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1.
Am J Chin Med ; : 1-24, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38328830

RESUMO

Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.

2.
J Agric Food Chem ; 72(7): 3695-3706, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38324412

RESUMO

Novel N-ethy-2-pyrrolidinone-substituted flavonols, myricetin alkaloids A-C (1-3), quercetin alkaloids A-C (4a, 4b, and 5), and kaempferol alkaloids A and B (6 and 7), were prepared from thermal reaction products of myricetin, quercetin, kaempferol─l-theanine, respectively. We used HPLC-ESI-HRMS/MS to detect 1-7 in 14 cultivars of green tea and found that they were all present in "Shuchazao," "Longjing 43", "Fudingdabai", and "Zhongcha 108" green teas. The structures of 1-4 and 6 were determined by extensive 1D and 2D NMR spectroscopies. These flavonol alkaloids along with their skeletal flavonols were assessed for anti-Alzheimer's disease effect based on molecular docking, acetylcholinesterase inhibition, and the transgenic Caenorhabditis elegans CL4176 model. Compound 7 strongly binds to the protein amyloid ß (Aß1-42) through hydrogen bonds (BE: -9.5 kcal/mol, Ki: 114.3 nM). Compound 3 (100 µM) is the strongest one in significantly extending the mean lifespan (13.4 ± 0.5 d, 43.0% promotion), delaying the Aß1-42-induced paralysis (PT50: 40.7 ± 1.9 h, 17.1% promotion), enhancing the locomotion (140.0% promotion at 48 h), and alleviating glutamic acid (Glu)-induced neurotoxicity (153.5% promotion at 48 h) of CL4176 worms (p < 0.0001).


Assuntos
Alcaloides , Doença de Alzheimer , Animais , Chá/química , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/farmacologia , Caenorhabditis elegans/genética , Quercetina/farmacologia , Acetilcolinesterase , Simulação de Acoplamento Molecular , Alcaloides/farmacologia , Alcaloides/química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Flavonóis/farmacologia
3.
Curr Med Imaging ; 20: 1-4, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389377

RESUMO

INTRODUCTION: Pulmonary enteric adenocarcinoma (PEAC) is an extremely rare variant of lung adenocarcinoma characterized by pathological features similar to those of colorectal adenocarcinoma. It is mostly observed on computed tomography (CT) and positron emission tomography (PET)/CT as solitary or multiple nodules/masses in the lung. It tends to grow rapidly and is difficult to distinguish from lung metastatic colorectal cancer. Herein, we have presented a case of PEAC with special imaging findings. CASE PRESENTATION: A chest CT scan of a 72-year-old man with suspected chronic pneumonia revealed a well-defined consolidation in the upper lobe of the left lung. The lesion was slightly enlarged at the 9-month follow-up, and low FDG accumulation was subsequently observed using 18F-fluorodeoxyglucose (18F-FDG) PET/CT scans. The patient was later diagnosed with PEAC through percutaneous lung biopsy. CONCLUSION: Our case has demonstrated specific imaging findings of PEAC.

5.
Chin Med J (Engl) ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38192233

RESUMO

BACKGROUND: There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients. METHODS: In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12. RESULTS: At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician's Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks 86.8% [92/106] vs. 82.4% [89/108] and maintained up to 52 weeks 91.3% [95/104] vs. 87.4% [90/103]. Most treatment-emergent adverse events were mild and not related to tildrakizumab. CONCLUSION: Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05108766.

6.
Int J Soc Psychiatry ; : 207640231221100, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38193432

RESUMO

BACKGROUND: Despite numerous literature studies on the short-term effects of diverse experiences of being left-behind, migrant, or both on children, the research on their long-term effects remains inadequate. The purpose of current study is to explore the long-term impact of being left-behind, migrant or experiencing both during childhood on health in adulthood. Simultaneously, we investigate the impact of psychological resilience on adults in the presence of diverse experiences of parental migration. METHOD: A total of 2,371 samples were selected from 28 provinces in China, consisting of 656 participants who had been left behind but never migrated (PLBNM), 205 participants who had migrated but never been left behind (PMNLB), 265 participants who had both been left behind and migrated (PLBM), and 1,245 participants who had no left-behind/migrant experiences (NLBM). The mental health, health condition, and psychological resilience were measured using the 12-item General Health Questionnaire (GHQ-12), Self-Rated Health, and the Connor-Davidson Resilience Scale (CD-RISC), respectively. RESULTS: The results of the regression model indicated that PLBNM (OR = 2.10, 95% CI [1.59, 2.77], p < .001), PMNLB (1.93, [1.27, 2.94], p < .01), and PLBM (2.01, [1.37, 2.94], p < .001) displayed lower self-rated health compared to NLBM. However, only PLBNM (1.29, [1.05, 1.58], p < .05) reported higher mental health problems compared to NLBM. Our results also showed a strong association between psychological resilience and adults' lower self-rated health (0.72, [0.64, 0.82], p < .001). CONCLUSION: The negative long-term impact of various experiences regarding being left-behind, migrant, or both, on adult's mental health and self-rated health were more pronounced. The Chinese government ought to create unique policy frameworks that offer assistance to those adults.

