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1.
Biomaterials ; 309: 122615, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38759486

RESUMO

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.

2.
Orthop Surg ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773680

RESUMO

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.

3.
ACS Chem Neurosci ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775291

RESUMO

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.

4.
Chaos ; 34(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38775682

RESUMO

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.

5.
J Environ Manage ; 359: 121061, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38728983

RESUMO

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.


Assuntos
Sequestro de Carbono , Carbono , Mudança Climática , Urbanização , China , Carbono/análise , Solo/química
6.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731413

RESUMO

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.


Assuntos
Arbutina , Envelhecimento da Pele , Raios Ultravioleta , Arbutina/farmacologia , Raios Ultravioleta/efeitos adversos , Animais , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Humanos , Pele/efeitos da radiação , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
7.
Ecotoxicol Environ Saf ; 278: 116444, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38728943

RESUMO

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO2 promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455-3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455-3p, and miR-455-3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455-3p Inhibitors down-regulated the expression level of miR-455-3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455-3p Mimics showed an opposite trend. These results suggest that miR-455-3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455-3p may provide a new therapeutic strategy for SiO2-induced silicosis injury.

8.
Sex Med Rev ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719619

RESUMO

INTRODUCTION: Androgens play important roles in regulating the growth and development of the male reproductive system and maintaining libido and erectile function. The specific mechanisms by which androgen deficiency leads to erectile dysfunction (ED) are not yet fully understood. OBJECTIVES: To understand the mechanisms and treatment of androgen deficiency-related ED. METHODS: A literature search in the past 10 years was conducted in PubMed and Google Scholar to determine the effects of androgen deficiency on erectile function and the treatment of androgen deficiency. RESULTS: Androgen deficiency can be caused by hypothalamic-pituitary lesions and injuries, testicular-related diseases and injuries, endocrine and metabolic disorders, the side effects of medication, and age. Androgen deficiency can lead to ED by inhibiting the NOS/NO/cGMP pathway (nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate) and altering the expression of ion channel proteins, as well as by inducing oxidative stress, death, and fibrosis in penile corpus cavernosum cells. Testosterone replacement therapy is effective at improving the serum testosterone levels and erectile function in patients with androgen deficiency. For patients who need to maintain a low androgenic state, erectile function can be improved by lifestyle changes, treatment with phosphodiesterase type 5 inhibitors, low-intensity extracorporeal shock wave therapy, and stem cell therapy. CONCLUSIONS: Androgen deficiency can affect the structure and function of the penile corpus cavernosum, leading to ED. Areas of further study include how androgen replacement therapy can improve erectile function and how to improve the maintenance of erectile function in patients with hypoandrogenic status.

9.
Bioresour Technol ; 402: 130827, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38734258

RESUMO

In this study, three distinct bioretention setups incorporating fillers, plants, and earthworms were established to evaluate the operational efficiency under an ecosystem concept across varying time scales. The results revealed that under short-term operating conditions, extending the drying period led to a notable increase in the removal of NO3--N, total phosphorus (TP), and chemical oxygen demand (COD) by 5 %-7%, 4 %-12 %, and 5 %-10 %, respectively. Conversely, under long-time operating conditions, the introduction of plants resulted in a significant boost in COD removal by 10 %-20 %, while the inclusion of earthworms improved NH4+-N and NO3--N removal, especially TP removal by 9 %-16 %. Microbial community analysis further indicated the favorable impact of the bioretention system on biological nitrogen and phosphorus metabolism, particularly with the incorporation of plants and earthworms. This study provides a reference for the operational performance of bioretention systems on different time scales.

10.
J Coll Physicians Surg Pak ; 34(5): 527-532, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720211

RESUMO

OBJECTIVE: To develop an intervention based on Notch-1 signalling pathway blockade by investigating the potential application of the neurogenic locus notch homologue protein 1(Notch-1) signalling pathway as a key regulator of chronic inflammation and adipogenesis in the treatment of hepatic insulin resistance (HIR). STUDY DESIGN: Experimental study. Place and Duration of the Study: Animal Laboratory of the Fourth Hospital of Hebei Medical University, Shijiazhuang, China, from April 2021 to June 2022. METHODOLOGY: HIR models were established in Notch-1WT and Notch-1MAC-KO mice by high fat diet (HFD) for 16 weeks. Haematoxylin and eosin (HE) staining and oil red O (ORO) staining were used to detect inflammatory infiltration and lipid accumulation in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α and IL-6. Free fatty acid (FFA) and total cholesterol (TC) were measured with relevant kits. Moreover, real-time quantitative polymerase chain reaction (PCR) was performed to detect the relative expressions of F4/80, Mcp1, and CD11b in hepatic tissues. Mass spectrometry was used to analyse the levels of triglyceride (TG), diacylglycerol (DAG) and conformite europeenne (CE) in liver tissue. Western blotting was used to detect the expression of related proteins. RESULTS: Specific knockdown of Notch-1 in macrophages decreases the relative fluorescence intensity of CD68 and attenuates inflammatory infiltration and lipid degeneration. There was no difference in plasma levels of FFA and TG. Specific knockdown of Notch-1 in macrophages decreases the expression of F4/80, Mcp1, and CD11b, as well as the levels of TG, DAG, CE, IL-6, and TNF-α. CONCLUSION: Specific knockout of Notch-1 in macrophages may reduce HIR by inhibiting the IRE1α-XBP1 signalling pathway. KEY WORDS: Hepatic insulin resistance, Macrophages, Notch-1, IRE1α, XBP1.


