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1.
Sci Total Environ ; 946: 174396, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950634

RESUMO

Salt marsh has an important 'purification' role in coastal ecosystems by removing excess nitrogen that could otherwise harm aquatic life and reduce water quality. Recent studies suggest that salt marsh root exudates might be the 'control centre' for nitrogen transformation, but empirical evidence is lacking. Here we sought to estimate the direction and magnitude of nitrogen purification by salt marsh root exudates and gain a mechanistic understanding of the biogeochemical transformation pathway(s). To achieve this, we used a laboratory incubation to quantify both the root exudates and soil nitrogen purification rates, in addition to the enzyme activities and functional genes under Phragmites australis populations with different nitrogen forms addition (NO3-, NH4+ and urea). We found that NO3- and urea addition significantly stimulate P. australis root exudation of total acids, amino acids, total sugars and total organic carbon, while NH4+ addition only significantly increased total acids, amino acids and total phenol exudation. High total sugars, amino acids and total organic carbon concentrations enlarged nitrogen purification potential by stimulating the nitrogen purifying bacterial activities (including enzyme activities and related genes expression). Potential denitrification rates were not significantly elevated under NH4+ addition in comparison to NO3- and urea addition, which should be ascribed to total phenol self-toxicity and selective inhibition. Further, urea addition stimulated urease and protease activities with providing more NH4+ and NO2- substrates for elevated anaerobic ammonium oxidation rates among the nitrogen addition treatments. Overall, this study revealed that exogenous nitrogen could increase the nitrogen purification-associated bacterial activity through accelerating the root exudate release, which could stimulate the activity of nitrogen transformation, and then improve the nitrogen removal capacity in salt marsh.

2.
Commun Biol ; 7(1): 787, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951550

RESUMO

Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFß ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.


Assuntos
Tecido Adiposo Branco , Análise de Célula Única , Gordura Subcutânea , Desmame , Animais , Camundongos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/citologia , Gordura Subcutânea/metabolismo , Gordura Subcutânea/citologia , Camundongos Endogâmicos C57BL , Adipócitos/metabolismo , Adipócitos/citologia , Masculino , Feminino
3.
Orthop Surg ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946660

RESUMO

BACKGROUND: Mobile bearing fracture is a rare long-term complication of unicompartmental knee arthroplasty (UKA), and relevant reports are sparse. Hence, its treatment options need further exploration. CASE PRESENTATION: This study presents the case of fracture of a polyethylene insert that occurred 12 years after mobile bearing medial UKA in a 75-year-old overweight woman who then underwent surgical intervention at our institution. However, we encountered significant challenges in removing the fragments from the broken bearing, resulting in retention of the remaining one-third of the fragment. We solved this problem by replacing the fractured insert with thicker mobile bearing. During the 1-month postoperative follow-up, the patient achieved good range of motion and excellent satisfaction, with no reported complications and a Knee Society Score of 90. Additionally, we reviewed the literature on the treatment for mobile bearing fractures after UKA. CONCLUSIONS: Bearing fracture is a rare cause of failure of mobile bearing UKA. This case highlights the challenges of UKA fracture bearing retrieval and underscores that mobile bearing replacement can be an effective intervention. The case we report shows that when removal of a residual meniscal bearing in a posterior dislocation is difficult to achieve, compromise may be an appropriate option because it does not cause additional complaints to the patient. This case emphasizes the importance of the surgeon having a thorough preoperative understanding of the location and potential pitfalls of fracture fragments in such situations.

4.
Phys Rev Lett ; 132(24): 247101, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38949337

RESUMO

We consider the effect of perturbing a single bond on ground states of nearest-neighbor Ising spin glasses, with a Gaussian distribution of the coupling constants, across various two- and three-dimensional lattices and regular random graphs. Our results reveal that the ground states are strikingly fragile with respect to such changes. Altering the strength of only a single bond beyond a critical threshold value leads to a new ground state that differs from the original one by a droplet of flipped spins whose boundary and volume diverge with the system size-an effect that is reminiscent of the more familiar phenomenon of disorder chaos. These elementary fractal-boundary zero-energy droplets and their composites feature robust characteristics and provide the lowest-energy macroscopic spin-glass excitations. Remarkably, within numerical accuracy, the size of such droplets conforms to a universal power-law distribution with exponents that depend on the spatial dimension of the system. Furthermore, the critical coupling strengths adhere to a stretched exponential distribution that is predominantly determined by the local coordination number.

