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1.
Adv Mater ; : e2409261, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39092687

RESUMO

The bottom contact in perovskite solar cells (PSCs) is easy to cause deep trap states and severe instability issues, especially under maximum power point tracking (MPPT). In this study, sodium gluconate (SG) is employed to disperse tin oxide (SnO2) nanoparticles (NPs) and regulate the interface contact at the buried interface. The SG-SnO2 electron transfer layer (ETL) enabled the deposition of pinhole-free perovskite films in ambient air and improved interface contact by bridging effect. SG-SnO2 PSCs achieved an impressive power conversion efficiency (PCE) of 25.34% (certified as 25.17%) with a high open-circuit voltage (VOC) exceeding 1.19 V. The VOC loss is less than 0.34 V relative to the 1.53 eV bandgap, and the fill factor (FF) loss is only 2.02% due to the improved contact. The SG-SnO2 PSCs retained around 90% of their initial PCEs after 1000 h operation (T90 = 1000 h), higher than T80 = 1000 h for the control SnO2 PSC. Microstructure analysis revealed that light-induced degradation primarily occurred at the buried holes and grain boundaries and highlighted the importance of bottom-contact engineering.

2.
Cell Mol Biol (Noisy-le-grand) ; 70(7): 100-105, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39097890

RESUMO

Goosecoid (GSC), translated from a homeobox gene, is a protein that participates in metastasis of various cancers. Pancreatic adenocarcinoma (PAAD) is one of the deadliest malignancies associated with a poor diagnosis and prognosis. To develop new treatment target or biomarker for PAAD, this study intended to assess the effects and the molecular mechanism of GSC on PAAD metastasis. The expressive discrepancy of GSC in PAAD and normal tissues/cells was compared by both the quantitative PCR and western blot. The effects of GSC silencing and GSC over-expression on PAAD cells and TGF-ß signaling were proved by wound-healing assay, cell counting kit-8, Transwell assay and western blot. From the results, GSC mRNA and protein levels were enriched in PAAD cancer tissues and cells. GSC silencing prohibited metastasis of PAAD cells including the ability to invade, migrate and epithelial-mesenchymal transition (EMT), whereas GSC upregulation stimulated these cells behaviors above. GSC silencing reversed the effects on cellular processes induced by activation of the TGF-ß pathway. Furthermore, silencing of GSC postponed tumor growth in xenograft model. In summary, GSC was abundantly expressed in PAAD, which activated the TGF-ß pathway to enhance cell metastasis and tumor development.


Assuntos
Adenocarcinoma , Transição Epitelial-Mesenquimal , Metástase Neoplásica , Neoplasias Pancreáticas , Transdução de Sinais , Fator de Crescimento Transformador beta , Animais , Humanos , Camundongos , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Fator de Crescimento Transformador beta/metabolismo
3.
J Biomater Sci Polym Ed ; : 1-23, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39163367

RESUMO

Conventional wound dressings used in trauma treatment have a single function and insufficient adaptability to the wound environment, making it difficult to meet the complex demands of the healing process. Stimuli-responsive hydrogels can respond specifically to the particular environment of the wound area and realize on-demand responsive release by loading active substances, which can effectively promote wound healing. In this paper, BC/PAA-pH responsive hydrogels (BPPRHs) were prepared by graft copolymerization of acrylic acid (AA) to the end of the molecular chain of bacterial cellulose (BC) network structure. Antibacterial pH-responsive 'smart' dressings were prepared by loading curcumin (Cur) onto the hydrogels. Surface morphology, chemical groups, crystallinity, rheological, and mechanical properties of BPPRHs were analyzed by different characterization methods. The drug release behavior under different physiological conditions and bacteriostatic properties of BPPRH-Cur dressings were also investigated. The results of structural characterization and performance studies show that the hydrogel has a three-dimensional mesh structure and can respond to wound pH in a 'smart' drug release capacity. The drug release behavior of the BPPRH-Cur dressings under different environmental conditions conformed to the logistic and Weibull kinetic models. BPPRH-Cur displayed good antimicrobial activity against common pathogens of wound infections such as E. coli, S. aureus, and P. aeruginosa by destroying the cell membrane and lysing the bacterial cells. This study lays the foundation for the development of new pharmaceutical dressings with positive health, economic and social benefits.

