonary inflammation of COPD. The accumulation of damaged materials caused by impaired autophagy triggers inflammatory response in macrophages. As a key transcription regulator, transcription factor EB (TFEB) activates the transcription of target genes related autophagy and lysosome by binding to promoters, whereas it is unclarified for the relationship between inflammatory response induced by cigarette smoke extract (CSE) and TFEB-mediated autophagy. Thus, we investigated the role of TFEB-mediated autophagy in inflammatory response induced by CSE in NR8383 cells, and to explore its potential mechanism. Methods: Based on cell viability and autophagy, cells treated with 20% concentration of CSE for 24 h were selected for further studies. Cells were divided into control group, chloroquine (CQ, the autophagy inhibitor) group, CSE group, CSE + rapamycin (the autophagy inducer) group and CSE + fisetin (the TFEB inducer) group. The levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 in supernatant were detected by ELISA kits. The protein expressions were tested by western blot. The intensity of fluorescence of Lysosome-associated membrane protein 1 (LAMP1) and TFEB was detected by immunofluorescence. Lyso-Tracker Red staining was applied to detect the lysosome environment. Results: CSE inhibited the cell viability, increased the contents of TNF-α, IL-1ß, IL-6, the ratio of LC3II/I, and the level of P62 protein. Besides, CSE decreased the fluorescence intensity of LAMP1 protein and Lyso-Tracker Red staining, as well as the ratio of nucleus/cytosol of TFEB protein. Activating autophagy with rapamycin alleviated CSE-induced inflammatory response. The activation of TFEB via fisetin alleviated CSE-induced autophagy impairment and lysosomal dysfunction, thus alleviated inflammatory response in NR8383 cells. Conclusion: CSE-induced inflammatory response in NR8383 cells, which may be related to the inhibition of TFEB-mediated autophagy.

10.
Talanta ; 255: 124219, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36580809

RESUMO

Nanozyme with the merit of excellent and adjustable catalytic activity, outstanding stability and low cost is a promising alternative for natural enzymes widely applied in a variety of fields. In the present study, a new two-dimensional cobalt-based MOF nanocomposite designated as MVCM@ß-CD was synthesized. Combined with the strategies of increasing the ratio of Co(Ⅲ)/Co(Ⅱ) and modifying with small molecule ß-cyclodextrin (ß-CD), MVCM@ß-CD displayed remarkably enhanced oxidase-mimicking activity, which was attributed to synergistic effect from large surface area of two dimensional Co-MOF nanosheet, numerous exposed active sites, high-proportioned trivalence of cobalt and regulating action of ß-cyclodextrin. The addition of aminophenol isomers inhibited the catalytic oxidation process, resulting in different color change of the solution and UV-Vis absorption behaviors, based on which a sensitive ratiometric colorimetry for m-aminophenol (m-Ap) and a simple colorimetric p-aminophenol (p-Ap) detection method were developed with the detection limit of 0.16 µM and 1.01 µM, respectively. This method realized the colorimetric differentiation of aminophenol isomers, which provided a simple, accurate and low-cost approach for visual discrimination without complicated instrument and procedure, especially appropriate for on-site detection.


Assuntos
Oxirredutases , beta-Ciclodextrinas , Oxirredutases/química , Colorimetria/métodos , Aminofenóis , Cobalto/química
11.
ACS Biomater Sci Eng ; 9(1): 449-457, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36475590

RESUMO

The combination of high-resolution computed tomography (CT) and the real-time sensitive second near-infrared window (NIR-II) fluorescence bioimaging can provide complementary information for the diagnosis, progression and prognosis of gastrointestinal disorders. Ag2Te quantum dots (QDs) are a kind of promising CT/NIR-II fluorescence dual-modal imaging probe due to their high atomic number and narrow bandgap. However, conventional Ag2Te QDs synthesized by oil phase approaches often suffer from complicated steps, harsh reaction conditions, and toxic organic solvents. Herein, we report the synthesis of bovine serum albumin (BSA)-Ag2Te QDs using a biomineralization approach for CT/NIR-II fluorescence dual-modal imaging of the gastrointestinal tract. The BSA-Ag2Te QDs are fabricated in a facile one-pot approach under mild conditions and exhibit homogeneous size, favorable monodispersity, admirable aqueous solubility, excellent X-ray attenuation properties, and outstanding NIR-II fluorescence performance. In vivo imaging experiments show that BSA-Ag2Te QDs can be used in gastrointestinal tract CT/NIR-II dual-modal imaging with high spatiotemporal resolution and sensitivity. In addition, in an intestinal obstruction mouse model, accurate lesion positioning and imaging-guided obstruction relief surgery are successfully realized based on BSA-Ag2Te QDs. Besides, BSA-Ag2Te QDs have outstanding biocompatibility in vitro and in vivo. This study presents a high-performance and biosafe CT/NIR-II fluorescence dual-modal imaging probe for visualizing the gastrointestinal tract in vivo.