7.
BMC Public Health ; 24(1): 261, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254090

RESUMO

BACKGROUND: Screen time and physical activity behaviors undergo development during early childhood and impact mental health. However, there is limited knowledge regarding the associations between physical activity, screen time, and mental health problems (MHP) in preschoolers. This study examines these associations using a large sample size and brief measures. METHODS: A multistage cluster stratified sampling method was used to conduct an observational cross-sectional study of 19,015 Chinese preschoolers in 2020. Information on physical activity, and screen time was collected by a self-administered questionnaire; MHP was assessed by the parent-reported Strengths and Difficulties Questionnaire (SDQ). Logistic regression models were used to obtain the odds ratios (ORs) and 95% confidence intervals (95% CIs) of preschoolers' MHP associated with screen time, total physical activities, moderate to vigorous physical activity (MVPA), and outdoor physical activities. RESULTS: A total of 19,015 participants from the 19,548 recruited population were included in the analyses (missing rate: 2.73%), 52.60% were boys. 64.01%, 57.96%, 35.98%, and 82.64% of preschoolers were reported to meet total physical activities, MVPA, and outdoor activities with screen time recommendations level. The results of multivariable-adjusted ORs (95% CIs) of preschoolers' MHP for comparisons of different levels of screen time (< 2 h/day, 2-4 h/day,≥4 h/day) show that screen time positively associated with MHP after adjusting for confounders (P < 0.05), but the association was not significant among girls with screen time ≥ 4 h/day. In addition, increased engagement in physical activity was reversely linked to MHP (P < 0.05). A stronger association between MHP and MVPA was observed in boys, however, this association was weakened when the total time spent engaging in MVPA exceeded two hours per day (P < 0.05). CONCLUSION: Less physical activity and more screen time positively relate to MHP, but the relationship differs by type of physical activity, total time, and gender. These findings provide novel insights and evidence supporting for guidelines on physical activity, screen time, and improvement of mental health for preschoolers.


Assuntos
Saúde Mental , Tempo de Tela , Pré-Escolar , Feminino , Humanos , Masculino , China/epidemiologia , Estudos Transversais , Exercício Físico
8.
Virus Res ; 339: 199268, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37949376

RESUMO

Hand, foot, and mouth disease (HFMD) caused by a group of enteroviruses is a global public health problem. In recent years, coxsackievirus A6 (CVA6) has emerged as an important HFMD agent. Previous studies have shown that mutations of glycine 64 in RNA-dependent RNA polymerase (3D polymerase), which is central to viral replication, cause phenotypic changes such as ribavirin resistance, increased replication fidelity, and virulence attenuation in poliovirus and enterovirus A71. In this study, we constructed CVA6 mutants with G64R, G64S, and G64T substitutions by site-directed mutagenesis in full-length cDNA of an infectious CVA6 strain cloned in pcDNA3.1. Viral RNA was obtained by in vitro transcription, and the rescued virus strains were propagated in RD cells. Sequencing after six passages revealed that G64S and G64T mutations were stably inherited, whereas G64R was genetically unstable and reversed to the wild type. Comparison of the biological characteristics of the wild-type and mutant CVA6 strains in an in vivo model (one-day-old ICR mice) revealed that the pathogenicity of CVA6-G64S and CVA6-G64T was significantly reduced compared to wild-type CVA6. In vitro experiments indicated the mutant CVA6-G64S and CVA6-G64T strains had increased resistance to 0.8 mM ribavirin and a decreased replication rate in the presence of 0.8 mM guanidine hydrochloride. Our results show that mutation of residue 64 reduces CVA6 susceptibility to ribavirin and increases CVA6 susceptibility to guanidine hydrochloride, together with increased replication fidelity and attenuated viral pathogenicity, thus laying a foundation for the development of safe and effective live attenuated CVA6 vaccine.


