RESUMO
We report the synthesis, crystal structure, and physical properties of a novel ternary compound, Th2Cu4As5. The material crystallizes in a tetragonal structure with lattice parameters a = 4.0639(3) Å and c = 24.8221(17) Å. Its structure can be described as an alternating stacking of fluorite-type Th2As2 layers with antifluorite-type double-layered Cu4As3 slabs. The measurement of electrical resistivity, magnetic susceptibility, and specific heat reveals that Th2Cu4As5 undergoes bulk superconducting transition at 4.2 K. Additionally, all these physical quantities exhibit anomalies at 48 K, accompanied by a sign change in the Hall coefficient, suggesting a charge-density-wave-like (CDW) phase transition. Drawing from both experimental data and band calculations, we propose that the superconducting and CDW-like phase transitions are, respectively, associated with the Cu4As3 slabs and the As plane in the Th2As2 layers.
RESUMO
A quaternary compound, ThCr2Si2C, was synthesized by using the arc-melting technique. The compound adopts a tetragonal CeCr2Si2C-type crystal structure. The electronic resistivity and specific heat data exhibit metallic behavior, while the magnetic susceptibility displays a pronounced broad peak at around 370 K, indicating the antiferromagnetic phase transition. The first-principles calculations suggest A-type antiferromagnetic ordering of the Cr sublattice, which is confirmed by neutron diffraction experiments. By comparing the crystal structure of ThCr2Si2C with the isostructural Cr-based compounds, the magnetic state of Cr 3d orbital is discussed in terms of the band-filling effects and indirect spin exchange interaction.
RESUMO
Background: Sarcopenia is defined as a progressive loss of skeletal muscle mass plus a decline in muscle strength and/or reduced physical performance with advancing age. The results of current studies on the relationship between drinking and sarcopenia remain controversial.Objectives: The aim of this meta-analysis was to evaluate the association of alcohol consumption with the risk of sarcopenia.Methods: Systematic searches were conducted without language restrictions from the beginning of each database to September 20, 2023 on PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, Chinese BioMedical Literature, and China national knowledge infrastructure databases. Meta-analysis was conducted to pool the study-specific odds ratios (ORs) with 95% confidence interval (CI).Results: Sixty-two studies with 454,643 participants were enrolled. The meta-analysis of proportions revealed that alcohol consumption was not associated with the presence of sarcopenia, with a pooled OR of 0.964 (95% CI = 0.912-1.019). Further subgroup analysis indicated that alcohol consumption was correlated with lower risk of sarcopenia in men (OR = 0.763; 95% CI = 0.622-0.938; P = .010). The nonlinear dose-response analysis suggested a J-shaped association between alcohol consumption and the risk of sarcopenia, with a nadir at the amounts of alcohol consumption of 6.6 grams/day (OR = 0.765; 95% CI = 0.608-0.957; P < .05).Conclusions: The results of this meta-analysis indicate that alcohol consumption is not a risk factor for the development of sarcopenia. Any suggestion of a putative protective effect of alcohol should be treated with caution, particularly in light of the overall lack of relationship reported in the present comprehensive meta-analysis.
