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1.
Org Lett ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587335

RESUMO

A catalyst system consisting of a chiral phosphoramidite ligand and Pd2(dba)3·CHCl3 causes the decarboxylation of 5-vinyloxazolidine-2,4-diones to generate amide-containing aza-π-allylpalladium 1,3-dipole intermediates, which are capable of triggering the dearomatization of 3-nitroindoles for diastereo- and enantioselective [3+2] cycloaddition, leading to the formation of a series of highly functionalized pyrroloindolines containing three contiguous stereogenic centers with excellent results (up to 99% yield, 88:12 dr, and 96% ee).

2.
Artigo em Inglês | MEDLINE | ID: mdl-38561515

RESUMO

Fibroblast activation protein (FAP) has emerged as a highly promising target for cancer diagnostic imaging and targeted radionuclide therapy. To exploit the therapeutic potential of suitably radiolabeled FAP inhibitors (FAPIs), this study presents the design and synthesis of a series of FAPI dimers to increase tumor uptake and retention. Preclinical evaluation and a pilot clinical PET imaging study were conducted to screen the lead compound with the potential for radionuclide therapy. METHODS: Three new FAPI dimers were synthesized by linking two quinoline-based FAPIs with different spacers. The in vitro binding affinity and preclinical small animal PET imaging of the compounds were compared with their monomeric counterparts, FAPI-04 and FAPI-46. The lead compound, [68Ga]Ga -LNC1013, was then evaluated in a pilot clinical PET imaging study involving seven patients with gastrointestinal cancer. RESULTS: The three newly synthesized FAPI homodimers had high binding affinity and specificity in vitro and in vivo. Small animal PET imaging and biodistribution studies showed that [68Ga]Ga-LNC1013 had persistent tumor retention for at least 4 h, also higher uptake than the other two dimers and the monomer counterparts, making it the lead compound to enter clinical investigation. In the pilot clinical PET imaging study, seven patients were enrolled. The effective dose of [68Ga]Ga-LNC1013 was 8.24E-03 mSv/MBq. The human biodistribution of [68Ga]Ga-LNC1013 demonstrated prominent tumor uptake and good tumor-to-background contrast. [68Ga]Ga-LNC1013 PET imaging showed potential in capturing primary and metastatic lesions and outperforming 18F-FDG PET in detecting pancreatic and esophageal cancers. The SUVmax for lesions with [68Ga]Ga-FAPI-46 decreased over time, whereas [68Ga]Ga-LNC1013 exhibited persistently high tumor uptake from 1 to 4 h post-injection. CONCLUSION: Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over its monomeric counterpart. We demonstrated that [68Ga]Ga-LNC1013, the lead compound without any piperazine moiety, had superior diagnostic potential over [68Ga]Ga-FAPI-46 and 18F-FDG, suggesting the future potential of LNC1013 for radioligand therapy of FAP-positive cancers.

3.
Br J Nutr ; : 1-8, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600624

RESUMO

Soft drink consumption has become a highly controversial public health issue. Given the pattern of consumption in China, sugar-sweetened beverage is the main type of soft drink consumed. Due to containing high levels of fructose, a soft drink may have a deleterious effect on handgrip strength (HGS) due to oxidative stress, inflammation and insulin resistance. However, few studies show an association between soft drink consumption and HGS in adults. We aimed to investigate the association between soft drink consumption and longitudinal changes in HGS among a Chinese adult population. A longitudinal population-based cohort study (5-year follow-up, median: 3·66 years) was conducted in Tianjin, China. A total of 11 125 participants (56·7 % men) were enrolled. HGS was measured using a handheld digital dynamometer. Soft drink consumption (mainly sugar-containing carbonated beverages) was measured at baseline using a validated FFQ. ANCOVA was used to evaluate the association between soft drink consumption and annual change in HGS or weight-adjusted HGS. After adjusting for multiple confounding factors, the least square means (95 % CI) of annual change in HGS across soft drink consumption frequencies were -0·70 (-2·49, 1·09) for rarely drinks, -0·82 (-2·62, 0·97) for < 1 cup/week and -0·86 (-2·66, 0·93) for ≥ 1 cup/week (Pfor trend < 0·05). Likewise, a similar association was observed between soft drink consumption and annual change in weight-adjusted HGS. The results indicate that higher soft drink consumption was associated with faster HGS decline in Chinese adults.

