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1.
ChemSusChem ; : e202400538, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38763902

ABSTRACT

Lithium-sulfur batteries (LSBs) have recently gained extensive attention due to their high energy density, low cost, and environmental friendliness. However, serious shuttle effect and uncontrolled growth of lithium dendrites restrict them from further commercial applications. As "the third electrode", functional separators are of equal significance as both anodes and cathodes in LSBs. The challenges mentioned above are effectively addressed with rational design and optimization in separators, thereby enhancing their reversible capacities and cycle stability. The review discusses the status/operation mechanism of functional separators, then primarily focuses on recent research progress in versatile separators with purposeful modifications for LSBs, and summarizes the methods and characteristics of separator modification, including heterojunction engineering, single atoms, quantum dots, and defect engineering. From the perspective of the anodes, distinct methods to inhibit the growth of lithium dendrites by modifying the separator are discussed. Modifying the separators with flame retardant materials or choosing a solid electrolyte is expected to improve the safety of LSBs. Besides, in-situ techniques and theoretical simulation calculations are proposed to advance LSBs. Finally, future challenges and prospects of separator modifications for next-generation LSBs are highlighted. We believe that the review will be enormously essential to the practical development of advanced LSBs.

2.
Chin Med ; 19(1): 68, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741130

ABSTRACT

BACKGROUND: Myocarditis refers to an autoimmune inflammatory response of the myocardium with characterization of self-reactive CD4+ T cell activation, which lacks effective treatment and has a poor prognosis. Acacetin is a natural flavonoid product that has been reported to have anti-inflammatory effects. However, acacetin has not been investigated in myocarditis. METHODS: Oral acacetin treatment was administered in an experimental autoimmune myocarditis model established with myosin heavy chain-alpha peptide. Echocardiography, pathological staining, and RT-qPCR were used to detect cardiac function, myocardial injury, and inflammation levels. Flow cytometry was utilized to detect the effect of acacetin on CD4+ T cell function. RNA-seq, molecular docking, and microscale thermophoresis (MST) were employed to investigate potential mechanisms. Seahorse analysis, mitoSOX, JC-1, and mitotracker were utilized to detect the effect of acacetin on mitochondrial function. RESULTS: Acacetin attenuated cardiac injury and fibrosis as well as heart dysfunction, and reduced cardiac inflammatory cytokines and ratio of effector CD4+ T and Th17 cells. Acacetin inhibited CD4+ T cell activation, proliferation, and Th17 cell differentiation. Mechanistically, the effects of acacetin were related to reducing mitochondrial complex II activity thereby inhibiting mitochondrial respiration and mitochondrial reactive oxygen species in CD4+ T cells. CONCLUSION: Acacetin may be a valuable therapeutic drug in treating CD4+ T cell-mediated myocarditis.

3.
Cell Biochem Funct ; 42(4): e4031, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38760985

ABSTRACT

Super-enhancers play prominent roles in driving robust pathological gene expression, but they are hidden in human genome at noncoding regions, making them difficult to explore. Leukemia inhibitory factor (LIF) is a multifunctional cytokine crucially involved in acute respiratory distress syndrome (ARDS) and lung cancer progression. However, the mechanisms governing LIF regulation in disease contexts remain largely unexplored. In this study, we observed elevated levels of LIF in the bronchoalveolar lavage fluid (BALF) of patients with sepsis-related ARDS compared to those with nonsepsis-related ARDS. Furthermore, both basal and LPS-induced LIF expression were under the control of super-enhancers. Through analysis of H3K27Ac ChIP-seq data, we pinpointed three potential super-enhancers (LIF-SE1, LIF-SE2, and LIF-SE3) located proximal to the LIF gene in cells. Notably, genetic deletion of any of these three super-enhancers using CRISPR-Cas9 technology led to a significant reduction in LIF expression. Moreover, in cells lacking these super-enhancers, both cell growth and invasion capabilities were substantially impaired. Our findings highlight the critical role of three specific super-enhancers in regulating LIF expression and offer new insights into the transcriptional regulation of LIF in ARDS and lung cancer.