Assuntos
Consumo de Bebidas Alcoólicas , Sarcopenia , Humanos , Sarcopenia/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Masculino , Fatores de Risco , Feminino , Relação Dose-Resposta a DrogaRESUMO
Automobile exhaust-derived particulate matter 2.5 (PM2.5) can cause spermatogenic cell damage, potentially resulting in male infertility. This study uses male prepubertal Sprague Dawley (SD) rats to explore the molecular mechanisms by which automobile exhaust-derived PM2.5 causes spermatogenic cell damage and induces spermatogenesis dysfunction during sexual maturity by disrupting the mitochondrial unfolded protein response (UPRmt) in spermatogenic cells. Male prepubertal SD rats were randomly divided into four groups: control (intratracheal instillation of normal saline), low-dose PM2.5 (5 mg/kg), high-dose PM2.5 (10 mg/kg), and PM2.5 10 mg/kg +Vit (100 mg/kg of vitamin C and 50 mg/kg of vitamin E). The rats were treated for four weeks, with five consecutive treatment days and two non-treatment days, followed by cohabitation. Testicular and epididymal tissues were harvested for analysis. The mitochondria in spermatogenic cells were observed under an electron microscope. UPRmt-, oxidative stress-, and apoptosis-related markers in spermatogenic cells were examined. Spermatogenic cell numbers and conception rate declined significantly with increasing PM2.5 dose, with their mitochondria becoming vacuolated, swollen, and degenerated to varying degrees. The apoptosis of spermatogenic cells was abnormally enhanced in PM2.5 exposed groups compared to the control group. Spermatogenic cell numbers of conception rate gradually recovered, mitochondrial damage in spermatogenic cells was alleviated, and spermatogenic cell apoptosis was significantly reduced after vitamin intervention. In addition, protein levels of superoxide dismutase 1 (Sod1), nuclear factor erythroid 2-related factor 2 (Nrf2), and B-cell lymphoma 2 (Bcl-2) were significantly lower, while those of Bcl2-associated X apoptosis regulator (Bax), cleaved caspase 3 (Casp3), and cytochrome c (Cyt-c) and malondialdehyde (MDA) levels were significantly higher in the high-dose PM2.5 group than in the control group. The levels of UPRmt-related proteins C/EBP homologous protein (Chop), heat shock protein 60 (Hsp60), and activating transcription factors 4 (Atf4) and 5 (Atf5) were higher in the low-dose PM2.5 group, lower in the high-dose PM2.5 group, and gradually recovered in PM2.5 10 mg/kg +Vit group. Our results show that exposure to automobile exhaust-derived PM2.5 induces oxidative stress responses, leads to post-sexual maturation UPRmt dysfunction and mitochondrial impairment, and abnormally enhances spermatogenic cell apoptosis in prepubertal rats, resulting in male infertility.
Assuntos
Infertilidade Masculina , Emissões de Veículos , Fatores Ativadores da Transcrição , Animais , Apoptose , Ácido Ascórbico , Caspase 3/metabolismo , Chaperonina 60 , Citocromos c , Humanos , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Material Particulado/toxicidade , Ratos , Ratos Sprague-Dawley , Solução Salina , Espermatogênese , Superóxido Dismutase-1 , Emissões de Veículos/toxicidade , Vitamina E/farmacologia , Vitaminas , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disease. To date, more than 1000 genes have been shown to be associated with ASD, and only a few of these genes account for more than 1% of autism cases. Klf7 is an important transcription factor of cell proliferation and differentiation in the nervous system, but whether klf7 is involved in autism is unclear. METHODS: We first performed ChIP-seq analysis of klf7 in N2A cells, then performed behavioral tests and RNA-seq in klf7+/- mice, and finally restored mice with adeno-associated virus (AAV)-mediated overexpression of klf7 in klf7+/- mice. RESULTS: Klf7 targeted genes are enriched with ASD genes, and 631 ASD risk genes are also differentially expressed in klf7+/- mice which exhibited the core symptoms of ASD. When klf7 levels were increased in the central nervous system (CNS) in klf7+/- adult mice, deficits in social interaction, repetitive behavior and majority of dysregulated ASD genes were rescued in the adults, suggesting transcriptional regulation. Moreover, knockdown of klf7 in human brain organoids caused dysregulation of 517 ASD risk genes, 344 of which were shared with klf7+/- mice, including some high-confidence ASD genes. CONCLUSIONS: Our findings highlight a klf7 regulation of ASD genes and provide new insights into the pathogenesis of ASD and promising targets for further research on mechanisms and treatments.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Animais , Transtorno do Espectro Autista/genética , Transtorno Autístico/complicações , Transtorno Autístico/genética , Diferenciação Celular , Regulação da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , CamundongosRESUMO
The plating/stripping of Li dendrites can fracture the static solid electrolyte interphase (SEI) and cause significant dynamic volume variations in the Li anode, which give rise to poor cyclability and severe safety hazards. Herein, a tough polymer with a slide-ring structure was designed as a self-adaptive interfacial layer for Li anodes. The slide-ring polymer with a dynamically crosslinked network moves freely while maintaining its toughness and fracture resistance, which allows it can to dissipate the tension induced by Li dendrites on the interphase layer. Moreover, the slide-ring polymer is highly stretchable, elastic, and displays an ultrafast self-healing ability, which allows even pulverized Li to remain coalesced without disintegrating upon consecutive cycling. The Li anodes demonstrate greatly improved suppression of Li dendrite formation, as evidenced by the high critical current density (6â mA cm-2 ) and stable cycling for the full cells with high-areal capacity LiFePO4 , high-voltage NCM, and S cathodes.
