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1.
Nucleic Acids Res ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860430

RESUMO

The abnormal GGGGCC hexanucleotide repeat expansions (HREs) in C9orf72 cause the fatal neurodegenerative diseases including amyotrophic lateral sclerosis and frontotemporal dementia. The transcribed RNA HREs, short for r(G4C2)n, can form toxic RNA foci which sequestrate RNA binding proteins and impair RNA processing, ultimately leading to neurodegeneration. Here, we determined the crystal structure of r(G4C2)2, which folds into a parallel tetrameric G-quadruplex composed of two four-layer dimeric G-quadruplex via 5'-to-5' stacking in coordination with a K+ ion. Notably, the two C bases locate at 3'- end stack on the outer G-tetrad with the assistance of two additional K+ ions. The high-resolution structure reported here lays a foundation in understanding the mechanism of neurological toxicity of RNA HREs. Furthermore, the atomic details provide a structural basis for the development of potential therapeutic agents against the fatal neurodegenerative diseases ALS/FTD.

2.
Medicine (Baltimore) ; 103(23): e38440, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847696

RESUMO

Network pharmacology and molecular docking methods were used in the present study to clarify the molecular mechanism of two traditional Chinese medicine prescriptions of climacteric syndrome. Based on oral availability and drug similarity, the main active components of Erzhi Pill and Erxian Decoction were screened through the platform of traditional Chinese medicine system pharmacology. The target database of climacteric syndrome was established by using GENECARD, OMIM, PharmGKB, Targets and Drugbank. The "component - target" network diagram was constructed using Cytoscape software (version 3.8.2). Topology analysis, module analysis, and GO and KEGG enrichment analyses were used to explore the core target and action pathway of Erzhi Pill-Erxian Decoction for treating climacteric syndrome of same disease with different treatments. There were 16 active components and 103 corresponding targets found in Erzhi Pill; 69 active components and 121 corresponding targets were found in Erxian Decoction; and 100 potential targets were found in Erzhi Pill and Erxian Decoction. Through network analysis, topology and module analysis, TP53, AKT1, Jun, ESR1, IL1B, CASP3, MMP9, PTGS2, HIF1A, MYC and EGFR could be considered as potential targets of the 2 prescriptions for alleviating climacteric syndrome. The effects of Erzhi pill and Erxian Decoction on climacteric syndrome are mainly in the pathway of lipid and atherosclerosis, AGE-RAGE signaling pathway and PI3K-Akt signaling pathway in diabetic complications. The active components in Erzhi Pill - Erxian Decoction, such as quercetin, show considerable potential as a candidate drug for the treatment of climacteric syndrome.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Farmacologia em Rede/métodos , Medicina Tradicional Chinesa/métodos , Feminino , Climatério/efeitos dos fármacos
4.
World J Gastrointest Surg ; 16(4): 1184-1188, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38690059

RESUMO

BACKGROUND: Splenic rupture associated with Behçet's syndrome (BS) is extremely rare, and there is no consensus on its management. In this case report, a patient with BS-associated splenic rupture was successfully treated with splenic artery embolization (SAE) and had a good prognosis after the intervention. CASE SUMMARY: The patient was admitted for pain in the left upper abdominal quadrant. He was diagnosed with splenic rupture. Multiple oral and genital aphthous ulcers were observed, and acne scars were found on his back. He had a 2-year history of BS diagnosis, with symptoms of oral and genital ulcers. At that time, he was treated with oral corticosteroids for 1 month, but the symptoms did not alleviate. He underwent SAE to treat the rupture. On the first day after SAE, the patient reported a complete resolution of abdominal pain and was discharged 5 d later. Three months after the intervention, a computed tomography examination showed that the splenic hematoma had formed a stable cystic effusion, suggesting a good prognosis. CONCLUSION: SAE might be a good choice for BS-associated splenic rupture based on good surgical practice and material selection.

