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1.
Neural Regen Res ; 20(3): 858-872, 2025 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38886958

RESUMEN

JOURNAL/nrgr/04.03/01300535-202503000-00030/figure1/v/2024-06-17T092413Z/r/image-tiff Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

2.
Environ Sci Technol ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235142

RESUMEN

Taste and odor (T&O) are among the most frequently encountered aesthetic issues in drinking water. While fungi have been reported to produce offensive odors, their contribution to T&O in drinking water remains understudied and often overlooked. In this study, the profiles of fungal community and odorants produced by 10 native fungal isolates were investigated in 36 samples collected from two drinking water treatment plants and a premise plumbing system. A total of 17 odorants were identified with Penicillium, Aspergillus, Paecilomyces, and Alternaria genera exhibiting the highest odorant yields. Significant concentrations of musty/earthy compounds were produced by these fungal isolates, such as 2-methylisoborneol (2-MIB) (26-256 ng/L), geosmin (10-13 ng/L), and 2-isobutyl-3-methoxy-pyrazine (IBMP) (3-13 ng/L). The high odor activity value of the odorants primarily occurred within 4 d, while toxicity continued to increase during the 8 d incubation. UV treatment in premise plumbing significantly (p < 0.05) reduced the gene read counts of Ascomycota phylum, Aspergillus spp., Fusarium spp., Rhizopus spp., and Trichoderma spp., by 2.3-4.0 times. These findings underscore the previously underestimated role of fungi in contributing to T&O issues in drinking water and corresponding risks to consumers and indicate UV as a promising strategy for fungal control in drinking water.

3.
Aging Dis ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39226161

RESUMEN

Stroke, a leading cause of death and disability, often results from ischemic events that cut off the brain blood flow, leading to neuron death. Despite treatment advancements, survivors frequently endure lasting impairments. A key focus is the ischemic penumbra, the area around the stroke that could potentially recover with prompt oxygenation; yet its monitoring is complex. Recent progress in bioluminescence-based oxygen sensing, particularly through the Green enhanced Nano-lantern (GeNL), offers unprecedented views of oxygen fluctuations in vivo. Utilized in awake mice, GeNL has uncovered hypoxic pockets within the cerebral cortex, revealing the brain's oxygen environment as a dynamic landscape influenced by physiological states and behaviors like locomotion and wakefulness. These findings illuminate the complexity of oxygen dynamics and suggest the potential impact of hypoxic pockets on ischemic injury and recovery, challenging existing paradigms and highlighting the importance of microenvironmental oxygen control in stroke resilience. This review examines the implications of these novel findings for stroke research, emphasizing the criticality of understanding pre-existing oxygen dynamics for addressing brain ischemia. The presence of hypoxic pockets in non-stroke conditions indicates a more intricate hypoxic scenario in ischemic brains, suggesting strategies to alleviate hypoxia could lead to more effective treatments and rehabilitation. By bridging gaps in our knowledge, especially concerning microenvironmental changes post-stroke, and leveraging new technologies like GeNL, we can pave the way for therapeutic innovations that significantly enhance outcomes for stroke survivors, promising a future where an understanding of cerebral oxygenation dynamics profoundly informs stroke therapy.

4.
Front Microbiol ; 15: 1452190, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282561

RESUMEN

Our research team previously reported the immunomodulatory effects of kombucha fermentation liquid. This study investigated the protective effects of turmeric kombucha (TK) against lipopolysaccharide (LPS)-induced sepsis and its impact on the intestinal microbiota of mice. A turmeric culture medium without kombucha served as the control (TW). Non-targeted metabolomics analysis was employed to analyze the compositional differences between TK and TW. Qualitative analysis identified 590 unique metabolites that distinguished TK from TW. TK improved survival from 40 to 90%, enhanced thermoregulation, and reduced pro-inflammatory factor expression and inflammatory cell infiltration in the lung tissue, suppressing the NF-κB signaling pathway. TK also altered the microbiome, promoting Allobaculum growth. Our findings shed light on the protective effects and underlying mechanisms of TK in mitigating LPS-induced sepsis, highlighting TK as a promising anti-inflammatory agent and revealing new functions of kombucha prepared through traditional fermentation methods.