RESUMO
Mn-based ZrCuSiAs-type pnictides ThMnPnN (Pn = P, As) containing PbO-type Th2N2 layers were synthesized. The crystal and magnetic structures are determined using X-ray and neutron powder diffraction. While neutron diffraction indicates a C-type antiferromagnetic state at 300 K, the temperature dependence of the magnetic susceptibility shows cusps at 36 and 52 K respectively for ThMnPN and ThMnAsN. The susceptibility cusps are ascribed to a spontaneous antiferromagnetic-to-antiferromagnetic transition for Mn2+ moments, which is observed for the first time in Mn-based ZrCuSiAs-type compounds. In addition, measurements of the resistivity and specific heat suggest an abnormal increase in the density of states at the Fermi energy. The result is discussed in terms of the internal chemical pressure effect.
RESUMO
BACKGROUND: The aim of this study is to examine miRNA profiling and miR-369-3p participates in endometrioid adenocarcinoma (EEC) via the regulation of autophagy. METHODS: EEC and its adjacent normal tissues were obtained from 20 clinical patients after surgery. MiRNA profiling was performed using next generation sequencing (NGS) and was validated with quantitative real time PCR (qRT-PCR). qRT-PCR was also employed to measure miR-369-3p and autophagy-related protein 10 (ATG10) expression levels. Western blotting assay was performed to measure the expressions of ATG10 and LC3B. Luciferase reporter assay was conducted to confirm the direct targeting of ATG10 by miR-369-3p. Cell proliferation and migration assays were utilized to analyze the role of miR-369-3p in HEC-1-A cells. RESULTS: We found that miR-369-3p expression levels were down-regulated in EEC compared to the control tissues. The overexpression of miR-369-3p inhibited cell proliferation and migration in EEC; furthermore, ATG10 expression increased in EEC tissues. ATG10 was found to be a potential target of miR-369-3p via a dual-luciferase reporter assay, and ATG10 was shown to be down-regulated by miR-369-3p in protein levels. CONCLUSIONS: This study revealed that miR-369-3p inhibited cell proliferation and migration by targeting ATG10 via autophagy in EEC.
RESUMO
BACKGROUND: With the rapidly increasing population of elderly people, dental extraction in elderly individuals with cardiovascular diseases (CVDs) has become quite common. The issue of how to assure the safety of elderly patients with CVDs undergoing dental extraction has perplexed dentists and internists for many years. And it is important to derive an appropriate risk prediction tool for this population. OBJECTIVES: The aim of this retrospective, observational study was to establish and validate a prediction model based on the random forest (RF) algorithm for the risk of cardiac complications of dental extraction in elderly patients with CVDs. METHODS: Between August 2017 and May 2018, a total of 603 patients who fulfilled the inclusion criteria were used to create a training set. An independent test set contained 230 patients between June 2018 and July 2018. Data regarding clinical parameters, laboratory tests, clinical examinations before dental extraction, and 1-week follow-up were retrieved. Predictors were identified by using logistic regression (LR) with penalized LASSO (least absolute shrinkage and selection operator) variable selection. Then, a prediction model was constructed based on the RF algorithm by using a 5-fold cross-validation method. RESULTS: The training set, based on 603 participants, including 282 men and 321 women, had an average participant age of 72.38 ± 8.31 years. Using feature selection methods, 11 predictors for risk of cardiac complications were screened out. When the RF model was constructed, its overall classification accuracy was 0.82 at the optimal cutoff value of 18.5%. In comparison to the LR model, the RF model showed a superior predictive performance. The AUROC (area under the receiver operating characteristic curve) scores of the RF and LR models were 0.83 and 0.80, respectively, in the independent test set. The AUPRC (area under the precision-recall curve) scores of the RF and LR models were 0.56 and 0.35, respectively, in the independent test set. CONCLUSION: The RF-based prediction model is expected to be applicable for preoperative clinical assessment for preventing cardiac complications in elderly patients with CVDs undergoing dental extraction. The findings may aid physicians and dentists in making more informed recommendations to prevent cardiac complications in this patient population.