5.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 38(5): 556-561, 2024 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-38752241

RESUMO

Objective: To compare the effect of sciatic nerve block (SNB) combined with continuted femoral nerve block (FNB) or continuted adductor canal block (ACB) on pain and motor function after total knee arthroplasty (TKA). Methods: A total of 60 patients with TKA-treated osteoarthritis of the knee who met the selection criteria were enrolled between November 2020 and February 2021 and randomised allocated into the study group (SNB combined with continuted ACB) and the control group (SNB combined with continuted FNB), with 30 cases in each group. There was no significant difference in gender, age, body mass, height, body mass index, preoperative Hospital for Special Surgery (HSS) score, femoral tibial angle, and medial proximal tibial angle between the two groups ( P>0.05). The operation time, the initial time to the ground, the initial walking distance, and the postoperative hospital stay were recorded. At 2, 4, 6, 12, 24, and 48 hours after operation, the numerical rating scale (NRS) score was used to evaluate the rest pain around the knee joint, the quadriceps femoris muscle strength was evaluated by the freehand muscle strength method, and the knee flexion and extension angles were measured. Results: There was no significant difference in the operation time and initial walking distance between the two groups ( P>0.05); the initial time to the ground and postoperative hospital stay of the study group were significantly shorter than those of the control group ( P<0.05). Except for the 48-hour postoperative NRS score of the study group, which was significantly lower than that of the control group ( P<0.05), there was no significant difference in the NRS scores between the two groups at the remaining time points ( P>0.05). The quadriceps femoris muscle strength from 4 to 24 hours postoperatively and the knee extension angle from 2 to 6 hours postoperatively of the study group were significantly better than those of the control group ( P<0.05); the differences in the quadriceps femoris muscle strength and knee extension and flexion angles between the two groups at the remaining time points were not significant ( P>0.05). Conclusion: SNB combined with either continuted ACB or continuted FNB can effectively relieve pain in patients after TKA, and compared with combined continuted FNB, combined continuted ACB has less effect on quadriceps femoris muscle strength, and patients have better recovery of knee flexion and extension mobility.


Assuntos
Artroplastia do Joelho , Nervo Femoral , Bloqueio Nervoso , Dor Pós-Operatória , Nervo Isquiático , Humanos , Artroplastia do Joelho/métodos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Osteoartrite do Joelho/cirurgia , Feminino , Masculino , Medição da Dor , Duração da Cirurgia , Idoso , Tempo de Internação
6.
World J Clin Cases ; 12(13): 2254-2262, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38808345

RESUMO

BACKGROUND: Gastric bronchogenic cysts (BCs) are extremely rare cystic masses caused by abnormal development of the respiratory system during the embryonic period. Gastric bronchial cysts are rare lesions that were first reported in 1956; as of 2023, only 33 cases are available in the PubMed online database. BCs usually have no clinical symptoms in the early stage, and imaging findings also lack specificity. Therefore, they are difficult to diagnose before histopathological examination. CASE SUMMARY: A 34-year-old woman with respiratory distress presented at our hospital. Endoscopic ultrasound revealed an anechoic mass between the spleen, left kidney and gastric fundus, with hyperechogenic and soft elastography textures and with a size of approximately 6.5 cm × 4.0 cm. Furthermore, a computed tomography scan demonstrated high density between the posterior stomach and the spleen and the left kidney, with uniform internal density and a small amount of calcification. The maximum cross section was approximately 10.1 cm × 6.1 cm, and the possibility of a cyst was high. Because the imaging findings did not suggest a malignancy and because the patient required complete resection, she underwent laparotomy surgery. Intraoperatively, this cystic lesion was found to be located in the posterior wall of the large curvature of the fundus and was approximately 8 cm × 6 cm in size. Finally, the pathologists verified that the cyst in the fundus was a gastric BC. The patient recovered well, her symptoms of chest tightness disappeared, and the abdominal drain was removed on postoperative day 6, after which she was discharged on day 7 for 6 months of follow-up. She had no tumor recurrence or postoperative complications during the follow-up. CONCLUSION: This is a valuable report as it describes an extremely rare case of gastric BC. Moreover, this was a very young patient with a large BC in the stomach.

