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1.
Biochim Biophys Acta Mol Basis Dis ; 1870(8): 167493, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39233261

RESUMEN

The immune landscape of distant unablated tumors following insufficient microwave ablation (iMWA) in hepatocellular carcinoma (HCC) remains to be clarified. The objective of this study is to define the abscopal immune landscape in distant unablated tumor before and after iMWA for HCC. Two treatment-naive patients were recruited for tumor tissue sampling, of each with two HCC lesions. Tumor samples were obtained at before and after microwave ablation in distant unablated sites for single-cell RNA sequencing (scRNA-seq). Mouse model with bilateral hepatoma tumors were developed, and distant unablated tumors were analyzed using multicolor immunofluorescence, RNA sequencing and flow cytometry. The scRNA-seq revealed that a reduced proportion of CD8+ T cells and an increased proportion of myeloid-derived suppressor cells (MDSCs) were observed in the distant unablated tumor microenvironment (TME). A notable disruption was observed in the lipid metabolism of tumor-associated immune cells, accompanied by an upregulated expression of CD36 in tumor-infiltrating immune cells in distant unablated tumor. The administration of a CD36 inhibitor has been demonstrated to ameliorate the adverse effects induced by iMWA, primarily by reinstating the anti-tumor responses of T cells in distant unablated tumor. These findings explain the recurrence and progression of tumors after iMWA and provide a new target of immunotherapy for HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Microondas , Células Supresoras de Origen Mieloide , Microambiente Tumoral , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Animales , Microondas/uso terapéutico , Ratones , Microambiente Tumoral/inmunología , Humanos , Masculino , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Ratones Endogámicos C57BL
2.
J Biomech Eng ; : 1-33, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39262049

RESUMEN

The aim of this study is to explore the effects of structure designs and wearing modes on the protective performance of safety helmets under falling object impact. Four helmet types (no helmet, V-shaped, dome-shaped, and motorcycle helmets) and five wearing modes (left and right tilt by 5°, backward tilt by 15°, 0° without chin strap, 0° with chin strap) were included in this study. and the axial impact of concrete block under different impact velocities is simulated. The results show the energy and shock absorption effects of the foam cushion are better than the suspension system of traditional industrial safety helmets. The structure of the top of V-shaped helmets is designed to withstand greater impact. As regards the wearing mode, the deflection angle of the helmet strap not only increases the stress in the brain tissue and skull as well as the magnitude of the intracranial pressure, but also leads to the diffusion of the pressure to the forehead.

3.
World J Microbiol Biotechnol ; 40(10): 326, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39299979

RESUMEN

Fusing insect derived neurotoxic peptides with Galanthus nivalis agglutinin (GNA) has been shown to enhance the insecticidal activity of the neuropeptides, especially when administered orally. This study produced a recombinant scorpion insect specific neurotoxin BjαIT, GNA, and a fusion protein BjαIT/GNA using Pichia pastoris as an expression host. Recombinant rBjαIT/GNA was found to be easily degraded during expression in yeast which and produced a main protein product with a molecular weight of approximately 14 kDa. Cytotoxicity results showed that rBjαIT, rGNA, and rBjαIT/GNA had no toxicity to mammalian NIH/3T3 cells. Adding rBjαIT or rBjαIT/GNA at a concentration as low as 1 ng/mL to insect cell culture medium inhibited the proliferation of insect Sf9 cells, with rBjαIT exhibiting stronger cytotoxicity, while 20 ng/mL rGNA did not inhibit the proliferation of Sf9 cells. Silkworm larval injection results showed that rBjαIT/GNA was the most toxic of the three proteins, followed by rBjαIT, and rGNA. When rBjαIT/GNA was injected at a concentration of 0.129 nmol/g body weight 46.7% of silkworm died within 48 h. Feeding newly hatched silkworms with rBjαIT/GNA at a leaf surface concentration of 40 µg/cm2 resulted in 76.7% mortality within 24 h. However, rBjαIT/GNA showed almost no oral insecticidal activity against second instar silkworms. The results indicated that rBjαIT/GNA has stronger injection insecticidal activity and feeding insecticidal activity than rBjαIT and rGNA individually, making it more suitable for biological control.