Subject(s)
Leukemia Inhibitory Factor , Lung Neoplasms , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/pathology , Leukemia Inhibitory Factor/metabolism , Leukemia Inhibitory Factor/genetics , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Bronchoalveolar Lavage Fluid/chemistry , Enhancer Elements, Genetic , Cell Proliferation , Male
4.
Adv Mater ; : e2307508, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728063

ABSTRACT

Halide perovskites are excellent candidate materials for use in solar cell, LED, and detector devices, in part because their composition can be tuned to achieve ideal optoelectronic properties. Empirical efficiency optimization has led the field toward compositions rich in FA (formamidinium) on the A-site and I on the X-site, with additional small amounts of MA (methylammonium) or Cs A-site cations and Br X-site anions. However, it is not clear how and why the specific compositions of alloyed, that is, mixed component, halide perovskites relate to photo-stability of the materials. Here, this work combines synchrotron grazing incidence wide-angle X-ray scattering, photoluminescence, high-resolution scanning electron diffraction measurements and theoretical modelling to reveal the links between material structure and photostability. Namely, this work finds that increased octahedral titling leads to improved photo-stability that is correlated with lower densities of performance-harming hexagonal polytype impurities. These results uncover the structural signatures underpinning photo-stability and can therefore be used to make targeted changes to halide perovskites, bettering the commercial prospects of technologies based on these materials.

5.
BMC Oral Health ; 24(1): 572, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760743

ABSTRACT

BACKGROUND: Cleidocranial dysplasia (CCD) is an autosomal dominant hereditary disorder. Besides skeletal abnormalities, CCD is often associated with dental complications, such as multiple supernumerary teeth and permanent teeth impaction or delayed eruption. METHODS: Supernumerary teeth of axial, sagittal and coronal CBCT view was characterized in detail and 3D image reconstruction was performed. Number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth, direction of supernumerary teeth in CCD patients were analyzed. RESULTS: The mean age of the 3 CCD patients in this study was 16.7 years. Among 36 supernumerary teeth, the majority of them were identified as apical side located and lingual side located. Normal orientation was the most common type in this study, followed by sagittal orientation, and horizontal orientation. Horizontal orientation teeth were all distributed in the mandible. Supernumerary teeth exhibited significantly shorter crown and dental-root lengths, as well as smaller crown mesiodistal and buccolingual diameters (P < 0.01). There was no difference in the number of supernumerary teeth between the maxilla and mandible, and the premolars region had the largest number of supernumerary teeth and the incisor region had the smallest number. CONCLUSIONS: This study compares number and location of teeth, morphology of supernumerary teeth, positional relationship between supernumerary and adjacent permanent teeth and direction of supernumerary teeth, this study also provides a reference for the comprehensive evaluation of CCD patients before surgery.


Subject(s)
Cleidocranial Dysplasia , Cone-Beam Computed Tomography , Imaging, Three-Dimensional , Tooth, Supernumerary , Humans , Cleidocranial Dysplasia/diagnostic imaging , Cleidocranial Dysplasia/complications , Tooth, Supernumerary/diagnostic imaging , Imaging, Three-Dimensional/methods , Adolescent , Male , Female , Tooth Crown/diagnostic imaging , Tooth Crown/abnormalities , Tooth Crown/pathology , Tooth Root/diagnostic imaging , Tooth Root/abnormalities , Odontometry/methods , Young Adult , Mandible/diagnostic imaging , Mandible/abnormalities , Bicuspid/abnormalities , Bicuspid/diagnostic imaging , Maxilla/diagnostic imaging , Image Processing, Computer-Assisted/methods
6.
Sensors (Basel) ; 24(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38793857