Assuntos
Doenças Cardiovasculares/epidemiologia , Modelos Cardiovasculares , Medição de Risco , Extração Dentária/efeitos adversos , Idoso , Algoritmos , Angina Instável/etiologia , Arritmias Cardíacas/etiologia , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Infarto do Miocárdio/etiologia , Complicações Pós-Operatórias , Estudos Retrospectivos , Choque Cardiogênico/etiologiaRESUMO
OBJECTIVE: To evaluate the efficacy of continuous passive motion (CPM) after total knee arthroplasty (TKA) and whether the use of CPM is related to improved clinical and functional outcomes. DATA SOURCES: A systematic MEDLINE search via Web of Science, Cochrane Library, and PubMed databases was conducted. STUDY SELECTION: English-language articles published between January 2000 and May 2018 reporting the related clinical outcomes of CPM after TKA were included. A total of 3334 titles and abstracts were preliminarily reviewed, of which 16 studies were included according to the eligibility criteria. DATA EXTRACTION: Two different reviewers were selected to perform the study extraction, independent of each other. If there were any disagreements regarding the final list of studies, the third reviewer reviewed the list as an arbitrator for completeness. DATA SYNTHESIS: A total of 16 trials with 1224 patients were included. The pooled results revealed that use of CPM did not show a statistically significant improvement of postoperative knee range of motion (ROM) except for middle-term passive knee extension and long-term active knee flexion ROM. Also, CPM therapy did not show a significant positive effect on the functional outcomes. No significant reduction in length of stay (LOS) and incidence of adverse events (AEs) was identified. CONCLUSION: Among patients undergoing TKA, neither the ROM nor the functional outcomes could be improved by CPM therapy. Moreover, the risk of AEs and LOS could not be reduced by application of CPM. The current available evidence suggested that this intervention was insufficient to be used routinely in clinical practice.
Assuntos
Artroplastia do Joelho/reabilitação , Articulação do Joelho/fisiopatologia , Terapia Passiva Contínua de Movimento , Artroplastia do Joelho/efeitos adversos , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Amplitude de Movimento Articular , Resultado do TratamentoRESUMO
We report the first nitrogen-containing iron-pnictide superconductor ThFeAsN, which is synthesized by a solid-state reaction in an evacuated container. The compound crystallizes in a ZrCuSiAs-type structure with the space group P4/nmm and lattice parameters a = 4.0367(1) Å and c = 8.5262(2) Å at 300 K. The electrical resistivity and dc magnetic susceptibility measurements indicate superconductivity at 30 K for the nominally undoped ThFeAsN.
RESUMO
PURPOSE: Triple-negative breast cancer (TNBC) features high aggressiveness, metastasis rate, drug resistance as well as poor prognosis. Osteopontin (OPN) is a key protein in the process of osteogenesis and has emerged as a new tumor marker in recent years. METHODS: Cell viability was tested with the CCK-8 kit. Transwell and wound healing were adopted to test cell invasive and migratory abilities. Tumor sphere formation was detected by tumor sphere formation assay. Human umbilical vein endothelial cell (HUVEC) tube formation assay was used to measure the angiogenesis of tumor cells. Western blot was applied for the estimation of the expression of cancer stem cell markers, angiogenesis-, signaling pathway-related proteins as well as OPN. Bioinformatics tools predicted OPN expression in breast cancer tissues. The levels of oxidative stress-related markers were assessed with ELISA. Following the overexpression of OPN in MD-MB-436 cells and the addition of the PI3K/AKT/mTOR pathway inhibitor LY294002, the aforementioned functional experiments were implemented again to investigate the mechanism. Finally, in vivo experiments of tumor-bearing mice were performed for further verification. RESULTS: The proliferative, invasive, migratory and tumor sphere formation capabilities as well as angiogenesis of TNBC cells were conspicuously increased in contrast to non-TNBC cell lines. OPN expression in TNBC tissues and cells was dramatically enhanced. OPN upregulation significantly elevated cell proliferative, invasive and migratory capabilities as well as tumor sphere formation and angiogenesis. The mechanism might be achieved by activating PI3K/AKT/mTOR signaling to regulate glutathione peroxidase 4 (GPX4)-mediated anti-lipid peroxidation. CONCLUSION: OPN promoted tumor sphere formation and angiogenesis in TNBC by activating the PI3K/AKT/mTOR pathway to regulate GPX4-mediated anti-lipid peroxidation levels.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Osteopontina/metabolismo , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células , Movimento Celular/fisiologiaRESUMO
The lining structures of tunnels are typically constructed using sprayed or cast concrete materials, and their performance and quality during tunnel excavation and blasting are crucial for the stability and safety of tunnels. Therefore, the safe distance between the lining structure and blasting source should be determined to avoid concrete damage caused by blasting vibrations. In this study, taking the subway tunnel of Danshan Station in Qingdao as an example, the JH-2 model is introduced as the constitutive model of the tunnel blasting simulation, and the JH-2 model parameters of the local surrounding rock are obtained by experiments, and finally the numerical simulation and theoretical verification are carried out to study the safety distance of shotcrete under various safety judgment standards. The results indicate that the JH-2 model can effectively simulate the propagation of stress waves under different media conditions, and the closer the strength parameters and pressure constant of the lining structure are to those of the surrounding rock, the safer the concrete-rock bonding interface. During tunnel blasting construction using the ring blasting method, the peak particle velocity (PPV) of the lining structure increases with an increase in the arch angle. Based on the numerical simulation results, we recommend that concrete lining be constructed at a distance of at least 62 m from the blasting source to avoid damage caused by vibrations. The effect of concrete tensile failure caused by longitudinal stress is much smaller than the damage to the bonding interface caused by the PPV and can be neglected.