Assuntos
Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Animais , Camundongos , Ribavirina/farmacologia , Virulência , RNA Polimerase Dependente de RNA/genética , Guanidina , Camundongos Endogâmicos ICR , Enterovirus/genética , Anticorpos Antivirais
9.
bioRxiv ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38105964

RESUMO

Neurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a novel kinesin-based mechanism for polarized transport of vesicles to dendrites. Significance: Our findings suggest that at least one type of vesicles, those containing transferrin receptor, travel exclusively to dendrites and are excluded from axons because the kinase MARK2 phosphorylates the kinesin KIF13A to promote its separation from vesicles at the proximal axon, preventing vesicle transport into axons, such that they travel only to dendrites. Future studies should explore how this mechanism of polarized vesicle transport supports neuronal function.

10.
Zhongguo Gu Shang ; 36(12): 1136-41, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38130221

RESUMO

OBJECTIVE: To explore pro-oxidative state of rotator cuff tissue and expression levels of Beclin-1 and mam-malian target of rapamycin(mTOR) in patients with acute and chronic rotator cuff injury, and then analyzed relationship between rotator cuff injury and oxidative stress and autophagy. METHODS: Forty patients with rotator cuff injury were seleceted from July 2019 to December 2020, and divided into male chronic injury group, male acute injury group, female chronic injury group, and female acute injury group, 10 patients in each group. All patients were performed rotator cuff repair under arthroscopy. The sample of tendon at the rotator cuff injury site of the patient was taken during operation, and total reactive oxygen species (ROS) and superoxide dismutase(SOD) were detected by detection kit;expression of Beclin-1 and mTOR mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and Western-blot was applied to detect protein expression of Beclin-1 and p-mTOR/mTOR. RESULTS: There were no significant difference in expression of ROS, SOD, Beclin-1mRNA and mTOR mRNA between male and female chronic injury groups, and between male and female acute injury groups (P>0.05); ROS, SOD and Beclin-1mRNA in male chronic injury group were higher than those in male chronic injury group, while mTOR mRNAand protein decreased (P<0.05);ROS, SOD and Beclin-1 mRNA in female chronic injury group were up-regulated compared with female acute injury group, while mTOR mRNA was down-regulated (P<0.05). CONCLUSION: Chronic rotator cuff injury is more likely to stimulate the pro-oxidation state of rotator cuff tissue than acute rotator cuff injury, which could up-regulating expression of autophagy factor Beclin-1 and down-regulating expression of mTOR. Therefore, patients with chronic rotator cuff injury may have higher levels of oxidative stress and autophagy.


Assuntos
Lesões do Manguito Rotador , Feminino , Humanos , Masculino , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , RNA Mensageiro/metabolismo , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
11.
Soc Sci Med ; 338: 116315, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37952432

RESUMO

Previous studies have primarily focused on the contemporaneous, short-term and medium-term effects of the childhood left-behind experience on subsequent health, but ignored its long-term effects and the mediating mechanisms of health outcomes. Using nationally representative data from the 2018 China Labor-force Dynamic Survey, this study uses self-rated health as a measure of health outcomes to examine the long-term effects of the left-behind experience and elucidate the underlying mechanisms that contribute to health inequality from a life-course perspective. The results show: (1) the childhood left-behind experience exerts a long-term negative impact on self-rated health in adulthood, and this impact persists and does not fade over time after ending the left-behind status; (2) the influence of the childhood left-behind experience on self-rated health demonstrates a cumulative disadvantage effect, with longer duration of being left-behind resulting in greater negative impacts; additionally, there's a critical window effect, with earlier left-behind experience leading to more significant negative outcomes; (3) the experience of being left behind during childhood has a negative impact and threshold effect on social trust in adulthood, meaning that the left-behind experience negatively affects social trust, but the duration of being left behind doesn't exacerbate this reduction; and (4) social trust is a key mediating factor between left-behind experiences and health, explaining 8.70% of this effect, and explaining 12.15% and 7.71% of mediation effects for adults with left-behind experience in middle and primary school stages, respectively.


