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1.
J Cancer Res Clin Oncol ; 150(7): 337, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971938

RESUMO

BACKGROUND: Nasopharyngeal amyloidoma is a rare, locally aggressive tumor that has been reported in the English literature in only 38 cases to date, most of which were in the form of case reports. The present study was aimed to summarize the characteristics of this rare tumor, with the goal of providing new insights for diagnosis and treatment. MATERIALS AND METHODS: We report three cases of nasopharyngeal amyloidoma diagnosed in our hospital following comprehensive medical examination and review the current literature on all cases of nasopharyngeal amyloidoma from PubMed. The journey of nasopharyngeal amyloidoma, including presentation, diagnostics, surgeries, and follow-up was outlined. RESULTS: None of the three patients had systemic amyloidosis. CT and nasal endoscopy showed irregular masses obstructing the nasopharyngeal cavity. Congo red staining confirmed the deposition of amyloid, and immunohistochemical analysis showed that the amyloid deposition was the AL light chain type. Through literature review, we found that nasopharyngeal amyloidoma most commonly occurred in individuals over the age of 40, patients usually had a good prognosis after complete tumor resection; however, there were still cases of recurrence, and unresected patients were at risk of progression to systemic amyloidosis. The efficacy of radiotherapy and chemotherapy was currently uncertain. CONCLUSION: Early clinical and pathological diagnosis is crucial, and surgical intervention is the primary treatment option for this disease. Although patients usually have a favorable prognosis, long-term monitoring is necessary to detect potential relapses and initiate timely intervention.


Assuntos
Amiloidose , Neoplasias Nasofaríngeas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Amiloidose/patologia , Amiloidose/diagnóstico , Amiloidose/metabolismo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/cirurgia , Adulto , Doenças Nasofaríngeas/patologia , Doenças Nasofaríngeas/diagnóstico , Doenças Nasofaríngeas/metabolismo , Doenças Nasofaríngeas/cirurgia
2.
Biodivers Data J ; 12: e127089, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974675

RESUMO

Background: Two species of Neoperla from Guizhou Province, China, N.bituberculata Du, 2000 and N.dashahena Du, 2005 were described with brief morphological descriptions available only in Chinese and original illustrations being somewhat blurry. Recently, we examined type material of these two species and re-described them with clear colour pictures for the first time. New information: In this paper, detailed English descriptions and colour pictures of Neoperlabituberculata and N.dashahena are provided for the first time. The type locality of N.mnong Stark is from Vietnam and its geographical distribution is also discussed. Additionally, we also recorded the distribution of N.mnong Stark, 1987 in Guizhou, Hunan and Jiangxi Provinces of China for the first time and provided a geographical distribution map of this species.