5.
Commun Biol ; 7(1): 1127, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271811

RESUMEN

Primordial germ cells (PGCs) are vital for producing sperm and eggs and are crucial for conserving chicken germplasm and creating genetically modified chickens. However, efforts to use PGCs for preserving native chicken germplasm and genetic modification via CRISPR/Cas9 are limited. Here we show that we established 289 PGC lines from eight Chinese chicken populations with an 81.6% success rate. We regenerated Piao chickens by repropagating cryopreserved PGCs and transplanting them into recipient chickens, achieving a 12.7% efficiency rate. These regenerated chickens carried mitochondrial DNA from female donor PGC and the rumplessness mutation from both male and female donors. Additionally, we created the TYRP1 (tyrosinase-related protein 1) knockout (KO) PGC lines via CRISPR/Cas9. Transplanting KO cells into male recipients and mating them with wild-type hens produced four TYRP1 KO chickens with brown plumage due to reduced eumelanin production. Our work demonstrates efficient PGC culture, cryopreservation, regeneration, and gene editing in chickens.


Asunto(s)
Sistemas CRISPR-Cas , Pollos , Criopreservación , Células Germinativas , Animales , Pollos/genética , Células Germinativas/metabolismo , Femenino , Masculino , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Edición Génica/métodos , Regeneración/genética , Animales Modificados Genéticamente , Quimera/genética , Técnicas de Inactivación de Genes
6.
Biol Res ; 57(1): 60, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227998

RESUMEN

BACKGROUND: Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. METHODS: Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. RESULTS: Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. CONCLUSIONS: Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.


Asunto(s)
Animales Modificados Genéticamente , Leptina , Reproducción , Animales , Femenino , Leptina/sangre , Porcinos , Reproducción/fisiología , Modelos Animales de Enfermedad
7.
Heliyon ; 10(16): e36133, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39229520

RESUMEN

Mutations in oncogenes such as KRAS, NRAS and BRAF promote the growth and survival of tumors, while excessive RAS/RAF/MEK/ERK activation inhibits tumor growth. In this study we examined the precise regulatory machinery that maintains a moderate RAS/RAF/MEK/ERK pathway activation during CRC. Here, using bioinformatic analysis, transcriptomic profiling, gene silencing and cellular assays we discovered that a circular RNA, circRAPGEF5, is significantly upregulated in KRAS mutant colorectal cancer (CRC) cells. CircRAPGEF5 suppressed mutant and constitutively activated KRAS and the expression of the death receptor TNFRSF10A. Silencing of circRAPGEF5-induced RAS/RAF/MEK/ERK signaling hyperactivation and apoptosis in CRC cells suggesting that an upregulation of circRAPEF5 may suppress the expression of TNFRSF10A and aid CRC progression by preventing apoptosis, while the direct interactions between circRAPGEF5 and elements of the RAS/RAF/MEK/ERK pathway was not identified, which nevertheless can be the basis for future research. Moreover, EIF4A3, was observed to share a similar expression pattern with circRAPEF5 and demonstrated to be a major controller of circRAPGEF5 via the promotion of circRAPGEF5 circularization and its silencing reduced circRAPGEF5 levels. Taken together, our findings reveal a mechanism of accurate RAS/RAF/MEK/ERK signaling regulation during CRC progression maintained by upregulation of circRAPGEF5 which may be a plausible target for future clinical applications that seek to induce CRC cell apoptosis via the RAS/RAF/MEK/ERK signaling pathway.