5.
Phys Rev Lett ; 132(24): 246501, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38949356

RESUMO

Electrons residing in a flat-band system can play a vital role in triggering spectacular phenomenology due to relatively large interactions and spontaneous breaking of different degeneracies. In this work, we demonstrate chirally twisted triple bilayer graphene, a new moiré structure formed by three pieces of helically stacked Bernal bilayer graphene, as a highly tunable flat-band system. In addition to the correlated insulators showing at integer moiré fillings, commonly attributed to interaction induced symmetry broken isospin flavors in graphene, we observe abundant insulating states at half-integer moiré fillings, suggesting a longer-range interaction and the formation of charge density wave insulators which spontaneously break the moiré translation symmetry. With weak out-of-plane magnetic field applied, as observed half-integer filling states are enhanced and more quarter-integer filling states appear, pointing toward further quadrupling moiré unit cells. The insulating states at fractional fillings combined with Hartree-Fock calculations demonstrate the observation of a new type of correlated charge density wave insulators in graphene and points to a new accessible twist manner engineering correlated moiré electronics.

6.
Small Methods ; : e2400408, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949412

RESUMO

Adverse side reactions and uncontrolled Zn dendrites growth are the dominant factors that have restricted the application of Zn ion batteries. Herein, a 3D self-supporting porous carbon fibers (denoted as PCFs) host is developed with "trap" effect to adjust the Zn deposition. The unique open structural design of N-doped carbon can act as the zincophilic sites to induce uniform deposition and inhibit adverse side reactions. More importantly, the porous hollow PCFs host with "trap" effect can induce Zn deposition in the fiber by adjusting the local electric field and current density, thereby increasing the specific energy density of the battery and inhibiting dendrite growth. In addition, the 3D open frameworks can regulate Zn2+ flux to enable outstanding cycling performance at ultra-high current densities. As expected, the PCFs framework guarantees the uniform Zn plating and stripping with an outstanding stability over 6000 cycles at the current density of 40 mA cm-2. And the Zn@PCFs||MnO2 full battery shows an excellent lifespan over 1300 cycles at 2000 mA g-1.

7.
Chaos ; 34(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949529

RESUMO

This paper studies a computational approach aimed at establishing equivalent dynamical responses within oscillatory impacting systems subject to soft and rigid constraints. The proposed method incorporates an adaptive differential evolution algorithm with the Metropolis criterion to determine the stiffness and damping parameters of the soft constraint for a prescribed coefficient of restitution governing the rigid constraint. The proposed algorithm aims to establish an equivalent dynamical response of the two models based on constraints regarding energy dissipation and contact time duration. Upon examining the dynamical responses of the two impact cases, they exhibit nearly identical outcomes in the two-parameter bifurcation diagrams when subjected to a large restitution coefficient. However, discrepancies arise between the results of the two models when the restitution coefficient is low. Detailed numerical tests, conducted using the proposed method, demonstrate enhanced effectiveness compared to previous techniques, such as the prediction formulas for the different related soft impact model outlined by Okolewski and Blazejczyk-Okolewska [Chaos 31(8), 083110 (2021)]. This method not only finds application in experimentally identifying the physical properties of an impact surface but also provides convenience in employing soft models within impacting systems, which could then avoid potential inaccuracies in handling discontinuities by some integrator during velocity jumps before and after impacts.

8.
Invest Ophthalmol Vis Sci ; 65(8): 1, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949632

RESUMO

Purpose: Glucocorticoid-induced glaucoma (GIG) is a prevalent complication associated with glucocorticoids (GCs), resulting in irreversible blindness. GIG is characterized by the abnormal deposition of extracellular matrix (ECM) in the trabecular meshwork (TM), elevation of intraocular pressure (IOP), and loss of retinal ganglion cells (RGCs). The objective of this study is to investigate the effects of nicotinamide riboside (NR) on TM in GIG. Methods: Primary human TM cells (pHTMs) and C57BL/6J mice responsive to GCs were utilized to establish in vitro and in vivo GIG models, respectively. The study assessed the expression of ECM-related proteins in TM and the functions of pHTMs to reflect the effects of NR. Mitochondrial morphology and function were also examined in the GIG cell model. GIG progression was monitored through IOP, RGCs, and mitochondrial morphology. Intracellular nicotinamide adenine dinucleotide (NAD+) levels of pHTMs were enzymatically assayed. Results: NR significantly prevented the expression of ECM-related proteins and alleviated dysfunction in pHTMs after dexamethasone treatment. Importantly, NR protected damaged ATP synthesis, preventing overexpression of mitochondrial reactive oxygen species (ROS), and also protect against decreased mitochondrial membrane potential induced by GCs in vitro. In the GIG mouse model, NR partially prevented the elevation of IOP and the loss of RGCs. Furthermore, NR effectively suppressed the excessive expression of ECM-associated proteins and mitigated mitochondrial damage in vivo. Conclusions: Based on the results, NR effectively enhances intracellular levels of NAD+, thereby mitigating abnormal ECM deposition and TM dysfunction in GIG by attenuating mitochondrial damage induced by GCs. Thus, NR has promising potential as a therapeutic candidate for GIG treatment.