4.
Autophagy ; : 1-18, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38566321

RESUMO

Lyssaviruses are well-known worldwide and often cause fatal encephalitis. Previous studies have shown that autophagy is beneficial for the replication of rabies virus (RABV), the representative lyssavirus, but the detailed mechanism remains obscure. In this study, we showed that the rabies virus matrix protein (RABV-M) used its PPxY motif to interact with the E3 ubiquitin-protein ligase NEDD4. NEDD4 then recruited MAP1LC3/LC3 via its LC3-interacting region (LIR). Interestingly, after binding to the ubiquitinated RABV-M, NEDD4 could bind more LC3 and enhance autophagosome accumulation, while NEDD4 knockdown significantly reduced M-induced autophagosome accumulation. Further study revealed that RABV-M prevented autophagosome-lysosome fusion and facilitated viral budding. Inhibition of RABV-M-induced autophagosome accumulation reduced the production of extracellular virus-like particles. We also found that M proteins of most lyssaviruses share the same mechanism to accumulate autophagosome by hijacking NEDD4. Collectively, this study revealed a novel strategy for lyssaviruses to achieve efficient viral replication by exploiting the host autophagy system.Abbreviations: ABLV: Australian bat lyssavirus; ATG5: autophagy related 5; Baf A1:bafilomycin A1;co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI:4',6-diamidino-2'-phenylindole; DMSO: dimethyl sulfoxide; EBLV:European bat lyssavirus; GFP: green fluorescent protein; GST:glutathione S-transferase; hpi: hours post-infection; hpt: hourspost-transfection; LIR: LC3-interactingregion;MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; mCherry:red fluorescent protein; MOI: multiplicity of infection; NC: negativecontrol; MVB: multivesicular body; NEDD4: neural precursorcell-expressed developmentally down-regulated 4; RABV: rabies virus;SQSTM1/p62: sequestosome 1; VLP: virus-like particle; VPS4B: vacuolarprotein sorting 4B; TEM: transmission electron microscopy; WB:western blotting; WT: wild-type; µm: micrometer; µM: micromole.

5.
Artigo em Chinês | MEDLINE | ID: mdl-38433692

RESUMO

Objective:This study aims to provide a comprehensive summary of the pathogenesis, screening modalities, treatment strategies, repair modalities and preliminary results associated with facial nerve tumors. Methods:A retrospective analysis was conducted on the clinical data of 12 patients with facial nerve tumors who were admitted to our department between May 2018 and February 2023. The study population consisted of 5 males and 7 females, with ages ranging from 35 to 90 years. Clinical symptoms observed in these patients included facial nerve palsy, hearing loss, tinnitus, headache, and otalgia, etc. The severity of facial nerve dysfunction was assessed using the House-Brackmann(H-B) facial nerve function classification, with 3 cases classified as grade Ⅰ, 4 cases as grade Ⅲ, 2 cases as grade Ⅳ, and 3 cases as grade Ⅴ. There was a total of 11 patients who presented with hearing loss. Among these patients, 7 cases were diagnosed with conductive hearing loss, 2 cases with sensorineural hearing loss, and 2 cases with mixed hearing loss. The selection of the observation or surgical route for tumor localization was based on clinical symptoms, facial nerve function grading, and imaging examination results including temporal bone CT and enhanced MRI. Specifically, the location of the tumor was selected for observation or the best surgical route: 2 cases were followed up for observation, 1 case underwent biopsy, and 9 cases underwent tumor resection(7 cases of trans-mastoid approach, 2 cases of combined parotid-mastoidal approach), concurrent repair of the facial nerve(4 cases of auricular nerve grafting, 3 cases of facial nerve diversion anastomosis, 2 cases of peroneal nerve grafting). (4 cases of auricular nerve graft, 3 cases of facial nerve diversion anastomosis and 2 cases of peroneal nerve grafting). Periodic postoperative evaluation of facial nerve function was conducted. Results:1-year follow-up was available. Intraoperatively, it was observed that 66.7%(6 out of 9) of the facial nerve tumors were present in multiple segments. Among these segments, the vertical segment had the highest proportion, accounting for 77.8%(7 out of 9), followed by the labyrinthine segment/geniculate ganglion with 66.7%(6 out of 9) and the horizontal segment with 55.6%(5 out of 9). Postoperative pathology confirmed 8 cases with nerve sheath meningioma, Ⅰ with seminal fibroma and 1 with hemangioma. Postoperative facial nerve function was graded as H-B grade I in one patient), grade Ⅲ in three, grade Ⅳ in four, grade Ⅴ in 2, and grade Ⅵ in 2 patients. The auditory outcomes following surgery are as follows: 8 individuals experienced postoperative hearing loss, while 2 individuals demonstrated postoperative hearing preservation. Conclusion:In the case of patients presenting with facial nerve palsy as their initial symptom, it is imperative to consider the potential presence of a facial nerve tumor. To determine the appropriate course of action, it is necessary to ascertain the size and location of the tumors through imaging examinations. This information will aid in the decision making process regarding whether surgical intervention is warranted, and so, the most suitable approach. Additionally, the choice of repair method during the operation should be guided by the extent of facial nerve defect.