8.
Water Res ; 266: 122427, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39276472

RESUMEN

Aniline accelerators and antioxidants (AAs) are high-production-volume industrial additives that have recently attracted emerging concern given their ubiquity in environmental compartments and the associated (eco)toxic effects. Nonetheless, available information on the multi-media behavior of AAs and their transformation products (TPs) remains scarce. Therefore, we determined the residues of twenty-four AA(TP)s in paired dissolved phases (i.e., filtered water), suspended particulate matter (SPM), and sediment samples collected from the Yangtze River Estuary (YRE), a highly urbanized estuary in the East China. The median total concentrations of targeted compounds were 0.73 ng/g dw, 34.4 ng/L, and 39.6 ng/L in sediments, surface and bottom water, respectively. Diphenylamine (DPA) was the most abundant congener in SPM, while 1,3-diphenylguanidine (DPG) and dicyclohexylamine (DChA) dominated in the dissolved phases and sediments. Various anthropogenic emissions and (a)biotic degradation may collectively shape the matrix-specific accumulation patterns and spatial trends of these compounds across the YRE. However, the vertical patterns of AA(TP)s were obscure, probably due to the estuarine hydrodynamics and/or the modest sample size. The SPM fractions of AA(TP)s in water (Ф: 7.9-100%) and the sediment sorption coefficients (KOC: 0.01-6.56) both positively correlated with their hydrophobicity as indicated by the octanol-water partition coefficient (KOW). Moreover, risk quotients implied moderate to high aquatic toxicity posed by several AA(TP)s at certain YRE sites. The estimated total annual fluxes of our analytes transported via water and sediments towards the East China Sea were 5.90-365.5 tons and 4.23-1,100 kg, respectively. This work provides a systematic investigation of multi-media processes and ecological risks of AA(TP)s in a highly-urbanized estuary, contributing to holistic comprehension of these emerging contaminants in estuarine environments.

9.
Animals (Basel) ; 14(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39272382

RESUMEN

Recombination-activating genes (RAGs) play a crucial role in the V(D)J recombination process and the development of immune cells. The development of the immune system and its mechanisms in pigs exhibit greater similarity to those of humans compared to other animals, thus rendering pigs a valuable tool for biomedical research. In this study, we utilized CRISPR/Cas9 gene editing and somatic cell nuclear transfer technology to generate RAG2 knockout (KO) pigs. Furthermore, we evaluated the impact of RAG2 KO on the immune organs and immune cell development through morphological observations, blood analysis and flow cytometry technology. RAG2 KO cell lines were used as donors for cloning. The reconstructed embryos were transplanted into 4 surrogate sows, and after 116 days of gestation, 2 sows gave birth to 12 live piglets, all of which were confirmed to be RAG2 KO. The thymus and spleen sizes of RAG2 KO pigs were significantly smaller than those of wild-type (WT) pigs. Hematoxylin-eosin staining results revealed that the thymus and spleen tissue structures of RAG2 KO pigs were disorganized and lacked the characteristic structures, indicating that RAG2 KO leads to dysplasia of the thymus and spleen. Hematological analysis demonstrated that the total number of white blood cells and lymphocytes in the circulation of RAG2 KO pigs was significantly lower, while the number of eosinophils was higher. Flow cytometry results indicated that the proportions of mature T and B lymphocytes were significantly reduced compared to WT pigs. These findings successfully verified the immunodeficiency phenotype of RAG2 KO pigs. This study may provide experimental animals for the development of tumor models and humanized animals.

10.
BMC Infect Dis ; 24(1): 960, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266946

RESUMEN

BACKGROUND: Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. METHODS: This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. RESULTS: A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW. CONCLUSION: This pilot trial preliminarily confirmed that nebulized inhalation of PAW can alleviate pneumonia in moderate COVID-19 patients with antiviral treatment failure, with no adverse reactions observed. This still needs to be verified by large-scale studies. TRIAL REGISTRATION: Chinese Clinical Trial Registry; No.: ChiCTR2300078706 (retrospectively registered, 12/15/2023); URL: www.chictr.org.cn .


Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Nebulizadores y Vaporizadores , SARS-CoV-2 , Insuficiencia del Tratamiento , Humanos , Masculino , Femenino , Persona de Mediana Edad , Proyectos Piloto , Administración por Inhalación , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Anciano , Agua , Adulto , Resultado del Tratamiento
11.
Adv Sci (Weinh) ; : e2403854, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120051

