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1.
Small ; : e2311427, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733219

RESUMO

MXene-based photocatalytic membranes provide significant benefits for wastewater treatment by effectively combining membrane separation and photocatalytic degradation processes. MXene represents a pioneering 2D photocatalyst with a variable elemental composition, substantial surface area, abundant surface terminations, and exceptional photoelectric performance, offering significant advantages in producing high-performance photocatalytic membranes. In this review, an in-depth overview of the latest scientific progress in MXene-based photocatalytic membranes is provided. Initially, a brief introduction to the structure and photocatalytic capabilities of MXene is provided, highlighting their pivotal role in promoting the photocatalytic process. Subsequently, in pursuit of the optimal MXene-based photocatalytic membrane, critical factors such as the morphology, hydrophilicity, and stability of MXenes are meticulously taken into account. Various preparation strategies for MXene-based photocatalytic membranes, including blending, vacuum filtration, and dip coating, are also discussed. Furthermore, the application and mechanism of MXene-based photocatalytic membranes in micropollutant removal, oil-water separation, and antibacterial are examined. Lastly, the challenges in the development and practical application of MXene-based photocatalytic membranes, as well as their future research direction are delineated.

2.
Cancer Cell ; 42(5): 833-849.e12, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38701792

RESUMO

Glucocorticoids have been used for decades to treat lymphomas without an established mechanism of action. Using functional genomic, proteomic, and chemical screens, we discover that glucocorticoids inhibit oncogenic signaling by the B cell receptor (BCR), a recurrent feature of aggressive B cell malignancies, including diffuse large B cell lymphoma and Burkitt lymphoma. Glucocorticoids induce the glucocorticoid receptor (GR) to directly transactivate genes encoding negative regulators of BCR stability (LAPTM5; KLHL14) and the PI3 kinase pathway (INPP5D; DDIT4). GR directly represses transcription of CSK, a kinase that limits the activity of BCR-proximal Src-family kinases. CSK inhibition attenuates the constitutive BCR signaling of lymphomas by hyperactivating Src-family kinases, triggering their ubiquitination and degradation. With the knowledge that glucocorticoids disable oncogenic BCR signaling, they can now be deployed rationally to treat BCR-dependent aggressive lymphomas and used to construct mechanistically sound combination regimens with inhibitors of BTK, PI3 kinase, BCL2, and CSK.


Assuntos
Glucocorticoides , Receptores de Antígenos de Linfócitos B , Humanos , Glucocorticoides/farmacologia , Receptores de Antígenos de Linfócitos B/metabolismo , Animais , Transdução de Sinais/efeitos dos fármacos , Receptores de Glucocorticoides/metabolismo , Camundongos , Linhagem Celular Tumoral , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Terapia de Alvo Molecular/métodos , Fosfatidilinositol 3-Quinases/metabolismo , Quinases da Família src/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
3.
Small ; : e2401497, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693067

RESUMO

Manganese-based lithium-rich layered oxides (Mn-LLOs) are promising candidate cathode materials for lithium-ion batteries, however, the severe voltage decay during cycling is the most concern for their practical applications. Herein, an Mn-based composite nanostructure constructed Li2MnO3 (LMO@Li2MnO3) is developed via an ultrathin amorphous functional oxide LixMnOy coating at the grain surface. Due to the thin and universal LMO amorphous surface layer etched from the lithiation process by the high-concentration alkaline solution, the structural and interfacial stability of Li2MnO3 are enhanced apparently, showing the significantly improved voltage maintenance, cycle stability, and energy density. In particular, the LMO@Li2MnO3 cathode exhibits zero voltage decay over 200 cycles. Combining with ex situ spectroscopic and microscopic techniques, the Mn2+/4+ coexisted behavior of the amorphous LMO is revealed, which enables the stable electrochemistry of Li2MnO3. This work provides new possible routes for suppressing the voltage decay of Mn-LLOs by modifying with the composite functional unit construction.