Assuntos
Modelos Animais de Doenças , Matriz Extracelular , Glaucoma , Glucocorticoides , Pressão Intraocular , Camundongos Endogâmicos C57BL , Mitocôndrias , Niacinamida , Compostos de Piridínio , Malha Trabecular , Animais , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Compostos de Piridínio/farmacologia , Glucocorticoides/toxicidade , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Camundongos , Glaucoma/metabolismo , Glaucoma/tratamento farmacológico , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Humanos , Malha Trabecular/metabolismo , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/patologia , Células Cultivadas , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Espécies Reativas de Oxigênio/metabolismo , Dexametasona/farmacologia , Masculino
9.
Sci Total Environ ; 946: 174332, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950630

RESUMO

Cathodic electroactive bacteria (C-EAB) which are capable of accepting electrons from solid electrodes provide fresh avenues for pollutant removal, biosensor design, and electrosynthesis. This review systematically summarized the burgeoning applications of the C-EAB over the past decade, including 1) removal of nitrate, aromatic derivatives, and metal ions; 2) biosensing based on biocathode; 3) electrosynthesis of CH4, H2, organic carbon, NH3, and protein. In addition, the mechanisms of electron transfer by the C-EAB are also classified and summarized. Extracellular electron transfer and interspecies electron transfer have been introduced, and the electron transport mechanism of typical C-EAB, such as Shewanella oneidensis MR-1, has been combed in detail. By bringing to light this cutting-edge area of the C-EAB, this review aims to stimulate more interest and research on not only exploring great potential applications of these electron-accepting bacteria, but also developing steady and scalable processes harnessing biocathodes.

10.
Opt Lett ; 49(13): 3818-3821, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950275

RESUMO

Photonic stepped-frequency radars based on optical frequency-shifting modulation have shown attractive properties such as wide bandwidth, centimeter range resolution, inherent frequency-time linearity with low spectrum spurs, and reduced system complexity. However, existing approaches typically exhibit meter- or centimeter-level radar range ambiguity, inversely proportional to the frequency step, due to the large frequency shift determined by acousto-optic or electro-optic (EO) modulators. Here, we overcome this limitation by injecting a narrowband, stepped-frequency signal into an optical frequency-shifting fiber cavity to achieve, for the first time, to our knowledge, a broadband photonic stepped-frequency radar with 150-m unambiguous detection and centimeter range resolution, surpassing the reported photonic- and electronic-based counterparts. The demonstrated approach effectively resolves the trade-off between ambiguity range and shifting frequency while maintaining the signal quality and bandwidth, bringing its practicality into reach for outdoor applications.

11.
World J Gastroenterol ; 30(22): 2829-2833, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38947294

RESUMO

In this editorial, we commented on a recently released manuscript by Zeng et al in the World Journal of Gastroenterology. We focused specifically on lifestyle changes in patients with non-alcoholic fatty liver disease (NAFLD). NAFLD is a hepatic manifestation of the metabolic syndrome, which ultimately leads to advanced hepatic fibrosis, cirrhosis, and hepatocellular carcinoma and affects more than 25% of the population globally. Existing therapeutic strategies against NAFLD such as pharmacologic therapies focus on liver protection, anti-inflammation, and regulating disease-related metabolic disorder symptoms. Although several drugs are in late-stage development, potent drugs against the diseases are lacking. Additionally, existing surgical approaches such as bariatric surgery are not routinely used to treat NAFLD. Intervening in patients' unhealthy lifestyles, such as weight loss through dietary changes and exercises to ameliorate patient-associated metabolic disorders and metabolic syndrome, is the first-line treatment for patients with NAFLD. With sufficient intrinsic motivation and adherence, the management of unhealthy lifestyles can reduce the severity of the disease, improve the quality of life, and increase the survival expectancy of patients with NAFLD.


