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1.
Placenta ; 153: 59-74, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38823320

ABSTRACT

INTRODUCTION: Preeclampsia (PE) is a pregnancy-specific complication. Its etiology and pathogenesis remain unclear. Previous studies have shown that neutrophil extracellular traps (NETs) cause placental dysfunction and lead to PE. Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) have been widely used to treat different diseases. We investigated whether hUCMSC-EXOs can protect against NET-induced placental damage. METHODS: NETs were detected in the placenta by immunofluorescence. The impact of NETs on cellular function and the effect of hUCMSC-EXOs on NET-induced placental damage were evaluated by 5-ethynyl-20-deoxyuridine (EdU) cell proliferation, lactate dehydrogenase (LDH), reactive oxygen species (ROS), and cell migration, invasion and tube formation assays; flow cytometry; and Western blotting. RESULTS: The number of placental NETs was increased in PE patients compared with control individuals. NETs impaired the function of endothelial cells and trophoblasts. These effects were partially reversed after N-acetyl-L-cysteine (NAC; ROS inhibitor) or DNase I (NET lysing agent) pretreatment. HUCMSC-EXOs ameliorated NET-induced functional impairment of endothelial cells and trophoblasts in vitro, partially reversed NET-induced inhibition of endothelial cell and trophoblast proliferation, and partially restored trophoblast migration and invasion and endothelial cell tube formation. Exosomes inhibited ROS production in these two cell types, suppressed p38 mitogen-activated protein kinase (p38 MAPK) signaling activation, activated extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, and modulated the Bax, Bim, Bcl-2 and cleaved caspase-3 levels to inhibit apoptosis. DISCUSSION: HUCMSC-EXOs can reverse NET-induced placental endothelial cell and trophoblast damage, possibly constituting a theoretical basis for the treatment of PE with exosomes.

2.
Biomaterials ; 309: 122615, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38759486

ABSTRACT

Enhancing the effectiveness of platelet-rich plasma (PRP) for endometrial regeneration is challenging, due to its limited mechanical properties and burst release of growth factors. Here, we proposed an injectable interpenetrating dual-network hydrogel that can locationally activate PRP within the uterine cavity, sustained release growth factors and further address the insufficient therapeutic efficacy. Locational activation of PRP is achieved using the dual-network hydrogel. The phenylboronic acid (PBA) modified methacrylated hyaluronic acid (HAMA) dispersion chelates Ca2+ by carboxy groups and polyphenol groups, and in situ crosslinked with PRP-loaded polyvinyl alcohol (PVA) dispersion by dynamic borate ester bonds thus establishing the soft hydrogel. Subsequently, in situ photo-crosslinking technology is employed to enhance the mechanical performance of hydrogels by initiating free radical polymerization of carbon-carbon double bonds to form a dense network. The PRP-hydrogel significantly promoted the endometrial cell proliferation, exhibited strong pro-angiogenic effects, and down-regulated the expression of collagen deposition genes by inhibiting the TGF-ß1-SMAD2/3 pathway in vitro. In vivo experiments using a rat intrauterine adhesion (IUA) model showed that the PRP-hydrogel significantly promoted endometrial regeneration and restored uterine functionality. Furthermore, rats treated with the PRP-hydrogel displayed an increase in the number of embryos, litter size, and birth rate, which was similar to normal rats. Overall, this injectable interpenetrating dual-network hydrogel, capable of locational activation of PRP, suggests a new therapeutic approach for endometrial repair.


Subject(s)
Endometrium , Hydrogels , Platelet-Rich Plasma , Rats, Sprague-Dawley , Regeneration , Animals , Female , Endometrium/drug effects , Hydrogels/chemistry , Regeneration/drug effects , Rats , Cell Proliferation/drug effects , Hyaluronic Acid/chemistry , Polyvinyl Alcohol/chemistry , Humans , Boronic Acids/chemistry , Injections , Tissue Adhesions
3.
Neurobiol Aging ; 140: 122-129, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38776615