ABSTRACT

Bearings are crucial components of machinery and equipment, and it is essential to inspect them thoroughly to ensure a high pass rate. Currently, bearing scratch detection is primarily carried out manually, which cannot meet industrial demands. This study presents research on the detection of bearing surface scratches. An improved YOLOV5 network, named YOLOV5-CDG, is proposed for detecting bearing surface defects using scratch images as targets. The YOLOV5-CDG model is based on the YOLOV5 network model with the addition of a Coordinate Attention (CA) mechanism module, fusion of Deformable Convolutional Networks (DCNs), and a combination with the GhostNet lightweight network. To achieve bearing surface scratch detection, a machine vision-based bearing surface scratch sensor system is established, and a self-made bearing surface scratch dataset is produced as the basis. The scratch detection final Average Precision (AP) value is 97%, which is 3.4% higher than that of YOLOV5. Additionally, the model has an accuracy of 99.46% for detecting defective and qualified products. The average detection time per image is 263.4 ms on the CPU device and 12.2 ms on the GPU device, demonstrating excellent performance in terms of both speed and accuracy. Furthermore, this study analyzes and compares the detection results of various models, demonstrating that the proposed method satisfies the requirements for detecting scratches on bearing surfaces in industrial settings.

7.
Molecules ; 29(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38792070

ABSTRACT

Ligustrazine (TMP) is the main active ingredient extracted from Rhizoma Chuanxiong, which is used in the treatment of cardiovascular and cerebrovascular diseases, with the drawback of being unstable and readily sublimated. Cocrystal technology is an effective method to improve the stability of TMP. Three benzoic acid compounds including P-aminobenzoic acid (PABA), 3-Aminobenzoic acid (MABA), and 3,5-Dinitrobenzoic acid (DNBA) were chosen for co-crystallization with TMP. Three novel cocrystals were obtained, including TMP-PABA (1:2), TMP-MABA (1.5:1), and TMP-DNBA (0.5:1). Hygroscopicity was characterized by the dynamic vapor sorption (DVS) method. Three cocrystals significantly improved the hygroscopicity stability, and the mass change in TMP decreased from 25% to 1.64% (TMP-PABA), 0.12% (TMP-MABA), and 0.03% (TMP-DNBA) at 90% relative humidity. The melting points of the three cocrystals were all higher than TMP, among which the TMP-DNBA cocrystal had the highest melting point and showed the best stability in reducing hygroscopicity. Crystal structure analysis shows that the mesh-like structure formed by the O-H⋯N hydrogen bond in the TMP-DNBA cocrystal was the reason for improving the stability of TMP.


Subject(s)
Crystallization , Pyrazines , Wettability , Pyrazines/chemistry , Drug Stability , Hydrogen Bonding , Crystallography, X-Ray , Molecular Structure , X-Ray Diffraction
8.
Toxins (Basel) ; 16(5)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38787060

ABSTRACT

Recent discoveries establish DNA and RNA as bona fide substrates for ADP-ribosylation. NADAR ("NAD- and ADP-ribose"-associated) enzymes reverse guanine ADP-ribosylation and serve as antitoxins in the DarT-NADAR operon. Although NADARs are widespread across prokaryotes, eukaryotes, and viruses, their specificity and broader physiological roles remain poorly understood. Using phylogenetic and biochemical analyses, we further explore de-ADP-ribosylation activity and antitoxin functions of NADAR domains. We demonstrate that different subfamilies of NADAR proteins from representative E. coli strains and an E. coli-infecting phage retain biochemical activity while displaying specificity in providing protection from toxic guanine ADP-ribosylation in cells. Furthermore, we identify a myxobacterial enzyme within the YbiA subfamily that functions as an antitoxin for its associated DarT-unrelated ART toxin, which we termed YarT, thus presenting a hitherto uncharacterised ART-YbiA toxin-antitoxin pair. Our studies contribute to the burgeoning field of DNA ADP-ribosylation, supporting its physiological relevance within and beyond bacterial toxin-antitoxin systems. Notably, the specificity and confinement of NADARs to non-mammals infer their potential as highly specific targets for antimicrobial drugs with minimal off-target effects.


