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1.
Biomed Opt Express ; 15(9): 5400-5410, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39296404

RESUMEN

The detection of tumor biomarkers in liquid biopsies requires high sensitivity and low-cost biosensing strategies. However, few traditional techniques can satisfy the requirements of target amplification-free and fluorescence-free at the same time. In this study, we have proposed a novel strategy for ctDNA detection with the combination of terahertz spectroscopy and the CRISPR/Cas12 system. The CRISPR/Cas12a system is activated by the target ctDNA, resulting in a series of reactions leading to the formation of an Au-Fe complex. This complex is easily extracted with magnets and when dropped onto the terahertz metamaterial sensor, it can enhance the frequency shift, providing sensitive and selective sensing of the target ctDNA. Results show that the proposed terahertz biosensor exhibits a relatively low detection limit of 0.8 fM and a good selectivity over interference species. This detection limit is improved by three orders of magnitude compared with traditional biosensing methods using terahertz waves. Furthermore, a ctDNA concentration of 100 fM has been successfully detected in bovine serum (corresponding to 50 fM in the final reaction system) without amplification.

2.
J Craniofac Surg ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39297662

RESUMEN

This study investigated the role of social media in the process of cleft lip and palate patients selecting surgeons. Patients utilized social media to obtain information about their health care providers and treatment teams and relied on this information to guide their decisions on where to seek medical care. A retrospective survey was conducted among patients who underwent surgery in our department from December 2020 to May 2023. Through an anonymous questionnaire titled "Factors Influencing the Decision to Choose a Particular Cleft Surgeon," we explored how patients discovered their primary surgeon via social media and the factors they deemed most important in selecting their surgeon. The questionnaire was completed by patients or their guardians. The cleft lip and palate patient population exhibited a distinct geographical distribution. A total of 548 individuals participated in the survey on media usage. Search engines (Baidu) were the most frequently visited (30.5%), followed by short video platforms (TikTok and Kwai), accounting for 21.7%, the hospital's official website at 20.8%, and WeChat at 15%. The primary factors influencing the selection of surgeons were the surgeon's reputation (66.2%), the hospital/medical team's reputation (49.2%), the quality of communication during consultations (15.4%), and the surgical outcomes depicted in postoperative photos (6.9%). The Internet remains the primary source of health information. Therefore, it is crucial to not only provide accurate medical information but also effectively communicate complex medical knowledge through easily accessible media channels in a manner that is comprehensible to patients.

3.
Biomark Insights ; 19: 11772719241275525, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39257715

RESUMEN

Background: Our previous research have identified Interleukin (IL)-7 and IL-15 as prognostic biomarkers for elderly septic patients, however, little is known about the link between the serum levels of IL-7, IL-15, and lactate as well as their potential roles in the regulation of inflammation in elderly septic patients. Objectives: This study aimed at investigating the link between the serum levels of IL-7, IL-15, and lactate as well as with other factors in elderly septic patients. Design: This is a retrospective study including 129 elderly patients with sepsis who were divided into the survival group (N = 34) and the nonsurvival group (N = 95) and further subgrouped based on the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Methods: The baseline data and clinical parameters were recorded within 24 h upon admission. Serum levels of the cytokines were quantified by the Luminex assay. Spearman correlation analysis were performed. Results: Serum levels of IL-6, IL-7, IL-15, and tumor necrosis factor-α (TNF-α) were significantly higher in the nonsurvival group (P < .05). Correlations between serum levels of IL-7 and platelet-derived growth factor-AA (PDGF-AA), as well as correlations between IL-15, IL-6, and TNF-α were confirmed (P < .05). Both the serum levels of lactate and IL-15 correlated with the total counts of platelet (PLT) in the survival subgroup with low APACHE Ⅱ scores while the serum levels of IL-7, IL-15, and total counts of monocytes correlated with each other in the nonsurvival subgroup with different APACHE Ⅱ scores (P < .05). Conclusion: Knowledge of the regulation networks between serum levels of IL-7, IL-15, lactate, and other cytokines may provide insights into potential mechanisms in the modulation of inflammation in elderly septic patients and facilitate more prompt and accurate treatment to reduce the mortality rate.