Asunto(s)
Bombyx , Insecticidas , Larva , Proteínas Recombinantes de Fusión , Venenos de Escorpión , Animales , Ratones , Insecticidas/farmacología , Larva/efectos de los fármacos , Venenos de Escorpión/química , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/genética , Células Sf9 , Células 3T3 NIH , Administración Oral , Escorpiones , Neurotoxinas , Lectinas de Plantas/farmacología , Saccharomycetales/metabolismo
4.
Hepatology ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39250463

RESUMEN

BACKGROUND AND AIMS: Hexokinases (HKs), a group of enzymes catalyzing the first step of glycolysis, have been shown to play important roles in liver metabolism and tumorigenesis. Our recent studies identified HKDC1 as a top candidate associated with liver cancer metastasis. We aimed to compare its cell type specificity with other HKs upregulated in liver cancer and investigate the molecular mechanisms underlying its involvement in liver cancer metastasis. APPROACH AND RESULTS: We found that, compared to HK1 and HK2, the other two commonly upregulated HKs in liver cancer, HKDC1 was most strongly associated with the metastasis potential of tumors and organoids derived from two liver cancer mouse models we previously established. RNA in situ hybridization and single-cell RNA-seq analysis revealed that HKDC1 was specifically upregulated in malignant cells in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patient tumors, whereas HK1 and HK2 were widespread across various tumor microenvironment lineages. An unbiased metabolomic profiling demonstrated that HKDC1 overexpression in HCC cells led to metabolic alterations distinct from those from HK1 and HK2 overexpression, with HKDC1 particularly impacting the tricarboxylic acid (TCA) cycle. HKDC1 was prometastatic in HCC orthotopic and tail vein injection mouse models. Molecularly, HKDC1 was induced by hypoxia and bound to glycogen synthase kinase 3ß to stabilize ß-catenin, leading to enhanced stemness of HCC cells. CONCLUSIONS: Overall, our findings underscore HKDC1 as a prometastatic HK specifically expressed in the malignant compartment of primary liver tumors, thereby providing a mechanistic basis for targeting this enzyme in advanced liver cancer.

5.
J Virol ; 98(9): e0063924, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39132992

RESUMEN

There are four genogroups and 18 genotypes of human sapoviruses (HuSaVs) responsible for acute gastroenteritis. To comprehend their antigenic and virological differences, it is crucial to obtain viral stocks of the different strains. Previously, we utilized the human duodenum-derived cell line HuTu80, and glycocholate, a conjugated bile acid, to replicate and propagate GI.1, GI.2, and GII.3 HuSaVs (H. Takagi et al., Proc Natl Acad Sci U S A 117:32078-32085, 2020, https://10.1073/pnas.2007310117). First, we investigated the impact of HuTu80 passage number on HuSaV propagation. Second, we demonstrated that taurocholate improved the initial replication success rate and viral RNA levels in fecal specimens relative to glycocholate. By propagating 15 HuSaV genotypes (GI.1-7, GII.1-5, -8, and GV.1-2) and accomplishing preparation of viral stocks containing 1.0 × 109 to 3.4 × 1011 viral genomic copies/mL, we found that all strains required bile acids for replication, with GII.4 showing strict requirements for taurocholate. The deduced VP1 sequences of the viruses during the scale-up of serial passaged virus cultures were either identical or differed by only two amino acids from the original sequences in feces. In addition, we purified virions from nine strains of different genotypes and used them as immunogens for antiserum production. Enzyme-linked immunosorbent assays (ELISAs) using rabbit and guinea pig antisera for each of the 15 strains of different genotypes revealed distinct antigenicity among the propagating viruses across genogroups and differences between genotypes. Acquisition of biobanked viral resources and determination of key culture conditions will be valuable to gain insights into the common mechanisms of HuSaV infection. IMPORTANCE: The control of human sapovirus, which causes acute gastroenteritis in individuals of all ages, is challenging because of its association with outbreaks similar to those caused by human norovirus. The establishment of conditions for efficient viral propagation of various viral strains is essential for understanding the infection mechanism and identifying potential control methods. In this study, two critical factors for human sapovirus propagation in a conventional human duodenal cell line were identified, and 15 strains of different genotypes that differed at the genetic and antigenic levels were isolated and used to prepare virus stocks. The preparation of virus stocks has not been successful for noroviruses, which belong to the same family as sapoviruses. Securing virus stocks of multiple human sapovirus strains represents a significant advance toward establishing a reliable experimental system that does not depend on limited virus-positive fecal material.