RESUMEN

Compressed ultrafast photography (CUP) can capture irreversible or difficult-to-repeat dynamic scenes at the imaging speed of more than one billion frames per second, which is obtained by compressive sensing-based image reconstruction from a compressed 2D image through the discretization of detector pixels. However, an excessively high data compression ratio in CUP severely degrades the image reconstruction quality, thereby restricting its ability to observe ultrafast dynamic scenes with complex spatial structures. To address this issue, a discrete illumination-based CUP (DI-CUP) with high fidelity is reported. In DI-CUP, the dynamic scenes are loaded into an ultrashort laser pulse train with controllable sub-pulse number and time interval, thus the data compression ratio, as well as the overlap between adjacent frames, is greatly decreased and flexibly controlled through the discretization of dynamic scenes based on laser pulse train illumination, and high-fidelity image reconstruction can be realized within the same observation time window. Furthermore, the superior performance of DI-CUP is verified by observing femtosecond laser-induced ablation dynamics and plasma channel evolution, which are hardly resolved in the spatial structures using conventional CUP. It is anticipated that DI-CUP will be widely and dependably used in the real-time observations of various ultrafast dynamics.

12.
Int Immunopharmacol ; 141: 112907, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39159557

RESUMEN

Sepsis, characterized by high mortality rates, causes over 50 % of acute lung injury (ALI) cases, primarily due to the heightened susceptibility of the lungs during this condition. Suppression of the excessive inflammatory response is critical for improving the survival of patients with sepsis; nevertheless, no specific anti-sepsis drugs exist. Huperzine A (HupA) exhibits neuroprotective and anti-inflammatory properties; however, its underlying mechanisms and effects on sepsis-induced ALI have yet to be elucidated. In this study, we demonstrated the potential of HupA for treating sepsis and explored its mechanism of action. To investigate the in vivo impacts of HupA, a murine model of sepsis was induced through cecal ligation and puncture (CLP) in both wild-type (WT) and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. Our results showed that HupA ameliorates sepsis-induced acute lung injury by activating the α7nAChR. We used the CLP sepsis model in wild-type and α7nAChR -/- mice and found that HupA significantly increased the survival rate through α7nAChR, reduced the pro-inflammatory cytokine levels and oxidative stress, ameliorated histopathological lung injury, altered the circulating immune cell composition, regulated gut microbiota, and promoted short-chain fatty acid production through α7nAChR in vivo. Additionally, HupA inhibited Toll-like receptor NF-κB signaling by upregulating the α7nAChR/protein kinase B/glycogen synthase kinase-3 pathways. Our data elucidate HupA's mechanism of action and support a "new use for an old drug" in treating sepsis. Our findings serve as a basis for further in vivo studies of this drug, followed by application to humans. Therefore, the findings have the potential to benefit patients with sepsis.


Asunto(s)
Lesión Pulmonar Aguda , Alcaloides , Ratones Endogámicos C57BL , Ratones Noqueados , Estrés Oxidativo , Sepsis , Sesquiterpenos , Receptor Nicotínico de Acetilcolina alfa 7 , Animales , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/genética , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/inmunología , Estrés Oxidativo/efectos de los fármacos , Alcaloides/uso terapéutico , Alcaloides/farmacología , Ratones , Masculino , Sesquiterpenos/uso terapéutico , Sesquiterpenos/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación/tratamiento farmacológico
13.
World Neurosurg ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39159675

RESUMEN

BACKGROUND: Sporadic Creutzfeldt-Jakob Disease (SCJD) is a severe neurodegenerative disorder characterized by rapid progression and extensive neuronal loss. Disulfidptosis is an innovative type of programmed cell demise characterized by an accumulation of disulfide bonds within the cellular cytoplasm, subsequently triggering functional disruption and cell demise. METHODS: Through literature review and analysis, we identified 18 candidate disulfidptosis-related genes (DRGs) involved in cellular processes. The dataset used for analysis, GSE124571, was obtained from the Gene Expression Omnibus database. Gene-gene and protein-protein interactions were analyzed using the GeneMANIA and STRING databases, respectively. We also performed enrichment analysis, differential expressed genes analysis, weighted gene correlation network analysis analysis, immune infiltration, consensus clustering, and matrix correlation. RESULTS: The analysis showed that 12 out of 18 DRGs were significantly changed between SCJD and control groups. The DRGs had strong interactions such as physical interactions, co-expression and genetic interactions, and were enriched in biological processes and pathways related to actin cytoskeletal regulation. The study most notably identified 3 hub genes (WASF2, TLN1 and G6PD) important for SCJD and emphasized the functional significance of the identified hub genes. The role of the immune system in the pathogenesis of SCJD. The study found that the composition of immune cells in SCJD brain tissue is altered. Consensus clustering provided insights into immune infiltration and hub gene expression in SCJD subgroup. CONCLUSIONS: Our study reveals the possible involvement of disulfidptosis in SCJD and highlights the significance of identified hub genes as potential biomarkers and therapeutic targets for SCJD.