4.
Materials (Basel) ; 17(17)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39274632

RESUMEN

The use of laser cladding technology to prepare coatings of AlCoCrFeNi high-entropy alloy holds enormous potential for application. However, the cladding quality will have a considerable effect on the properties of the coatings. In this study, considering the complex coupling relationship between cladding quality and the process parameters, an orthogonal experimental design was employed, with laser power, scanning speed, and powder feed rate as correlation factor variables, and microhardness, dilution rate, and aspect ratio as characteristic variables. The experimental data underwent gray correlation analysis to determine the effect of various process parameters on the quality of cladding. Then, the NSGA-II algorithm was used to establish a multi-objective optimization model of process parameters. Finally, the ANSYS Workbench simulation model was employed to conduct numerical simulations on a group of optimized process parameters and analyze the change rule of the temperature field. The results demonstrate that the laser cladding coating of AlCoCrFeNi high-entropy alloy with the single pass is of high quality within the determined orthogonal experimental parameters. The powder feed rate exerts the most significant influence on microhardness, while laser power has the greatest impact on dilution rate, and scanning speed predominantly affects aspect ratio. The designed third-order polynomial nonlinear regression model exhibits a high fitting accuracy, and the NSGA-II algorithm can be used for multi-objective optimization to obtain the Pareto front solution set. The numerical simulation results demonstrate that the temperature field of AlCoCrFeNi high-entropy alloy laser cladding exhibits a "comet tail" phenomenon, where the highest temperature of the molten pool is close to 3000 °C. The temperature variations in the molten pool align with the features of laser cladding technology. This study lays the groundwork for the widespread application of laser cladding AlCoCrFeNi high-entropy alloy in surface engineering, additive manufacturing, and remanufacturing. Researchers and engineering practitioners can utilize the findings from this research to judiciously manage processing parameters based on the results of gray correlation analysis. Furthermore, the outcomes of multi-objective optimization can assist in the selection of appropriate process parameters aligned with specific application requirements. Additionally, the methodological approach adopted in this study offers valuable insights applicable to the exploration of various materials and diverse additive manufacturing techniques.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39300051

RESUMEN

Numerous studies have indicated that both the broaden-and-build model and the motivational dimensional model emphasize the impact of emotion on spatial attention by altering the attentional scope. However, no prior research has investigated the impact of emotional valence and motivational intensity on spatial attention within the same paradigm. Furthermore, object-based attention, characterized by distinct neural mechanisms from space-based attention and also susceptible to attentional scope, represents a major pattern of selective attention. Nevertheless, it is still unclear whether and how emotional valence and motivation play a role in object-based attentional selection. Therefore, the present study aimed to explore these areas. Using a two-rectangle paradigm, Experiment 1 found that motivational intensity modulated space-based effects, whereas emotional valence modulated object-based effects. Experiment 2 used a traditional spatial cueing paradigm to further study the stability of modulating effect of motivation intensity on space-based attention, yielding results consistent with those of Experiment 1. The present study indicated that the broaden-and-build model and motivational dimensional model were not either one or the other, but both played a role in object- and space-based attention. This study provides crucial empirical evidence for theoretical complementation and integration of emotional attention.