Subject(s)
ADP-Ribosylation , Escherichia coli , Escherichia coli/genetics , Escherichia coli Proteins/metabolism , Escherichia coli Proteins/genetics , Bacterial Toxins/metabolism , Adenosine Diphosphate Ribose/metabolism , Phylogeny , Toxin-Antitoxin Systems/genetics , DNA, Bacterial/metabolism , DNA, Bacterial/genetics , DNA/metabolism
9.
Gene ; 923: 148575, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38762017

ABSTRACT

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is a disease characterized by a collapsed femoral head caused by the overuse of glucocorticoids. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) is an important pathological feature of SONFH. In this study, we investigated whether exosomes from SHEDs (stem cells from human exfoliated deciduous teeth) have a therapeutic effect on glucocorticoid-induced inhibition of proliferation and osteogenesis in BMSCs, and elucidated the underlying mechanisms involved. METHODS: Primary dental pulp cells were isolated and cultured from human deciduous tooth pulp, SHEDs were isolated and purified by the limiting dilution method and exosomes were isolated from the supernatants of SHEDs by ultracentrifugation. The cell surface markers CD31, CD34, CD45, CD73, CD90 and CD105 were detected by flow cytometry. A Cell-Counting-Kit-8 assay was used to detect cell activity. ALP and Alizarin Red staining were used to identify osteogenic differentiation ability, and exosomes were identified using transmission electron microscopy, NanoFCM and Western blotting. PKH67 fluorescence was used to track the uptake of exosomes by BMSCs. Transcriptome analysis combined with quantitative real-time PCR was used to explore the underlying mechanism involved. RESULTS: Exosomes secreted by SHEDs can be endocytosed by BMSCs, and can partially reverse the inhibitory effects of glucocorticoids on the viability and osteogenic differentiation of BMSCs. Transcriptome sequencing analysis revealed that the differentially expressed mRNAs regulated by SHED-derived exosomes were enriched mainly in signaling pathways such as the apoptosis pathway, the PI3K-Akt signaling pathway, the Hippo signaling pathway and the p53 signaling pathway. qPCR showed that SHED-derived exosomes reversed the dexamethasone-induced upregulation of HGF and ITGB8 expression and the inhibition of EFNA1 expression, but further increased the dexamethasone-induced downregulation of IL7 expression. In conclusion, SHED-derived exosomes partially reversed the inhibitory effects of glucocorticoids on BMSC proliferation and osteogenesis by inhibiting the expression of HGF, ITGB8 and IL7, and upregulating the expression of EFNA1.

10.
J Agric Food Chem ; 72(19): 11259-11267, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38691423

ABSTRACT

Peanut allergen monitoring is currently an effective strategy to avoid allergic diseases, while food matrix interference is a critical challenge during detection. Here, we developed an antifouling surface plasmon resonance sensor (SPR) with stratified zwitterionic peptides, which provides both excellent antifouling and sensing properties. The antifouling performance was measured by the SPR, which showed that stratified peptide coatings showed much better protein resistance, reaching ultralow adsorption levels (<5 ng/cm2). Atomic force microscopy was used to further analyze the antifouling mechanism from a mechanical perspective, which demonstrated lower adsorption forces on hybrid peptide coatings, confirming the better antifouling performance of stratified surfaces. Moreover, the recognition of peanut allergens in biscuits was performed using an SPR with high efficiency and appropriate recovery results (98.2-112%), which verified the feasibility of this assay. Therefore, the fabrication of antifouling sensors with stratified zwitterionic peptides provides an efficient strategy for food safety inspection.