Assuntos
Neoplasias dos Nervos Cranianos , Surdez , Paralisia Facial , Neoplasias de Cabeça e Pescoço , Feminino , Masculino , Humanos , Nervo Facial , Estudos Retrospectivos , Paralisia Facial/cirurgia
6.
PeerJ Comput Sci ; 10: e1864, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435586

RESUMO

With the development of computer technology leading to a broad range of virtual technology implementations, the construction of virtual tasks has become highly demanded and has increased rapidly, especially in animation scenes. Constructing three-dimensional (3D) animation characters utilizing properties of actual characters could provide users with immersive experiences. However, a 3D face reconstruction (3DFR) utilizing a single image is a very demanding operation in computer graphics and vision. In addition, limited 3D face data sets reduce the performance improvement of the proposed approaches, causing a lack of robustness. When datasets are large, face recognition, transformation, and animation implementations are relatively practical. However, some reconstruction methods only consider the one-to-one processes without considering the correlations or differences in the input images, resulting in models lacking information related to face identity or being overly sensitive to face pose. A face model composed of a convolutional neural network (CNN) regresses 3D deformable model coefficients for 3DFR and alignment tasks. The manuscript proposes a reconstruction method for 3D animation scenes employing fuzzy LSMT-CNN (FLSMT-CNN). Multiple collected images are employed to reconstruct 3D animation characters. First, the serialized images are processed by the proposed method to extract the features of face parameters and then improve the conventional deformable face modeling (3DFDM). Afterward, the 3DFDM is utilized to reconstruct animation characters, and finally, high-precision reconstructions of 3D faces are achieved. The FLSMT-CNN has enhanced both the precision and strength of the reconstructed 3D animation characters, which provides more opportunities to be applied to other animation scenes.

7.
iScience ; 27(3): 109213, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38439953

RESUMO

Patients with Graves' disease (GD) can develop Graves' ophthalmopathy (GO), but the underlying pathological mechanisms driving this development remain unclear. In our study, which included patients with GD and GO, we utilized single-cell RNA sequencing (scRNA-seq) and multiplatform analyses to investigate CD169+ classical monocytes, which secrete proinflammatory cytokines and are expanded through activated interferon signaling. We found that CD169+ clas_mono was clinically significant in predicting GO progression and prognosis, and differentiated into CD169+ macrophages that promote inflammation, adipogenesis, and fibrosis. Our murine model of early-stage GO showed that CD169+ classical monocytes accumulated in orbital tissue via the Cxcl12-Cxcr4 axis. Further studies are needed to investigate whether targeting circulating monocytes and the Cxcl12-Cxcr4 axis could alleviate GO progression.

8.
Front Neurol ; 15: 1268433, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440116

RESUMO

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

9.
Nutrition ; 122: 112399, 2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38493542

RESUMO

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

10.
Biomater Sci ; 12(7): 1898-1913, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38426394

RESUMO

Masquelet's induced membrane (IM) technique is a promising treatment strategy for the repair of substantial bone defects. The formation of an IM around polymethylmethacrylate bone cement plays a crucial role in this technique. Several studies have indicated that IMs have bioactivity because they contain abundant blood vessels, a variety of cells, and biological factors. The bioactivity of an IM increases during the initial stages of formation, thereby facilitating bone regeneration and remodeling. Nevertheless, the precise mechanisms underlying the enhancement of IM bioactivity and the promotion of bone regeneration necessitate further investigation. In this study, we successfully developed a Masquelet IM model of critical femur defects in rats. By employing proteomics analysis and biological detection techniques, we identified fibromodulin (FMOD) as a pivotal factor contributing to angiogenesis and the enhanced bioactivity of the IM. A significant increase in angiogenesis and the expression of bioactive factors in the IM was also observed with the upregulation of FMOD expression. Furthermore, this effect is mediated through the inhibition of the transforming growth factor beta (TGF-ß)/SMAD signaling pathway. We also demonstrated that administering recombinant human FMOD enhanced osteogenesis in rat bone marrow mesenchymal stem cells and angiogenesis in human umbilical vein endothelial cells in vitro. Furthermore, the negative regulatory effect of the TGF-ß signaling pathway was verified. In conclusion, this study provides a novel theoretical basis for the application of IMs in bone-defect reconstruction and explores possible new mechanisms that may play an important role in promoting the bioactivity and osteogenic potential of IMs.