6.
Theranostics ; 14(13): 5123-5140, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267775

RESUMEN

Background: Vasculogenic mimicry (VM) induced by Epstein-Barr virus (EBV) infection plays an important role in resistance to anti-vascular endothelial growth factor (VEGF) therapy in EBV-associated epithelial cancers; however, the interaction between VM and the immune microenvironment has not been systematically investigated. Methods: IHC and multiplex IHC analysis the relationships among tumour-associated macrophage (TAM), VM and EBV infection in EBV-associated epithelial cancer biopsies. In vitro and in vivo evidence using CRISPR-Cas9 system engineered EBV-infected epithelial cancer cells and mouse models support functional role and mechanism for M2c-like macrophages in the VM formation. The prediction of VM in the effectiveness of anti-angiogenic agent was analysed using clinical datasets. Results: EBV-associated epithelial cancer biopsies revealed that infiltration of the TAM surrounding the VM is closely associated with EBV infection. AKT/mTOR/HIF-1α pathway in EBV-infected epithelial cancer cells control the secretion of CCL5 and CSF-1, enabling the recruitment of monocytes and their differentiation into M2c macrophages which promote VM formation by MMP9. Combination of anti-angiogenesis agents and HIF-1α inhibitor caused marked decreases in CD31-positive micro-vessels, VM, and M2c-like macrophages. VM scores can be used as biomarkers to predict the efficacy of anti-angiogenic agent therapy in EBV-associated epithelial cancers. Conclusions: Our findings define a secretory cross-talk between tumour cells and the immune microenvironment in EBV-associated epithelial cancer, revealing an unexpected role of EBV in epithelial cancer cells, controlling VM formation via M2c-like macrophages.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Neovascularización Patológica , Microambiente Tumoral , Macrófagos Asociados a Tumores , Humanos , Microambiente Tumoral/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/metabolismo , Animales , Neovascularización Patológica/metabolismo , Neovascularización Patológica/virología , Ratones , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Línea Celular Tumoral , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Quimiocina CCL5/metabolismo , Inhibidores de la Angiogénesis/farmacología , Metaloproteinasa 9 de la Matriz/metabolismo , Femenino
7.
Environ Sci Technol ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254632

RESUMEN

We propose coupling electrochemical leaching with solvent extraction to separate and recover Li and Co from spent lithium-ion batteries (LIBs). Electrochemical leaching occurs in the aqueous electrolyte for converting solid LiCoO2 into soluble Li+ and Co2+, in which electrons act as reductants to reduce Co(III) to Co(II). Simultaneously, solvent extraction occurs at the interface of aqueous and organic phases to separate Co2+ and Li+. By capturing and utilizing the protons from P507, leaching yields for both Co and Li exceed ∼7 times than acid leaching without solvent extraction. The extraction efficiency of Co2+ reaches 86% at 60 °C, 3.5 V, while simultaneously retaining the majority of Li+ in the H2SO4 solution. The total leaching amount was improved because the organic phase provides protons to help the leaching of Co2+, and the continuous extraction process of Co(II) maintains the low Co2+ concentration in the aqueous solution. The synergistic interaction between electrochemical leaching and solvent extraction processes significantly reduces the consumption of chemicals, enhances the utilization efficiency of protons, and simplifies the recovery process. The leaching kinetics of Li and Co both conforms well to the residue layer diffusion control model and the activation energy (Ea) values of the leaching for Li and Co are 4.03 and 7.80 kJ/mol, respectively. Lastly, the economic and environmental assessment of this process also demonstrates the advantages of this method in reducing inputs, lowering environmental pollution, and enhancing economic benefits.

8.
Int J Biol Macromol ; 277(Pt 4): 134548, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39116973

RESUMEN

Edible films are effective alternatives to plastic packaging, however, the hydrophilicity of edible films based on protein and polysaccharide limits the application. Therefore, we fabricated a water-stable hybrid film with a linear-spherical interpenetrating molecular topology network using egg white (EW), chitosan (CS), and pectin. Meanwhile, the nisin-tannin acid self-assembly complex nanoparticles were employed as a multifunctional cross-linker, antibacterial and antioxidant agent to improve the performance of films. The FTIR, XRD, and SEM analysis revealed that the conformation and crystalline structure rearrangement of chitosan induced by the alkaline environment provided by egg white enhanced the network structure of films, effectively avoided the addition of modifying reagents. The proposed hybrid films exhibited excellent properties, with EW/TNPCS3 showing the best overall performance. The water contact angle (WCA) increased to 105.27 ± 1.62°, and its dissolution and swelling rates were significantly lower than pure egg white and pure chitosan films. Moreover, tannin-nisin (TN) nanoparticles endowed the films with excellent antimicrobial activity against the common Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Thus, the prepared blending films have great application potential in food preservation, especially to maintain stable performance in high humidity environment.