Subject(s)
Allergens , Arachis , Peptides , Surface Plasmon Resonance , Surface Plasmon Resonance/methods , Arachis/chemistry , Arachis/immunology , Peptides/chemistry , Peptides/immunology , Allergens/analysis , Allergens/immunology , Allergens/chemistry , Biofouling/prevention & control , Food Contamination/analysis , Plant Proteins/immunology , Plant Proteins/chemistry , Plant Proteins/analysis , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Adsorption
11.
BMC Oral Health ; 24(1): 552, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735923

ABSTRACT

Patients who suffer from myofascial orofacial pain could affect their quality of life deeply. The pathogenesis of pain is still unclear. Our objective was to assess Whether Voltage-gated calcium channel α2δ-1(Cavα2δ-1) is related to myofascial orofacial pain. Rats were divided into the masseter tendon ligation group and the sham group. Compared with the sham group, the mechanical pain threshold of the masseter tendon ligation group was reduced on the 4th, 7th, 10th and 14th day after operation(P < 0.05). On the 14th day after operation, Cavα2δ-1 mRNA expression levels in trigeminal ganglion (TG) and the trigeminal spinal subnucleus caudalis and C1-C2 spinal cervical dorsal horn (Vc/C2) of the masseter tendon ligation group were increased (PTG=0.021, PVc/C2=0.012). Rats were divided into three groups. On the 4th day after ligating the superficial tendon of the left masseter muscle of the rats, 10 ul Cavα2δ-1 antisense oligonucleotide, 10 ul Cavα2δ-1 mismatched oligonucleotides and 10 ul normal saline was separately injected into the left masseter muscle of rats in Cavα2δ-1 antisense oligonucleotide group, Cavα2δ-1 mismatched oligonucleotides group and normal saline control group twice a day for 4 days. The mechanical pain threshold of the Cavα2δ-1 antisense oligonucleotides group was higher than Cavα2δ-1 mismatched oligonucleotides group on the 7th and 10th day after operation (P < 0.01). After PC12 cells were treated with lipopolysaccharide, Cavα2δ-1 mRNA expression level increased (P < 0.001). Cavα2δ-1 may be involved in the occurrence and development in myofascial orofacial pain.


Subject(s)
Calcium Channels , Masseter Muscle , Rats, Sprague-Dawley , Trigeminal Ganglion , Animals , Rats , Masseter Muscle/metabolism , Male , Calcium Channels/metabolism , Trigeminal Ganglion/metabolism , Pain Threshold , Facial Pain/metabolism , Spinal Cord Dorsal Horn/metabolism , Oligonucleotides, Antisense/pharmacology , Myofascial Pain Syndromes , RNA, Messenger/metabolism , Calcium Channels, L-Type
12.
Environ Res ; 255: 119209, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38782336

ABSTRACT

Nitrate/nitrite-dependent anaerobic methane oxidation (n-DAMO) process is a promising wastewater treatment technology, but the slow microbial growth rate greatly hinders its practical application. Although high-level nitrogen removal and excellent biomass accumulation have been achieved in n-DAMO granule process, the formation mechanism of n-DAMO granules remains unresolved. To elucidate the role of functional microbes in granulation, this study attempted to cultivate granules dominated by n-DAMO microorganisms and granules coupling n-DAMO with anaerobic ammonium oxidation (Anammox). After long-term operation, dense granules were developed in the two systems where both n-DAMO archaea and n-DAMO bacteria were enriched, whereas granulation did not occur in the other system dominated by n-DAMO bacteria. Extracellular polymeric substances (EPS) measurement indicated the critical role of EPS production in the granulation of n-DAMO process. Metagenomic and metatranscriptomic analyses revealed that n-DAMO archaea and Anammox bacteria were active in EPS biosynthesis, while n-DAMO bacteria were inactive. Consequently, more EPS were produced in the systems containing n-DAMO archaea and Anammox bacteria, leading to the successful development of n-DAMO granules. Furthermore, EPS biosynthesis in n-DAMO systems is potentially regulated by acyl-homoserine lactones and c-di-GMP. These findings not only provide new insights into the mechanism of granule formation in n-DAMO systems, but also hint at potential strategies for management of the granule-based n-DAMO process.