Assuntos
Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Qualidade de Vida , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Síndrome Metabólica/terapia , Síndrome Metabólica/complicações , Estilo de Vida , Redução de Peso , Exercício Físico , Cirurgia Bariátrica , Comportamento de Redução do Risco , Estilo de Vida Saudável , Fatores de Risco
12.
Cancer Innov ; 3(3): e112, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38947760

RESUMO

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined. Methods: Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes. Results: In total, 27 canonical cancer gene mutations were identified, with TP53 the most frequently mutated gene, followed by KRAS. Interestingly, most TP53 and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs. Conclusions: We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.

13.
Open Life Sci ; 19(1): 20220876, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947770

RESUMO

The common squid, Todarodes pacificus, is an important commercial species that inhabits the northwest Pacific Ocean, particularly the East Japan Sea, the Pacific coast of Japan, and the East China Sea. In this study, we chose 29 individuals from three areas: one type from the Sea of Japan and two types from the East China Sea. A total of 43,529 SNPs were obtained using genotyping-by-sequencing (GBS). Our analyses revealed low genetic diversity and genetic differentiation in each type. Heterozygote deficiency and inbreeding have caused this low level of genetic diversity. Population structure analysis indicated that the three types were genetically similar, which may be attributed to strong gene flow combined with the demographic history events during the last 2 million years. This new GBS application technique provides valuable information for the conservation of marine species genetics and could be useful for the effective management of this resource.

14.
Front Endocrinol (Lausanne) ; 15: 1385167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948526

RESUMO

Background: Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on ultrasound features. This study explores machine learning for screening using demographic and biochemical indicators. Methods: Analyzing data from 6,102 individuals and 61 variables, we identified 17 key variables to construct models using six machine learning classifiers: Logistic Regression, SVM, Multilayer Perceptron, Random Forest, XGBoost, and LightGBM. Performance was evaluated by accuracy, precision, recall, F1 score, specificity, kappa statistic, and AUC, with internal and external validations assessing generalizability. Shapley values determined feature importance, and Decision Curve Analysis evaluated clinical benefits. Results: Random Forest showed the highest internal validation accuracy (78.3%) and AUC (89.1%). LightGBM demonstrated robust external validation performance. Key factors included age, gender, and urinary iodine levels, with significant clinical benefits at various thresholds. Clinical benefits were observed across various risk thresholds, particularly in ensemble models. Conclusion: Machine learning, particularly ensemble methods, accurately predicts thyroid nodule presence using demographic and biochemical data. This cost-effective strategy offers valuable insights for thyroid health management, aiding in early detection and potentially improving clinical outcomes. These findings enhance our understanding of the key predictors of thyroid nodules and underscore the potential of machine learning in public health applications for early disease screening and prevention.


Assuntos
Aprendizado de Máquina , Nódulo da Glândula Tireoide , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Humanos , Feminino , Masculino , China/epidemiologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Detecção Precoce de Câncer/métodos , Idoso , Programas de Rastreamento/métodos , Ultrassonografia/métodos
15.
Transl Androl Urol ; 13(6): 970-982, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38983474

RESUMO

Background: Erectile dysfunction (ED) is a prevalent condition in aging men. Meanwhile, platelet-rich plasma (PRP), an emerging treatment alternative, has demonstrated potential in mitigating symptoms associated with ED. Our research aimed to explore the safety and effectiveness of employing PRP as a treatment strategy for ED. Methods: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols, our research involved a thorough search across multiple databases: PubMed, Web of Science, Embase, and the Cochrane Controlled Trials Register. To assess the methodological rigor of the studies selected, we applied the modified Jadad scale and the Methodological Index for Non-Randomized Studies (MINORS) scale as evaluation tools. Subsequent to these evaluations, data analysis was conducted. Results: Our analysis included seven non-randomized studies and three randomized controlled trials (RCTs). These studies showed that the International Index of Erectile Function-Erectile Function (IIEF-EF) scores improved significantly after 1, 3, and 6 months of PRP treatment, with increases of 4.05 [95% confidence interval (CI): 2.42, 5.68; P<0.001], 3.73 (95% CI: 2.93, 4.53; P<0.001), and 3.92 (95% CI: 3.00, 4.85; P<0.001) respectively, compared to the baseline scores. Additionally, compared to the placebo group, the PRP group showed significantly higher IIEF-EF scores. PRP treatment also had a beneficial impact on minimal clinically important difference (MCID) and peak systolic velocity (PSV). However, no significant differences were found between the PRP and placebo groups in terms of erectile hardness score (EHS) [mean difference (MD) =0.63; 95% CI: 0.26, 0.99; P<0.001] or visual analog scale (VAS) pain scores (MD =0.24; 95% CI: -0.05, 0.54; P=0.11). Conclusions: Our study results demonstrated significant efficacy and safety of PRP in treating ED. Due to the fact that most of the literature we included was single-arm studies, it was imperative for future research to provide higher-quality evidence for validation.