4.
Materials (Basel) ; 17(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38673279

RESUMO

Using the Split Hopkinson Pressure Bar technique, strain-limited dynamic compressive loading experiments were performed on TA1/TA15 heterostructure (HS) materials. The plastic deformation mechanisms, fracture forms, and energy absorption properties of an HS material with a metallurgical bonding interface (MB) and an HS material without a metallurgical bonding interface (NMB) are compared and analyzed. The results show that there is no significant difference between the two deformation mechanisms. The fracture forms are all "V-shaped" fractures within the TA1 part. The NMB was carried for 57 µs before failure and absorbed 441 J/cm3 of energy. The MB was carried for 72 µs before failure and absorbed 495 J/cm3 of energy. Microstructure observations show that there is a coordinated deformation effect near the MB interface compared to the NMB, with both TA1 and TA15 near the interface carrying stresses. This causes an enhancement of the MB load-bearing time and a 12% increase in energy absorption.

5.
Brain Behav Immun ; 119: 129-145, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38552923

RESUMO

GSDMD-mediated pyroptosis occurs in the nigrostriatal pathway in Parkinson's disease animals, yet the role of GSDMD in neuroinflammation and death of dopaminergic neurons in Parkinson's disease remains elusive. Here, our in vivo and in vitro studies demonstrated that GSDMD, as a pyroptosis executor, contributed to glial reaction and death of dopaminergic neurons across different Parkinson's disease models. The ablation of the Gsdmd attenuated Parkinson's disease damage by reducing dopaminergic neuronal death, microglial activation, and detrimental transformation. Disulfiram, an inhibitor blocking GSDMD pore formation, efficiently curtailed pyroptosis, thereby lessening the pathology of Parkinson's disease. Additionally, a modification in GSDMD was identified in the blood of Parkinson's disease patients in contrast to healthy subjects. Therefore, the detected alteration in GSDMD within the blood of Parkinson's disease patients and the protective impact of disulfiram could be promising for the diagnostic and therapeutic approaches against Parkinson's disease.

6.
Small ; 20(1): e2305066, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37641187

RESUMO

Photocatalytic membranes can effectively integrate membrane separation and photocatalytic degradation processes to provide an eco-friendly solution for efficient water purification. It is of great significance to develop highly efficient photocatalytic membranes driven by visible light to ensure the long-term stability of membrane separation systems and the maximum utilization of solar energy. Metal-organic framework (MOF) is an emerging photocatalyst with a well-defined structure and tunable chemical properties, showing a broad application prospect in the construction of high-performance photocatalytic membranes. Herein, this work provides a comprehensive review of recent advancements in MOF-based photocatalytic membranes. Initially, this work outlines the main tailoring strategies that facilitate the enhancement of the photocatalytic activity of MOF-based photocatalysts. Next, this work introduces commonly used methods for fabricating MOF-based photocatalytic membranes. Subsequently, this work discusses the application and mechanisms of MOF-based photocatalytic membranes toward organic pollutant degradation, metal ion removal, and membrane fouling mitigation. Finally, challenges in developing MOF-based photocatalytic membranes and their practical applications are presented, while also pointing out future research directions toward overcoming these existing limitations.

7.
Small ; 20(11): e2306528, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37922525

RESUMO

Assembling metal-organic frameworks (MOFs) into high-performance macroscopic membranes is crucial but still challenging. MOF-containing hybrid membranes can effectively integrate the advantages of flexible guest materials and MOFs. Nevertheless, the inherent limitations in fully harnessing the distinct characteristics of MOFs persist due to the substantial guest material content necessitated in membrane fabrication. Herein, inspired by the rigid and flexible structures in biological systems, rigid MIP-202(Zr) and defective MIP-202(Zr) (D-MIP-202(Zr)) modified flexible graphene oxide (GO) sheets are synthesized in situ and then assembled into a rigid-flexible coupled MOF-based membrane. The defects in D-MIP-202(Zr) are introduced by using acetic acid as the modulation agent. The obtained GO@MIP-202(Zr) membrane possesses a hierarchical porous structure with a 99 wt% MOF proportion, which is higher than the GO@D-MIP-202(Zr) (75 wt%) membrane with a compact bulge-structured surface. The water permeability of the GO@MIP-202(Zr) membrane attains remarkedly 5762.92 L h-1 m-2 bar-1 , which is 960 and 2.6 times higher than that of the GO membrane and GO@D-MIP-202(Zr) membrane. Additionally, benefiting from the superhydrophilicity and underwater superoleophobicity, the resultant membrane not only demonstrates high rejection for oil-water emulsions but also exhibits exceptional recyclability and anti-fouling ability. These findings provide valuable insights into the assembly of MOFs into high-performance membranes.