14.
Xenotransplantation ; 31(4): e12881, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185796

RESUMEN

BACKGROUND: The number of multigene-modified donor pigs for xenotransplantation is increasing with the advent of gene-editing technologies. However, it remains unclear which gene combination is suitable for specific organ transplantation. METHODS: In this study, we utilized CRISPR/Cas9 gene editing technology, piggyBac transposon system, and somatic cell cloning to construct GTKO/hCD55/hTBM/hCD39 four-gene-edited cloned (GEC) pigs and performed kidney transplantation from pig to rhesus monkey to evaluate the effectiveness of these GEC pigs. RESULTS: First, 107 cell colonies were obtained through drug selection, of which seven were 4-GE colonies. Two colonies were selected for somatic cell nuclear transfer (SCNT), resulting in seven fetuses, of which four were GGTA1 biallelic knockout. Out of these four, two fetuses had higher expression of hCD55, hTBM, and hCD39. Therefore, these two fetuses were selected for two consecutive rounds of cloning, resulting in 97 live piglets. After phenotype identification, the GGTA1 gene of these pigs was inactivated, and hCD55, hTBM, and hCD39 were expressed in cells and multiple tissues. Furthermore, the numbers of monkey IgM and IgG binding to the peripheral blood mononuclear cells (PBMCs) of the 4-GEC pigs were markedly reduced. Moreover, 4-GEC porcine PBMCs had greater survival rates than those from wild-type pigs through complement-mediated cytolysis assays. In pig-to-monkey kidney xenotransplantation, the kidney xenograft successfully survived for 11 days. All physiological and biochemical indicators were normal, and no hyperacute rejection or coagulation abnormalities were found after transplantation. CONCLUSION: These results indicate that the GTKO/hCD55/hTBM/hCD39 four-gene modification effectively alleviates immune rejection, and the pig kidney can functionally support the recipient monkey's life.


Asunto(s)
Animales Modificados Genéticamente , Galactosiltransferasas , Edición Génica , Trasplante de Riñón , Trasplante Heterólogo , Animales , Trasplante Heterólogo/métodos , Trasplante de Riñón/métodos , Porcinos , Edición Génica/métodos , Galactosiltransferasas/genética , Sistemas CRISPR-Cas , Macaca mulatta , Técnicas de Transferencia Nuclear , Xenoinjertos , Humanos , Supervivencia de Injerto/inmunología , Rechazo de Injerto/inmunología , Apirasa , Antígenos CD
15.
ChemSusChem ; : e202401307, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39176998

RESUMEN

Solar-to-hydrogen (STH) is emerging as a promising approach for energy storage and conversion to contribute to carbon neutrality. The lack of efficient catalysts and sustainable reaction systems is stimulating the fast development of photothermal hydrogen production based on floating carriers to achieve unprecedented STH efficiency. This technology involves three major components: floating carriers with hierarchically porous structures, photothermal materials for solar-to-heat conversion and photocatalysts for hydrogen production. Under solar irradiation, the floating photothermal system realizes steam generation which quickly diffuses to the active site for sustainable hydrogen generation with the assistance of a hierarchically porous structure. Additionally, this technology is endowed with advantages in the high utilization of solar energy and catalyst retention, making it suitable for various scenarios, including domestic water supply, wastewater treatment, and desalination. A comprehensive overview of the photothermal hydrogen production system is present due to the economic feasibility for industrial application. The in-depth mechanism of a floating photothermal system, including the solar-to-heat effect, steam diffusion, and triple-phase interaction are highlighted by elucidating the logical relationship among buoyant carriers, photothermal materials, and catalysts for hydrogen production. Finally, the challenges and new opportunities facing current photothermal catalytic hydrogen production systems are analyzed.