3.
Infect Genet Evol ; 123: 105634, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950667

RESUMO

BACKGROUND: Aedes albopictus is an important vector of chikungunya, dengue, yellow fever and Zika viruses. Insecticides are often the most effective tools for rapidly decreasing the density of vector populations, especially during arbovirus disease outbreaks. However, the intense use of insecticides, particularly pyrethroids, has led to the selection of resistant mosquito populations worldwide. Mutations in the voltage-gated sodium channel (VGSC) gene are one of the main drivers of insecticide resistance in Ae. albopictus and are also known as "knockdown resistance" (kdr) mutations. Knowledge about genetic mutations associated with insecticide resistance is a prerequisite for developing techniques for rapid resistance diagnosis. Here, we report studies on the origin and dispersion of kdr haplotypes in samples of Ae. albopictus from the Yangtze River Basin, China; METHODS: Here, we report the results of PCR genotyping of kdr mutations in 541 Ae. albopictus specimens from 22 sampling sites in 7 provinces and municipalities in the Yangtze River Basin. Partial DNA sequences of domain II and domain III of the VGSC gene were amplified. These DNA fragments were subsequently sequenced to discover the possible genetic mutations mediating knockdown resistance (kdr) to pyrethroids. The frequency and distribution of kdr mutations were assessed in 22 Ae. albopictus populations. Phylogenetic relationships among the haplotypes were used to infer whether the kdr mutations had a single or multiple origins; RESULTS: The kdr mutation at the 1016 locus had 2 alleles with 3 genotypes: V/V (73.38%), V/G (26.43%) and G/G (0.18%). The 1016G homozygous mutation was found in only one case in the CQSL strain in Chongqing, and no 1016G mutations were detected in the SHJD (Shanghai), NJDX (Jiangsu) or HBQN (Hubei) strains. A total of 1532 locus had two alleles and three genotypes, I/I (88.35%), I/T (8.50%) and T/T (3.14%). A total of 1534 locus had four alleles and six genotypes: F/F (49.35%), F/S (19.96%), F/C (1.48%) and F/L (0.18%); S/S (23.66%); and C/C (5.36%). Haplotypes with the F1534C mutation were found only in Ae. albopictus populations in Chongqing and Hubei, and C1534C was found only in three geographic strains in Chongqing. Haplotypes with the 1534S mutation were found only in Ae. albopictus populations in Sichuan and Shanghai. F1534L was found only in HBYC. The Ae. albopictus populations in Shanghai were more genetically differentiated from those in the other regions (except Sichuan), and the genetic differentiation between the populations in Chongqing and those in the middle-lower reaches of the Yangtze River (Huber, Jiangsu, Jiangxi, and Anhui) was lower. Shanghai and Sichuan displayed low haplotype diversity and low nucleotide diversity. Phylogenetic analysis and sequence comparison revealed that the 1016 locus was divided into three branches, with the Clade A and Clade B branches bearing the 1016 mutation occurring mostly in Jiangsu and the Clade C branch bearing the 1016 mutation occurring mostly in Chongqing, suggesting at least two origins for 1016G. IIIS6 phylogenetic analysis and sequence comparison revealed that F1534S, F1534C and I1532T can be divided into two branches, indicating that IIIS6 has two origins; CONCLUSIONS: Combined with the distribution of kdr mutations and the analysis of population genetics, we infer that besides the local selection of pyrethroid resistance mutations, dispersal and colonization of Ae. albopictus from other regions may explain why kdr mutations are present in some Ae. albopictus populations in the Yangtze River Basin.

4.
J Agric Food Chem ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951118

RESUMO

Enzymatic oxygenation of various cyclic ketones into lactones via Baeyer-Villiger monooxygenases (BVMOs) could provide a promising route for synthesizing fragrances and pharmaceutical ingredients. However, unsatisfactory catalytic activity and thermostability restricted their applications in the pharmaceutical and food industries. In this study, we successfully improved the catalytic activity and thermostability of a Baeyer-Villiger monooxygenase (OgBVMO) from Oceanicola granulosus by reshaping the binding pocket. As a result, mutant OgBVMO-Re displayed a 1.0- to 6.4-fold increase in the activity toward branched cyclic ketones tested, accompanied by a 3 °C higher melting point, and a 2-fold longer half-life time (t1/2 (45 °C)). Molecular dynamics simulations revealed that reshaping the binding pocket achieved strengthened motion correlation between amino acid residues, appropriate size of the substrate-binding pocket, beneficial surface characteristics, lower energy barriers, and shorter nucleophilic distance. This study well demonstrated the trade-off between the enzyme activity and thermostability by reshaping the substrate-binding pocket, paving the way for further engineering other enzymes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38968001

RESUMO

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38967075

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) patients often benefit from EGFR inhibitors like gefitinib. However, drug resistance remains a significant challenge in treatment. The unique properties of 1,2,3-triazole, a nitrogen-based compound, hold promise as potential solutions due to its versatile structural attributes and diverse biological effects, including anticancer properties. MATERIALS AND METHODS: Our synthesis process involved the huisgen cycloaddition chemical method, which generated diverse icotinib derivatives. We evaluated the anticancer capabilities of these derivatives against various cancer cell lines, with a specific focus on NSCLC cells that exhibit drug resistance. Additionally, we investigated the binding affinity of selected compounds, including 3l, towards wild-type EGFR using surface plasmon resonance (SPR) experiments. RESULTS: Notably, icotinib derivatives such as derivative 3l demonstrated significant efficacy against different cancer cell lines, including those resistant to conventional therapies. Compound 3l exhibited potent activity with IC50 values below 10 µM against drug-resistant cells. SPR experiments revealed that 3l exhibited enhanced affinity towards wild-type EGFR compared to icotinib. Our research findings suggest that 3l acts as a compelling antagonist for the protein tyrosine kinase of EGFR (EGFR-PTK). CONCLUSION: Icotinib derivative 3l, featuring a 1,2,3-triazole ring, demonstrates potent anticancer effects against drug-resistant NSCLC cells. Its enhanced binding affinity to EGFR and modulation of the EGFR-RAS-RAF-MAPK pathway position 3l as a promising candidate for the future development of anticancer drugs.