ABSTRACT

Brain biological age, which measures the aging process in the brain using neuroimaging data, has been used to assess advanced brain aging in neurodegenerative diseases, including Parkinson disease (PD). However, assuming that whole brain degeneration is uniform may not be sufficient for assessing the complex neurodegenerative processes in PD. In this study we constructed a multiscale brain age prediction models based on structural MRI of 1240 healthy participants. To assess the brain aging patterns using the brain age prediction model, 93 PD patients and 91 healthy controls matching for sex and age were included. We found increased global and regional brain age in PD patients. The advanced aging regions were predominantly noted in the frontal and temporal cortices, limbic system, basal ganglia, thalamus, and cerebellum. Furthermore, region-level rather than global brain age in PD patients was associated with disease severity. Our multiscale brain age prediction model could aid in the development of objective image-based biomarkers to detect advanced brain aging in neurodegenerative diseases.

4.
Orthop Surg ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773680

ABSTRACT

OBJECTIVE: For precise and minimally invasive treatment of ossification of the posterior longitudinal ligament of the cervical spine, the lifting segment is minimized, anterior controllable antedisplacement and fusion (ACAF) was refined and improved. In addition, the development of appropriate surgical procedures for the ossification of each segment was rarely reported. Therefore, this study aimed to compare the efficacy and safety of hybrid anterior controlled antedisplacement fusion (Hybrid ACAF) with laminoplasty for multilevel ossification of the posterior longitudinal ligament (OPLL). METHODS: Between May 2018 and May 2021, 70 patients with multilevel OPLL were divided into a hybrid ACAF group and a laminoplasty group according to surgical methods. All patients were followed up for at least 1 year. Japanese Orthopaedic Association (JOA) score and recovery rate (JOARR), (VAS, NDI) score and C2-C7 Cobb angle, the sagittal vertical axis of the neck (SVA), and complications (cerebrospinal fluid leakage, C5 paralysis, etc.) were compared between the two groups by t test or non-parametric test. RESULTS: The operation time of hybrid ACAF was longer. C5 paralysis and axial pain were more common in the laminoplasty group, while dysphagia and hoarseness were more common in the hybrid ACAF group. At the last follow-up, the hybrid ACAF group had better recovery and maintenance of cervical lordosis and sagittal plane balance and a higher JOA score and recovery rate than the laminoplasty group. CONCLUSIONS: Hybrid ACAF can reduce the number of vertebral bodies and expand the decompression range, which is safe, effective, and tailored to local conditions. Compared with laminoplasty, hybrid ACAF is a precise alternative for patients with OPLL.

5.
ACS Chem Neurosci ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775291

ABSTRACT

Mapping brain activities is necessary for understanding brain physiology and discovering new treatments for neurological disorders. Such efforts have greatly benefited from the advancement in technologies for analyzing neural activity with improving temporal or spatial resolution. Here, we constructed a multielectrode array based brain activity mapping (BAM) system capable of stabilizing and orienting zebrafish larvae for recording electroencephalogram (EEG) like local field potential (LFP) signals and brain-wide calcium dynamics in awake zebrafish. Particularly, we designed a zebrafish trap chip that integrates with an eight-by-eight surface electrode array, so that brain electrophysiology can be noninvasively recorded in an agarose-free and anesthetic-free format with a high temporal resolution of 40 µs, matching the capability typically achieved by invasive LFP recording. Benefiting from the specially designed hybrid system, we can also conduct calcium imaging directly on immobilized awake larval zebrafish, which further supplies us with high spatial resolution brain-wide activity data. All of these innovations reconcile the limitations of sole LFP recording or calcium imaging, emphasizing a synergy of combining electrical and optical modalities within one unified device for activity mapping across a whole vertebrate brain with both improved spatial and temporal resolutions. The compatibility with in vivo drug treatment further makes it suitable for pharmacology studies based on multimodal measurement of brain-wide physiology.