4.
Small Methods ; : e2400796, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169726

RESUMO

Cesium lead triiodide (CsPbI3) perovskites have garnered significant attention owing to their suitable bandgap for tandem silicon substrates and excellent chemical stability. However, γ-CsPbI3 prepared via low-temperature co-evaporation is limited by a narrow black phase processing window and random crystal orientation, hindering its optoelectronic performance and industrial applications. This study introduced trace amounts of methylammonium iodide (MAI) into the co-evaporation system, enhancing the crystallization process, promoting columnar grain growth, and stabilizing the γ-phase perovskite, resulting in films with improved structural integrity and reduced defect density. The optimal Pb/Cs ratio for achieving the best photoelectric performance shifted from 1:1 to 1.1:1 in the presence of MAI. Additionally, the incorporation of MAI allowed for more efficient longitudinal carrier transport, as evidenced by the enhanced photoluminescence (PL) intensity. The bandgap of CsPbI3 remained approximately at 1.7 eV before the δ-phase transition, ensuring suitability for photovoltaic applications. Ultimately, a photovoltaic device with 12% efficiency is achieved in the p-i-n structure without additional post-annealing of the CsPbI3 perovskite films, demonstrating the practical benefits of MAI incorporation.

5.
QJM ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39186005

RESUMO

BACKGROUND: Mucopolysaccharidosis (MPS) IVA is a lysosomal storage disorder caused by mutations in the gene encoding the galactosamine (N-acetyl)-6-sulfatase (GALNS) enzyme. Children with MPS IVA usually develop pectus carinatum, genu valgum, and multiple skeletal abnormalities. AIM: To establish a patient-derived induced pluripotent stem cell (iPSC) disease model to investigate the effects of two GALNS missense mutations. METHODS: The medical history and clinical manifestations of a patient with MPS IVA were first inspected. The effects of the identified GALNS mutations were predicted through bioinformatic analysis. iPSCs were then generated by using Sendai virus to introduce Yamanaka reprogramming factors to urinary cells isolated from the patient. The pluripotency, karyotypic integrity, genetic mutations, and differentiation ability of the iPSCs were tested. The effects of the GALNS mutations were further experimentally characterized using patient-derived cells. RESULTS: The patient exhibited a typical MPS IVA phenotype. Enzyme replacement therapy could not correct her skeletal abnormalities. GALNS c.485C>A (p.S162Y) and c.494G>T (p.C165F) mutations, inherited from her father and mother respectively, were identified in the patient. These two mutations were predicted to disturb the hydrophobic core of the GALNS catalytic domain. Patient-derived iPSCs were successfully generated, and further characterization indicated that the two missense mutations significantly diminished GALNS activity without affecting its amount at both the RNA and protein levels. CONCLUSIONS: We established a novel clinically relevant MPS IVA disease model that will be useful not only for investigating the pathogenic mechanisms of MPS IVA variants but also for drug screening and preclinical evaluation of novel therapies.