RESUMO
Photothermal therapy (PTT) is an effective cancer treatment that circumvents the resistance caused by chemotherapy drugs. Conventional PTT has a relatively high temperature, which is better able to kill tumor tissues, but it is also more damaging to normal tissues. Mild PTT avoids these high temperatures, but its corresponding killing ability becomes lower and enhances the heat resistance of cancer cells, causing tumor self-protection and reducing the therapeutic effect of PTT. Here, we reported a new, remotely stimulable, mild-temperature PTT combined with electrical stimulation-induced ionic interference therapy. We introduced MXenes into alginate based thermoresponsive PVA/P(NIPAm-co-SA) hydrogel (PPS) to formulate mechanically reliable hydrogel electrolyte-based supercapacitors as an ion homeostasis perturbator. The artificially controlled duration of near-infrared radiation modulates the PTT cycle temperature, which is controllably maintained at a little under 45⯰C to reduce Hsp90 overexpression. Light-induced phase transitions in the hydrogel produce voltages that resemble low-intensity, alternating electric fields. Moreover, chronic piezoelectric stimulation can inhibit cancer cell proliferation by upregulating the expression of genes encoding Kir3.2 inwardly rectifying potassium channels, by interfering with Ca2+ homeostasis, and by affecting mitotic spindle organization during mitosis. In vivo and in vitro antitumor studies on the 4â¯T1 model suggest that this functionalized, remote, light-responsive transducer is an effective and promising tool for the treatment of tumors.
RESUMO
Calcium (Ca2+) acts as a second messenger and constitutes a complex and large information exchange system between the endoplasmic reticulum (ER) and mitochondria; this process is involved in various life activities, such as energy metabolism, cell proliferation and apoptosis. Increasing evidence has suggested that alterations in Ca2+ crosstalk between the ER and mitochondria, including alterations in ER and mitochondrial Ca2+ channels and related Ca2+ regulatory proteins, such as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), inositol 1,4,5-trisphosphate receptor (IP3R), and calnexin (CNX), are closely associated with the development of kidney disease. Therapies targeting intracellular Ca2+ signaling have emerged as an emerging field in the treatment of renal diseases. In this review, we focused on recent advances in Ca2+ signaling, ER and mitochondrial Ca2+ monitoring methods and Ca2+ homeostasis in the development of renal diseases and sought to identify new targets and insights for the treatment of renal diseases by targeting Ca2+ channels or related Ca2+ regulatory proteins.