7.
EJNMMI Phys ; 11(1): 60, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985382

RESUMO

PURPOSE: 123I-Ioflupane SPECT is an effective tool for the diagnosis and progression assessment of Parkinson's disease (PD). Radiomics and deep learning (DL) can be used to track and analyze the underlying image texture and features to predict the Hoehn-Yahr stages (HYS) of PD. In this study, we aim to predict HYS at year 0 and year 4 after the first diagnosis with combined imaging, radiomics and DL-based features using 123I-Ioflupane SPECT images at year 0. METHODS: In this study, 161 subjects from the Parkinson's Progressive Marker Initiative database underwent baseline 3T MRI and 123I-Ioflupane SPECT, with HYS assessment at years 0 and 4 after first diagnosis. Conventional imaging features (IF) and radiomic features (RaF) for striatum uptakes were extracted from SPECT images using MRI- and SPECT-based (SPECT-V and SPECT-T) segmentations respectively. A 2D DenseNet was used to predict HYS of PD, and simultaneously generate deep features (DF). The random forest algorithm was applied to develop models based on DF, RaF, IF and combined features to predict HYS (stage 0, 1 and 2) at year 0 and (stage 0, 1 and ≥ 2) at year 4, respectively. Model predictive accuracy and receiver operating characteristic (ROC) analysis were assessed for various prediction models. RESULTS: For the diagnostic accuracy at year 0, DL (0.696) outperformed most models, except DF + IF in SPECT-V (0.704), significantly superior based on paired t-test. For year 4, accuracy of DF + RaF model in MRI-based method is the highest (0.835), significantly better than DF + IF, IF + RaF, RaF and IF models. And DL (0.820) surpassed models in both SPECT-based methods. The area under the ROC curve (AUC) highlighted DF + RaF model (0.854) in MRI-based method at year 0 and DF + RaF model (0.869) in SPECT-T method at year 4, outperforming DL models, respectively. And then, there was no significant differences between SPECT-based and MRI-based segmentation methods except for the imaging feature models. CONCLUSION: The combination of radiomic and deep features enhances the prediction accuracy of PD HYS compared to only radiomics or DL. This suggests the potential for further advancements in predictive model performance for PD HYS at year 0 and year 4 after first diagnosis using 123I-Ioflupane SPECT images at year 0, thereby facilitating early diagnosis and treatment for PD patients. No significant difference was observed in radiomics results obtained between MRI- and SPECT-based striatum segmentations for radiomic and deep features.

8.
Phytomedicine ; 132: 155658, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38981149

RESUMO

BACKGROUND: Alcohol-related liver damage is the most prevalent chronic liver disease, which creates a heavy public health burden worldwide. The leaves of Ampelopsis grossedentata have been considered a popular tea and traditional herbal medicine in China for more than one thousand years, and possess anti-inflammatory, antioxidative, hepatoprotective, and antiviral activities. PURPOSE: We explored the protective effects of Ampelopsis grossedentata extract (AGE) against chronic alcohol-induced hepatic injury (alcoholic liver disease, ALD), aiming to elucidate its underlying mechanisms. METHODS: Firstly, UPLC-Q/TOF-MS analysis and network pharmacology were used to identify the constituents and elucidate the potential mechanisms of AGE against ALD. Secondly, C57BL/6 mice were pair-fed the Lieber-DeCarli diet containing either isocaloric maltodextrin or ethanol, AGE (150 and 300 mg/kg/d) and silymarin (200 mg/kg) were administered to chronic ethanol-fed mice for 7 weeks to evaluate the hepatoprotective effects. Serum biochemical parameters were determined, hepatic and ileum sections were used for histologic examination, and levels of inflammatory cytokines and oxidative stress in the liver were examined. The potential molecular mechanisms of AGE in improving ALD were demonstrated by RNA-seq, Western blotting analysis, and immunofluorescence staining. RESULTS: Ten main constituents of AGE were identified using UPLC-Q/TOF-MS and 274 potential ALD-related targets were identified. The enriched KEGG pathways included Toll-like receptor signaling pathway, NF-κB signaling pathway, and necroptosis. Moreover, in vivo experimental studies demonstrated that AGE significantly reduced serum aminotransferase levels and improved pathological abnormalities after chronic ethanol intake. Meanwhile, AGE improved ALD in mice by down-regulating oxidative stress and inflammatory cytokines. Furthermore, AGE notably repaired damaged intestinal epithelial barrier and suppressed the production of gut-derived lipopolysaccharide by elevating intestinal tight junction protein expression. Subsequent RNA-seq and experimental validation indicated that AGE inhibited NF-κB nuclear translocation, suppressed IκB-α, RIPK3 and MLKL phosphorylation and alleviated hepatic necroptosis in mice. CONCLUSION: In this study, we have demonstrated for the first time that AGE protects against alcoholic liver disease by regulating the gut-liver axis and inhibiting the TLR4/NF-κB/MLKL-mediated necroptosis pathway. Therefore, our present work provides important experimental evidence for AGE as a promising candidate for protection against ALD.