Asunto(s)
Antibacterianos , Quitosano , Clara de Huevo , Nanopartículas , Nisina , Pectinas , Taninos , Agua , Quitosano/química , Taninos/química , Nanopartículas/química , Pectinas/química , Antibacterianos/química , Antibacterianos/farmacología , Agua/química , Clara de Huevo/química , Nisina/química , Nisina/farmacología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antioxidantes/química , Antioxidantes/farmacología , Películas Comestibles
9.
J Infect ; 89(4): 106254, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39182653

RESUMEN

OBJECTIVES: Using a sporadic case of listeriosis suspected to have been caused by consuming a pre-packaged cold-chain ready-to-eat (RTE) food in Beijing, China in 2021 as an exemplar, this study demonstrated the importance of thoroughly investigating the source of listeriosis up to the production point for mitigating infection risk during routine monitoring of Listeria in food facilities and national surveillance program using whole-genome sequencing (WGS). METHODS: Epidemiological, laboratory, traceback, and plant investigations were used to identify the source of infection. RESULTS: WGS showed the isolate from the patient was genetically indistinguishable from that of the implicated food. During a plant investigation, L. monocytogenes was detected in 26% (9/35) of the environmental samples and one of two raw material samples, confirming the source. CONCLUSION: To our knowledge, this is the first investigation in China linking a case of L. monocytogenes infection to a suspected food and its production environment. This report highlights the risk of L. monocytogenes contamination of RTE food and demonstrates the role of food safety risk monitoring in identifying potential sources of infection. Reinforcing control programs in RTE processing plants, intensified surveillance of microorganisms in food products and targeted health education is required to mitigate the infection risk.


Asunto(s)
Microbiología de Alimentos , Listeria monocytogenes , Listeriosis , Humanos , Listeriosis/epidemiología , Listeriosis/microbiología , Listeria monocytogenes/genética , Listeria monocytogenes/aislamiento & purificación , Listeria monocytogenes/clasificación , Beijing/epidemiología , Comida Rápida/microbiología , Secuenciación Completa del Genoma , Enfermedades Transmitidas por los Alimentos/microbiología , Enfermedades Transmitidas por los Alimentos/epidemiología , Masculino , China/epidemiología , Contaminación de Alimentos/análisis , Femenino
10.
BMC Biotechnol ; 24(1): 55, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39135175

RESUMEN

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a malignant tumour. Although some standard therapies have been established to improve the cure rate, they remain ineffective for specific individuals. Therefore, it is meaningful to find more novel therapeutic approaches. Macrophage polarisation is extensively involved in the process of tumour development. Recombinant hirudin (rH) affects macrophages and has been researched frequently in clinical trials lately. Our article validated the regulatory role of rH in macrophage polarisation and the mechanism of PAR-1 by collecting clinical samples and subsequently establishing a cellular model to provide a scientifically supported perspective for discovering new therapeutic approaches. METHOD: We assessed the expression of macrophage polarisation markers, cytokines and PAR-1 in clinical samples. We established a cell model by co-culture with THP-1 and OCI-Ly10 cell. We determined the degree of cell polarisation and expression of validation cytokines by flow cytometry, ELISA, and RT-qPCR to confirm the success of the cell model. Subsequently, different doses of rH were added to discover the function of rH on cell polarisation. We confirmed the mechanism of PAR-1 in macrophage polarisation by transfecting si-PAR-1 and pcDNA3.1-PAR-1. RESULTS: We found higher expression of M2 macrophage markers (CD163 + CMAF+) and PAR-1 in 32 DLBCL samples. After inducing monocyte differentiation into M0 macrophages and co-culturing with OCI-Ly10 lymphoma cells, we found a trend of these expressions in the cell model consistent with the clinical samples. Subsequently, we discovered that rH promotes the polarisation of M1 macrophages but inhibits the polarisation of M2 macrophages. We also found that PAR-1 regulates macrophage polarisation, inhibiting cell proliferation, migration, invasion and angiogenic capacity. CONCLUSION: rH inhibits macrophage polarisation towards the M2 type and PAR-1 regulates polarisation, proliferation, migration, invasion, and angiogenesis of DLBCL-associated macrophages.