Assuntos
Pontos Quânticos , Animais , Camundongos , Soroalbumina Bovina , Fluorescência , Tomografia Computadorizada por Raios X , Trato Gastrointestinal/diagnóstico por imagem
12.
Biomed Pharmacother ; 158: 114134, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36525821

RESUMO

Cancer is currently the most important problem endangering human health. As antitumor drugs have always been the most common methods for treating cancers, searching for new antitumor agents is of great significance. Brusatol, a quassinoid from the seeds of Brucea javanica, exhibits a potent tumor-suppressing effect with improved disease outcome. Studies have shown that brusatol not only shows potential tumor inhibition through multiple pharmacological effects, such as promoting apoptosis and inhibiting metastasis but also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents and overcoming chemical resistance in a wide range of cancer types. In this paper, the antitumor effects and mechanisms of brusatol were reviewed to provide evidence that brusatol has the exact antitumor efficacy of chemotherapeutic agents and show the potential of brusatol to be developed as a promising antitumor drug.


Assuntos
Antineoplásicos , Neoplasias , Quassinas , Humanos , Brucea javanica , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sementes , Quassinas/farmacologia , Quassinas/uso terapêutico , Neoplasias/tratamento farmacológico
13.
Analyst ; 148(2): 344-353, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36533333

RESUMO

Urinary potassium is an important parameter in clinical health diagnosis. Rapid and convenient detection of potassium ions (K+) in urine is essential for personal healthcare and health management. Here, crown ether (4-aminodibenzo-18-crown-6, ADC) modified silver nanoparticles (ADC-Ag NPs) were successfully prepared for one-step rapid colorimetric detection of urinary potassium. The detection mechanism is as follows: due to the matching sizes of the diameter of K+ and the cavity in crown ether 6, K+ is encapsulated between the cavities of two crown ethers, resulting in the clumping of ADC-Ag NPs and the color of the solution being altered. The colorimetric detection method has a fast response and is completed within 20 minutes. It also shows good selectivity and interference immunity. The lowest detectable concentration is 20 µM with the naked eye and 2.16 µM for UV-vis absorption spectroscopy. A good linear relationship (R2 = 0.9931) between the absorption intensity ratio and K+ concentration (0-100 µM) indicates that this colorimetric probe can be used to detect K+. The method was also applied for quantitative analysis of K+ in real urine samples with recovery between 116 and 120%.


Assuntos
Éteres de Coroa , Nanopartículas Metálicas , Nanopartículas Metálicas/química , Prata/química , Colorimetria/métodos , Espectrofotometria Ultravioleta/métodos , Íons
14.
J Environ Sci (China) ; 123: 545-559, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36522014

RESUMO

The formation and aging mechanism of secondary organic aerosol (SOA) and its influencing factors have attracted increasing attention in recent years because of their effects on climate change, atmospheric quality and human health. However, there are still large errors between air quality model simulation results and field observations. The currently undetected components during the formation and aging of SOA due to the limitation of current monitoring techniques and the interactions among multiple SOA formation influencing factors might be the main reasons for the differences. In this paper, we present a detailed review of the complex dynamic physical and chemical processes and the corresponding influencing factors involved in SOA formation and aging. And all these results were mainly based the studies of photochemical smog chamber simulation. Although the properties of precursor volatile organic compounds (VOCs), oxidants (such as OH radicals), and atmospheric environmental factors (such as NOx, SO2, NH3, light intensity, temperature, humidity and seed aerosols) jointly influence the products and yield of SOA, the nucleation and vapor pressure of these products were found to be the most fundamental aspects when interpreting the dynamics of the SOA formation and aging process. The development of techniques for measuring intermediate species in SOA generation processes and the study of SOA generation and aging mechanism in complex systems should be important topics of future SOA research.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Aerossóis/análise , Envelhecimento , Poluentes Atmosféricos/análise , Smog
15.
J Infect Public Health ; 16(1): 125-132, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36516647