7.
Plant Commun ; : 100942, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38720463

RESUMO

Feralization is an important evolutionary process, but the mechanisms behind it remain poorly understood. Here, we use the ancient fiber crop, ramie (Boehmeria nivea (L.) Gaudich.) as a model to investigate genomic changes associated with both domestication and fertilization. We first produced a chromosome-scale de novo genome assembly of feral ramie and investigated structural variations between feral and domesticated ramie genomes. Next, 915 accessions from 20 countries were gathered, comprising cultivars, major landraces, feral populations and wild progenitor. Based on whole genome resequencing of these accessions, the most comprehensive ramie genomic variation map to date was constructed. Phylogenetic, demographic, and admixture signal detection analyses indicate that feral ramie is of exoferal or exo-endo origin, i.e., descended from hybridization between domesticated ramie and wild progenitor or ancient landraces. Feral ramie has greater genetic diversity than wild or domesticated ramie, and genomic regions affected by natural selection during feralization are different from those under selection during domestication. Ecological analyses showed that feral and domesticated ramie have similar ecological niches which are substantially different from the niche of the wild progenitor, and three environmental variables were associated with habitat-specific adaptation in feral ramie. Our findings advance our understanding of feralization, providing a scientific basis for the excavation of new crop germplasm resources and offering novel insights into the evolution of feralization in nature.

8.
Mol Neurobiol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780721

RESUMO

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1ß, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke.

9.
Plant Physiol Biochem ; 211: 108726, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744083

RESUMO

Tea is one of the most prevalent non-alcoholic beverages. The leaves of tea plants hyperaccumulate anthocyanins under cold stress, resulting in enhanced bitterness. Previously, we determined that the RING-type E3 ubiquitin ligase CsMIEL1 from the tea plant (Camellia sinensis (L.) O. Kuntze) is involved in the response to stress conditions. This study aimed to determine the role of CsMIEL1 in anthocyanin accumulation at the post-translational modification level. The results showed that the heterologous expression of CsMIEL1 led to an 86% decrease in anthocyanin levels, resulting in a significant decrease in the mRNA levels of related genes in Arabidopsis at low temperatures but no significant differences in other phenotypes. Furthermore, multi-omics analysis and yeast two-hybrid library screening were performed to identify potential downstream targets of CsMIEL1. The results showed that the overexpression of CsMIEL1 resulted in 45% (448) of proteins being differentially expressed, of which 8% (36) were downregulated in A.thaliana, and most of these differentially expressed proteins (DEPs) were clustered in the plant growth and secondary metabolic pathways. Among the 71 potential targets that may interact with CsMIEL1, CsMYB90 and CsGSTa, which are related to anthocyanin accumulation, were selected. In subsequent analyses, these two proteins were verified to interact with CsMIEL1 via yeast two-hybrid (Y2H) and pull-down analyses in vitro. In summary, we explored the potential mechanism by which the E3 ligase relieves anthocyanin hyperaccumulation at low temperatures in tea plants. These results provide a new perspective on the mechanisms of anthocyanin regulation and the molecular breeding of tea plants.


Assuntos
Antocianinas , Camellia sinensis , Temperatura Baixa , Proteínas de Plantas , Antocianinas/metabolismo , Camellia sinensis/metabolismo , Camellia sinensis/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Arabidopsis/genética , Arabidopsis/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Plantas Geneticamente Modificadas/metabolismo
10.
J Med Chem ; 67(9): 7504-7515, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38640354

RESUMO

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives (2-19). Among them, BTL-MK (19) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, Cmax and area under the concentration-time curve (AUC0-∞) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.