6.
Clin Proteomics ; 21(1): 46, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951753

RESUMO

PURPOSE: The primary objective of this investigation is to systematically screen and identify differentially expressed proteins (DEPs) within the plasma of individuals afflicted with sepsis. This endeavor employs both Data-Independent Acquisition (DIA) and enzyme-linked immunosorbent assay (ELISA) methodologies. The overarching goal is to furnish accessible and precise serum biomarkers conducive to the diagnostic discernment of sepsis. METHOD: The study encompasses 53 sepsis patients admitted to the Affiliated Hospital of Southwest Medical University between January 2019 and December 2020, alongside a control cohort consisting of 16 individuals devoid of sepsis pathology. Subsequently, a subset comprising 10 randomly selected subjects from the control group and 22 from the sepsis group undergoes quantitative proteomic analysis via DIA. The acquired data undergoes Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses, facilitating the construction of a Protein-Protein Interaction (PPI) network to discern potential markers. Validation of core proteins is then accomplished through ELISA. Comparative analysis between the normal and sepsis groups ensues, characterized by Receiver Operating Characteristic (ROC) curve construction to evaluate diagnostic efficacy. RESULT: A total of 187 DEPs were identified through bioinformatic methodologies. Examination reveals their predominant involvement in biological processes such as wound healing, coagulation, and blood coagulation. Functional pathway analysis further elucidates their engagement in the complement pathway and malaria. Resistin emerges as a candidate plasma biomarker, subsequently validated through ELISA. Notably, the protein exhibits significantly elevated levels in the serum of sepsis patients compared to the normal control group. ROC curve analysis underscores the robust diagnostic capacity of these biomarkers for sepsis. CONCLUSION: Data-Independent Acquisition (DIA) and Enzyme-Linked Immunosorbent Assay (ELISA) show increased Resistin levels in sepsis patients, suggesting diagnostic potential, warranting further research.

7.
Nat Commun ; 15(1): 5705, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977710

RESUMO

In nature, coenzyme-independent oxidases have evolved in selective catalysis using isolated substrate-binding pockets. Single-atom nanozymes (SAzymes), an emerging type of non-protein artificial enzymes, are promising to simulate enzyme active centers, but owing to the lack of recognition sites, realizing substrate specificity is a formidable task. Here we report a metal-ligand dual-site SAzyme (Ni-DAB) that exhibited selectivity in uric acid (UA) oxidation. Ni-DAB mimics the dual-site catalytic mechanism of urate oxidase, in which the Ni metal center and the C atom in the ligand serve as the specific UA and O2 binding sites, respectively, characterized by synchrotron soft X-ray absorption spectroscopy, in situ near ambient pressure X-ray photoelectron spectroscopy, and isotope labeling. The theoretical calculations reveal the high catalytic specificity is derived from not only the delicate interaction between UA and the Ni center but also the complementary oxygen reduction at the beta C site in the ligand. As a potential application, a Ni-DAB-based biofuel cell using human urine is constructed. This work unlocks an approach of enzyme-like isolated dual sites in boosting the selectivity of non-protein artificial enzymes.


Assuntos
Oxirredução , Urato Oxidase , Ácido Úrico , Especificidade por Substrato , Urato Oxidase/química , Urato Oxidase/metabolismo , Ácido Úrico/química , Ácido Úrico/metabolismo , Ácido Úrico/urina , Ligantes , Humanos , Níquel/química , Níquel/metabolismo , Sítios de Ligação , Domínio Catalítico , Catálise , Modelos Moleculares , Espectroscopia por Absorção de Raios X
8.
J Fungi (Basel) ; 10(6)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38921382

RESUMO

Sterigmatocystins and aflatoxins are a group of mycotoxins mainly isolated from fungi of the genera Aspergillus. Since the discovery of sterigmatocystins in 1954 and aflatoxins in 1961, many scholars have conducted a series of studies on their structural identification, synthesis and biological activities. Studies have shown that sterigmatocystins and aflatoxins have a wide range of biological activities such as antitumour, antibacterial, anti-inflammatory, antiplasmodial, etc. The sterigmatocystins and aflatoxins had been shown to be hepatotoxic and nephrotoxic in animals. This review attempts to give a comprehensive summary of progress on the chemical structural features, synthesis, and bioactivity of sterigmatocystins and aflatoxins reported from 1954 to April 2024. A total of 72 sterigmatocystins and 20 aflatoxins are presented in this review. This paper reviews the chemical diversity and potential activity and toxicity of sterigmatocystins and aflatoxins, enhances the understanding of sterigmatocystins and aflatoxins that adversely affect humans and animals, and provides ideas for their prevention, research and development.

9.
Sci Rep ; 14(1): 13831, 2024 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879647

RESUMO

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as EPAS1, LIFR, and NID1, as well as several previously revealed markers, such as CLEC4M, CLEC1B, CRHBP and FCN3. These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.