8.
Exp Biol Med (Maywood) ; 248(23): 2449-2463, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38073524

RESUMO

In clinical trials, rhubarb extract (Rb) was demonstrated to efficiently alleviate constipation. We would like to find out the underlying mechanism of rhubarb relieving constipation. However, there are few studies on the effects of rhubarb on colonic mucus secretion and constipation. The aim of this study was to investigate the effects of rhubarb on colonic mucus secretion and its underlying mechanism. The mice were randomly divided into four groups. Group I was the control group and Group II was the rhubarb control group, with Rb (24 g/kg body weight [b.w.]) administered through intragastric administration for three days. Group III mice were given diphenoxylate (20 mg/kg b.w.) for five days via gavage to induce constipation. Group IV received diphenoxylate lasting five days before undergoing Rb administration for three days. The condition of the colon was evaluated using an endoscope. Particularly, the diameter of blood vessels in the colonic mucosa expanded considerably in constipation mice along with diminishing mucus output, which was in line with the observation via scanning electron microscope (SEM) and transmission electron microscope (TEM). We also performed metagenomic analysis to reveal the microbiome related to mucin gene expression level referring to mucin secretion. In conclusion, Rb relieves constipation by rebuilding mucus homeostasis and regulating the microbiome.


Assuntos
Rheum , Camundongos , Animais , Difenoxilato/metabolismo , Difenoxilato/farmacologia , Difenoxilato/uso terapêutico , Mucinas/metabolismo , Mucinas/farmacologia , Mucinas/uso terapêutico , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/metabolismo , Colo/metabolismo , Muco/metabolismo , Homeostase
9.
Small ; : e2310174, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38126899

RESUMO

To address current energy crises and environmental concerns, it is imperative to develop and design versatile porous materials ideal for water purification and energy storage. The advent of covalent organic frameworks (COFs), a revolutionary terrain of porous materials, is underscored by their superlative features such as divinable structure, adjustable aperture, and high specific surface area. However, issues like inferior electric conductivity, inaccessible active sites impede mass transfer and poor processability of bulky COFs restrict their wider application. As a herculean stride forward, COF/graphene hybrids amalgamate the strengths of their constituent components and have in consequence, enticed significant scientific intrigue. Herein, the current progress on the structure and properties of graphene-based materials and COFs are systematically outlined. Then, synthetic strategies for preparing COF/graphene hybrids, including one-pot synthesis, ex situ synthesis, and in situ growth, are comprehensively reviewed. Afterward, the pivotal attributes of COF/graphene hybrids are dissected in conjunction with their multifaceted applications spanning adsorption, separation, catalysis, sensing, and energy storage. Finally, this review is concluded by elucidating prevailing challenges and gesturing toward prospective strides within the realm of COF/graphene hybrids research.