16.
Macromol Rapid Commun ; : e2400519, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39169814

RESUMEN

In recent years, with the development of solar seawater desalination technology, many solar evaporators are affected by precipitated salts during the evaporation process, which can reduce efficiency. In this work, flexible fabrics made of polypyrrole (PPy)/MXene are obtained by impregnating the prepared PPy ink onto waffle like fabrics. The combination of PPy and fabric greatly improves the water absorption and evaporation performance of the fabric. The average evaporation rate of this structure is 1.43 kg m-2 h-1, and the average evaporation efficiency under a single light source is 85.13%. After a 15-h testing cycle and a total of 8 cycles, lasting nearly 120 h, the performance of the device remained stable. The structural characteristics of waffle fabric, based on the Marangoni thermal effect, make it possible to suppress salt precipitation during evaporation, avoiding large salt particles covering the evaporation surface and reducing efficiency. This experiment successfully demonstrated long-term stable water evaporation, providing new ideas for the development of fabric evaporators.

17.
Int J Endocrinol ; 2024: 8501696, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966821

RESUMEN

Exposure to particulate matter 2.5 (PM2.5) is detrimental to multiple organ systems. Given the factor that aging also alters the cellularity and response of immune system and dysfunction of hypothalamic-pituitary-adrenal, -gonad and -thyroid axes, it is imperative to investigate whether chronic exposure to PM2.5 interacts with aging in these aspects. In this study, two-months-old Sprague-Dawley rats were exposed to real world PM2.5 for 16 months. PM2.5 exposure diminished the relative numbers of CD4+ T cells and CD8+ T cells and increased the relative number of B cells in the peripheral blood of male rats. Conversely, only reduced relative number of CD4+ T cells was seen in the blood of female rats. These shifts resulted in elevated levels of proinflammatory factors interleukin-6 and tumor necrosis factor-α in the circulatory systems of both sex, with females also evidencing a rise in interleukin-1ß levels. Moreover, heightened interleukin-6 was solely discernible in the hippocampus of female subjects, while increased tumor necrosis factor-α concentrations were widespread in female brain regions but confined to the male hypothalamus. Notable hormonal decreases were observed following PM2.5 exposure in both sex. These comprised declines in biomolecules such as corticotrophin-releasing hormone and cortisol, generated by the hypothalamic-pituitary-adrenal axis, and thyroid-releasing hormone and triiodothyronine, produced by the hypothalamic-pituitary-thyroid axis. Hormonal elements such as gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone, derived from the hypothalamic-pituitary-gonad axis, were also diminished. Exclusive to male rats was a reduction in adrenocorticotropic hormone levels, whereas a fall in thyroid-stimulating hormone was unique to female rats. Decreases in sex-specific hormones, including testosterone, estradiol, and progesterone, were also noted. These findings significantly enrich our comprehension of the potential long-term health repercussions associated with PM2.5 interaction particularly among the aging populace.

18.
Huan Jing Ke Xue ; 45(7): 4137-4151, 2024 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-39022961

RESUMEN

Ecosystem service assessment and prediction play a crucial role in sustainable regional development and resource management. Liaoning Province, as a typical representative of Northeast China, faces rapid development challenges such as urbanization, industrialization, and agricultural modernization. At the same time, there is an urgent need for a deeper understanding of the evolution trends of its ecosystems and their impact on ecosystem services. This study employed the InVEST-Markov-PLUS model to conduct simulated research on the assessment of past and future ecosystem services and multi-scenario predictions in Liaoning Province. Based on the land-use changes in Liaoning Province from 2000 to 2020, the InVEST model was used to evaluate the spatiotemporal variations in carbon storage, soil conservation, and water yield in the ecosystem services from 2000 to 2020. Additionally, the equivalent factor method was employed to calculate the value of ecosystem services in Liaoning Province during the same period. Furthermore, by integrating the PLUS and Markov models with the actual conditions of Liaoning Province, four land-use development scenarios for 2030 were constructed, including natural development, economic priority, ecological protection, and cropland protection. The land-use distribution and the quantities and values of ecosystem services under these scenarios were simulated. The study revealed the following findings: ① From 2000 to 2020, carbon storage and soil retention in Liaoning Province showed an overall increasing trend, whereas water yield exhibited a fluctuating decrease trend initially, followed by an increase and then another decrease. ② Carbon storage and soil retention in Liaoning Province showed higher values in the eastern mountainous areas and western hilly regions, with lower values in the central region. Water yield showed a decreasing trend from east to west. ③ The value of ecosystem services increased from 547.94 billion yuan to 565.53 billion yuan, with a total increase of 17.58 billion yuan during the study period. All four types of services showed an increase, with cultural services experiencing the fastest change. ④ In 2030, carbon storage and soil retention in Liaoning Province decreased in all scenarios except for in the ecological protection scenario. Water yield increased only in the cropland protection scenario, whereas it decreased in the other three scenarios. The value of ecosystem services in the study area increased in all scenarios except for in the economic priority scenario.