13.
Nat Commun ; 15(1): 4440, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789422

ABSTRACT

Inorganic semiconductors typically have limited p-type behavior due to the scarcity of holes and the localized valence band maximum, hindering the progress of complementary devices and circuits. In this work, we propose an inorganic blending strategy to activate the hole-transporting character in an inorganic semiconductor compound, namely tellurium-selenium-oxygen (TeSeO). By rationally combining intrinsic p-type semimetal, semiconductor, and wide-bandgap semiconductor into a single compound, the TeSeO system displays tunable bandgaps ranging from 0.7 to 2.2 eV. Wafer-scale ultrathin TeSeO films, which can be deposited at room temperature, display high hole field-effect mobility of 48.5 cm2/(Vs) and robust hole transport properties, facilitated by Te-Te (Se) portions and O-Te-O portions, respectively. The nanosphere lithography process is employed to create nanopatterned honeycomb TeSeO broadband photodetectors, demonstrating a high responsibility of 603 A/W, an ultrafast response of 5 µs, and superior mechanical flexibility. The p-type TeSeO system is highly adaptable, scalable, and reliable, which can address emerging technological needs that current semiconductor solutions may not fulfill.

14.
Eur J Med Chem ; 272: 116468, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38718626

ABSTRACT

High expression of ubiquitin-specific protease 10 (USP10) promote the proliferation of hepatocellular carcinoma (HCC), thus the development of USP10 inhibitors holds promise as a novel therapeutic approach for HCC treatment. However, the development of selective USP10 inhibitor is still limited. In this study, we developed a novel USP10 inhibitor for investigating the feasibility of targeting USP10 for the treatment of HCC. Due to high USP10 inhibition potency and prominent selectivity, compound D1 bearing quinolin-4(1H)-one scaffold was identified as a lead compound. Subsequent research revealed that D1 significantly inhibits cell proliferation and clone formation in HCC cells. Mechanistic insights indicated that D1 targets the ubiquitin pathway, facilitating the degradation of YAP (Yes-associated protein), thereby triggering the downregulation of p53 and its downstream protein p21. Ultimately, this cascade leads to S-phase arrest in HCC cells, followed by cell apoptosis. Collectively, our findings highlight D1 as a promising starting point for USP10-positive HCC treatment, underscoring its potential as a vital tool for unraveling the functional intricacies of USP10.


Subject(s)
Adaptor Proteins, Signal Transducing , Antineoplastic Agents , Carcinoma, Hepatocellular , Cell Proliferation , Drug Discovery , Liver Neoplasms , Transcription Factors , Ubiquitin Thiolesterase , YAP-Signaling Proteins , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitin Thiolesterase/metabolism , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism , Structure-Activity Relationship , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , YAP-Signaling Proteins/metabolism , Molecular Structure , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Apoptosis/drug effects , Small Molecule Libraries/pharmacology , Small Molecule Libraries/chemistry , Small Molecule Libraries/chemical synthesis , Cell Line, Tumor
15.
Talanta ; 276: 126277, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38761658

ABSTRACT

Nitroreductase (NTR) is a frequently used biomarker for the assessment of hypoxia level in tumors. As one of the main sources of enzymes, the dysfunction of lysosomes typically leads to various diseases. In this study, an NTR-triggered lysosome-targeting probe, M-TPE-P, was designed based on a tetraphenylethylene core. DFT calculation indicated that the probe possessed a narrow singlet-triplet energy gap (ΔEST), rendering it an efficient photosensitizer. The docking affinity of M-TPE-P to NTR revealed a strong structural match between them. Photophysical properties demonstrated that the probe exhibited high selectivity and sensitivity in a broad pH rang for detecting NTR with kcat/Km as 2.18 × 104 M-1 s-1. The detection limit was determined to be 53.6 ng/mL in 80 % PBS/DMSO solution. Cell imaging studies showed the probe could trace intracellular NTR behavior with green fluorescence. The colocalization analysis indicated its excellent lysosome-targeting specificity. In addition, the probe exhibited effective ROS generation ability and significant PDT effect after NIR irradiation, positioning it as a promising photosensitizer for cancer treatment.