10.
BMJ Open ; 13(11): e076644, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-38016796

RESUMO

INTRODUCTION: The high incidences of both the developmental delay among young children and the mental health problems of their caregivers are major threats to public health in low-income and middle-income countries. Parental training interventions during early childhood have been shown to benefit early development, yet evidence on strategies to promote caregiver mental health remains limited. In addition, evidence on the optimal design of scalable interventions that integrate early child development and maternal mental health components is scarce. METHODS AND ANALYSIS: We design a single-blind, factorial, cluster-randomised controlled, superiority trial that will be delivered and supervised by local agents of the All China Women's Federation (ACWF), the nationwide, government-sponsored social protection organisation that aims to safeguard the rights and interests of women and children. We randomise 125 villages in rural China into four arms: (1) a parenting stimulation arm; (2) a caregiver mental health arm; (3) a combined parenting stimulation and caregiver mental health arm and (4) a pure control arm. Caregivers and their children (aged 6-24 months at the time of baseline data collection) are selected and invited to participate in the 12-month-long study. The parenting stimulation intervention consists of weekly, one-on-one training sessions that follow a loose adaptation of the Reach Up and Learn curriculum. The caregiver mental health intervention is comprised of fortnightly group activities based on an adaptation of the Thinking Healthy curriculum from the WHO. Primary outcomes include measures of child development and caregiver mental health. Secondary outcomes include a comprehensive set of physical, psychological and behavioural outcomes. This protocol describes the design and evaluation plan for this programme. ETHICS AND DISSEMINATION: This study received approval from the Institutional Review Board of Stanford University (IRB Protocol #63680) and the Institutional Review Board of the Southwestern University of Finance and Economics in Chengdu, Sichuan, China. Informed oral consent will be obtained from all caregivers for their own and their child's participation in the study. The full protocol will be publicly available in an open-access format. The study findings will be published in economics, medical and public health journals, as well as Chinese or English policy briefs. TRIAL REGISTRATION NUMBER: AEA RCT Registry (AEARCTR-0010078) and ISRCTN registry (ISRCTN84864201).


Assuntos
Cuidadores , Desenvolvimento Infantil , Criança , Humanos , Pré-Escolar , Feminino , Cuidadores/psicologia , Saúde Mental , Método Simples-Cego , Governo , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Front Neurol ; 14: 1253915, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37885473

RESUMO

Ossified intracranial meningiomas (OIM) and ossified spinal meningiomas (OSM) are rare neoplasms of mesenchymal origin that predominantly manifest in the spinal cord and infrequently in the cranial region, accounting for ~0. 7-5.5% of all meningiomas. It is extremely rare to have multiple intracranial and spinal lesions accompanied by ossification. Herein, we report this rare case for the first time. A 34-year-old woman presented with paresthesia and limb weakness in the right lower limb and gradually worsened. Approximately half a year later, she could only walk with crutches. Magnetic resonance imaging of the brain and spinal cord showed multiple meningiomas, and histopathological examination confirmed multiple OIM and OSM (WHO grade 1). Multiple OIM and OSM are extremely rare with diverse imaging features, and it is easily confused with other tumors. Histopathological examination is the final diagnostic method.

12.
J Am Chem Soc ; 145(44): 24284-24293, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37888942

RESUMO

Zinc metal-based aqueous batteries (ZABs) offer a sustainable, affordable, and safe energy storage alternative to lithium, yet inevitable dendrite formation impedes their wide use, especially under long-term and high-rate cycles. How the battery can survive after dendrite formation remains an open question. Here, we pivot from conventional Zn dendrite growth suppression strategies, introducing proactive dendrite-digesting chemistry via a mesoporous Ti3C2 MXene (MesoTi3C2)-wrapped polypropylene separator. Spectroscopic characterizations and electrochemical evaluation demonstrate that MesoTi3C2, acting as an oxidant, can revive the formed dead Zn0 dendrites into electroactive Zn2+ ions through a spontaneous redox process. Density functional theory reveals that the abundant edge-Ti-O sites in our MesoTi3C2 facilitate high oxidizability and electron transfer from Zn0 dendrites compared to their in-plane counterparts. The resultant asymmetrical cell demonstrates remarkable ultralong cycle life of 2200 h at a practical current of 5 mA cm-2 with a low overpotential (<50 mV). The study reveals the unexpected edge effect of mesoporous MXenes and uncovers a new proactive dendrite-digesting chemistry to survive ZABs, albeit with inevitable dendrite formation.