6.
Chaos ; 34(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38775682

ABSTRACT

This paper investigates the formation, annihilation, and evolution mechanisms of potential energy wells in nonlinear energy sink systems. The nonlinear energy sink system is composed of multiple inner and outer magnets. Two multi-magnet energy sink (MES) architectures are designed: a single-magnet vibrator and a double-magnet vibrator. Multi-stable (bi-, tri-, quad-, penta-, hexa-, and hepta-stable) mechanisms are elaborated by the Poincaré section and bifurcation diagram concerning the magnet length, the link length, and the MES configuration. The results show that the change in the internal structural parameters of the MES system will generate different types of bifurcations (i.e., saddle-node, subcritical, and super pitchfork bifurcations) and phase trajectories and have rich nonlinear response behaviors in the low frequency and wide frequency range, which can be used for damping and vibration reduction of engineering structures, vibration control, and energy source of the microgrid.

7.
Molecules ; 29(9)2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38731413

ABSTRACT

Ultraviolet radiation can heighten tyrosinase activity, stimulate melanocyte production, impede the metabolism of numerous melanocytes, and result in the accumulation of plaques on the skin surface. α-Arbutin, a bioactive substance extracted from the arbutin plant, has been widely used for skin whitening. In this study, the whitening effect of α-arbutin by inhibiting tyrosinase activity and alleviating the photoaging effect induced by UVB are investigated. The results indicate that α-arbutin can inhibit skin inflammation, and its effectiveness is positively correlated with concentration. Moreover, α-arbutin can reduce the skin epidermal thickness, decrease the number of inflammatory cells, and down-regulate the expression levels of IL-1ß, IL-6 and TNF-α, which are inflammatory factors. It also promotes the expression of COL-1 collagen, thus playing an important role in anti-inflammatory action. Network pharmacology, metabolomics and transcriptomics further confirm that α-arbutin is related to the L-tyrosine metabolic pathway and may interfere with various signaling pathways related to melanin and other photoaging by regulating metabolic changes. Therefore, α-arbutin has a potential inhibitory effect on UVB-induced photoaging and possesses a whitening effect as a cosmetic compound.


Subject(s)
Arbutin , Skin Aging , Ultraviolet Rays , Arbutin/pharmacology , Ultraviolet Rays/adverse effects , Animals , Skin Aging/drug effects , Skin Aging/radiation effects , Mice , Monophenol Monooxygenase/metabolism , Monophenol Monooxygenase/antagonists & inhibitors , Humans , Skin/radiation effects , Skin/drug effects , Skin/metabolism , Skin/pathology
8.
Reprod Sci ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769248

ABSTRACT

Endometrial elasticity is a potential new marker for assessing endometrial receptivity and pregnancy outcomes based on endometrial thickness and type. Currently, little research has been conducted on the elasticity of the endometrium using shear wave elasticity imaging (SWEI). This study aimed to explore whether endometrial elasticity is an ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer. A total of 245 infertile women underwent ultrasonography before embryo transfer at the Peking University Third Hospital. We compared the endometrial elasticity and sub-endometrial blood flow rate using SWEI in the groups with different pregnancy outcomes. Trends in clinical pregnancy outcomes across the quartiles of endometrial elasticity in the fundus of the uterus (E1) were assessed. Logistic regression analysis was performed to obtain odds ratios for clinical pregnancy outcomes based on the quartiles of E1, with or without adjusting for potential confounding variables. Women in the clinical pregnancy group had higher E1 values and sub-endometrial blood flow rates in the uterine fundus than those in the non-pregnancy group. Women in the highest quartile of E1 had the most favorable clinical pregnancy rates. Endometrial elasticity measured using SWEI is a promising ultrasound marker for predicting clinical pregnancy outcomes after embryo transfer.