16.
Acta Pharmacol Sin ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802569

ABSTRACT

Graft-versus-host disease (GVHD), an immunological disorder that arises from donor T cell activation through recognition of host alloantigens, is the major limitation in the application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Traditional immunosuppressive agents can relieve GVHD, but they induce serious side effects. It is highly required to explore alternative therapeutic strategy. Human amniotic epithelial stem cells (hAESCs) were recently considered as an ideal source for cell therapy with special immune regulatory property. In this study, we evaluated the therapeutic role of hAESCs in the treatment of GVHD, based on our previous developed cGMP-grade hAESCs product. Humanized mouse model of acute GVHD (aGVHD) was established by injection of huPBMCs via the tail vein. For prevention or treatment of aGVHD, hAESCs were injected to the mice on day -1 or on day 7 post-PBMC infusion, respectively. We showed that hAESCs infusion significantly alleviated the disease phenotype, increased the survival rate of aGVHD mice, and ameliorated pathological injuries in aGVHD target organs. We demonstrated that hAESCs directly induced CD4+ T cell polarization, in which Th1 and Th17 subsets were downregulated, and Treg subset was elevated. Correspondingly, the levels of a series of pro-inflammatory cytokines were reduced while the levels of the anti-inflammatory cytokines were upregulated in the presence of hAESCs. We found that hAESCs regulated CD4+ subset polarization in a paracrine mode, in which TGFß and PGE2 were selectively secreted to mediate Treg elevation and Th1/Th17 inhibition, respectively. In addition, transplanted hAESCs preserved the graft-versus-leukemia (GVL) effect by inhibiting leukemia cell growth. More intriguingly, hAESCs infusion in HSCT patients displayed potential anti-GVHD effect with no safety concerns and confirmed the immunoregulatory mechanisms in the preclinical study. We conclude that hAESCs infusion is a promising therapeutic strategy for post-HSCT GVHD without compromising the GVL effect. The clinical trial was registered at www.clinicaltrials.gov as #NCT03764228.

17.
Adv Mater ; : e2400196, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734875

ABSTRACT

The activation of sequential events in the cancer-immunity cycle (CIC) is crucial for achieving effective antitumor immunity. However, formidable challenges, such as innate and adaptive immune resistance, along with the off-target adverse effects of nonselective immunomodulators, persist. In this study, a tumor-selective nano-regulator named PNBJQ has been presented, focusing on targeting two nonredundant immune nodes: inducing immunogenic cancer cell death and abrogating immune resistance to fully activate endogenous tumor immunity. PNBJQ is obtained by encapsulating the immunomodulating agent JQ1 within a self-assembling system formed by linking a Type-I photosensitizer to polyethylene glycol through a hypoxia-sensitive azo bond. Benefiting from the Type-I photosensitive mechanism, PNBJQ triggers the immunogenic cell death of hypoxic tumors under near-infrared (NIR) light irradiation. This process resolves innate immune resistance by stimulating sufficient cytotoxic T-lymphocytes. Simultaneously, PNBJQ smartly responds to the hypoxic tumor microenvironment for precise drug delivery, adeptly addressing adaptive immune resistance by using JQ1 to downregulate programmed death ligand 1 (PD-L1) and sustaining the response of cytotoxic T lymphocytes. The activatable synergic photoimmunotherapy promotes an immune-promoting tumor microenvironment by activating an iterative revolution of the CIC, which remarkably eradicates established hypoxic tumors and suppresses distal lesions under low light dose irradiation.