9.
Nat Med ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858523

RESUMO

Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively. The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF. Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo. The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo). At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants. LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism. The ClinicalTrials.gov registration is NCT04881760 .

10.
Poult Sci ; 103(8): 103864, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38838590

RESUMO

The earlobe is a featherless, exposed thickening located beneath the ear canal of chickens, which plays a visual signaling role in age, performance, mental vitality, reproduction, and other aspects. However, despite its importance, there have been few studies on the color differences and formation mechanisms of chicken earlobes, particularly the structurally blue earlobes characteristic of the Jiangshan black-bone chicken. In this study, we explored the physiological mechanisms that may influence the formation of differently colored earlobes using 3 types of earlobes from Jiangshan black-bone chickens: light peacock green (Green group), dark peacock green (Blue group), and dark reddish purple (Black group). All 3 earlobe colors exhibited positive melanin Masson-Fontana staining, and the thickness of collagen fibers in the dermis decreased in the order of Green, Blue, and Black groups. A total of 1,953 differentially expressed genes (DEGs) were detected in the 3 earlobes through mRNA sequencing, among which the GO term "collagen trimer" was significantly enriched in DEGs between groups. Additionally, 716 differentially expressed proteins (DEPs) were identified in the 3 earlobes using 4D-DIA proteomics, with the term "collagen fibril organization" being significantly enriched in DEPs between the Green and Black groups. Integrated analysis of transcriptome and proteome data revealed that 12 DEGs and DEPs were commonly differentially expressed between the Green and Black groups, including the gene LUM (corneal keratan sulfate proteoglycan), which was significantly enriched in the "collagen fibril organization" GO term. In conclusion, our study suggests that LUM plays a crucial role in the formation of peacock green earlobes in Jiangshan black-bone chickens. The high level of LUM in peacock green (Green and Blue groups) may affect collagen nanostructures, leading to a stronger effect of melanin-supported dermal collagen on the production of non-iridescent structural colors through coherent scattering, resulting in a bright structural blue color in Jiangshan black-bone chickens. In contrast, the low expression of LUM in dark reddish purple (Black group) reduces the reflection of non-iridescent structural colors, making the earlobe color appear almost black, similar to melanin.

11.
PLoS Pathog ; 20(6): e1012318, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38865374

RESUMO

Many plant arboviruses are persistently transmitted by piercing-sucking insect vectors. However, it remains largely unknown how conserved insect Toll immune response exerts antiviral activity and how plant viruses antagonize it to facilitate persistent viral transmission. Here, we discover that southern rice black-streaked dwarf virus (SRBSDV), a devastating planthopper-transmitted rice reovirus, activates the upstream Toll receptors expression but suppresses the downstream MyD88-Dorsal-defensin cascade, resulting in the attenuation of insect Toll immune response. Toll pathway-induced the small antibacterial peptide defensin directly interacts with viral major outer capsid protein P10 and thus binds to viral particles, finally blocking effective viral infection in planthopper vector. Furthermore, viral tubular protein P7-1 directly interacts with and promotes RING E3 ubiquitin ligase-mediated ubiquitinated degradation of Toll pathway adaptor protein MyD88 through the 26 proteasome pathway, finally suppressing antiviral defensin production. This virus-mediated attenuation of Toll antiviral immune response to express antiviral defensin ensures persistent virus infection without causing evident fitness costs for the insects. E3 ubiquitin ligase also is directly involved in the assembly of virus-induced tubules constructed by P7-1 to facilitate viral spread in planthopper vector, thereby acting as a pro-viral factor. Together, we uncover a previously unknown mechanism used by plant arboviruses to suppress Toll immune response through the ubiquitinated degradation of the conserved adaptor protein MyD88, thereby facilitating the coexistence of arboviruses with their vectors in nature.