13.
Immun Inflamm Dis ; 11(9): e1005, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37773693

RESUMO

Plasmacytoid dendritic cells (pDCs), a subtype of DC, possess unique developmental, morphological, and functional traits that have sparked much debate over the years whether they should be categorized as DCs. The digestive system has the greatest mucosal tissue overall, and the pDC therein is responsible for shaping the adaptive and innate immunity of the gastrointestinal tract, resisting pathogen invasion through generating type I interferons, presenting antigens, and participating in immunological responses. Therefore, its alleged importance in the gut has received a lot of attention in recent years, and a fresh functional overview is still required. Here, we summarize the current understanding of mouse and human pDCs, ranging from their formation and different qualities compared with related cell types to their functional characteristics in intestinal disorders, including colon cancer, infections, autoimmune diseases, and intestinal graft-versus-host disease. The purpose of this review is to convey our insights, demonstrate the limits of existing research, and lay a theoretical foundation for the rational development and use of pDCs in future clinical practice.

14.
Proc Natl Acad Sci U S A ; 120(37): e2217330120, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37669382

RESUMO

DNA is an incredibly dense storage medium for digital data. However, computing on the stored information is expensive and slow, requiring rounds of sequencing, in silico computation, and DNA synthesis. Prior work on accessing and modifying data using DNA hybridization or enzymatic reactions had limited computation capabilities. Inspired by the computational power of "DNA strand displacement," we augment DNA storage with "in-memory" molecular computation using strand displacement reactions to algorithmically modify data in a parallel manner. We show programs for binary counting and Turing universal cellular automaton Rule 110, the latter of which is, in principle, capable of implementing any computer algorithm. Information is stored in the nicks of DNA, and a secondary sequence-level encoding allows high-throughput sequencing-based readout. We conducted multiple rounds of computation on 4-bit data registers, as well as random access of data (selective access and erasure). We demonstrate that large strand displacement cascades with 244 distinct strand exchanges (sequential and in parallel) can use naturally occurring DNA sequence from M13 bacteriophage without stringent sequence design, which has the potential to improve the scale of computation and decrease cost. Our work merges DNA storage and DNA computing, setting the foundation of entirely molecular algorithms for parallel manipulation of digital information preserved in DNA.


Assuntos
Computadores Moleculares , DNA , Replicação do DNA , Algoritmos , Bacteriófago M13
15.
Microorganisms ; 11(8)2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37630578

RESUMO

(1) Background: Depression is the most prevalent psychiatric symptom present among individuals of all ages and backgrounds, impacting an estimated 300 million people globally. Therefore, it demands a significant amount of attention when it comes to managing depression. A growing amount of data reveal that probiotics and fatty acids could be beneficial to depression. However, the opposing position maintains that they have no influence on depression. A network meta-analyses of existing datasets aid in the estimation of comparative efficacy as well as in achieving an understanding of the relative merits of different therapies. The purpose of this study was to investigate the current evidence for probiotic or fatty acid depression therapy and to establish a practical alternative for depression patients using a meta-analysis and metagenomic data from a Wistar-Kyoto (WKY) depressed rat model. (2) Methods: Probiotic data were obtained from seven randomized controlled trial studies (n = 394), and fatty acid data were obtained from 24 randomized controlled trial studies (n = 1876). Meanwhile, a metagenomics analysis of data on animal gut flora was also applied to validate the preceding evidence. (3) Results: The fatty acid studies were separated into three sections based on the duration of probiotic delivery: ≤8 weeks, 9-12 weeks, and >12 weeks. The results were as follows: for ≤8 weeks, MD = -1.65 (95% CI: -2.96--0.15), p = 0.01; for 9-12 weeks, MD = -2.22 (95% CI: -3.03--1.22), p < 0.001; for >12 weeks, MD = -1.23 (95% CI: -2.85-0.39), p = 0.14. Regarding the probiotics, the meta-analysis revealed MD = -2.19 (95% CI: -3.38--2.43), p < 0.001. The research presented herein illustrates that probiotics and fatty acids may successfully lower depression scores. Additionally, the probiotics were drastically reduced in the WKY rats. (4) Conclusions: According to the data, a depression intervention utilizing probiotics outperformed the control, implying that the use of probiotics and fatty acids may be a successful strategy for depression treatment.