Assuntos
Disparidades nos Níveis de Saúde , Adulto , Humanos , Estudos Transversais , Inquéritos e Questionários , China , Fatores de Tempo
12.
Front Pharmacol ; 14: 1294966, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954841

RESUMO

The human immunodeficiency virus (HIV) persists in latently infected CD4+T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome (AIDS) is associated with HIV-1. Possibly, treating HIV/AIDS is an essential but challenging clinical goal. This review provides a detailed account of the types and mechanisms of monotherapy and combination therapy against HIV-1 and describes nanoparticle and hydrogel delivery systems. In particular, the recently developed capsid inhibitor (Lenacapavir) and the Ainuovirine/tenofovir disoproxil fumarate/lamivudine combination (ACC008) are described. It is interestingly to note that the lack of the multipass transmembrane proteins serine incorporator 3 (SERINC3) and the multipass transmembrane proteins serine incorporator 5 (SERINC5) may be one of the reasons for the enhanced infectivity of HIV-1. This discovery of SERINC3 and SERINC5 provides new ideas for HIV-1 medication development. Therefore, we believe that in treating AIDS, antiviral medications should be rationally selected for pre-exposure and post-exposure prophylaxis to avoid the emergence of drug resistance. Attention should be paid to the research and development of new drugs to predict HIV mutations as accurately as possible and to develop immune antibodies to provide multiple guarantees for the cure of AIDS.

13.
Heliyon ; 9(10): e20595, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37928387

RESUMO

Parkinson's disease is a common neurodegenerative disease characterized by intracellular aggregation of misfolded α-synuclein as a major pathological hallmark. Exosomes are cell-derived lipid bilayer membrane vesicles with various components, including proteins, RNA, and lipids, that mediate intercellular communication. Currently, exosomes are found to be responsible for transporting misfolded proteins from unhealthy neurons to nearby cells, spreading the disease from cell to cell. Such exosomes can also be found in the cerebrospinal fluid and blood. Thus, exosomes may serve as a potential tool to detect the pathology of Parkinson's disease for clinical diagnosis. In this article, the role and challenges of exosomes in the diagnosis of Parkinson's disease are outlined.

14.
Transl Pediatr ; 12(10): 1800-1809, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37969126

RESUMO

Background: Early recurrent intussusception (ERI) in children is common and seriously affects the physical and mental health of the children. There are few reports discussing risk factors for ERI in children, and this study aims to identify risk factors for ERI in children and build predictive models. Methods: We conducted a retrospective study of 787 children with no relapse intussusception (NRI) and 82 children with ERI between January 2011 and December 2021. Univariate and multifactorial stepwise logistic regression analysis was used to analyze the correlation between 11 factors and ERI, to determine the independent risk factors for ERI in children. The prediction model was established by independent risk factors and then verified. Results: Age, vomiting, bloody stools, and monocyte ratios were independently correlated with the composite endpoint (P<0.05). A nomogram was constructed and a calibration curve was plotted, using independent risk factors. Based on the disease's diagnostic score, the predictive model's performance was validated by using logistic regression receiver operating characteristic (ROC) curve detection, with area under the curve (AUC) value of 0.883 [95% confidence interval (CI): 0.846-0.920], and the calibration curve was close to the ideal diagonal line. In addition, the decision curve analysis (DCA) showed that the model had significant net benefits. Conclusions: Independent risk factors for ERI in children are age, vomiting, bloody stool, and monocyte ratio. Children older than 1 year in age, who lacked vomiting and bloody stool symptoms, and who exhibited an elevated ratio of monocytes were more likely to relapse early. The predictive model constructed herein can predict the early recurrence of children with ERI, providing a reference for clinicians' individualized judgments.

15.
Drug Discov Today ; 29(1): 103833, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37992888

RESUMO

The demand for human cytomegalovirus (HCMV) vaccines was first raised by a committee convened during the 1990s. A comprehensive investigation into the mechanism of viral infection supports the prioritization of developing drugs or vaccines that specifically target receptors and ligands involved in the infection process. As primary targets for neutralizing antibodies to combat HCMV, viral ligands (trimer, pentamer, and glycoprotein B) have crucial roles and exhibit substantial antiviral potential, which could be exploited for breakthroughs in antiviral research.