Assuntos
Diferenciação Celular , Células Endoteliais , Células-Tronco Pluripotentes Induzidas , Fígado , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/citologia , Fígado/metabolismo , Fígado/citologia , Análise de Célula Única/métodos , Células Cultivadas , Biomarcadores/metabolismo , Lipoproteínas LDL/metabolismo , Perfilação da Expressão Gênica
10.
Chem Biodivers ; : e202400752, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38923373

RESUMO

Myricetin (1), Quercetin (2), Kaempferol (3) and Kaempferide (4) were flavonoids with phenolic hydroxyl groups. The antioxidant and pharmacological mechanisms of them were investigated in detail. The lowest hydroxyl dissociation enthalpies of 1, 2, 3 and 4 were calculated by DFT, respectively. The hydroxyl dissociation enthalpies of the four flavonoids at the O2 site are the highest. By analyzing the intramolecular hydrogen bonds and HOMO-LUMO orbitals of the four flavonoids, the reasons for their divergence of hydroxyl dissociation enthalpies and antioxidant mechanisms were further investigated. The UV-vis and IR spectra of four flavonoids were compared. The interactions about electrostatic attraction, p-π conjugation and hydrogen bond combined the flavonoid with the target protein closely. The root mean square deviation of peroxisome proliferator-activated receptor γ combined with 1, 2 and 3 increased, while that of PPARγ combined with 4 decreased.

11.
J Expo Sci Environ Epidemiol ; 34(4): 555-569, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38871958

RESUMO

BACKGROUND: The importance of building ventilation to protect health has been more widely recognized since the COVID-19 pandemic. Outdoor air ventilation in buildings dilutes indoor-generated air pollutants (including bioaerosols) and reduces resulting occupant exposures. Many countries and organizations have advisory guidelines or mandatory standards for minimum ventilation rates (VRs) to maintain indoor air quality (IAQ). Because directly measuring VRs is often difficult, many IAQ guidelines instead specify indoor concentration limits for carbon dioxide (CO2), using CO2 exhaled by building occupants as an indicator of VR. Although indoor CO2 guidelines are common, the evidence basis for the various CO2 limits has not been clear. OBJECTIVE: To review current indoor CO2 guidelines worldwide and the supportive evidence provided. METHODS: We identified worldwide CO2-based guidelines for IAQ or ventilation, along with any supportive evidence provided. We excluded occupational guidelines for CO2 levels ≥5000 ppm. RESULTS: Among 43 guidelines identified, 35 set single CO2 concentration limits and eight set multi-tiered limits; 16 mentioned no specific human effect to be controlled, 19 specified only odor dissatisfaction, five specified non-infectious health effects, and three specified airborne infectious disease transmission. The most common indoor CO2 limit was 1000 ppm. Thirteen guidelines specified maximum CO2 limits as extended time-weighted averages, none with evidence linking averaged limits to occupant effects. Of only 18 guidelines citing evidence to support limits set, we found this evidence persuasive for eight. Among these eight guidelines, seven set limits to control odor perception. One provided 17 scientifically-based CO2 limits, for specific example space uses and occupancies, to control long-range COVID-19 transmission indoors. IMPACT: Many current indoor carbon dioxide (CO2) guidelines for indoor air quality specified no adverse effects intended for control. Odor dissatisfaction was the effect mentioned most frequently, few mentioned health, and three mentioned control of infectious disease. Only one CO2 guideline was developed from scientific models to control airborne transmission of COVID-19. Most guidelines provided no supportive evidence for specified limits; few provided persuasive evidence. No scientific basis is apparent for setting one CO2 limit for IAQ across all buildings, setting a CO2 limit for IAQ as an extended time-weighted average, or using any arbitrary one-time CO2 measurement to verify a desired VR.