Assuntos
Dieta Hiperlipídica , Resistência à Insulina , Macrófagos , Camundongos Knockout , Proteínas Serina-Treonina Quinases , Receptor Notch1 , Transdução de Sinais , Animais , Camundongos , Modelos Animais de Doenças , Endorribonucleases/metabolismo , Endorribonucleases/genética , Resistência à Insulina/fisiologia , Fígado/metabolismo , Macrófagos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptor Notch1/metabolismo , Receptor Notch1/genética , Proteína 1 de Ligação a X-Box/metabolismo , Proteína 1 de Ligação a X-Box/genética
11.
Nat Commun ; 15(1): 3737, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702313

RESUMO

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.

12.
Plant Physiol Biochem ; 211: 108676, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38714125

RESUMO

ATP-binding cassette (ABC) transporters were crucial for various physiological processes like nutrition, development, and environmental interactions. Selenium (Se) is an essential micronutrient for humans, and its role in plants depends on applied dosage. ABC transporters are considered to participate in Se translocation in plants, but detailed studies in soybean are still lacking. We identified 196 ABC genes in soybean transcriptome under Se exposure using next-generation sequencing and single-molecule real-time sequencing technology. These proteins fell into eight subfamilies: 8 GmABCA, 51 GmABCB, 39 GmABCC, 5 GmABCD, 1 GmABCE, 10 GmABCF, 74 GmABCG, and 8 GmABCI, with amino acid length 121-3022 aa, molecular weight 13.50-341.04 kDa, and isoelectric point 4.06-9.82. We predicted a total of 15 motifs, some of which were specific to certain subfamilies (especially GmABCB, GmABCC, and GmABCG). We also found predicted alternative splicing in GmABCs: 60 events in selenium nanoparticles (SeNPs)-treated, 37 in sodium selenite (Na2SeO3)-treated samples. The GmABC genes showed differential expression in leaves and roots under different application of Se species and Se levels, most of which are belonged to GmABCB, GmABCC, and GmABCG subfamilies with functions in auxin transport, barrier formation, and detoxification. Protein-protein interaction and weighted gene co-expression network analysis suggested functional gene networks with hub ABC genes, contributing to our understanding of their biological functions. Our results illuminate the contributions of GmABC genes to Se accumulation and tolerance in soybean and provide insight for a better understanding of their roles in soybean as well as in other plants.

13.
Sci Transl Med ; 16(745): eadh1763, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38691618

RESUMO

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.


Assuntos
Aneurisma da Aorta Abdominal , Modelos Animais de Doenças , Fator de Crescimento Insulin-Like I , Receptor IGF Tipo 1 , Animais , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/antagonistas & inibidores , Humanos , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/tratamento farmacológico , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/prevenção & controle , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Suínos , Camundongos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Ratos
14.
Artigo em Inglês | MEDLINE | ID: mdl-38700489

RESUMO

OBJECTIVES: The aim of this study was to evaluating the performance of the automated insulin delivery (AID) in adolescents, and children with type 1 diabetes (T1D) during physical activity. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Child", "Insulin Infusion Systems", and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of the AID in adolescents, and children with T1D during physical activity. RESULTS: Twelve studies involving 514 patients were identified. AID did not show a beneficial effect on duration of hypoglycemia<70 mg/dL during study period (p>0.05; I 2=96 %) and during the physical activity (p>0.99). Percentage of sensor glucose values in TIR was higher in AID than the non-AID pumps during study period (p<0.001; I 2=94 %). The duration of hyperglycemic time was significantly decreased in AID group compared to the non-AID pumps group during study period (p<0.05; I 2>50 %). CONCLUSIONS: AID improved TIR and decreased the duration of hyperglycemic time, but did not appear to have a significant beneficial effect on the already low post-exercise duration of hypoglycemia achievable by open loop or sensor-augmented pumps in adolescents and children with T1D during physical activity; further research is needed to confirm the beneficial effect of AID on duration of hypoglycemia.