Assuntos
Arbovírus , Insetos Vetores , Transdução de Sinais , Receptores Toll-Like , Animais , Arbovírus/imunologia , Receptores Toll-Like/metabolismo , Insetos Vetores/virologia , Insetos Vetores/imunologia , Doenças das Plantas/virologia , Doenças das Plantas/imunologia , Reoviridae/fisiologia , Reoviridae/imunologia , Hemípteros/virologia , Hemípteros/imunologia , Oryza/virologia , Oryza/imunologia , Proteínas de Insetos/metabolismo , Imunidade Inata
12.
Heliyon ; 10(11): e32498, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912473

RESUMO

Dental follicle cells (DFCs) promote bone regeneration in vivo and in vitro. Circular RNAs (circRNAs) play crucial roles in bone development and regeneration. Our previous study demonstrated the upregulation of circFgfr2 expression during the osteogenic differentiation of DFCs. However, the molecular mechanisms and functional roles of circFgfr2 in DFCs osteogenesis remain unclear. In this study, we aimed to investigate the subcellular localization of circFgfr2 in DFCs using fluorescence in situ hybridization. In vitro investigations demonstrated that circFgfr2 overexpression promoted osteogenic differentiation, as evidenced by real-time quantitative polymerase chain reaction. By integrating the outcomes of bioinformatics analyses, dual luciferase reporter experiments, and chromatin isolation by RNA purification, we identified circFgfr2 as a sponge for miR-133a-3p, a key regulator of osteogenic differentiation. Moreover, miR-133a-3p suppressed osteogenic differentiation by targeting DLX3 and RUNX2 in DFCs. We validated that circFgfr2 promoted the osteogenic differentiation of DFCs through the miR-133a-3p/DLX3 axis. To further investigate the therapeutic potential of circFgfr2 in bone regeneration, we conducted in vivo experiments and histological analyses. Overall, these results confirmed the crucial role of circFgfr2 in promoting osteogenesis. In summary, our findings demonstrated that the circFgfr2/miR-133a-3p/DLX3 pathway acts as a cascade, thereby identifying circFgfr2 as a promising molecular target for bone tissue engineering.

13.
Fish Shellfish Immunol ; 151: 109724, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942251

RESUMO

Takifugu rubripes is a highly valued cultured fish in Asia, while pathogen infections can result in severe diseases and lead to substantial economic losses. Toll-like receptors (TLRs), as pattern recognition receptors, play a crucial role on recognition pathogens and initiation innate immune response. However, the immunological properties of teleost-specific TLR23 remain largely unknown. In this study, we investigated the biological functions of TLR23 (TrTLR23) from T. rubripes, found that TrTLR23 existed in various organs. Following bacterial pathogen challenge, the expression levels of TrTLR23 were significantly increased in immune related organs. TrTLR23 located on the cellular membrane and specifically recognized pathogenic microorganism. Co-immunoprecipitation and antibody blocking analysis revealed that TrTLR23 recruited myeloid differentiation primary response protein (MyD88), thereby mediating the activation of the ERK signaling pathway. Furthermore, in vivo showed that, when TrTLR23 is overexpressed in T. rubripes, bacterial replication in fish tissues is significantly inhibited. Consistently, when TrTLR23 expression in T. rubripes is knocked down, bacterial replication is significantly enhanced. In conclusion, these findings suggested that TrTLR23 played a critical role on mediation TLR23-MyD88-ERK axis against bacterial infection. This study revealed that TLR23 involved in the innate immune mechanism, and provided the foundation for development disease control strategies in teleost.

15.
Molecules ; 29(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38893312

RESUMO

Gain-of-function mutations in the KCNT1 gene, which encodes the sodium-activated potassium channel known as SLACK, are associated with the rare but devastating developmental and epileptic encephalopathy known as epilepsy of infancy with migrating focal seizures (EIMFS). The design of small molecule inhibitors of SLACK channels represents a potential therapeutic approach to the treatment of EIMFS, other childhood epilepsies, and developmental disorders. Herein, we describe a hit optimization effort centered on a xanthine SLACK inhibitor (8) discovered via a high-throughput screen. Across three distinct regions of the chemotype, we synthesized 58 new analogs and tested each one in a whole-cell automated patch-clamp assay to develop structure-activity relationships for inhibition of SLACK channels. We further evaluated selected analogs for their selectivity versus a variety of other ion channels and for their activity versus clinically relevant SLACK mutants. Selectivity within the series was quite good, including versus hERG. Analog 80 (VU0948578) was a potent inhibitor of WT, A934T, and G288S SLACK, with IC50 values between 0.59 and 0.71 µM across these variants. VU0948578 represents a useful in vitro tool compound from a chemotype that is distinct from previously reported small molecule inhibitors of SLACK channels.