Asunto(s)
Hirudinas , Linfoma de Células B Grandes Difuso , Macrófagos , Receptor PAR-1 , Proteínas Recombinantes , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/genética , Humanos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Receptor PAR-1/metabolismo , Receptor PAR-1/genética , Hirudinas/farmacología , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Línea Celular Tumoral , Técnicas de Cocultivo , Polaridad Celular/efectos de los fármacos , Femenino , Masculino , Citocinas/metabolismo , Persona de Mediana Edad , Células THP-1 , Anciano
11.
J Hazard Mater ; 477: 135304, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39088957

RESUMEN

The utilization of biomass-assisted pyrolysis in the recycling of spent lithium-ion batteries has emerged as a promising and reliable process. This article furnishes theoretical underpinnings and analytical insights into this method, showcasing sawdust pyrolysis reduction as an efficient means to recycle spent LiMn2O4 and LiNi0.6Co0.2Mn0.2O2 batteries. Through advanced thermogravimetry-gas chromatography-mass spectrometry analysis complemented by traditional thermodynamic demonstration, the synergistic effects of biomass pyrolysis reduction are elucidated, with minor autodecomposition and major carbothermal and gasthermal reduction pathways identified. The controlled manipulation of transition metals has demonstrated the capability to modulate surface pyrolysis gas catalytic reactions and facilitate the preparation of composite materials with diverse morphologies. Optimization of process conditions has culminated in recovery efficiency exceeding 99.0 % for LiMn2O4 and 99.5 % for LiNi0.6Co0.2Mn0.2O2. Economic and environmental analyses underscore the advantages of biomass reduction and recycling for these two types of spent LIBs: low energy consumption, environmental compatibility, and high economic viability.

12.
Biomed Mater ; 19(5)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39121885

RESUMEN

Osteonecrosis of the femoral head (ONFH) is a refractory disease affecting young adults, resulting in severe hip pain, femoral head collapse, and disabling dysfunction. By far, the underlying mechanism of its pathology is unclear, and still lack of a mature and effective treatment. Exosomes, a regulator of cell-cell communication, their cargos may vary in response to different physiological or pathological conditions. To date, many studies have demonstrated that exosomes have the potential to become a diagnostic marker and therapeutic agent in many human diseases including ONFH. As a cell-free therapeutic agent, exosomes are becoming a promising tool within this field due to their crucial role in osteogenesis and angiogenesis in recent decades. Usually, exosomes from ONFH tissues could promote ONFH damage, while stem cells derived exosomes could delay diseases and repair femoral head necrosis. Herein, we describe the properties of exosomes, discuss its effect on pathogenesis, diagnosis, and treatment potential in ONFH, and examine the involvement of different signaling pathways. We also propose our suggestions for the future research of exosomes in ONFH field and hope to provide a potential therapeutic strategy for patients with ONFH.


Asunto(s)
Exosomas , Necrosis de la Cabeza Femoral , Transducción de Señal , Exosomas/metabolismo , Humanos , Necrosis de la Cabeza Femoral/terapia , Necrosis de la Cabeza Femoral/metabolismo , Animales , Cabeza Femoral/patología , Cabeza Femoral/metabolismo , Comunicación Celular , Osteogénesis , Biomarcadores/metabolismo , Células Madre/citología , Células Madre/metabolismo
13.
Cancer Gene Ther ; 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39183354