Assuntos
Sinalização do Cálcio , Retículo Endoplasmático , Nefropatias , Mitocôndrias , Humanos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Nefropatias/metabolismo , Nefropatias/tratamento farmacológico , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Animais , Desenvolvimento de Medicamentos/métodos , Cálcio/metabolismoRESUMO
Triple negative breast cancer (TNBC) is insensitive to conventional targeted therapy and endocrine therapy, and is characterized by high invasiveness and high recurrence rate. This study aimed to explore the role and mechanism of RHOXF2 and HOXC13 on the malignant progression of TNBC. RT-qPCR and western blot were used to detect RHOXF2 and HOXC13 expression in TNBC cells. The proliferation, colony formation, invasion, migration, apoptosis and cell cycle of TNBC cells after transfection were analyzed by CCK-8 assay, colony formation assay, transwell assay, wound healing assay and flow cytometry analysis. Co-Immunoprecipitation and GST pull-down assays were used to analyze the combination between RHOXF2 and HOXC13. ChIP-PCR and luciferase reporter gene assay were used to examine the regulation of H3K27ac on RHOXF2. Besides, the expression of Ki67 and cleaved Caspase3 in tumor tissues of nude mice was determined by immunofluorescence. Results revealed that RHOXF2 and HOXC13 expression was increased in TNBC cells. RHOXF2 knockdown suppressed the proliferation, invasion and migration, as well as induced G0/G1 cell cycle arrest and apoptosis of TNBC cells. Besides, RHOXF2 could bind to HOXC13 and RHOXF2 knockdown suppressed HOXC13 expression in TNBC cells. Furthermore, HOXC13 overexpression reversed the impacts of RHOXF2 downregulation on the proliferation, invasion, migration, G0/G1 cell cycle arrest and apoptosis of TNBC cells. In addition, RHOXF2 silencing limited the tumor volume in nude mice, which was reversed by HOXC13 overexpression. Moreover, RHOXF2 knockdown interfered with Wnt2/ß-catenin pathway in vitro and in vivo by binding to HOXC13. Importantly, H3K27ac acetylation could activate the expression of RHOXF2 promoter region. In conclusion, RHOXF2 activated by H3K27ac functioned as a tumor promoter in TNBC via mediating Wnt2/ß-catenin pathway by binding to HOXC13, which provided promising insight into exploration on TNBC therapy.
Assuntos
Movimento Celular , Proliferação de Células , Proteínas de Homeodomínio , Camundongos Nus , Neoplasias de Mama Triplo Negativas , Via de Sinalização Wnt , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Humanos , Animais , Feminino , Via de Sinalização Wnt/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Histonas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Progressão da Doença , beta Catenina/metabolismoRESUMO
Primary open-angle glaucoma (POAG) is the most common form of glaucoma and the leading cause of irreversible vision loss and blindness worldwide. Intraocular pressure (IOP) is the only modifiable risk factor, and prompt treatment to lower IOP can effectively slow the rate of vision loss due to glaucoma. Trabecular meshwork (TM) cells can maintain IOP homeostasis by correcting and adjusting the resistance to aqueous humor outflow in response to sustained pressure changes. TM cells' function is reduced, and membrane ion channels are impaired in POAG. The dysfunction of Large conductance Ca2+-activated K+ (BKCa) plays a central role in the pathogenesis of POAG. In this work, we targeted MXene nanoparticles (MXene-RGD) with piezoelectric response to TM cells in a 3D model of glaucoma in vitro as well as in the rabbit Transient Ocular Hypertension (OHT) Model in vivo. MXene-RGD gives the TM electromechanical transfer properties, while the self-enhancing and self-generated electricity properties of the TM are determined by the aqueous humor flow rate and the size of the deformation of the TM. MXene-RGD is nontoxic, as illustrated by a cell toxicity study and histological examination. In a 3D in vitro model of high-pressure glaucoma, whole-cell patch-clamp confirmed that piezoelectric stimulation turns on BKCa, which reduces the volume of the cell. MXene-RGD was injected into the anterior chamber with minimal trauma, i.e., anterior chamber injection, and specifically targeted to TM cells. The OHT model in vivo confirmed the potential IOP-lowering ability of MXene-RGD. We evaluated the ion channels involved in the reduction of IOP by MXene-RGD by pre-treatment with a BKCa channel blocker (iberiotoxin, IbTX) and a voltage-gated Ca2+channel blocker (nifedipine). Quantitative qPCR analysis showed that MXene-RGD inhibited the upregulation of mRNA expression levels of the myofibroblast marker α-smooth muscle actin (α-SMA) and the inflammatory response marker interleukin-6 (IL-6) induced by IOP. Histology confirmed that MXene-RGD attenuated IOP-induced proliferation and collagen production in the TM. Taken together, we present for the first time a minimally invasive surgical approach for targeting TM cells for POAG by utilizing piezoresponse nanomaterials to target BKCa to repair or awaken the ability of TM cells to regulate IOP homeostasis on their own.