9.
J Environ Manage ; 359: 121061, 2024 May.
Article in English | MEDLINE | ID: mdl-38728983

ABSTRACT

China's commitment to attaining carbon neutrality by 2060 has galvanized research into carbon sequestration, a critical approach for mitigating climate change. Despite the rapid urbanization observed since the turn of the millennium, a comprehensive analysis of how urbanization influences urban carbon storage throughout China remains elusive. Our investigation delves into the nuanced effects of urbanization on carbon storage, dissecting both the direct and indirect influences by considering urban-suburban gradients and varying degrees of urban intensity. We particularly scrutinize the roles of climatic and anthropogenic factors in mediating the indirect effects of urbanization on carbon storage. Our findings reveal that urbanization in China has precipitated a direct reduction in carbon storage by approximately 13.89 Tg of carbon (Tg C). Remarkably, urban sprawl has led to a diminution of vegetation carbon storage by 8.65 Tg C and a decrease in soil carbon storage by 5.24 Tg C, the latter resulting from the sequestration of impervious surfaces and the elimination of organic matter inputs following vegetation removal. Meanwhile, carbon storage in urban greenspaces has exhibited an increase of 6.90 Tg C and offsetting 49.70% of the carbon loss induced by direct urbanization effects. However, the indirect effects of urbanization predominantly diminish carbon storage in urban greenspaces by an average of 5.40%. The degree of urban vegetation management emerges as a pivotal factor influencing the indirect effects of urbanization on carbon storage. To bolster urban carbon storage, curbing urban sprawl and augmenting urban green spaces are imperative strategies. Insights from this study are instrumental in steering sustainable urban planning and advancing towards the goal of carbon neutrality.


Subject(s)
Carbon Sequestration , Carbon , Climate Change , Urbanization , China , Carbon/analysis , Soil/chemistry
10.
Photodiagnosis Photodyn Ther ; 47: 104216, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38740318

ABSTRACT

OBJECTIVE: In this study, we aimed to determine how different factors influence the effectiveness of repeated low-level red-light (RLRL) therapy in preventing and treating myopia in children. METHODS: Between June 2022 and April 2023, 336 children who visited our hospital due to myopia or significant decreases in hyperopia reserve were enrolled. The children were treated twice daily for three minutes with a head-mounted low-level red-light (single wavelength of 650 nm) therapeutic device. Each of the two treatment sessions was separated by at least four hours. The axial lengths and diopters of the children's eyes were compared before and three months after treatment, and the effects of gender, age, and baseline diopter on the efficacy of RLRL therapy were analyzed. RESULTS: Following three months of treatment, the average axial length of the eyes decreased by 0.031 mm. The condition was better for the boys than for girls, but the difference was not statistically significant. As age increased (F = 8.112, P = 0.000) or as the absolute value of baseline myopia degree increased (F = 10.51, P = 0.000), axial lengths of the eyes tended to decrease. The spherical equivalent refraction (SER) of children decreased by an average of 0.012 ± 0.355D. The condition was better for the boys than for girls, but the difference was not statistically significant. SER increased in the direction of hyperopic drift as age increased (F = 2.48, P = 0.031), or as the absolute value of baseline myopia degrees increased (F = 6.835, P = 0.000). There were no obvious side effects following the treatment. CONCLUSION: This study showed that RLRL therapy is a potential efficient, easily operable, and practically feasible method for the prevention and control of myopia.

11.
J Plant Res ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758249

ABSTRACT

Various environmental stresses induce the production of reactive oxygen species (ROS), which have deleterious effects on plant cells. Glutathione (GSH) is an antioxidant used to counteract reactive oxygen species. Glutathione is produced by glutamylcysteine synthetase (GCS) and glutathione synthetase (GS). However, evidence for the GCS gene in sweetpotato remains scarce. In this study, the full-length cDNA sequence of IbGCS isolated from sweetpotato cultivar Xu18 was 1566 bp in length, which encodes 521 amino acids. The qRT-PCR analysis revealed a significantly higher expression of the IbGCS in sweetpotato flowers, and the gene was induced by salinity, abscisic acid (ABA), drought, extreme temperature and heavy metal stresses. The seed germination rate, root elongation and fresh weight were promoted in T3 Arabidopsis IbGCS-overexpressing lines (OEs) in contrast to wild type (WT) plants under mannitol and salt stresses. In addition, the soil drought and salt stress experiment results indicated that IbGCS overexpression in Arabidopsis reduced the malondialdehyde (MDA) content, enhanced the levels of GCS activity, GSH and AsA content, and antioxidant enzyme activity. In summary, overexpressing IbGCS in Arabidopsis showed improved salt and drought tolerance.