Asunto(s)
Infecciones por Caliciviridae , Duodeno , Genotipo , Sapovirus , Replicación Viral , Sapovirus/genética , Humanos , Duodeno/virología , Duodeno/inmunología , Línea Celular , Animales , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/inmunología , Gastroenteritis/virología , Antígenos Virales/inmunología , Antígenos Virales/genética , Heces/virología , Conejos , Cobayas , Variación Genética , ARN Viral/genética , Cultivo de Virus , Ácidos y Sales Biliares
6.
Asian J Androl ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39091129

RESUMEN

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.

7.
Sci Rep ; 14(1): 19889, 2024 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191800

RESUMEN

When IL-1 receptor antagonist (IL-1rn) is knocked out, mice have shown strain background dependent and major QTL regulated susceptibility to spontaneously inflammatory arthritis disease (SAD). The impact on bone properties resulting from the interactions of IL-1rn, genomic background strains, and the QTL locus, is unknown. Bone properties in the four specifically bred mouse strains with mutation of IL-1rn and variations in genomic components were investigated with high-resolution MicroCT and genomic analytical tools. Two congenic mouse strains were also measured to evaluate the influence on bone properties by a QTL in the region in chromosome 1. Our results reveal that several bone phenotypes, including bone mineral density (BMD), bone volume, tibial length, and cortical thickness of the tibia are different between wild type and IL-1rn knockout mice in both Balb/c and DBA/1 backgrounds, but IL-1rn knockout affects BMD differently between the two mouse strains. The absence of IL-1rn decreases BMD in Balb/c mice but increases BMD in DBA/1-/- mice compared to their respective wild type counterparts. A QTL transferred from the Balb/c genetic background which affects arthritis in congenic strains appears to also regulate BMD. While several genes, including Ctsg and Prg2, may affect BMD, Ifi202b is the most favored candidate gene for regulating BMD as well as SAD. In conclusion, the previously mentioned bone phenotypes are each influenced in different ways by the loss of IL-1ra when considered in mice from varying genomic backgrounds.


Asunto(s)
Densidad Ósea , Proteína Antagonista del Receptor de Interleucina 1 , Ratones Noqueados , Sitios de Carácter Cuantitativo , Animales , Ratones , Densidad Ósea/genética , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/deficiencia , Ratones Endogámicos BALB C , Huesos/metabolismo , Huesos/diagnóstico por imagen , Huesos/patología , Ratones Endogámicos DBA , Masculino , Fenotipo , Microtomografía por Rayos X , Enfermedades Autoinflamatorias Hereditarias
8.
Foods ; 13(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38998546

RESUMEN

Electrospinning biopolymer nanofibers have emerged as promising candidates for food packaging applications. In this study, dextran/zein nanofibers were fabricated using electro-blown spinning and subsequently cross-linked via the Maillard reaction (MR) at 60 °C and 50% relative humidity. Compared to traditional electrospinning, the introduction of air-blowing improved the sample preparation speed by 10 times. SEM analysis revealed that the nanofiber morphology remained stable upon MR treatment for 24 h. FTIR spectroscopy confirmed that the MR led to a deformation in the protein conformation and an increase in hydrophilicity and elasticity in the nanofibers cross-linked for 6 h. MR treatment for 18 h considerably enhanced the hydrophobicity and elastic modulus owing to covalent bond formation. Thermal analysis indicated an improved thermal stability with increasing MR duration. Mechanical property analysis revealed an increase in elastic modulus and a decrease in elongation at break for the nanofibers cross-linked for more than 6 h, indicating a trade-off between rigidity and flexibility. Notably, the water vapor permeability of the nanofibers cross-linked for 6 and 18 h was remarkably higher, which can be ascribed to the fiber morphology retention upon water evaporation. Overall, MR-cross-linked dextran/zein/xylose nanofibers showed tunable properties, making them a suitable encapsulation system for bioactive compounds.