RESUMEN

Metastatic rhabdomyosarcoma is associated with poor survival and unsatisfactory treatment outcomes. Therefore, new immunotherapeutic methods are urgently required. Fibroblast growth factor receptor 4 (FGFR4), a new therapeutic target for rhabdomyosarcoma, plays a crucial role in its onset and development. This study aimed to generate FGFR4 single-chain variable fragment-based chimeric antigen receptor (CAR) T cells without causing evident toxicity and incorporating an inducible caspase-9 (iCasp9) suicide gene system to enhance their safety. FGFR4 antigen expression was evaluated in normal murine tissues, normal human tissues, and specimens from patients with rhabdomyosarcoma. Combined with a 4-1BB co-stimulatory domain, a CD3ζ signaling domain, and an iCasp9 suicide gene, CAR-T cells with an FGFR4-specific single-chain variable fragment were developed. The specific cytotoxic effects, T-cell proliferation, cytokine secretion, apoptosis induction by chemical dimerization (AP20187), and toxicity of FGFR4 CAR-T cells were investigated in vitro and in vivo. FGFR4 CAR-T cells generated a variety of immune-promoting cytokines, including tumor necrosis factor α, interleukin 2, and interferon γ, and displayed effective cytotoxic activity against FGFR4-overexpressing rhabdomyosarcoma cells in vitro. FGFR4 CAR-T cells were relatively effective against FGFR4-overexpressing rhabdomyosarcoma, with tumor regression and poor survival in a subcutaneous xenograft model. The iCasp9 gene was incorporated into FGFR4 CAR-T cells and it was demonstrated that effective and reliable suicide gene activity depends on the administration of AP20187. By making use of the cross-reaction of FGFR4 CAR-T cells with murine FGFR4 in a syngeneic tumor model, this study found that FGFR4 CAR-T cells could regulate the growth of tumors without evident toxicity. Our study demonstrates that FGFR4 is a prospective target for CAR-T cell therapy in rhabdomyosarcoma without serious on-target off-tumor toxicity. FGFR4 CAR-T cells with the iCasp9 suicide gene system as a safety switch to limit toxicity may broaden the clinical applications of cellular therapy.

14.
Mol Cancer Ther ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162031

RESUMEN

Pyruvate dehydrogenase complex is a crucial enzyme involved in the oxidation of glucose. It is regulated by pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase. Studies have demonstrated that pyruvate dehydrogenase kinase 1 (PDHK1), a key enzyme in glucose metabolism, behaves like oncogenes. It is highly expressed in tumors and is associated with poor patient prognosis. However, there is limited research on how PDHK1 affects immune cell function. We have established a model of natural killer (NK) cell exhaustion to investigate the impact of dichloroacetate (DCA) on NK cell function. The production of Granzyme B, IFN-γ, TNF-α, and CD107a by NK cells was explored by flow cytometry. The real-time live cell imaging system was used to monitor the ability of NK cells against tumor cells. The Seahorse analyzer was utilized to measure the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of NK cells. The mouse model was used to investigate the potential of combining DCA with adjuvant NK cell infusion. Our study demonstrated that the hepatocellular carcinoma (HCC) microenvironment mediated NK cellular exhaustion, high expression of PDHK1 and reduced cytokine secretion. We discovered that the PDHK1 inhibitor DCA enhances the activity and function of exhausted NK cells infiltrating the tumor microenvironment. Furthermore, in a subcutaneous HCC mouse model, DCA combined with NK cell treatment resulted in retarding cancer progression. This study indicates the potential of DCA in rescuing NK cell exhaustion and eliciting anti-tumor immunity.

15.
Nat Biomed Eng ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134683

RESUMEN

A prevalent recessive mutation (c.2485C>T, p.Q829X) within the OTOF gene leads to profound prelingual hearing loss. Here we show that in Otof mice harbouring a mutation (c.2482C>T, p.Q828X) homozygous to human OTOF that faithfully mimics the hearing-loss phenotype, a base editor (consisting of the deaminase ABE7.10max and the Cas9 variant SpCas9-NG) packaged in adeno-associated viruses and injected into the inner ear of the mice via the round-window membrane effectively corrected the pathogenic mutation, with no apparent off-target effects. The treatment restored the levels of the otoferlin protein in 88% of the inner hair cells and stably rescued the auditory function of the mice to near-wild-type levels for over 1.5 years while improving synaptic exocytosis in the inner hair cells. We also show that an adenine base editor that targets the prevalent human OTOF mutation restored hearing in humanized mice to levels comparable to those of the wild-type counterparts. Base editors may be effective for the treatment of hereditary deafness.