12.
ACS Appl Mater Interfaces ; 16(19): 24987-24998, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38712685

ABSTRACT

For traditional ferroelectric field-effect transistors (FeFETs), enhancing the polarization domain of bulk ferroelectric materials is essential to improve device performance. However, there has been limited investigation into the enhancement of polarization field in two-dimensional (2D) ferroelectric material such as CuInP2S6 (CIPS). In this study, similar to bulk ferroelectric materials, CIPS exhibited enhanced polarization field upon application of external cyclic voltage. Moreover, unlike traditional ferroelectric materials, the polarization enhancement of CIPS is not due to redistribution of the defect but rather originates from a mechanism: the long-distance migration of Cu ions. We termed this mechanism the "wake-up-like effect". After incorporating the wake-up-like effect into the graphene/CIPS/WSe2 FeFET device, we successfully increased the hysteresis window and enhanced the current on/off ratio by 4 orders of magnitude. Moreover, the FeFET yielded remarkable achievements, such as multilevel nonvolatile memory with 21 distinct conductance levels, a high on/off ratio exceeding 106, a long retention time exceeding 103 s, and neuromorphic computing with 93% accuracy at recognizing handwritten digits. Introducing the wake-up-like effect to 2D CIPS may pave the way for innovative approaches to achieve advanced multilevel nonvolatile memory and neuromorphic computing capabilities for next-generation micro-nanoelectronic devices.

13.
Virulence ; 15(1): 2349768, 2024 12.
Article in English | MEDLINE | ID: mdl-38736039

ABSTRACT

ST11 is the most common lineage among carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in Asia. Diverse morphotypes resulting from genetic mutations are associated with significant differences in microbial characteristics among K. pneumoniae isolates. Here, we investigated the genetic determinants and critical characteristics associated with distinct morphotypes of ST11 CRKP. An ST11-KL47 CRKP isolate carrying a pLVPK-like virulence plasmid was isolated from a patient with a bloodstream infection; the isolate had the "mcsw" morphotype. Two distinct morphotypes ("ntrd" and "msdw") were derived from this strain during in vitro passage. Whole genome sequencing was used to identify mutations that cause the distinct morphotypes of ST11 CRKP. Transmission electron microscopy, antimicrobial susceptibility tests, growth assays, biofilm formation, virulence assays, membrane permeability assays, and RNA-seq analysis were used to investigate the specific characteristics associated with different morphotypes of ST11 CRKP. Compared with the parental mcsw morphotype, the ntrd morphotype resulted from mutation of genes involved in capsular polysaccharide biosynthesis (wza, wzc, and wbaP), a result validated by gene knockout experiments. This morphotype showed capsule deficiency and lower virulence potential, but higher biofilm production. By contrast, the msdw morphotype displayed competition deficiency and increased susceptibility to chlorhexidine and polymyxin B. Further analyses indicated that these characteristics were caused by interruption of the sigma factor gene rpoN by insertion mutations and deletion of the rpoN gene, which attenuated membrane integrity presumably by downregulating the phage shock protein operon. These data expand current understanding of genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 CRKP.


Subject(s)
Anti-Bacterial Agents , Biofilms , Carbapenems , Klebsiella Infections , Klebsiella pneumoniae , Microbial Sensitivity Tests , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/pathogenicity , Virulence , Klebsiella Infections/microbiology , Humans , Anti-Bacterial Agents/pharmacology , Biofilms/growth & development , Carbapenems/pharmacology , Animals , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenem-Resistant Enterobacteriaceae/drug effects , Mice , Mutation , Whole Genome Sequencing , Plasmids/genetics , Drug Resistance, Bacterial
14.
Nat Commun ; 15(1): 3669, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38693119

ABSTRACT

Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.


Subject(s)
Fusobacterium nucleatum , Herpesvirus 1, Human , Oncolytic Virotherapy , Oncolytic Viruses , RNA-Binding Proteins , Herpesvirus 1, Human/immunology , Herpesvirus 1, Human/genetics , Oncolytic Viruses/genetics , Oncolytic Viruses/immunology , Animals , Humans , Oncolytic Virotherapy/methods , Mice , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/immunology , Cell Line, Tumor , Fusobacterium nucleatum/immunology , Neoplasms/therapy , Neoplasms/immunology , Female , Immunity, Innate , Mice, Inbred BALB C
15.
Nat Commun ; 15(1): 3737, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702313