Assuntos
4-Butirolactona , Antialérgicos , Animais , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , 4-Butirolactona/química , 4-Butirolactona/farmacocinética , 4-Butirolactona/administração & dosagem , Administração Oral , Ratos , Humanos , Antialérgicos/farmacocinética , Antialérgicos/farmacologia , Antialérgicos/química , Antialérgicos/administração & dosagem , Relação Estrutura-Atividade , Masculino , Ratos Sprague-Dawley , Disponibilidade Biológica , Hipersensibilidade Alimentar/tratamento farmacológico , Camundongos
11.
J Ethnopharmacol ; 328: 118116, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548118

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochic acids (AAs) are naturally occurring nitro phenanthrene carboxylic acids primarily found in plants of the Aristolochiaceae family. Aristolochic acid D (AAD) is a major constituent in the roots and rhizomes of the Chinese herb Xixin (the roots and rhizomes of Asarum heterotropoides F. Schmidt), which is a key material for preparing a suite of marketed Chinese medicines. Structurally, AAD is nearly identical to the nephrotoxic aristolochic acid I (AAI), with an additional phenolic group at the C-6 site. Although the nephrotoxicity and metabolic pathways of AAI have been well-investigated, the metabolic pathway(s) of AAD in humans and the influence of AAD metabolism on its nephrotoxicity has not been investigated yet. AIM OF THE STUDY: To identify the major metabolites of AAD in human tissues and to characterize AAD O-glucuronidation kinetics in different enzyme sources, as well as to explore the influence of AAD O-glucuronidation on its nephrotoxicity. MATERIALS AND METHODS: The O-glucuronide of AAD was biosynthesized and its chemical structure was fully characterized by both 1H-NMR and 13C-NMR. Reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses were conducted to assess the crucial enzymes involved in AAD O-glucuronidation in humans. Docking simulations were performed to mimic the catalytic conformations of AAD in human UDP-glucuronosyltransferases (UGTs), while the predicted binding energies and distances between the deprotonated C-6 phenolic group of AAD and the glucuronyl moiety of UDPGA in each tested human UGT isoenzyme were measured. The mitochondrial membrane potentials (MMP) and reactive oxygen species (ROS) levels in HK-2 cells treated with either AAI, or AAD, or AAD O-glucuronide were tested, to elucidate the impact of O-glucuronidation on the nephrotoxicity of AAD. RESULTS: AAD could be rapidly metabolized in human liver and intestinal microsomes (HLM and HIM, respectively) to form a mono-glucuronide, which was purified and fully characterized as AAD-6-O-ß-D-glucuronide (AADG) by NMR. UGT1A1 was the predominant enzyme responsible for AAD-6-O-glucuronidation, while UGT1A9 contributed to a lesser extent. AAD-6-O-glucuronidation in HLM, HIM, UGT1A1 and UGT1A9 followed Michaelis-Menten kinetics, with the Km values of 4.27 µM, 9.05 µM, 3.87 µM, and 7.00 µM, respectively. Docking simulations suggested that AAD was accessible to the catalytic cavity of UGT1A1 or UGT1A9 and formed catalytic conformations. Further investigations showed that both AAI and AAD could trigger the elevated intracellular ROS levels and induce mitochondrial dysfunction and in HK-2 cells, but AADG was hardly to trigger ROS accumulation and mitochondrial dysfunction. CONCLUSION: Collectively, UGT1A-catalyzed AAD 6-O-glucuronidation represents a crucial detoxification pathway of this naturally occurring AAI analogs in humans, which is very different from that of AAI.


Assuntos
Ácidos Aristolóquicos , Doenças Mitocondriais , Humanos , Ácidos Aristolóquicos/toxicidade , Glucuronídeos/metabolismo , Microssomos Hepáticos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Glucuronosiltransferase/metabolismo , Cinética , Catálise , Difosfato de Uridina/metabolismo
12.
Int J Biol Macromol ; 267(Pt 1): 131150, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38556236

RESUMO

Gut microbial ß-glucuronidases (gmß-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmß-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmß-GUS enzymes. Subsequently, the anti-gmß-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmß-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmß-GUS in a non-competitive manner, with the Ki values ranging from 0.12 µM to 1.29 µM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmß-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmß-GUS activity in mice feces, with the IC50 value of 1.24 µM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmß-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmß-GUS associated enterotoxicity.