16.
Amino Acids ; 56(1): 55, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39215872

RESUMEN

Carnosine is an endogenous dipeptide that buffers intracellular pH and quenches toxic products of lipid peroxidation. Used as a dietary supplement, it also supports exercise endurance. However, the accumulation and distribution of carnosine after supplementation has not been rigorously evaluated. To do this, we randomized a cohort to receive daily supplements of either placebo or carnosine (2 g/day). Blood and urine samples were collected twice over the subsequent 12 week supplementation period and we measured levels of red blood cell (RBC) carnosine, urinary carnosine, and urinary carnosine-propanol and carnosine-propanal conjugates by LC/MS-MS. We found that, when compared with placebo, supplementation with carnosine for 6 or 12 weeks led to an approximate twofold increase in RBC carnosine, while levels of urinary carnosine increased nearly sevenfold. Although there were no changes in the urinary levels of carnosine propanol, carnosine propanal increased nearly twofold. RBC carnosine levels were positively associated with urinary carnosine and carnosine propanal levels. No adverse reactions were reported by those in the carnosine or placebo arms, nor did carnosine supplementation have any effect on kidney, liver, and cardiac function or blood electrolytes. In conclusion, irrespective of age, sex, or BMI, oral carnosine supplementation in humans leads to its increase in RBC and urine, as well as an increase in urinary carnosine-propanal. RBC carnosine may be a readily accessible pool to estimate carnosine levels. Clinical trial registration: This study is registered with ClinicalTrials.gov (Nucleophilic Defense Against PM Toxicity (NEAT Trial)-Full Text View-ClinicalTrials.gov), under the registration: NCT03314987.


Asunto(s)
Carnosina , Suplementos Dietéticos , Humanos , Carnosina/metabolismo , Masculino , Femenino , Adulto , Persona de Mediana Edad , Eritrocitos/metabolismo , Eritrocitos/efectos de los fármacos , Método Doble Ciego
17.
J Dairy Sci ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38969003

RESUMEN

Human milk oligosaccharides (HMOs) promote the growth and adhesion of bifidobacteria, thus exerting multiple biological functions on intestinal epithelial cells. Bacterial surface proteins play an important role in bacterial-host intestinal epithelial interactions. In this study, we aim to investigate the effects of surface proteins extracted from Bifidobacterium bifidum DNG6 (B. bifidum DNG6) consuming 2'-fucosyllactose (2'-FL) on Caco-2 cells monolayer barrier injury induced by lipopolysaccharide, compared with lactose (Lac) and galacto-oligosaccharides (GOS). Our results indicated that 2'-FL may promote the surface proteins of B. bifidum DNG6 to improve intestinal barrier injury by positively regulating the NF-κB signaling pathway, reducing inflammation(TNF-α reduced to 50.34%, IL-6 reduced to 22.83%, IL-1ß reduced to 37.91%, and IL-10 increased to 63.47%)and strengthening tight junction (ZO-1 2.39 times, Claudin-1 2.79 times, and Occludin 4.70 times). The findings of this study indicate that 2'-FL can further regulate intestinal barrier damage by promoting the alteration of B. bifidum DNG6 surface protein. The findings of this research will also provide theoretical support for the development of synbiotic formulations.