16.
Sci Total Environ ; 904: 166220, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37591402

RESUMO

The integration of catalytic degradation and membrane separation processes not only enables continuous degradation of contaminants but also effectively alleviates inevitable membrane fouling, demonstrating fascinating practical value for efficient water purification. Such membrane-catalysis integrated system (MCIS) has attracted tremendous research interest from scientists in chemical engineering and environmental science recently. In this review, the advantages of MCIS are discussed, including the membrane structure regulation, stable catalyst loading, nano-confinement effect, and efficient natural organic matter (NOM) exclusion, highlighting the synergistic effect between membrane separation and catalytic process. Subsequently, the design considerations for the fabrication of catalytic membranes, including substrate membrane, catalytic material, and fabrication method, are comprehensively summarized. Afterward, the mechanisms and performance of MCIS based on different catalytic types, including liquid-phase oxidants/reductants involved MCIS, gas involved MCIS, photocatalysis involved MCIS, and electrocatalysis involved MCIS are reviewed in detail. Finally, the research direction and future perspectives of catalytic membranes for water purification are proposed. The current review provides an in-depth understanding of the design of catalytic membranes and facilitates their further development for practical applications in efficient water purification.

17.
J Res Med Sci ; 28: 47, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37496645

RESUMO

Background: Glioma is one of the most malignant and aggressive tumors, with an extremely poor prognosis. Human telomerase reverse transcriptase (hTERT) promoter mutation is regarded as a risk factor in tumor growth. Although the prevalence of hTERT promoter (pTERT) mutation in gliomas has been investigated, the results are inconsistent. This meta-analysis aims to investigate the prognostic value of hTERT in glioma patients and its interaction with other biomarkers. Materials and Methods: We searched 244 citations from four databases: PubMed (2000-2021), Web of Science (2000-2021), Embase (2010-2021), and Cochrane Library (2000-2021) with 28 articles included. Results: We calculated hazard ratios (HRs) using the random effect model and the pooled result suggested that TERT promoter mutation predicted poorer overall survival (HR: 1.53, 95% confidence interval [CI]: 1.34-1.75, P < 0.001, I2: 49.9%, pheterogeneity:0.002) and progression-free survival (HR: 1.55, 95% CI: 1.27-1.88, P < 0.001, I2: 0.0%, pheterogeneity: 0.473). For subgroup analysis, we analyzed multiple factors including iso-citrate dehydrogenase (IDH) genotype, age, diagnosis, pTERT region, so as to locate the sources of heterogeneity. Interestingly, in IDH mutant subgroup, pTERT mutation became a beneficial prognostic factor (HR: 0.73, 95% CI: 0.57-0.93, I2: 22.3%, pheterogeneity: 0.277), which is contrary to the results in pooled analysis. Conclusion: In general, pTERT mutation may result in shorter survival time in glioma patients, but longer survival time when glioma patients are combined with IDH mutation.

18.
Int J Biol Sci ; 19(11): 3360-3382, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37496997

RESUMO

Targeted therapies in cancer treatment can improve in vivo efficacy and reduce adverse effects by altering the tissue exposure of specific biomolecules. However, there are still large number of target proteins in cancer are still undruggable, owing to the following factors including (1) lack of ligand-binding pockets, (2) function based on protein-protein interactions (PPIs), (3) the highly specific conserved active sites among protein family members, and (4) the variability of tertiary docking structures. The current status of undruggable targets proteins such as KRAS, TP53, C-MYC, PTP, are carefully introduced in this review. Some novel techniques and drug designing strategies have been applicated for overcoming these undruggable proteins, and the most classic and well-known technology is proteolysis targeting chimeras (PROTACs). In this review, the novel drug development strategies including targeting protein degradation, targeting PPI, targeting intrinsically disordered regions, as well as targeting protein-DNA binding are described, and we also discuss the potential of these strategies for overcoming the undruggable targets. Besides, intelligence-assisted technologies like Alpha-Fold help us a lot to predict the protein structure, which is beneficial for drug development. The discovery of new targets and the development of drugs targeting them, especially those undruggable targets, remain a huge challenge. New drug development strategies, better extraction processes that do not disrupt protein-protein interactions, and more precise artificial intelligence technologies may provide significant assistance in overcoming these undruggable targets.