RESUMO
Myocardial ischemia-reperfusion (IR) injury is a severe rhythmic disease with a high prevalence in the early morning. IR injury has a significant circadian rhythm in reactive oxygen species (ROS) and inflammation levels. The development of rhythmic drugs has become a priority in myocardial IR injury. In this study, resveratrol (RES) and proanthocyanidins (OPC) were utilized to design nanoparticles (NPs), with hyaluronic acid (HA) as the core, grafted with MMP-targeting peptides to improve delivery to injured myocardial regions (HA-RES-OPC-MMP NPs). NPs significantly scavenged ROS, attenuated inflammation, and activated the rhythm gene. Notably, the difference in therapeutic effects on myocardial IR injury in mice at Zeitgeber time (ZT)1 and ZT13 confirms that NPs are rhythm-dependent drugs. At ZT13, echocardiographic and MRI confirm that IR injury in mice was not as severe as at ZT1, yet NPs were also less effective in treatment. Further, Per1/2 knockout mice confirmed the rhythm-dependent treatment of myocardial IR injury by NPs. Molecular studies have shown that rhythmic characteristics of inflammation and Sirt1 transcript levels are the main reasons for the different rhythmic therapeutic effects of NPs. Circadian rhythm-dependent treatment of HA-RES-OPC-MMP NPs has excellent potential for more precise treatment of myocardial IR injury in the future.
Assuntos
Ritmo Circadiano , Traumatismo por Reperfusão Miocárdica , Nanopartículas , Resveratrol , Animais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Nanopartículas/química , Camundongos , Resveratrol/farmacologia , Resveratrol/química , Ritmo Circadiano/efeitos dos fármacos , Camundongos Knockout , Masculino , Proantocianidinas/química , Proantocianidinas/farmacologia , Ácido Hialurônico/química , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Sirtuína 1/metabolismo , Proteínas Circadianas Period/metabolismo , Proteínas Circadianas Period/genética , Polifenóis/química , Polifenóis/farmacologiaRESUMO
Correction for 'A novel nano delivery system targeting different stages of osteoclasts' by Bosong Zhang et al., Biomater. Sci., 2022, 10, 1821-1830, https://doi.org/10.1039/D2BM00076H.
RESUMO
This research assesses the effects of COVID-19-associated shocks on financial constraints and sustainable development goal (SDG) performance to shed light on the impact of SDGs on economic recovery. We construct a large sample of Chinese listed firms from quarterly firm-level accounting data from the China Stock Market & Accounting Research Database for the period 2019Q1-2021Q1, matched with environmental, social, and governance (ESG) scores, SDG performance from the WIND Database, and complemented with data on cumulative and new cases of COVID-19 from the World Health Organization. We use difference-in-differences to investigate any causal effect from COVID-19. We find that COVID-19 induces financial constraints in firms. Further, differing from the existing literature on the determinants of SDGs, we explore the supportive role of SDG performance on firm financial performance and show that ESG can better describe SDG performance and alleviate financial constraints. Moreover, both internal and external financial intermediaries improve with enhanced ESG performance in overcoming financial constraints. Our findings strongly indicate that a sustainable development strategy facilitates efficient adaptation to financial challenges and assists in overcoming external shocks.
Cette étude évalue les effets des chocs associés à la COVID-19 sur les contraintes financières et la performance des objectifs de développement durable (ODD) pour mettre en lumière l'impact des ODD sur la reprise économique. Nous rassemblons un large échantillon d'entreprises chinoises cotées en Bourse à partir de données comptables trimestrielles émanant de la base de données de recherche sur la comptabilité et sur le marché boursier chinois, du premier trimestre 2019 au premier trimestre 2021. Ces données sont appariées avec des critères environnementaux, sociaux et de gouvernance (ESG), avec la performance des ODD tirée de la base de données WIND, et sont complétées par des données issues de l'Organisation mondiale de la santé sur le nombre de cas cumulatifs et de nouveaux cas de COVID-19. Nous utilisons la méthode des différences de différences pour étudier l'effet de causalité lié à la COVID-19. Nous constatons que la COVID-19 provoque des contraintes financières au sein des entreprises. De plus, contrairement à ce qui est réalisé dans la littérature existante sur les déterminants des ODD, nous explorons le rôle d'appui que jouent les bons résultats des ODD sur la performance financière des entreprises et montrons que les critères ESG permettent de décrire de façon plus adéquate les résultats des ODD et d'alléger les contraintes financières. De plus, les intermédiaires financiers à la fois internes et externes, grâce à de meilleures performances des critères ESG, sont en gré d'améliorer leur réponse aux contraintes financières. Nos résultats fournissent des donnéees probantes selon lesquelles une stratégie de développement durable facilite une adaptation efficiente aux défis financiers et aide à surmonter les chocs externes.