9.
Sci Rep ; 14(1): 15475, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969689

RESUMEN

The Yangtze River (hereafter referred to as the YZR), the largest river in China, is of paramount importance for ensuring water resource security. The Yangtze River Basin (hereafter referred to as the YRB) is one of the most densely populated areas in China, and complex human activities have a significant impact on the ecological security of water resources. Therefore, this paper employs theories related to ecological population evolution and the Driving Force-Pressure-State-Impact-Response (DPSIR) model to construct an indicator system for the ecological security of water resources in the YRB. The report evaluates the ecological security status of water resources in each province of the YRB from 2010 to 2019, clarifies the development trend of its water resource ecological security, and proposes corresponding strategies for regional ecological security and coordinated economic development. According to the results of the ecological population evolution competition model, the overall indicator of the ecological security of water resources in the YRB continues to improve, with the safety level increasing annually. Maintaining sound management of water resources in the YRB is crucial for sustainable socioeconomic development. To further promote the ecological security of water resources in the YRB and the coordinated development of the regional economy, this paper proposes policy suggestions such as promoting the continuous advancement of sustainable development projects, actively adjusting industrial structure, continuously enhancing public environmental awareness, and actively participating in international ecological construction and seeking cooperation among multiple departments.

10.
Molecules ; 29(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38999088

RESUMEN

Dihydromyricetin (DMY) has been encapsulated in delivery systems to address the solubility limitations of DMY in water and improve its bioavailability. Air-assisted electrospinning has been used as a novel technology to load DMY. To evaluate the impact of adding DMY to dextran/zein nanofibers and understand the effects of the Maillard reaction (MR) on the physical and functional properties of DMY-loaded nanofibers, dextran/zein/xylose nanofibers with 0%, 1%, 2%, 3%, and 4% DMY were fabricated, followed by MR crosslinking. Scanning electron microscopy (SEM) observations indicated that the addition of DMY and the MR did not affect the morphology of the nanofibers. X-ray diffraction (XRD) results indicated amorphous dispersion of DMY within the nanofibers and a decreased crystalline structure within the nanofibers following the MR, which might improve their molecular flexibility. The nanofibrous film formed after the MR exhibited both increased tensile strength and elastic modulus due to hydrogen bonding within the nanofibers and increased elongation at break attributed to the increased amorphization of the structure after crosslinking. The nanofibers were also found to exhibit improved heat stability after the MR. The antioxidant activity of the nanofibers indicated a dose-dependent effect of DMY on radical scavenging activity and reducing power. The maintenance of antioxidant activity of the nanofibers after the MR suggested heat stability of DMY during heat treatment. Overall, dextran/zein nanofibers with various DMY contents exhibited tunable physical properties and effective antioxidant activities, indicating that dextran/zein nanofibers offer a successful DMY delivery system, which can be further applied as an active package.

11.
Am J Med Sci ; 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39009282

RESUMEN

BACKGROUND: Whether Astragalus membranaceus is an effective drug in treatment of ulcerative colitis (UC) and how it exhibit activity effect on UC is unclear. METHODS: TCMSP, GeneCards, String, and DAVID database were used to screening target genes construct PPI network and performed for GO and KEGG pathway enrichment analysis respectively. Molecular docking and animal experiment were performed. The body weight and disease activity index (DAI) of mice were recorded. ELISA kits were used to detect the levels of CAT, SOD, MDA and IL-6, IL-10, TNF-α in the blood of mice. Western blot kits were utilized to measured the expressions of MAPK14, RB1, MAPK1, JUN, ATK1, and IL2 proteins. RESULTS: The active components of Astragalus membranaceus mainly including 7-O-methylisomucronulatol, quercetin, kaempferol, formononetin and isrhamnetin. Astragalus membranaceus may inhibited the expression of TNF-α, IL-6, MDA, and promoted the expression of CAT, SOD, IL-10. The expression levels of MAPK14, RB1, MAPK1, JUN and ATK1 proteins were significantly decreased while IL2 protein increased administrated with Astragalus membranaceus. CONCLUSIONS: Astragalus membranaceus is an effective drug in treatment of UC according to related to above targets that may exhibits the anti-UC effect via its antioxidant pathway and regulating the balance of pro-inflammatory and anti-inflammatory factors.

12.
Mil Med Res ; 11(1): 46, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992778

RESUMEN

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.