Assuntos
Bloqueadores dos Canais de Potássio , Relação Estrutura-Atividade , Humanos , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Ativados por Sódio , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Xantina/química , Xantina/farmacologia , Técnicas de Patch-Clamp , Células HEK293 , Estrutura Molecular , Xantinas/química , Xantinas/farmacologia
16.
Mikrochim Acta ; 191(7): 424, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922365

RESUMO

The enumeration of circulating tumor cells (CTCs) in peripheral blood plays a crucial role in the early diagnosis, recurrence monitoring, and prognosis assessment of cancer patients. There is a compelling need to develop an efficient technique for the capture and identification of these rare CTCs. However, the exclusive reliance on a single criterion, such as the epithelial cell adhesion molecule (EpCAM) antibody or aptamer, for the specific recognition of epithelial CTCs is not universally suitable for clinical applications, as it usually falls short in identifying EpCAM-negative CTCs. To address this limitation, we propose a straightforward and cost-effective method involving triplex fluorescently labelled aptamers (FAM-EpCAM, Cy5-PTK7, and Texas Red-CSV) to modify Fe3O4-loaded dendritic SiO2 nanocomposite (dmSiO2@Fe3O4/Apt). This multi-recognition-based strategy not only enhanced the efficiency in capturing heterogeneous CTCs, but also facilitated the rapid and accurate identification of CTCs. The capture efficiency of heterogenous CTCs reached up to 93.33%, with a detection limit as low as 5 cells/mL. Notably, the developed dmSiO2@Fe3O4/Apt nanoprobe enabled the swift identification of captured cells in just 30 min, relying solely on the fluorescently modified aptamers, which reduced the identification time by approximately 90% compared with the conventional immunocytochemistry (ICC) technique. Finally, these nanoprobe characteristics were validated using blood samples from patients with various types of cancers.


Assuntos
Aptâmeros de Nucleotídeos , Corantes Fluorescentes , Nanocompostos , Células Neoplásicas Circulantes , Dióxido de Silício , Humanos , Células Neoplásicas Circulantes/patologia , Dióxido de Silício/química , Aptâmeros de Nucleotídeos/química , Nanocompostos/química , Corantes Fluorescentes/química , Separação Imunomagnética/métodos , Molécula de Adesão da Célula Epitelial/imunologia , Limite de Detecção , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química
17.
Langmuir ; 40(26): 13636-13647, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38885969

RESUMO

For the conventional type-II heterojunction photocatalyst, their photocatalytic activity is affected by the limited separation efficiency of electron-hole pairs, exquisitely designed heterojunction photocatalysts are highly prospective materials for inducing charge transfer efficiently. Typically, enhancing the separation efficiency of electron-hole pairs in photocatalysts has been a formidable challenge. Here, the hollow mesoporous TiO2 (H-TiO2), the bulk g-C3N4 (B-CN), and g-C3N4 with bamboo shape (BS-CN) are prepared by simple processes. Among them, it is surprising to find that the band structure of g-C3N4 can be regulated and controlled by adjusting its structure. The B-CN/H-TiO2/BS-CN (CNTOCN) dual-type-II heterojunction photocatalyst and B-CN/H-TiO2 (CNTO) type-II heterojunction photocatalyst are designed to improve the separation efficiency of electron-hole pairs. The superiority of CNTOCN dual-type-II heterojunction photocatalyst is demonstrated by the photocatalysis experiment, the band structure analysis, and the photoelectric characterization. The results show that CNTOCN (0.8428 h-1) has much higher photocatalytic activity than H-TiO2 (0.0812 h-1), B-CN (0.3569 h-1), and CNTO (0.5934 h-1). The improvement of photocatalytic activity is ascribed to the establishment of the dual-type-II heterojunction charge transfer mechanism. This work presents an approach to designing efficient dual-type-II heterojunction photocatalysts for the sustainable conversion of solar energy to photodegrade dyes in dyeing wastewater.