16.
Nat Prod Res ; : 1-8, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38962949

RESUMO

The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.

17.
Transl Psychiatry ; 14(1): 272, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961057

RESUMO

Valproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.


Assuntos
Transtorno do Espectro Autista , Modelos Animais de Doenças , Efeitos Tardios da Exposição Pré-Natal , Receptores de N-Metil-D-Aspartato , Transmissão Sináptica , Ácido Valproico , Animais , Receptores de N-Metil-D-Aspartato/metabolismo , Ácido Valproico/farmacologia , Gravidez , Feminino , Camundongos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Transmissão Sináptica/efeitos dos fármacos , Transtorno do Espectro Autista/induzido quimicamente , Masculino , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Anticonvulsivantes/farmacologia
18.
Adv Sci (Weinh) ; : e2404886, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973161

RESUMO

Immune checkpoint blockade (ICB) immunotherapy remains hampered by insufficient immunogenicity and a high-lactate immunosuppressive tumor microenvironment (TME). Herein, a nanobody-engineered NIR-II nanoadjuvant with targeting metabolic reprogramming capability is constructed for potentiating NIR-II photothermal-ferroptosis immunotherapy. Specifically, the nanoadjuvant (2DG@FS-Nb) is prepared by metallic iron ion-mediated coordination self-assembly of D-A-D type NIR-II molecules and loading of glycolysis inhibitor, 2-deoxy-D-glucose (2DG), followed by modification with aPD-L1 nanobody (Nb), which can effectively target the immunosuppressive TME and trigger in situ immune checkpoint blockade. The nanoadjuvants responsively release therapeutic components in the acidic TME, enabling the precise tumor location by NIR-II fluorescence/photoacoustic imaging while initiating NIR-II photothermal-ferroptosis therapy. The remarkable NIR-II photothermal efficiency and elevated glutathione (GSH) depletion further sensitize ferroptosis to induce severe lipid peroxidation, provoking robust immunogenic cell death (ICD) to trigger anti-tumor immune response. Importantly, the released 2DG markedly inhibits lactate generation through glycolysis obstruction. Decreased lactate efflux remodels the immunosuppressive TME by suppressing M2 macrophage proliferation and downregulating regulatory T cell levels. This work provides a new paradigm for the integration of NIR-II phototheranostics and lactate metabolism regulation into a single nanoplatform for amplified anti-tumor immunotherapy combined with ICB therapy.

19.
Front Chem ; 12: 1427451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952891

RESUMO

In solid propellants, combustion catalysts play a crucial role. Here, we introduce a convenient method for the self-assembly of UIO-66 (Mn) in the presence of water, leading to the preparation of Mn/C aerogels. The aerogels were successfully utilized in the thermocatalytic decomposition of ammonium perchlorate (AP). The results indicate that the incorporation of 2% mass fraction of Mn/C aerogels enhances the peak temperature of AP decomposition by approximately 87.5°C. Mn/C aerogels demonstrate excellent catalytic performance. In combination with kinetics, we propose a thermal catalytic mechanism.

20.
Future Med Chem ; 16(12): 1267-1281, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989985

RESUMO

Cancer exhibits heterogeneity that enables adaptability and remains grand challenges for effective treatment. Chemotherapy is a validated and critically important strategy for the treatment of cancer, but the emergence of multidrug resistance which may lead to recurrence of disease or even death is a major hurdle for successful chemotherapy. Azoles and sulfonamides are important anticancer pharmacophores, and azole-sulfonamide hybrids have the potential to simultaneously act on dual/multiple targets in cancer cells, holding great promise to overcome drug resistance. This review outlines the current scenario of azole-sulfonamide hybrids with the anticancer potential, and the structure-activity relationships as well as mechanisms of action are also discussed, covering articles published from 2020 onward.


[Box: see text].


Assuntos
Antineoplásicos , Azóis , Neoplasias , Sulfonamidas , Humanos , Sulfonamidas/química , Sulfonamidas/farmacologia , Azóis/química , Azóis/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Relação Estrutura-Atividade , Estrutura Molecular
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