Asunto(s)
Carga Global de Enfermedades , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/epidemiología , Masculino , Femenino , Incidencia , Persona de Mediana Edad , Anciano , Adulto , Carga Global de Enfermedades/tendencias , Años de Vida Ajustados por Discapacidad/tendencias , Salud Global/estadística & datos numéricos , Anciano de 80 o más Años
13.
Hepatol Res ; 54(8): 1-30, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38874115

RESUMEN

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.

14.
Appl Opt ; 63(12): 3334-3342, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38856485

RESUMEN

A channelized multi-frequency measurement system based on asymmetric double sideband detection is proposed. In this scheme, the sub-modulators of the dual-parallel Mach-Zehnder modulator are utilized for optical frequency comb (OFC) generation and under-test signal modulation. Subsequently, a sawtooth wave voltage is applied to the main modulator to introduce frequency shift to the modulated signals, breaking the symmetry between the RF signals and the OFC. The coupled signal is then divided into upper and lower sidebands for frequency down-conversion. By calibrating the measurement results of the two sidebands with each other, the frequency of the signal can be accurately measured. Simulation is preformed to realize multi-frequency measurement of microwave signals with measurement error less than 2 MHz in the range of 2.2-20 GHz. It is also found that the proposal can solve the problem of frequency ambiguity.

15.
Phys Rev E ; 109(5-1): 054123, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38907436

RESUMEN

In this study, we explore the quantum critical phenomena in generalized Aubry-André models, with a particular focus on the scaling behavior at various filling states. Our approach involves using quantum fidelity susceptibility to precisely identify the mobility edges in these systems. Through a finite-size scaling analysis of the fidelity susceptibility, we are able to determine both the correlation-length critical exponent and the dynamical critical exponent at the critical point of the generalized Aubry-André model. Based on the Diophantine equation conjecture, we can determines the number of subsequences of the Fibonacci sequence and the corresponding scaling functions for a specific filling fraction, as well as the universality class. Our findings demonstrate the effectiveness of employing the generalized fidelity susceptibility for the analysis of unconventional quantum criticality and the associated universal information of quasiperiodic systems in cutting-edge quantum simulation experiments.

16.
Med Eng Phys ; 128: 104169, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38789212

RESUMEN

Despite the fact that lower back pain caused by degenerative lumbar spine pathologies seriously affects the quality of life, however, there is a paucity of research on the biomechanical properties of different auxiliary fixation systems for its primary treatment (oblique lumbar interbody fusion) under vibratory environments. In order to study the effects of different fixation systems of OLIF surgery on the vibration characteristics of the human lumbar spine under whole-body vibration (WBV), a finite element (FE) model of OLIF surgery with five different fixation systems was established by modifying a previously established model of the normal lumbar spine (L1-S1). In this study, a compressive follower load of 500 N and a sinusoidal axial vertical load of ±40 N at the frequency of 5 Hz with a duration of 0.6 s was applied. The results showed that the bilateral pedicle screw fixation model had the highest resistance to cage subsidence and maintenance of disc height under WBV. In contrast, the lateral plate fixation model exerted very high stresses on important tissues, which would be detrimental to the patient's late recovery and reduction of complications. Therefore, this study suggests that drivers and related practitioners who are often in vibrating environments should have bilateral pedicle screws for OLIF surgery, and side plates are not recommended to be used as a separate immobilization system. Additionally, the lateral plate is not recommended to be used as a separate fixation system.


Asunto(s)
Análisis de Elementos Finitos , Vértebras Lumbares , Fusión Vertebral , Vibración , Fusión Vertebral/instrumentación , Vértebras Lumbares/cirugía , Humanos , Fenómenos Biomecánicos , Tornillos Pediculares
17.
Bioorg Chem ; 148: 107463, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38776649

RESUMEN

Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated thrombin generation, and represents a promising target for anticoagulant therapy. We herein isolated novel DNA aptamers that specifically bind to HFIXa through systematic evolution of ligands by exponential enrichment (SELEX) method. We identified two distinct aptamers, seq 5 and seq 11, which demonstrated high binding affinity to HFIXa (Kd = 74.07 ± 2.53 nM, and 4.93 ± 0.15 nM, respectively). Computer software was used for conformational simulation and kinetic analysis of DNA aptamers and HFIXa binding. These aptamers dose-dependently prolonged activated partial thromboplastin time (aPTT) in plasma. We further rationally optimized the aptamers by truncation and site-directed mutation, and generated the truncated forms (Seq 5-1t, Seq 11-1t) and truncated-mutated forms (Seq 5-2tm, Seq 11-2tm). They also showed good anticoagulant effects. The rationally and structurally designed antidotes (seq 5-2b and seq 11-2b) were competitively bound to the DNA aptamers and effectively reversed the anticoagulant effect. This strategy provides DNA aptamer drug-antidote pair with effective anticoagulation and rapid reversal, developing advanced therapies by safe, regulatable aptamer drug-antidote pair.