18.
Biodivers Data J ; 12: e121451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827584

RESUMO

Background: The family Nemouridae, belonging to Plecoptera, comprises 21 genera and over 700 species found globally, with the greatest diversity observed in temperate regions. Nemoura Latreille, 1796 and Amphinemura Ris, 1902 are two largest genera of the family with the highest diversity in China. New information: Two new species of Nemoura Latreille, 1796 of the family Nemouridae, Nemouraexterclava Zhu, Rehman & Du sp. nov. and Nemouracerciserrata Zhu, Du & Rehman sp. nov., are described and illustrated from the Nanling Mountains Region in Guangdong Province, southern China. The morphological characteristics of the new species are compared with related taxa. Additionally, the status of Indonemouravoluta Li & Yang, 2008, originally from Maoershan National Natural Reserve in Guangxi Zhuang Autonomous Region, was addressed and moved to the genus Amphinemura Ris, 1902 on the basis of newly-caught topotypes.

19.
Microorganisms ; 12(6)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38930610

RESUMO

Streptomyces species are attractive sources of secondary metabolites that serve as major sources of antibiotics and other drugs. In this study, genome mining was used to determine the biosynthetic potential of Streptomyces sp. 21So2-11 isolated from Antarctic soil. 16S rRNA gene sequencing revealed that this strain is most closely related to Streptomyces drozdowiczii NBRC 101007T, with a similarity of 98.02%. Genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) showed that strain 21So2-11 represents a novel species of the genus Streptomyces. In addition to a large number of genes related to environmental adaptation and ecological function, a total of 28 putative biosynthetic gene clusters (BGCs) responsible for the biosynthesis of known and/or novel secondary metabolites, including terpenes, lantipeptides, polyketides, nonribosomal peptides, RiPPs and siderophores, were detected in the genome of strain 21So2-11. In addition, a total of 1456 BGCs were predicted to contribute to the biosynthesis of more than 300 secondary metabolites based on the genomes of 47 Streptomyces strains originating from polar regions. The results indicate the potential of Streptomyces sp. 21So2-11 for bioactive secondary metabolite production and are helpful for understanding bacterial adaptability and ecological function in cold terrestrial environments.

20.
Front Endocrinol (Lausanne) ; 15: 1302510, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694946

RESUMO

Purpose: This study aimed to introduce a new modified en-bloc resection method and evaluate its feasibility and safety in endoscopic thyroid surgery via bilateral areolar approach (BAA). Methods: Papillary thyroid carcinoma (PTC) patients who underwent lobectomy and ipsilateral central node dissection (CND) via the BAA approach were retrospectively reviewed. Their clinical characteristics and outcomes were evaluated, including operative duration, lymph node yield (LNY), surgical complications, recurrence rate, and metastasis rate, over a ten-year follow-up period. Simultaneous lobectomy and CND were performed in the modified en-bloc group, whereas lobectomy was performed first, followed by CND in the conventional group. Results: The study included 108 patients in the modified en-bloc group and 213 in the conventional group. There were no significant differences in gender, age, tumor locations, tumor dominant nodule size, or the incidence of concomitant Hashimoto thyroiditis when comparing clinicopathologic characteristics. The comparison of operative duration (P = 0.14), blood loss (P = 0.13), postoperative hospital stay (P = 0.58), incidence of transient vocal cord paralysis (P = 0.90) and hypocalcemia (P = 0.60) did not show any differences. The mean LNY achieved in the central compartment of the modified en-bloc group (7.5 ± 4.5) was significantly higher than that in the conventional group (5.6 ± 3.6). Two patients in the modified en-bloc group and two in the conventional group experienced metastasis after surgery during the ten-year follow-up (1.8% vs. 0.9%, P = 0.60). The learning curve analysis showed a significant decrease in operative duration after the 25-35th cases for modified en-bloc resection. Conclusions: The modified en-bloc resection method in endoscopic thyroid surgery via BAA is a technically feasible and safe procedure with excellent cosmetic outcomes for selective PTC patients.


Assuntos
Endoscopia , Estudos de Viabilidade , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Feminino , Masculino , Tireoidectomia/métodos , Tireoidectomia/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Adulto , Endoscopia/métodos , Endoscopia/efeitos adversos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Seguimentos , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Glândula Tireoide/cirurgia , Glândula Tireoide/patologia , Duração da Cirurgia
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