Assuntos
Inibidores Enzimáticos , Microbioma Gastrointestinal , Simulação de Acoplamento Molecular , Rhodiola , Rhodiola/química , Animais , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Medicina Tradicional Tibetana , Cinética , Masculino
13.
Molecules ; 29(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543028

RESUMO

The burgeoning demand for miniaturized energy storage devices compatible with the miniaturization trend of electronic technologies necessitates advancements in micro-supercapacitors (MSCs) that promise safety, cost efficiency, and high-speed charging capabilities. However, conventional aqueous MSCs face a significant limitation due to their inherently narrow electrochemical potential window, which restricts their operational voltage and energy density compared to their organic and ionic liquid counterparts. In this study, we introduce an innovative aqueous NaCl/H2O/EG hybrid gel electrolyte (comprising common salt (NaCl), H2O, ethylene glycol (EG), and SiO2) for Ti3C2Tx MXene MSCs that substantially widens the voltage window to 1.6 V, a notable improvement over traditional aqueous system. By integrating the hybrid electrolyte with 3D-printed MXene electrodes, we realized MSCs with remarkable areal capacitance (1.51 F cm-2) and energy density (675 µWh cm-2), significantly surpassing existing benchmarks for aqueous MSCs. The strategic formulation of the hybrid electrolyte-a low-concentration NaCl solution with EG-ensures both economic and environmental viability while enabling enhanced electrochemical performance. Furthermore, the MSCs fabricated via 3D printing technology exhibit exceptional flexibility and are suitable for modular device integration, offering a promising avenue for the development of high-performance, sustainable energy storage devices. This advancement not only provides a tangible solution to the challenge of limited voltage windows in aqueous MXene MSCs but also sets a new precedent for the design of next-generation MSCs that align with the needs of an increasingly microdevice-centric world.

14.
In Vitro Cell Dev Biol Anim ; 60(3): 287-299, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38485818

RESUMO

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1ß-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1ß, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1ß to simulate IVDD environment and divided into the control group, IL-1ß group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway-related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1ß, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1ß-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1ß-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.


Assuntos
Ginsenosídeos , Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Animais , Ratos , Agrecanas/genética , Apoptose , Colágeno/farmacologia , Inflamação/patologia , Interleucina-6/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Metaloproteinase 3 da Matriz/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
15.
World J Gastrointest Oncol ; 16(2): 300-313, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425402

RESUMO

MicroRNAs (miRNAs) have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells (CSCs). The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells (GCSCs). Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs. This review summarizes the coding process and biological functions of miRNAs and demonstrates their role and efficacy in gastric cancer (GC) metastasis, drug resistance, and apoptosis, especially in the regulatory mechanism of GCSCs. It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis, apart from the initial formation of GC. It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC. We believe that this review may help in designing novel therapeutic approaches for GC.

16.
J Acoust Soc Am ; 155(2): 854-866, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38310609

RESUMO

This paper proposes a high-performance receiver for underwater acoustic communications based on time reversal processing for multiple-input multiple-output (MIMO) systems. The receiver employs the vector approximate message passing (VAMP) algorithm as a soft equalizer in turbo equalization. By performing self-iteration between the inner soft slicer and the inner soft equalizer, the VAMP algorithm achieves near-optimal performance. Furthermore, an iterative channel-estimation-based soft successive interference cancellation method is incorporated to suppress co-channel interference in the MIMO system. Additionally, the introduction of passive time reversal technology can combine multiple channels into a single channel, which greatly reduces the computational complexity of the MIMO system, especially for large MIMO systems. The effectiveness of the proposed receiver is verified using experimental data collected in Songhua Lake, China in 2019. The results demonstrate that the proposed receiver significantly reduces the complexity of the traditional parallel-VAMP receiver without sacrificing performance and outperforms other receivers of the same type. Moreover, our experimental results also verify that the VAMP-turbo outperforms the generalized approximate message passing (GAMP)-turbo in terms of bit error rate and convergence performance.