RESUMO

BACKGROUND: Considering the adverse reactions to vaccination against coronavirus disease 2019 (COVID-19), some people, particularly the elderly and those with underlying medical conditions, are hesitant to be vaccinated. This study aimed to explore the prevalence of adverse reactions and provide direct evidence of vaccine safety, mainly for the elderly and people with underlying medical conditions, to receive COVID-19 vaccination. METHODS: From 1st March to 30th April 2022, we conducted an online survey of people who had completed three doses of COVID-19 vaccination by convenience sampling. Adverse reaction rates and 95% confidence intervals were calculated. In addition, conditional logistic regression was used to compare the differences in adverse reactions among the elderly and those with underlying medical conditions with the general population. RESULTS: A total of 3339 individuals were included in this study, of which 2335 (69.9%) were female, with an average age of 32.1 ± 11.4 years. The prevalence of adverse reactions after the first dose of inactivated vaccine was 24.6% (23.1-26.2%), 19.2% (17.8-20.7%) for the second dose, and 19.1% (17.7-20.6%) for the booster dose; among individuals using messenger RNA vaccines, the prevalence was 42.7% (32.3-53.6%) for the first dose, 47.2% (36.5-58.1%) for the second dose, and 46.1% (35.4-57.0%) for the booster dose. Compared with the general population, the prevalence of adverse events did not differ in individuals with underlying medical conditions and those aged 60 and above. CONCLUSIONS: For individuals with underlying medical conditions and those aged 60 and above, the prevalence of adverse reactions is similar to that of the general population, which provides a scientific basis regarding vaccination safety for these populations.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Idoso , Feminino , Humanos , Masculino , Adulto Jovem , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Prevalência , Projetos de Pesquisa , Vacinação/efeitos adversos
16.
Int J Biol Macromol ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464185

RESUMO

In recent years, frequent oil spills and increasing industrial wastewater discharge have caused serious water pollution problems. In addition, there are often microbial and dye pollutants in oil-containing wastewater. The development of materials that can simultaneously treat these three pollutants is very important for the safe treatment and recovery of wastewater. In this work, a modified calcium alginate-based aerogel membrane (CTW) was prepared through sol spraying, Ca2+ crosslinking and freeze drying by using tetrabutylammonium hydroxide (TBA) quaternary ammonium salt modified sodium alginate (SA) as raw material and waterborne polyurethane (WPU) as adhesive. The results show that CTW membrane has super hydrophilic and underwater super-oleophobic properties, and can realize the separation oil-water emulsions under gravity, with the separation efficiency of >99 %. CTW membrane can also remove bacteria and dye such as Congo red from water by filtration, with removal rates of 100 % and 99 % respectively. The filtration results of mixed wastewater show that CTW membrane can realize one-step separation of oil, bacteria and dye in wastewater, and can also be recycled, having potential application prospect.

17.
World J Surg Oncol ; 20(1): 383, 2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36464671

RESUMO

BACKGROUND: The switch/sucrose nonfermentable (SWI/SNF) complex is an evolutionarily conserved chromatin remodeling complex that displays dysfunction in many tumors, especially undifferentiated carcinoma. Cancer stem cells (CSC), a special type of undifferentiated cancer cells with stem cell-like properties, play an essential role in tumor cell proliferation, invasion, and metastasis. In undifferentiated gastric carcinomas, the association of SWI/SNF complexes with clinicopathological features, CSC phenotype, and the prognosis is not fully understood. METHODS: We collected a cohort of 21 patients with undifferentiated/dedifferentiated gastric carcinoma. We next performed immunohistochemistry staining for the five subunits of the SWI/SNF complex (ARID1A, ARID1B, SMARCA2, SMARCA4, and SMARCB1), and four mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), as well as other markers such as p53, PD-L1, and cancer stem cell (CSC) markers (SOX2, SALL4). Then, we investigated the correlation of SWI/SNF complex subunits with clinicopathological characters and performed prognostic analysis. RESULTS: We observed SMARCA2 loss in 12 cases (57.14%), followed by ARID1A (5 cases, 23.81%) and SMARCA4 (3 cases, 14.29%). Fourteen cases (66.67%) lost any one of the SWI/SNF complex subunits, including 3 cases with SMARCA2 and ARID1A co-loss, and 3 cases with SMARCA2 and SMARCA4 co-loss. Correlation analysis revealed that the CSC phenotype occurred more frequently in the SWI/SNF complex deficient group (P = 0.0158). Survival analysis revealed that SWI/WNF complex deficiency, undifferentiated status, CSC phenotype, and the loss of SMARCA2 and SMARCA4 resulted in worse survival. Univariate and multivariate Cox regression analyses screened out three independent factors associated with worse prognosis: undifferentiated status, SWI/SNF complex deficiency, and lymph node metastasis. CONCLUSIONS: The SWI/SNF complex deficiency was more likely to result in a CSC phenotype and worse survival and was an independent prognostic factor in undifferentiated/dedifferentiated gastric carcinoma.