Assuntos
Osteogênese , Fator de Crescimento Transformador beta , Ratos , Humanos , Animais , Fibromodulina , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Transdução de Sinais
11.
Nat Commun ; 15(1): 2017, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443376

RESUMO

HIV-1 infection elevates the risk of developing various cancers, including T-cell lymphoma. Whether HIV-1-encoded proteins directly contribute to oncogenesis remains unknown. We observe that approximately 1-5% of CD4+ T cells from the blood of people living with HIV-1 exhibit over-duplicated centrioles, suggesting that centrosome amplification underlies the development of HIV-1-associated cancers by driving aneuploidy. Through affinity purification, biochemical, and cellular analyses, we discover that Vpr, an accessory protein of HIV-1, hijacks the centriole duplication machinery and induces centrosome amplification and aneuploidy. Mechanistically, Vpr forms a cooperative ternary complex with an E3 ligase subunit, VprBP, and polo-like kinase 4 (Plk4). Unexpectedly, however, the complex enhances Plk4's functionality by promoting its relocalization to the procentriole assembly and induces centrosome amplification. Loss of either Vpr's C-terminal 17 residues or VprBP acidic region, the two elements required for binding to Plk4 cryptic polo-box, abrogates Vpr's capacity to induce these events. Furthermore, HIV-1 WT, but not its Vpr mutant, induces multiple centrosomes and aneuploidy in human primary CD4+ T cells. We propose that the Vpr•VprBP•Plk4 complex serves as a molecular link that connects HIV-1 infection to oncogenesis and that inhibiting the Vpr C-terminal motif may reduce the occurrence of HIV-1-associated cancers.


Assuntos
HIV-1 , Linfócitos T , Humanos , Centrossomo , Carcinogênese , Transformação Celular Neoplásica , Aneuploidia , Linfócitos T CD4-Positivos
12.
J Biol Chem ; 300(4): 107168, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38490434

RESUMO

Lipids have been previously implicated in the lifecycle of neuroinvasive viruses. However, the role of lipids in programmed cell death and the relationship between programmed cell death and lipid droplets (LDs) in neuroinvasive virus infection remains unclear. Here, we found that the infection of neuroinvasive virus, such as rabies virus and encephalomyocarditis virus could enhance the LD formation in N2a cells, and decreasing LDs production by targeting diacylglycerol acyltransferase could suppress viral replication. The lipidomics analysis revealed that arachidonic acid (AA) was significantly increased after reducing LD formation by restricting diacylglycerol acyltransferase, and AA was further demonstrated to induce ferroptosis to inhibit neuroinvasive virus replication. Moreover, lipid peroxidation and viral replication inhibition could be significantly alleviated by a ferroptosis inhibitor, ferrostatin-1, indicating that AA affected neuroinvasive virus replication mainly through inducing ferroptosis. Furthermore, AA was demonstrated to activate the acyl-CoA synthetase long-chain family member 4-lysophosphatidylcholine acyltransferase 3-cytochrome P450 oxidoreductase axis to induce ferroptosis. Our findings highlight novel cross-talks among viral infection, LDs, and ferroptosis for the first time, providing a potential target for antiviral drug development.

13.
Diabetes Metab J ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503277

RESUMO

Background: The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. Methods: A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. Results: The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. Conclusion: Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

14.
Org Lett ; 26(13): 2623-2628, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38522081

RESUMO

An efficient dearomative cyclization of 2-nitrobenzofurans via a thiol-triggered tandem Michael addition/intramolecular Henry reaction has been developed. A range of thiochromeno[3,2-b]benzofuran-11-ols and tetrahydrothieno[3,2-b]benzofuran-3-ols could be obtained in up to 99% yield and up to >20:1 dr. The valuable thiochromone fused benzofurans could be prepared with the reaction of 2-nitrobenzofurans and 2-mercaptobenzaldehyde via the tandem dearomative Michael addition/intramolecular Henry reaction/rearomatization/oxidative dehydrogenation process in a one-pot two-step operation. A mechanism for the reaction was tentatively proposed.