ABSTRACT

Twisted bilayer graphene (tBLG) provides a fascinating platform for engineering flat bands and inducing correlated phenomena. By designing the stacking architecture of graphene layers, twisted multilayer graphene can exhibit different symmetries with rich tunability. For example, in twisted monolayer-bilayer graphene (tMBG) which breaks the C2z symmetry, transport measurements reveal an asymmetric phase diagram under an out-of-plane electric field, exhibiting correlated insulating state and ferromagnetic state respectively when reversing the field direction. Revealing how the electronic structure evolves with electric field is critical for providing a better understanding of such asymmetric field-tunable properties. Here we report the experimental observation of field-tunable dichotomic electronic structure of tMBG by nanospot angle-resolved photoemission spectroscopy (NanoARPES) with operando gating. Interestingly, selective enhancement of the relative spectral weight contributions from monolayer and bilayer graphene is observed when switching the polarity of the bias voltage. Combining experimental results with theoretical calculations, the origin of such field-tunable electronic structure, resembling either tBLG or twisted double-bilayer graphene (tDBG), is attributed to the selectively enhanced contribution from different stacking graphene layers with a strong electron-hole asymmetry. Our work provides electronic structure insights for understanding the rich field-tunable physics of tMBG.

16.
Mol Cell Biochem ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38782835

ABSTRACT

Thioredoxin reductase (TrxR) is a pivotal regulator of redox homeostasis. It is frequently overexpressed in various cancer cells, including prostate cancer, making it a promising target for the development of anti-cancer drugs. In this study, we screened a series of newly designed complexes of gold(I) phosphine. Specifically, Compound 5 exhibited the highest cytotoxicity against prostate cancer cells and demonstrated stronger antitumor effects than commonly used drugs, such as cisplatin and auranofin. Importantly, our mechanistic study revealed that Compound 5 effectively inhibits the TrxR system in vitro. Additionally, Compound 5 promoted intracellular accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction and irreversible apoptosis in prostate cancer cells. Our in vivo xenograft study further demonstrated that Compound 5 has excellent antitumor activity against prostate cancer cells, but does not cause severe side effects. These findings provide a promising lead Compound for the development of novel antitumor agents targeting prostate cancer and offer a valuable tool for investigating biological pathways involving TrxR and ROS modulation.

17.
Int Immunopharmacol ; 135: 112317, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796965

ABSTRACT

Colorectal cancer (CRC) is a significant global health challenge, with increasing rates of incidence and mortality. Despite advancements in immunotherapy, resistance, particularly due to T cell exhaustion, remains a major hurdle. This study explores the role of YWHAH, mediated by N4-acetylcytidine (ac4C) modification, in CRC progression and its impact on CD8+ T cell exhaustion. Analysis of five paired CRC patient tissue samples using acetylated RNA immunoprecipitation and sequencing (acRIP-seq)identified ac4C-modified mRNAs. Functional assays, including cell culture, transfection, qRT-PCR, and immune assays, investigated the influence of YWHAH expression on CRC advancement. Bioinformatics analysis of TCGA data assessed the correlation between YWHAH and immune responses, as well as checkpoint inhibitors. Flow cytometry and Immunohistochemistry validated these findings, complemented by a co-culture experiment involving CD8+ T cells and CRC cell lines (LOVO and HCT116). acRIP-seq revealed YWHAH as a potential driver of CRC progression, exhibiting ac4C modification-mediated stability and upregulation. High YWHAH levels correlated with adverse outcomes and immune evasion in CRC patients, showing strong associations with immune checkpoint proteins and modest correlations with CD8+ T cell infiltration. Co-culture experiments demonstrated YWHAH-induced CD8+ T cell exhaustion, characterized by decreased proliferation and increased exhaustion markers. NAT10-mediated ac4C modification enhanced YWHAH stability in CRC. The involvement of YWHAH in CD8 + T cell exhaustion suggests its potential as a therapeutic target and prognostic marker in CRC immunotherapy, highlighting the intricate interplay between epitranscriptomic modifications, the tumor microenvironment, and immune responses in CRC progression.