18.
Foods ; 13(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38998614

RESUMEN

Broad bean paste (BBP) is a traditional fermented soy food, and its high salt content not only prolongs the fermentation time but also threatens human health. In this study, three BBP-meju with different salt concentrations were prepared, and the effects of varying salinity on fermentation were comprehensively compared. The results showed that salt-reduced fermentation contributed to the accumulation of amino acid nitrogen, reducing sugars, free amino acids, and organic acids. Alcohols, esters, aldehydes, and acids were the main volatile flavor compounds in BBP-meju, and the highest total volatile flavor compounds were found in medium-salt meju. Bacillus, Staphylococcus, Aspergillus, and Mortierella were the dominant microbial communities during fermentation, and there were also three opportunistic pathogens, Enterobacter, Pantoea, and Brevundimonas, respectively. According to Spearman correlation analysis, Wickerhamomyces, Bacillus, Staphylococcus, and Mortierella all showed highly significant positive correlations with ≥3 key flavor compounds, which may be the core functional flora. Furthermore, the dominant microbial genera worked synergistically to promote the formation of high-quality flavor compounds and inhibit the production of off-flavors during salt-reduced fermentation. This study provides a theoretical reference for the quality and safety control of low-salt fermented soy foods.

19.
Neuroimage ; 297: 120719, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38971485

RESUMEN

It is increasingly clear that unconscious information impairs the performance of the corresponding action when the instruction to act is delayed. However, whether this impairment occurs at the response level or at the perceptual level remains controversial. This study used fMRI and a computational model with a pre-post design to address this elusive issue. The fMRI results showed that when the unconscious information containing strong stimulus-response associations was irrelevant to subsequent stimuli, the precuneus in the parietal lobe, which is thought to be involved in sensorimotor processing, was activated. In contrast, when the unconscious information was relevant to subsequent stimuli, regardless of the strength of the stimulus-response associations, some regions in the occipital and temporal cortices, which are thought to be involved in visual perceptual processing, were activated. In addition, the percent signal change in the regions of interest associated with motor inhibition was modulated by compatibility in the irrelevant but not in the relevant stimuli conditions. Modeling of behavioral data further supported that the irrelevant and relevant stimuli conditions involved fundamentally different mechanisms. Our finding reconciles the debate about the mechanism by which unconscious information impairs action performance and has important implications for understanding of unconscious cognition.


Asunto(s)
Imagen por Resonancia Magnética , Desempeño Psicomotor , Inconsciente en Psicología , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Desempeño Psicomotor/fisiología , Simulación por Computador , Mapeo Encefálico/métodos , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Modelos Neurológicos
20.
Artículo en Inglés | MEDLINE | ID: mdl-39083039

RESUMEN

Taiwan is situated in the subtropical region and its geographical location and topographical features contribute to a rich ecological diversity and scenic landscapes. We investigated the diversity of methanogens in different environments of Taiwan using a culture-dependent method. This report presents the characterization and taxonomy of six hydrogenotrophic methanogens obtained from cold seep sediments (strain FWC-SCC1T and FWC-SCC3T), marine sediments (strain CWC-02T and YWC-01T), estuarine sediments (strain Afa-1T), and a hot spring well (strain Wushi-C6T) in Taiwan. The proposed names of the six novel species are Methanoculleus frigidifontis (type strain FWC-SCC1T=BCRC AR10056T=NBRC 113993T), Methanoculleus oceani (CWC-02T=BCRC AR10055T=NBRC 113992T), Methanoculleus methanifontis (FWC-SCC3T=BCRC AR10057T=NBRC 113994T), Methanoculleus nereidis (YWC-01T=BCRC AR10060T=NBRC 114597T), Methanoculleus formosensis (Afa-1T=BCRC AR10054T=NBRC 113995T), and Methanoculleus caldifontis (Wushi-06T=BCRC AR10059T= NBRC 114596T).


Asunto(s)
ADN de Archaea , Sedimentos Geológicos , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Taiwán , ARN Ribosómico 16S/genética , Sedimentos Geológicos/microbiología , ADN de Archaea/genética , Methanomicrobiaceae/genética , Methanomicrobiaceae/clasificación , Methanomicrobiaceae/aislamiento & purificación , Composición de Base , Manantiales de Aguas Termales/microbiología
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