Assuntos
Carcinoma , Neoplasias Gástricas , Humanos , Prognóstico , Sacarose , Neoplasias Gástricas/cirurgia , Células-Tronco Neoplásicas , DNA Helicases , Proteínas Nucleares , Fatores de Transcrição
18.
Front Cell Infect Microbiol ; 12: 1045109, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452299

RESUMO

In this study we aimed to determine whether treatment with maternal Bifidobacterium bifidum TMC3115 could affect the composition of the gut microbiota and the development of the immune system and intestinal tract of offspring, and protect the offspring from IgE-mediated allergic disease. Pregnant BALB/c mice were gavaged with TMC3115 until delivery. Offspring were sensitized with ovalbumin from postnatal days 21 to 49. After maternal treatment with TMC3115, the microbiota of the offspring's feces, intestinal contents, and stomach contents (a proxy for breast milk) at the newborn and weaning stages exhibited the most change, and levels of immunoglobulin in the sera and stomach contents and of splenic cytokines, as well as the mRNA levels of colonic intestinal development indicators were all significantly altered in offspring at different stages. After sensitization with ovalbumin, there were no significant changes in the levels of serum IgE or ovalbumin-specific IgE/IgG1 in the TMC3115 group; however, IgM, the expression of intestinal development indicators, and the production of fecal short chain fatty acid (SCFA) were significantly increased, as were the relative abundances of Lactobacillus and the Lachnospiraceae NK4A136 group. Our results suggested that maternal treatment with TMC3115 could have a profound modulatory effect on the composition of the gut microbiota and the development of the immune system and intestinal tissue in offspring at different stages of development, and may induce immune tolerance to allergens in ovalbumin-stimulated offspring by modulating the gut microbiota and SCFA production.


Assuntos
Bifidobacterium bifidum , Microbioma Gastrointestinal , Animais , Camundongos , Feminino , Gravidez , Ovalbumina , Sistema Imunitário , Tolerância Imunológica , Imunoglobulina E , Alérgenos
19.
Proc Natl Acad Sci U S A ; 119(49): e2209256119, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36454752

RESUMO

Auxin inactivation is critical for plant growth and development. To develop plant growth regulators functioning in auxin inactivation pathway, we performed a phenotype-based chemical screen in Arabidopsis and identified a chemical, nalacin, that partially mimicked the effects of auxin. Genetic, pharmacological, and biochemical approaches demonstrated that nalacin exerts its auxin-like activities by inhibiting indole-3-acetic acid (IAA) conjugation that is mediated by Gretchen Hagen 3 (GH3) acyl acid amido synthetases. The crystal structure of Arabidopsis GH3.6 in complex with D4 (a derivative of nalacin) together with docking simulation analysis revealed the molecular basis of the inhibition of group II GH3 by nalacin. Sequence alignment analysis indicated broad bioactivities of nalacin and D4 as inhibitors of GH3s in vascular plants, which were confirmed, at least, in tomato and rice. In summary, our work identifies nalacin as a potent inhibitor of IAA conjugation mediated by group II GH3 that plays versatile roles in hormone-regulated plant development and has potential applications in both basic research and agriculture.


Assuntos
Arabidopsis , Ligases , Arabidopsis/genética , Ácidos Indolacéticos/farmacologia , Fenômenos Químicos , Reguladores de Crescimento de Plantas/farmacologia , Testes Genéticos
20.
Sci Rep ; 12(1): 20743, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456849

RESUMO

Perceived government corruption is an important indicator of depressive symptoms. Recent studies have explored the relationship between perceived government corruption and depressive symptoms in a cross-cultural context, but the underlying mechanisms need further research. This paper examines the impact of perceived government corruption on depressive symptoms in China and the moderating role of social status. Based on the 2018 wave of China Family Panel Studies (CFPS2018), 14,116 respondents aged between 16 and 96 were selected. The results revealed: (1) Perceived government corruption was significantly positively correlated with depressive symptoms. (2) Social class had an inhibitory effect in moderating the relationship between perceived government corruption and depressive symptoms. (3) The moderating effect was only significant for respondents who received education between junior high school and a bachelor's degree. The findings provide policy implications for developing countries and transitional societies like China. To build a more psychologically healthy society, we need to strengthen anti-corruption, stimulate social mobility, and improve people's sense of gain in the future.


Assuntos
Depressão , Status Social , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Governo , Classe Social , Escolaridade
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