Assuntos
Poluição do Ar em Ambientes Fechados , COVID-19 , Dióxido de Carbono , Guias como Assunto , SARS-CoV-2 , Ventilação , Poluição do Ar em Ambientes Fechados/análise , Humanos , Dióxido de Carbono/análise , Ventilação/normas , COVID-19/prevenção & controle , COVID-19/transmissão , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Monitoramento Ambiental/normas
12.
Int J Mol Sci ; 25(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38928141

RESUMO

Unlike sedentary plant-parasitic nematodes, migratory plant endoparasitic nematodes (MPENs) are unable to establish permanent feeding sites, and all developmental stages (except eggs) can invade and feed on plant tissues and can be easily overlooked because of the unspecific symptoms. They cause numerous economic losses in agriculture, forestry, and horticulture. In order to understand the pathogenetic mechanism of MPENs, here we describe research on functions and host targets focused on currently identified effectors from six MPENs, namely Radopholus similis, Pratylenchus spp., Ditylenchus destructor, Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Hirschmanniella oryzae. This information will provide valuable insights into understanding MPEN effectors and for future fostering advancements in plant protection.


Assuntos
Interações Hospedeiro-Parasita , Doenças das Plantas , Plantas , Animais , Doenças das Plantas/parasitologia , Plantas/parasitologia , Nematoides/patogenicidade , Proteínas de Helminto/metabolismo
13.
Chem Commun (Camb) ; 60(45): 5828-5831, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38747249

RESUMO

The salt metathesis of a boryl-ethynyl lithium salt {[(HCDipN)2]B-CC-Li} with a monochlorosilylene [LSi(:)Cl; L = PhC(NtBu)2] produced an isolable boryl-ethynyl silylene {1; [(HCDipN)2]B-CC-Si(L)}. The Si(II) center in 1 possesses a nonbonding lone pair and forms a covalent bond with the ethynyl group. The characterization of 1 was carried out by multinuclear NMR spectroscopy, single-crystal X-ray structure analysis and DFT calculations. Additionally, a reactivity study of 1 was conducted towards oxygen-containing and aryl C-F substrates.

14.
J Colloid Interface Sci ; 671: 553-563, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38820840

RESUMO

Recently, the solar-driven interfacial evaporation desalination has attracted more and more attentions due to the advantages of low cost, zero energy consumption, and high water purification rate, etc. One of the bottlenecks of this emerging technique lies in a lack of simple and low-cost ways to construct three-dimensional (3D) hierarchical microstructures for photothermal membranes. To this end, a two-step strategy is carried out by combining surface functionalization with substrate engineering. Firstly, a silane coupling agent 3-aminopropyltriethoxysilane (APTES) is grafted onto an ideal photothermal material of Ti3C2Tx MXene, to improve the nanochannel sizes and hydrophilicity, which are attributed to enlarged interspaces of MXene and introduced hydrophilic group e.g., -NH2 and -OH, respectively. Secondly, a low-cost and robust nonwoven fiber (NWF) substrate, which has a 3D micron-sized mesh structure with interlaced fiber stacks, is employed as the skeleton to load enough APTES-grafted MXene by a simple soaking method. Benefited from above design, the Ti3C2Tx-APTES/NWF composite membrane with a 3D hierarchical structure shows enhanced light scattering and utilization, water transport and vapor escape. A remarkable evaporation rate of 1.457 kg m-2 h-1 and an evaporation efficiency of 91.48 % are attained for a large-area (5 × 5 cm2) evaporator, and the evaporation rate is further increased to 1.672 kg m-2 h-1 for a small-area (2 × 2 cm2) device. The rejection rates of salt ions and heavy metal ions are higher than 99 % and 99.99 %, respectively, and the removal rates of organic dye molecules are nearly to 100 %. Besides, the composite photothermal membrane exhibits great stabilities in harsh conditions such as high salinities, long cycling, large light intensities, strong acid/alkali environments, and mechanical bending. Most importantly, the photothermal membrane shows a considerable cost-effectiveness of 89.4 g h-1/$. Hence, this study might promote the commercialization of solar-driven interfacial evaporation desalination by collaboratively considering surface modification and substrate engineering for MXene.