15.
Anal Chem ; 96(13): 5340-5347, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38501977

RESUMO

Fully integrated devices that enable full functioning execution without or with minimum external accessories or equipment are deemed to be one of the most desirable and ultimate objectives for modern device design and construction. Escherichia coli O157:H7 (E. coli O157:H7) is often linked to outbreaks caused by contaminated water and food. However, the sensors that are currently used for point-of-care E. coli O157:H7 (E. coli O157:H7) detection are often large and cumbersome. Herein, we demonstrate the first example of a handheld and pump-free fully integrated electrochemical sensing platform with the capability to point-of-care test E. coli O157:H7 in the actual samples of E. coli O157:H7-spiked tap water and E. coli O157:H7-spiked watermelon juice. This platform was made possible by overcoming major engineering challenges in the seamless integration of a microfluidic module for pump-free liquid sample collection and transportation, a sensing module for efficient E. coli O157:H7 testing, and an electronic module for automatically converting and wirelessly transmitting signals into a single and compact electrochemical sensing platform that retains its inimitable stand-alone, handheld, pump-free, and cost-effective feature. Although our primary emphasis in this study is on detecting E. coli O157:H7, this pump-free fully integrated handheld electrochemical sensing platform may also be used to monitor other pathogens in food and water by including specific antipathogen antibodies.


Assuntos
Escherichia coli O157 , Anticorpos , Testes Imediatos , Sistemas Automatizados de Assistência Junto ao Leito , Água , Microbiologia de Alimentos
16.
iScience ; 27(3): 109290, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38469562

RESUMO

Our research addresses the critical intersection of communication and power systems in the era of advanced information technologies. We highlight the strategic importance of communication base station placement, as its optimization is vital for minimizing operational disruptions in energy systems. Our study introduces a communications and power coordination planning (CPCP) model that encompasses both distributed energy resources and base stations to improve communication quality of service. This model facilitates optimal resource distribution, ensuring communication reliability over 96% and downlink transmission rates above 450 Mbps, enhancing network resilience and cost-effectiveness. Through case studies, we demonstrate CPCP's potential to significantly reduce planning costs, particularly with increased renewable energy integration, supporting the transition to low-carbon energy systems. Our findings contribute to a comprehensive understanding of the symbiotic relationship between communication and power networks, emphasizing the need for coordinated planning in building future-proof energy infrastructures.

17.
Molecules ; 29(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474676

RESUMO

An efficient dearomative (3 + 2) cycloaddition of para-quinamines and 2-nitrobenzofurans has been developed. This reaction proceeds smoothly under mild conditions and affords a series of benzofuro[3,2-b]indol-3-one derivatives in good to excellent yields (up to 98%) with perfect diastereoselectivities (all cases > 20:1 dr). The scale-up synthesis and versatile derivatizations demonstrate the potential synthetic application of the protocol. A plausible reaction mechanism is also proposed to account for the observed reaction process. This work represents the first instance of the N-triggered dearomative (3 + 2) cycloaddition of 2-nitrobenzofurans.

18.
iScience ; 27(4): 109367, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38500836

RESUMO

Acetylation of histones by lysine acetyltransferases (KATs) provides a fundamental mechanism by which chromatin structure and transcriptional programs are regulated. Here, we describe a dual binding activity of the first winged helix domain of human MORF KAT (MORFWH1) that recognizes the TAZ2 domain of p300 KAT (p300TAZ2) and CpG rich DNA sequences. Structural and biochemical studies identified distinct DNA and p300TAZ2 binding sites, allowing MORFWH1 to independently engage either ligand. Genomic data show that MORF/MOZWH1 colocalizes with H3K18ac, a product of enzymatic activity of p300, on CpG rich promoters of target genes. Our findings suggest a functional cooperation of MORF and p300 KATs in transcriptional regulation.

19.
J Cell Biol ; 223(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38530252

RESUMO

The integrity of the plasma membrane is critical to cell function and survival. Cells have developed multiple mechanisms to repair damaged plasma membranes. A key process during plasma membrane repair is to limit the size of the damage, which is facilitated by the presence of tetraspanin-enriched rings surrounding damage sites. Here, we identify phosphatidylserine-enriched rings surrounding damaged sites of the plasma membrane, resembling tetraspanin-enriched rings. Importantly, the formation of both the phosphatidylserine- and tetraspanin-enriched rings requires phosphatidylserine and its transfer proteins ORP5 and ORP9. Interestingly, ORP9, but not ORP5, is recruited to the damage sites, suggesting cells acquire phosphatidylserine from multiple sources upon plasma membrane damage. We further demonstrate that ORP9 contributes to efficient plasma membrane repair. Our results thus unveil a role for phosphatidylserine and its transfer proteins in facilitating the formation of tetraspanin-enriched macrodomains and plasma membrane repair.


Assuntos
Membrana Celular , Fosfatidilserinas , Tetraspaninas , Humanos , Células HeLa , Proteínas de Membrana/metabolismo , Receptores de Esteroides/metabolismo
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