17.
Dalton Trans ; 53(15): 6583-6591, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38353272

RESUMO

Recently, it has been reported that MXene is a promising pseudocapacitive material for energy storage, primarily due to its intercalation mechanism. However, Ti3C2Tx MXenes face challenges, such as inadequate layer spacing and low specific capacity, which greatly hinder their potential as anode materials for sodium storage. In this study, MXene was doped with sulfur to create a three-dimensional porous structure that resulted in an increased layer spacing. The sulfur-doped porous MXene (SPM) demonstrated exceptional performance as sodium ion battery anodes, with a capacity of 335.2 mA h g-1 after 490 cycles at 2 A g-1 and a long-term cycling performance of 256.1 mA h g-1 even after 2480 cycles at 5 A g-1. It is worth noting that the porous structure formed after sulfur-doping exhibits superior sodium storage performance compared to previously reported MXene-based electrodes. This highlights the feasibility of the structural construction strategy, offering an effective solution for energy storage and conversion applications.

18.
Chem Commun (Camb) ; 60(22): 3067-3070, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38386357

RESUMO

MnO2-Mn3O4 heterostructure materials are applied in aqueous magnesium ion energy storage for the first time. The heterostructure yields an exceptionally high pseudocapacitance contribution, resulting in a specific capacitance of 313.5 F g-1 at 1 A g-1, which contrasts with that of MnO2 (108.8 F g-1) and Mn3O4 (123.5 F g-1). Additionally, it shows potential for practical applications as a cathode for magnesium ion hybrid supercapacitors (MHS).

19.
Int J Biol Macromol ; 260(Pt 1): 129487, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237821

RESUMO

Guanine (G)-rich nucleic acid sequences can form diverse G-quadruplex structures located in functionally significant genome regions, exerting regulatory control over essential biological processes, including DNA replication in vivo. During the initiation of DNA replication, Cdc6 is recruited by the origin recognition complex (ORC) to target specific chromosomal DNA sequences. This study reveals that human Cdc6 interacts with G-quadruplex structure through a distinct region within the N-terminal intrinsically disordered region (IDR), encompassing residues 7-20. The binding region assumes a hook-type conformation, as elucidated by the NMR solution structure in complex with htel21T18. Significantly, mutagenesis and in vivo investigations confirm the highly specific nature of Cdc6's recognition of G-quadruplex. This research enhances our understanding of the fundamental mechanism governing the interaction between G-quadruplex and the N-terminal IDR region of Cdc6, shedding light on the intricate regulation of DNA replication processes.


Assuntos
DNA , Quadruplex G , Humanos , DNA/química , Replicação do DNA , Complexo de Reconhecimento de Origem/química , Complexo de Reconhecimento de Origem/genética , Complexo de Reconhecimento de Origem/metabolismo , Sequência de Bases
20.
Waste Manag ; 176: 74-84, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266477

RESUMO

Aeration plays a crucial role in accelerating the secondary compression of municipal solid waste (MSW) for the scientific implementation of aerobic bioreactor technology. There are few comparative reports on the secondary compaction characteristics of MSW in aerobic and anaerobic bioreactors. In this study, six long-term compression tests were conducted to analyze the impact of aeration on MSW compression characteristics, considering two degradation conditions (i.e. aerobic and anaerobic conditions) and three overburden stresses (i.e. 30, 50 and 100 kPa). Model-fitting analysis was employed to examine the data from the tests and exiting literatures. The results showed that aeration effectively increased the rate of secondary compression, and slightly enhanced the steady-state secondary compression strain. In addition, these enhancements tended to decrease with increasing stresses. The increment ratio of the secondary compression rate constant (Rk) was concentrated in the range of 25 % to 100 %, and increases with the increase of aeration rate. The increment ratio of the steady-state secondary compression strain (Rε) ranged from 10 % to 90 %, for the MSW with higher content of paper and wood exhibited higher Rε. The advance ratio of the secondary compression stabilization time (Rt) fell within the range of 20-50 %, and Rt is higher when the moisture content is in the range of 50-65 %. These findings provide valuable guidance on the accelerated stabilization in aerobic bioreactors, providing practical references for the application of aerobic technology to informal landfills.


Assuntos
Eliminação de Resíduos , Resíduos Sólidos , Resíduos Sólidos/análise , Eliminação de Resíduos/métodos , Anaerobiose , Reatores Biológicos , Instalações de Eliminação de Resíduos
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