15.
Research (Wash D C) ; 7: 0355, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694202

RESUMO

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

16.
Chemphyschem ; 25(15): e202400290, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38695835

RESUMO

Dye-sensitized solar cells (DSSCs), quantum dot-sensitized solar cells (QDSSCs) and perovskite solar cells (PSCs) have attracted wide attention. DSSCs, QDSSCs and PSCs can be prepared by liquid phase or solid phase, which causes a certain range of interface micro-mass changes during preparation. In addition, the photoelectric conversion process occurring inside the device also inevitably causes interface micro-mass changes. Interpretation of these interface micro-mass changes can help to optimize the cell structure, improve the stability and performance repeatability of the device, as well as directly or indirectly infer, track and predict the internal photoelectric conversion mechanism of the device. Quartz crystal microbalance (QCM) is a powerful tool for studying surface mass changes, extending this technology to the fields of solar cells to directly obtain interface micro-mass changes, which makes the research more in-depth and opens up a new perspective for explaining the basic principles of solar cells. This review summarizes the research progress of QCM application in DSSCs, QDSSCs and PSCs in recent years, and explores the challenges and new opportunities of QCM application in new solar cells in the future.

17.
FASEB J ; 38(10): e23646, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38795328

RESUMO

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.


Assuntos
Autofagia Mediada por Chaperonas , Glicogênio Sintase Quinase 3 beta , Inflamação , Proteína 2 de Membrana Associada ao Lisossomo , Células-Tronco Mesenquimais , Osteogênese , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , beta Catenina , Animais , Osteogênese/fisiologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , beta Catenina/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/genética , Transdução de Sinais , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Diferenciação Celular , Osteoclastos/metabolismo
18.
Sci Immunol ; 9(94): eadh0085, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669317

RESUMO

Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)-mediated ablation of PD-1+ cells reshaped the TCR repertoire through peripheral clonal deletion of alloreactive T cells and promoted tolerance in mouse transplantation models. In addition, by using PD-1-specific depleting antibodies, we found that antibody-mediated depletion of PD-1+ cells prevented heart transplant rejection and the development of experimental autoimmune encephalomyelitis (EAE) in humanized PD-1 mice. Thus, these data suggest that PD-1 is an attractive target for peripheral clonal deletion and induction of immune tolerance.


Assuntos
Deleção Clonal , Tolerância Imunológica , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1 , Animais , Receptor de Morte Celular Programada 1/imunologia , Camundongos , Deleção Clonal/imunologia , Tolerância Imunológica/imunologia , Humanos , Encefalomielite Autoimune Experimental/imunologia , Transplante de Coração , Linfócitos T/imunologia , Camundongos Knockout , Camundongos Endogâmicos BALB C , Feminino
19.
Sci Rep ; 14(1): 9676, 2024 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678059

RESUMO

To utilize metabolomics in conjunction with RNA sequencing to identify biomarkers in the blood of sepsis patients and discover novel targets for diagnosing and treating sepsis. In January 2019 and December 2020, blood samples were collected from a cohort of 16 patients diagnosed with sepsis and 11 patients diagnosed with systemic inflammatory response syndrome (SIRS). Non-targeted metabolomics analysis was conducted using liquid chromatography coupled with mass spectrometry (LC-MS/MS technology), while gene sequencing was performed using RNA sequencing. Afterward, the metabolite data and sequencing data underwent quality control and difference analysis, with a fold change (FC) greater than or equal to 2 and a false discovery rate (FDR) less than 0.05.Co-analysis was then performed to identify differential factors with consistent expression trends based on the metabolic pathway context; KEGG enrichment analysis was performed on the crossover factors, and Meta-analysis of the targets was performed at the transcriptome level using the public dataset. In the end, a total of five samples of single nucleated cells from peripheral blood (two normal controls, one with systemic inflammatory response syndrome, and two with sepsis) were collected and examined to determine the cellular location of the essential genes using 10× single cell RNA sequencing (scRNA-seq). A total of 485 genes and 1083 metabolites were found to be differentially expressed in the sepsis group compared to the SIRS group. Among these, 40 genes were found to be differentially expressed in both the metabolome and transcriptome. Functional enrichment analysis revealed that these genes were primarily involved in biological processes related to inflammatory response, immune regulation, and amino acid metabolism. Furthermore, a meta-analysis identified four genes, namely ITGAM, CD44, C3AR1, and IL2RG, which were highly expressed in the sepsis group compared to the normal group (P < 0.05). Additionally, scRNA-seq analysis revealed that the core genes ITGAM and C3AR1 were predominantly localized within the macrophage lineage. The primary genes ITGAM and C3AR1 exhibit predominant expression in macrophages, which play a significant role in inflammatory and immune responses. Moreover, these genes show elevated expression levels in the plasma of individuals with sepsis, indicating their potential as valuable subjects for further research in sepsis.