18.
Cell Death Dis ; 15(5): 359, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789450

ABSTRACT

Chimeric antigen receptor engineered T (CAR T) cell therapy has developed rapidly in recent years, leading to profound developments in oncology, especially for hematologic malignancies. However, given the pressure of immunosuppressive tumor microenvironments, antigen escape, and diverse other factors, its application in solid tumors is less developed. Urinary system tumors are relatively common, accounting for approximately 24% of all new cancers in the United States. CAR T cells have great potential for urinary system tumors. This review summarizes the latest developments of CAR T cell therapy in urinary system tumors, including kidney cancer, bladder cancer, and prostate cancer, and also outlines the various CAR T cell generations and their pathways and targets that have been developed thus far. Finally, the current advantages, problems, and side effects of CAR T cell therapy are discussed in depth, and potential future developments are proposed in view of current shortcomings.


Subject(s)
Immunotherapy, Adoptive , Receptors, Chimeric Antigen , Urologic Neoplasms , Humans , Immunotherapy, Adoptive/methods , Urologic Neoplasms/therapy , Urologic Neoplasms/immunology , Receptors, Chimeric Antigen/immunology , T-Lymphocytes/immunology , Animals , Treatment Outcome , Tumor Microenvironment/immunology , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism
19.
Materials (Basel) ; 17(10)2024 May 11.
Article in English | MEDLINE | ID: mdl-38793338

ABSTRACT

Creating lightweight and impact-resistant box structures has been an enduring pursuit among researchers. A new energy-absorbing structure consisting of a bionic gradient lattice-enhanced thin-walled tube is presented in this article. The gradient lattice and thin-walled tube were prepared using selective laser melting (SLM) and wire-cutting techniques, respectively. To analyze the effects of gradient pattern, mass ratio, diameter range and impact speed on structural crashworthiness, low-speed impact at 4 m/s and finite element simulation experiments were conducted. The study demonstrates that the design of inward radial gradient lattice-reinforced thin-walled tubes can effectively enhance structure's energy-absorption efficiency and provide a more stable mode of deformation. It also shows a 17.44% specific energy-absorption advantage over the uniformly lattice-reinforced thin-walled tubes, with no significant overall gain in peak crushing force. A complex scale evaluation method was used to determine the optimum structure and the structure type with the best crashworthiness was found to be a gradient lattice-filled tube with a thickness of 0.9 mm and a slope index of 10. The gradient lattice-reinforced thin-walled tube suggested in this investigation offers guidance for designing a more efficient thin-walled energy-absorption structure.

20.
Environ Sci Technol ; 58(21): 9283-9291, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38752583

ABSTRACT

The concerns about the fate of per- and polyfluoroalkyl substances (PFAS) in the atmosphere are continuously growing. In this study, size-fractionated particles, gas, and rainwater samples were simultaneously collected in Shijiazhuang, China, to investigate the multiphase distribution of PFAS in the atmosphere. Perfluoroalkyl carboxylic acids (PFCAs) dominated the total concentration of PFAS in atmospheric media. A strong positive relationship (0.79 < R2 < 0.99) was observed between the concentration of PFCAs and organic matter fraction (fOM) in different particle size fractions, while no such relationship for perfluoroalkyl sulfonic acids (PFSAs) and fOM, suggesting fOM may be an important factor influencing the size-dependent distribution of PFCAs. Temperature played a key role in the gas-particle partitioning of PFAS, while it did not significantly affect their particle-size-dependent distribution. The associative concentration fluctuation of particle and particle-bound PFAS during precipitation suggested that precipitation scavenging was an important mechanism for the removal of PFAS from the atmosphere. Furthermore, temporary increases in atmospheric PFAS concentrations were observed during the precipitation. Fugacity ratios of PFAS in rainwater and gas phase (log fR/fG ranged between 2.0 and 6.6) indicated a strong trend for PFAS to diffuse from the rainwater to the gas phase during the precipitation, which may explain that the concentration of PFAS in the gas phase continued to increase even at the end of the precipitation.


Subject(s)
Atmosphere , Fluorocarbons , Particle Size , Fluorocarbons/analysis , Atmosphere/chemistry , Air Pollutants/analysis , Rain/chemistry , China , Environmental Monitoring , Gases , Chemical Precipitation
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