Asunto(s)
Antídotos , Aptámeros de Nucleótidos , Factor IXa , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/farmacología , Humanos , Factor IXa/antagonistas & inhibidores , Factor IXa/metabolismo , Antídotos/farmacología , Antídotos/química , Antídotos/síntesis química , Relación Dosis-Respuesta a Droga , Anticoagulantes/farmacología , Anticoagulantes/química , Relación Estructura-Actividad , Estructura Molecular , Técnica SELEX de Producción de Aptámeros
18.
Nutrients ; 16(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38794735

RESUMEN

Maintaining the balance and stability of the gut microbiota is crucial for the gut health and growth development of humans and animals. Bacillus licheniformis (B. licheniformis) has been reported to be beneficial to the gut health of humans and animals, whereas the probiotic effects of a new strain, B. licheniformis HD173, remain uncertain. In this study, nursery piglets were utilized as animal models to investigate the extensive impact of B. licheniformis HD173 on gut microbiota, metabolites, and host health. The major findings were that this probiotic enhanced the growth performance and improved the health status of the nursery piglets. Specifically, it reduced the level of pro-inflammatory cytokines IL-1ß and TNF-α in the serum while increasing the level of IL-10 and SOD. In the gut, B. licheniformis HD173 reduced the abundance of pathogenic bacteria such as Mycoplasma, Vibrio, and Vibrio metschnikovii, while it increased the abundance of butyrate-producing bacteria, including Oscillospira, Coprococcus, and Roseburia faecis, leading to an enhanced production of butyric acid. Furthermore, B. licheniformis HD173 effectively improved the gut metabolic status, enabling the gut microbiota to provide the host with stronger metabolic abilities for nutrients. In summary, these findings provide scientific evidence for the utilization of B. licheniformis HD173 in the development and production of probiotic products for maintaining gut health in humans and animals.


Asunto(s)
Bacillus licheniformis , Microbioma Gastrointestinal , Probióticos , Animales , Microbioma Gastrointestinal/fisiología , Porcinos , Modelos Animales , Bacterias/crecimiento & desarrollo , Bacterias/clasificación , Bacterias/metabolismo
19.
World J Pediatr ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806855

RESUMEN

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

20.
Int J Mol Sci ; 25(7)2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38612477

RESUMEN

Cell division cycle 23 (CDC23) is a component of the tetratricopeptide repeat (TPR) subunit in the anaphase-promoting complex or cyclosome (APC/C) complex, which participates in the regulation of mitosis in eukaryotes. However, the regulatory model and mechanism by which the CDC23 gene regulates muscle production in pigs are largely unknown. In this study, we investigated the expression of CDC23 in pigs, and the results indicated that CDC23 is widely expressed in various tissues and organs. In vitro cell experiments have demonstrated that CDC23 promotes the proliferation of myoblasts, as well as significantly positively regulating the differentiation of skeletal muscle satellite cells. In addition, Gene Set Enrichment Analysis (GSEA) revealed a significant downregulation of the cell cycle pathway during the differentiation process of skeletal muscle satellite cells. The protein-protein interaction (PPI) network showed a high degree of interaction between genes related to the cell cycle pathway and CDC23. Subsequently, in differentiated myocytes induced after overexpression of CDC23, the level of CDC23 exhibited a significant negative correlation with the expression of key factors in the cell cycle pathway, suggesting that CDC23 may be involved in the inhibition of the cell cycle signaling pathway in order to promote the differentiation process. In summary, we preliminarily determined the function of CDC23 with the aim of providing new insights into molecular regulation during porcine skeletal muscle development.


Asunto(s)
Músculo Esquelético , Células Satélite del Músculo Esquelético , Animales , Ciclosoma-Complejo Promotor de la Anafase , Células Musculares , Porcinos
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