Assuntos
Biomarcadores , Metabolômica , Sepse , Humanos , Sepse/genética , Sepse/sangue , Sepse/metabolismo , Biomarcadores/sangue , Metabolômica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Transcriptoma , Perfilação da Expressão Gênica , Idoso , Adulto , Cromatografia Líquida , Espectrometria de Massas em Tandem , Síndrome de Resposta Inflamatória Sistêmica/genética , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
20.
BMC Musculoskelet Disord ; 25(1): 338, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671421

RESUMO

OBJECTIVES: The application of a growing rod technique can retain the growth and development potential of the spine and thorax while controlling the progression of scoliosis deformity. Theoretically, convex side short fusion combined with a concave side single growing rod technique can significantly reduce the asymmetric growth of the spine in the vertex region in most patients. However, the final clinical outcome of various techniques is yet to be clearly determined and compared between studies. Therefore, we compared the efficacy of these two growing rod techniques in treating early onset scoliosis. METHODS: In a retrospective study of 152 EOS patients seen between 2013.1 and 2019.12, 36 cases of EOS patients were selected for inclusion. Among the 36 cases, 11 cases were treated with convex side short fusion combined with a concave side single growing rod technique, group (A) The remaining 25 cases were treated with traditional bilateral growing rod technique, group (B) Age, gender, etiology, follow-up time, Cobb angle of main curve, T1-S1 height, coronal trunk shift, sagittal vertical axis (SVA), Cobb angle of thoracic kyphosis at last follow-up, and Cobb angle at proximal junction kyphosis of the first and last post-operation follow-up were recorded. In addition, internal fixation related complications, infection, nervous system complications were recorded as well. RESULTS: There was no statistically significant difference between group A and group B in preoperative age, Cobb angle of main curve, coronal trunk shift, T1-S1 height, SVA, Cobb angle of thoracic kyphosis (p > 0.05). However, at the last follow-up (Group A, mean 4.4 ± 1.01 years; Group B, mean 3.6 ± 0.01 years) the Cobb angle of the main curve was less and T1-S1 height greater in group A compared with group B (p < 0.05). There was no statistically significant difference between group A and group B in the correction rate of the Cobb angle of the main curve or the growth rate of T1-S1 height (p > 0.05). There was no statistically significant difference in the coronal imbalance ratio, thoracic kyphosis abnormality ratio, or the occurrence PJK ratio between group A and group B at the last follow-up (p > 0.05), but the sagittal imbalance ratio and internal fixation abnormality ratio were higher in group A than in the group B (p < 0.05). CONCLUSIONS: During the treatment of EOS, both the convex side short fusion combined with concave side single growing rod technique and traditional bilateral growing rod technique can correct the Cobb angle of main curve with no significant hindering of the spinal growth observed. The traditional bilateral growing rod technique has advantages in control of the sagittal balance of the spine, and the complications associated with internal fixation were lower.


Assuntos
Escoliose , Fusão Vertebral , Humanos , Escoliose/cirurgia , Escoliose/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Masculino , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/instrumentação , Criança , Resultado do Tratamento , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Pré-Escolar , Seguimentos , Idade de Início
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