19.
Quant Imaging Med Surg ; 14(7): 5205-5223, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39022260

RESUMEN

Owing to advances in diagnosis and treatment methods over past decades, a growing number of early-stage hepatocellular carcinoma (HCC) diagnoses has enabled a greater of proportion of patients to receive curative treatment. However, a high risk of early recurrence and poor prognosis remain major challenges in HCC therapy. Microvascular invasion (MVI) has been demonstrated to be an essential independent predictor of early recurrence after curative therapy. Currently, biopsy is not generally recommended before treatment to evaluate MVI in HCC according clinical guidelines due to sampling error and the high risk of tumor cell seeding following biopsy. Therefore, the postoperative histopathological examination is recognized as the gold standard of MVI diagnosis, but this lagging indicator greatly impedes clinicians in selecting the optimal effective treatment for prognosis. As imaging can now noninvasively and completely assess the whole tumor and host situation, it is playing an increasingly important role in the preoperative assessment of MVI. Therefore, imaging criteria for MVI diagnosis would be highly desirable for optimizing individualized therapeutic decision-making and achieving a better prognosis. In this review, we summarize the emerging image characteristics of different imaging modalities for predicting MVI. We also discuss whether advances in imaging technique have generated evidence that could be practice-changing and whether advanced imaging techniques will revolutionize therapeutic decision-making of early-stage HCC.

20.
Artículo en Chino | MEDLINE | ID: mdl-38973045

RESUMEN

Objective:To investigate the clinical phenotype of a family with branchio-oto syndrome (BOS) and to explore the genetic etiology of the syndrome in this family. Methods:Clinical data were collected from a child diagnosed with BOS and his family members. Genomic DNA was extracted from peripheral blood of the proband and his family members. Whole-exome sequencing was performed, and the mutation sites were verified and analyzed by Sanger sequencing. Results:The family consists of two generations with four members, three of whom exhibit the phenotype. Two members have hearing loss and bilateral preauricular fistulas and bilateral branchial cleft fistulas. One member has bilateral preauricular fistulas and bilateral branchial cleft fistulas. All of which were in line with the clinical diagnosis of gill ear syndrome, the inheritance mode of the family was autosomal dominant inheritance, genetic testing showed that all members of the family had c. 1744delC(p. L592Cfs*47) mutation in the EYA1 gene, while unaffected members have the wild-type allele at this locus. This mutation is a frameshift mutation, which results in the early appearance of the stop codon, and has not been reported so far. According to ACMG guidelines, the variant was preliminarily determined to be suspected pathogenic. Conclusion:The newly discovered EYA1c. 1744delC(p. L592Cfs*47) mutation in this family is the pathogenic mutant gene of the patients in this family, which further expands the mutation spectrum of EYA1 gene, gives us a new understanding of the disease, and provides an important reference for clinical diagnosis and genetic counseling.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Proteínas Nucleares , Linaje , Fenotipo , Proteínas Tirosina Fosfatasas , Humanos , Masculino , Proteínas Tirosina Fosfatasas/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas Nucleares/genética , Femenino , Secuenciación del Exoma , Síndrome Branquio Oto Renal/genética , Mutación del Sistema de Lectura , Mutación , Pruebas Genéticas , Niño , Adulto
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