16.
Nanoscale ; 15(44): 17793-17807, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37916998

RESUMO

Superhydrophobic surfaces have attracted broad attention because of their unique water repellency but are restricted by poor wear resistance, weak adhesion to the substrate, and complex fabrication processes. Herein, a double-layer coating strategy consisting of the amino fluorine-silicone resin/epoxy resin (AFSR/EP) system is created. The system features a high hardness and transparent hydrophobic interface adhesive layer through the amine-epoxy "click" chemical reaction. The environmentally friendly resin system and low-cost nano-silica particles (n-SiO2) are composited and sprayed onto the substrate surface to form a superhydrophobic layer with outstanding robustness and excellent environmental stability. The prepared AFSR/EP@n-SiO2 composite coatings have a water contact angle of 161.1° and a sliding angle of 3.4°, demonstrating high superhydrophobic properties. Benefitting from the complementary advantages of silicone/epoxy resin, the prepared composite coatings maintain remarkable water repellency after various harsh environmental tests, including cyclic mechanical abrasion and tape-stripping, acid-base (pH 1 and pH 14) treatment, 10 wt% NaCl (pH 7) salt solution immersion, temperature treatment, knife scratching, and long-term ultraviolet radiation treatment, showing reinforced mechanical robustness and durable anti-corrosion stability. Notably, surface hardness of 5H and optical transparency over 80% can be achieved. The simple method offers a novel approach for the large-scale preparation of multifunctional superhydrophobic coatings.

18.
Ecotoxicol Environ Saf ; 266: 115559, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37820475

RESUMO

Cadmium (Cd) contamination in wheat fields has become a major environmental issue in many regions of the world. Mercapto-palygorskite (MPAL) is a high-performance amendment that can effectively immobilize Cd in alkaline wheat soil. However, MAPL as an in-situ Cd immobilization strategy for alkaline wheat soil remains to be evaluated on a field-scale and the underlying mechanisms requires further evaluation. Here, MPAL were used as soil amendment to evaluate their immobilization efficiency on Cd-contaminated alkaline soil in the field experiments. The field experiments showed that MPAL application significantly reduced wheat grain Cd concentration from 0.183 mg/kg to 0.056 mg/kg, with Cd concentration in wheat grain treated with MPAL all falling below the limit value of 0.1 mg/kg as defined in China's food safety standard (GB 2762-2022). The maximal immobilization efficiency of MPAL on soil Cd figured out by diethylenetriaminepentaacetic acid (DTPA) extraction was 61.5%. The mechanisms involved in Cd immobilization by MPAL were mainly related to the enhanced sorption of Cd onto Fe oxides, and the removal of amorphous or free Fe oxides from soil had a substantial impact on Cd immobilization efficiency by MPAL. Furthermore, the antagonistic effect between Mn and Cd uptake may also contribute to the reduction of wheat Cd accumulation after MPAL application. The current research can provide theoretical and technical support for the large-scale application of MPAL in Cd-contaminated wheat fields.


Assuntos
Poluentes do Solo , Solo , Cádmio/análise , Triticum , Poluentes do Solo/análise , Óxidos
19.
J Fungi (Basel) ; 9(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37888283

RESUMO

Pichia pastoris is the most widely used microorganism for the production of secreted industrial proteins and therapeutic proteins. Recently, this yeast has been repurposed as a cell factory for the production of chemicals and natural products. In this review, the general physiological properties of P. pastoris are summarized and the readily available genetic tools and elements are described, including strains, expression vectors, promoters, gene editing technology mediated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9, and adaptive laboratory evolution. Moreover, the recent achievements in P. pastoris-based biosynthesis of proteins, natural products, and other compounds are highlighted. The existing issues and possible solutions are also discussed for the construction of efficient P. pastoris cell factories.

20.
Proc Natl Acad Sci U S A ; 120(39): e2308079120, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37733743

RESUMO

TAK1 is a key modulator of both NF-κB signaling and RIPK1. In TNF signaling pathway, activation of TAK1 directly mediates the phosphorylation of IKK complex and RIPK1. In a search for small molecule activators of RIPK1-mediated necroptosis, we found R406/R788, two small molecule analogs that could promote sustained activation of TAK1. Treatment with R406 sensitized cells to TNF-mediated necroptosis and RIPK1-dependent apoptosis by promoting sustained RIPK1 activation. Using click chemistry and multiple biochemical binding assays, we showed that treatment with R406 promotes the activation of TAK1 by directly binding to TAK1, independent of its original target Syk kinase. Treatment with R406 promoted the ubiquitination of TAK1 and the interaction of activated TAK1 with ubiquitinated RIPK1. Finally, we showed that R406/R788 could promote the cancer-killing activities of TRAIL in vitro and in mouse models. Our studies demonstrate the possibility of developing small molecule TAK1 activators to potentiate the effect of TRAIL as anticancer therapies.


Assuntos
Apoptose , Neoplasias , Animais , Camundongos , Morte Celular , Citosol , Neoplasias/tratamento farmacológico , Neoplasias/genética , Ubiquitinação
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