18.
Nat Commun ; 15(1): 4033, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740743

ABSTRACT

Monolayer two-dimensional (2D) materials possess excellent in-plane mechanical strength yet extremely low bending stiffness, making them particularly susceptible to instability, which is anticipated to have a substantial impact on their physical functionalities such as 2D-based Micro/Nanoelectromechanical systems (M/NEMS), nanochannels, and proton transport membrane. In this work, we achieve quantitatively tuning instability in suspended 2D materials including monolayer graphene and MoS2 by employing a push-to-shear strategy. We comprehensively examine the dynamic wrinkling-splitting-smoothing process and find that monolayer 2D materials experience stepwise instabilities along with different recovery processes. These stepwise instabilities are governed by the materials' geometry, pretension, and the elastic nonlinearity. We attribute the different instability and recovery paths to the local stress redistribution in monolayer 2D materials. The tunable instability behavior of suspended monolayer 2D materials not only allows measuring their bending stiffness but also opens up new opportunities for programming the nanoscale instability pattern and even physical properties of atomically thin films.

19.
Hortic Res ; 11(5): uhae084, 2024 May.
Article in English | MEDLINE | ID: mdl-38766533

ABSTRACT

Seed hardness is an important quality trait of vegetable soybean. To determine the factors underlying seed hardness, two landraces with contrasting seed hardness, Niumaohuang (low seed hardness) and Pixiansilicao (high seed hardness), were selected from 216 soybean accessions originating from 26 provinces in China. The contents of the main components in vegetable soybean seeds such as water, soluble sugar, starch, protein and oil were measured, and transcriptome analyses performed during five stages of seed developmental. Transcriptome analysis indicates that during the middle and late stages of seed development, a large number of genes involved in the synthesis or degradation of starch, storage protein, and fatty acids were differentially expressed, leading to differences in the accumulation of stored substances during seed maturation among Niumaohuang and Pixiansilicao. The activity of cell proliferation and the formation of cell walls in the middle and late stages of seed development may also affect the hardness of seeds to a certain extent. In addition, weighted gene co-expression network analysis (WGCNA) was undertaken to identify co-expressed gene modules and hub genes that regulate seed hardness. Overexpression of a candidate seed hardness regulatory hub gene, GmSWEET2, resulted in increased seed hardness. In this study, the important role of GmSWEET2 in regulating the hardness of vegetable soybean seeds was verified and numerous potential key regulators controlling seed hardness and the proportion of seed components were identified, laying the groundwork for improving the texture of vegetable soybean.

20.
J Colloid Interface Sci ; 670: 626-634, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38781653

ABSTRACT

On-site quantitative analysis of pesticide residues is crucial for monitoring environmental quality and ensuring food safety. Herein, we have developed a reliable hydrogel portable kit using NaYbF4@NaYF4: Yb, Tm upconversion nanoparticles (UCNPs) combined with MnO2 nanoflakes. This portable kit is integrated with a smartphone reader and Python-assisted analysis platform to enable sample-to-result analysis for chlorpyrifos. The novel UCNPs maximizes energy donation to MnO2 acceptor by employing 100 % of activator Yb3+ in the nucleus for NIR excitation energy collection and confining emitter Tm3+ to the surface layer to shorten energy transfer distance. Under NIR excitation, efficient quenching of upconversion blue-violet emission by MnO2 nanoflakes occurs, and the quenched emission is recovered with acetylcholinesterase-mediated reactions. This process allows for the determination of chlorpyrifos by inhibiting enzymatic activity. The UCNPs/MnO2 were embedded to fabricate a hydrogel portable kit, the blue-violet emission images captured by smartphone were converted into corresponding gray values by Python-assisted superiority chart algorithm which achieves a real-time rapid quantitative analysis of chlorpyrifos with a detection limit of 0.17 ng mL-1. At the same time, pseudo-color images were also added by Python in "one run" to distinguish images clearly. This sensor detection with Python-assisted analysis platform provides a new perspective on pesticide monitoring and broadens the application prospects in bioanalysis.

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