15.
Front Plant Sci ; 15: 1381071, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699538

RESUMO

Introduction: The biosynthesis of secondary metabolites like anthocyanins is often governed by metabolic gene clusters (MGCs) in the plant ancestral genome. However, the existence of gene clusters specifically regulating anthocyanin accumulation in certain organs is not well understood. Methods and results: In this study, we identify MGCs linked to the coloration of cotton reproductive organs, such as petals, spots, and fibers. Through genetic analysis and map-based cloning, we pinpointed key genes on chromosome A07, such as PCC/GhTT19, which is involved in anthocyanin transport, and GbBM and GhTT2-3A, which are associated with the regulation of anthocyanin and proanthocyanidin biosynthesis. Our results demonstrate the coordinated control of anthocyanin and proanthocyanidin pathways, highlighting the evolutionary significance of MGCs in plant adaptation. The conservation of these clusters in cotton chromosome A07 across species underscores their importance in reproductive development and color variation. Our study sheds light on the complex biosynthesis and transport mechanisms for plant pigments, emphasizing the role of transcription factors and transport proteins in pigment accumulation. Discussion: This research offers insights into the genetic basis of color variation in cotton reproductive organs and the potential of MGCs to enhance our comprehension of plant secondary metabolism.

16.
Nat Commun ; 15(1): 3669, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38693119

RESUMO

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.


Assuntos
Fusobacterium nucleatum , Herpesvirus Humano 1 , Terapia Viral Oncolítica , Vírus Oncolíticos , Proteínas de Ligação a RNA , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/genética , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , Animais , Humanos , Terapia Viral Oncolítica/métodos , Camundongos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/imunologia , Linhagem Celular Tumoral , Fusobacterium nucleatum/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Feminino , Imunidade Inata , Camundongos Endogâmicos BALB C
17.
ACS Appl Mater Interfaces ; 16(19): 24987-24998, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38712685

RESUMO

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.

18.
Clinics (Sao Paulo) ; 79: 100376, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733690

RESUMO

OBJECTIVE: This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). STUDY DESIGN: A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. RESULTS: General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). CONCLUSIONS: Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value.

19.
Med Mycol ; 62(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38692846

RESUMO

Candida albicans is a pathogenic fungus that undergoes morphological transitions between hyphal and yeast forms, adapting to diverse environmental stimuli and exhibiting distinct virulence. Existing research works on antifungal blue light (ABL) therapy have either focused solely on hyphae or neglected to differentiate between morphologies, obscuring potential differential effects. To address this gap, we established a novel dataset of 150 C. albicans-infected mouse skin tissue slice images with meticulously annotated hyphae and yeast. Eleven representative convolutional neural networks were trained and evaluated on this dataset using seven metrics to identify the optimal model for segmenting hyphae and yeast in original high pixel size images. Leveraging the segmentation results, we analyzed the differential impact of blue light on the invasion depth and density of both morphologies within the skin tissue. U-Net-BN outperformed other models in segmentation accuracy, achieving the best overall performance. While both hyphae and yeast exhibited significant reductions in invasion depth and density at the highest ABL dose (180 J/cm2), only yeast was significantly inhibited at the lower dose (135 J/cm2). This novel finding emphasizes the importance of developing more effective treatment strategies for both morphologies.


We studied the effects of blue light therapy on hyphal and yeast forms of Candida albicans. Through image segmentation techniques, we discovered that the changes in invasion depth and density differed between these two forms after exposure to blue light.


Assuntos
Candida albicans , Hifas , Animais , Camundongos , Candida albicans/efeitos da radiação , Pele/microbiologia , Fototerapia/métodos , Processamento de Imagem Assistida por Computador/métodos , Luz , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Redes Neurais de Computação , Modelos Animais de Doenças , Candidíase/microbiologia
20.
PeerJ ; 12: e17382, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766483

RESUMO

Background: Preoperative inflammatory factors and nutritional status are strongly associated with the prognosis of a variety of cancers. We explored the relationship between preoperative lymphocytes, neutrophils and albumin (LANR) and progression-free survival in breast cancer patients. Methods: The clinical and follow-up data of 200 breast cancer patients were retrospectively analyzed in this study, and the value of LANR was determined as follows: LANR, lymphocytes × albumin/neutrophils. ROC curves, COX proportional risk regression analysis and subgroup analysis were used to assess the prognostic value of LANR in progression-free survival of breast cancer patients. Results: The median age of the patients was 55.5 years (range 50-62 years). The median follow-up time was 46 months (range 33-55 months). In progression-free survival, the area under the LANR curve was 0.748 and the HR (95% CI) was 0.035 (0.679-0.817). LANR was associated with age (p = 0.02), positive axillary lymph nodes (p < 0.001), TNM stage (p < 0.001) and human epidermal growth factor receptor 2(p = 0.004). The results indicated that preoperative LANR may be a reliable predictor of progression-free survival in patients with operable breast cancer. Conclusion: LANR may be an essential predictor for breast cancer patients and provides a therapeutic basis for clinicians and patients.


Assuntos
Neoplasias da Mama , Linfócitos , Neutrófilos , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/mortalidade , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neutrófilos/metabolismo , Neutrófilos/patologia , Prognóstico , Linfócitos/patologia , Linfócitos/metabolismo , Período Pré-Operatório , Intervalo Livre de Progressão , Albumina Sérica/análise , Albumina Sérica/metabolismo , Curva ROC
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