Assuntos
Inteligência Artificial , Neoplasias , Humanos , Proteínas/metabolismo , Proteólise , Neoplasias/tratamento farmacológico , Descoberta de Drogas
19.
BMC Genomics ; 24(1): 248, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37165306

RESUMO

BACKGROUND: Real-time quantitative PCR (RT-qPCR) is a crucial and widely used method for gene expression analysis. Selecting suitable reference genes is extremely important for the accuracy of RT-qPCR results. Commonly used reference genes are not always stable in various organisms or under different environmental conditions. With the increasing application of high-throughput sequencing, transcriptome analysis has become an effective method for identifying novel stable reference genes. RESULTS: In this study, we identified candidate reference genes based on transcriptome data covering embryos and larvae of early development, normal adult tissues, and the hindgut under sulfide stress using the coefficient of variation (CV) method in the echiuran Urechis unicinctus, resulting in 6834 (15.82%), 7110 (16.85%) and 13880 (35.87%) candidate reference genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the candidate reference genes were significantly enriched in cellular metabolic process, protein metabolic process and ribosome in early development and normal adult tissues as well as in cellular localization and endocytosis in the hindgut under sulfide stress. Subsequently, ten genes including five new candidate reference genes and five commonly used reference genes, were validated by RT-qPCR. The expression stability of the ten genes was analyzed using four methods (geNorm, NormFinder, BestKeeper, and ∆Ct). The comprehensive results indicated that the new candidate reference genes were more stable than most commonly used reference genes. The commonly used ACTB was the most unstable gene. The candidate reference genes STX12, EHMT1, and LYAG were the most stable genes in early development, normal adult tissues, and hindgut under sulfide stress, respectively. The log2(TPM) of the transcriptome data was significantly negatively correlated with the Ct values of RT-qPCR (Ct = - 0.5405 log2(TPM) + 34.51), which made it possible to estimate the Ct value before RT-qPCR using transcriptome data. CONCLUSION: Our study is the first to select reference genes for RT-qPCR from transcriptome data in Echiura and provides important information for future gene expression studies in U. unicinctus.


Assuntos
Poliquetos , Transcriptoma , Animais , Perfilação da Expressão Gênica , Poliquetos/genética , Sulfetos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Padrões de Referência
20.
Anal Chim Acta ; 1267: 341333, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37257968

RESUMO

Acute myocardial infarction (AMI) is acute necrosis of a portion of the myocardium caused by myocardial ischemia, which seriously threatens people's health and life safety. Its early diagnosis is a difficult problem in clinical medicine. Research has found that the abnormal expression of microRNA-199a (miR-199a) and microRNA-499 (miR-499) was closely related to AMI disease. In this work, we took advantage of the structural advantages of nitrogen-doped hollow carbon nanospheres (N-HCNSs) to design an ultra-sensitive, portable real-time monitoring visual self-powered biosensor system, which based on dual-target miRNAs triggered catalytic hairpin assembly (CHA) for sensitive detection of miR-199a and miR-499. In addition, the capacitor and the smartphone are introduced into the system to realize the secondary improvement of system sensitivity and portable real-time visual monitoring. Under optimized conditions, in the linear range of 0.1-100000 aM, the detection limits of miR-199a and miR-499 are 0.031 and 0.027 aM, respectively. At the same time, the ultra-sensitive detection of miRNAs is realized in the serum sample, and the recovery rate of miR-199a and miR-499 are 98.0-106.0% (RSD: 0.6-8.1%) and 94.0-109.7% (RSD: 1.8-7.7%), respectively. The method is simple, sensitive and can be used for real-time tracking and portable monitoring of related diseases.


Assuntos
MicroRNAs , Infarto do Miocárdio , Nanosferas , Humanos , Nitrogênio , Carbono , Infarto do Miocárdio/diagnóstico
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