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Genetic studies of blood pressure (BP) traits to date have been performed on conventional measures by brachial cuff sphygmomanometer for systolic BP (SBP) and diastolic BP, integrating several physiologic occurrences. Genetic associations with central SBP (cSBP) have not been well-studied. Genetic discovery studies of BP have been most often performed in European-ancestry samples. Here, we investigated genetic associations with cSBP in a Chinese population and functionally validated the impact of a novel associated coiled-coil domain containing 93 (CCDC93) gene on BP regulation. An exome-wide association study (EWAS) was performed using a mixed linear model of non-invasive cSBP and peripheral BP traits in a Han Chinese population (N = 5,954) from Beijing, China genotyped with a customized Illumina ExomeChip array. We identified four SNP-trait associations with three SNPs, including two novel associations (rs2165468-SBP and rs33975708-cSBP). rs33975708 is a coding variant in the CCDC93 gene, c.535C>T, p.Arg179Cys (MAF = 0.15%), and was associated with increased cSBP (ß = 29.3 mmHg, P = 1.23x10-7). CRISPR/Cas9 genome editing was used to model the effect of Ccdc93 loss in mice. Homozygous Ccdc93 deletion was lethal prior to day 10.5 of embryonic development. Ccdc93+/- heterozygous mice were viable and morphologically normal, with 1.3-fold lower aortic Ccdc93 protein expression (P = 0.0041) and elevated SBP as compared to littermate Ccdc93+/+ controls (110±8 mmHg vs 125±10 mmHg, P = 0.016). Wire myography of Ccdc93+/- aortae showed impaired acetylcholine-induced relaxation and enhanced phenylephrine-induced contraction. RNA-Seq transcriptome analysis of Ccdc93+/- mouse thoracic aortae identified significantly enriched pathways altered in fatty acid metabolism and mitochondrial metabolism. Plasma free fatty acid levels were elevated in Ccdc93+/- mice (96±7mM vs 124±13mM, P = 0.0031) and aortic mitochondrial dysfunction was observed through aberrant Parkin and Nix protein expression. Together, our genetic and functional studies support a novel role of CCDC93 in the regulation of BP through its effects on vascular mitochondrial function and endothelial function.
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The study aims to evaluate the prognosis and risk factors of sepsis-associated thrombocytopenia (SAT) among patients with coagulopathy, and to provide evidence of the relationship between adverse outcomes and potential risks. Patients with sepsis-associated coagulopathy were included in the study from January 2014 to December 2022. The primary outcome was sepsis-associated thrombocytopenia (platelet count less than 100 *109/L), which was evaluated by logistic regression models adjusted for demographic characteristics and comorbidities. Among patients in the SAT group, 54% developed severe SAT, while 16% of these patients recovered from thrombocytopenia. The in-hospital mortality rate was significantly higher in the SAT group compared to the non-SAT group (31% in SAT group vs 23.9% in non-SAT group, p = 0.029). Even after adjusting for age, gender, Charlson comorbidity, white blood cell, and Sequential Organ Failure Assessment score, the differences in mortality rate persisted (Odds Ratio 0.72, [95% Confidence Interval 0.52-0.92]). Correlation analyses revealed that prothrombin time (r = 0.08, p = 0.50), international normalized ratio (r = 0.08, p = 0.42), prothrombin activity (r = -0.06, p > 0.999), D-dimer (r = -0.02, p > 0.999), and inflammatory parameters such as C-reactive protein (r = -0.11, p = 0.37) were not significantly correlated with platelet counts. According to subgroup analyses, patients with lung infection complicated by SAT had slightly higher mortality (OR 0.66, [95% CI, 0.46 to 0.94]). Sepsis-associated coagulopathy indicates a subset of critical ill patients, with those experiencing thrombocytopenia at greater risk for in-hospital death compared to those without it.
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Trastornos de la Coagulación Sanguínea , Sepsis , Trombocitopenia , Humanos , Sepsis/complicaciones , Sepsis/mortalidad , Sepsis/sangre , Masculino , Femenino , Factores de Riesgo , Trombocitopenia/sangre , Anciano , Persona de Mediana Edad , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/mortalidad , Mortalidad HospitalariaRESUMEN
INTRODUCTION: Talaromyces marneffei (T. marneffei), a kind of endemic opportunistic pathogen, was previously thought to occur in HIV-positive individuals and non-HIV hosts with impaired immune function. However, the infection of T. marneffei in patient with normal immune function was rarely reported. CASE PRESENTATION: We report a case of severe pneumonia caused by T. marneffei in an immunocompetent and HIV-negative patient, which was rapidly confirmed by metagenomics next-generation sequencing (mNGS) and treated successfully. The patient was a previously healthy 63-year-old male, who was admitted to hospital with fever for 11 days, cough and sputum for 1 week, and chest distress for 4 days. The infection of T. marneffei was quickly determined by alveolar lavage under bedside bronchoscope and mNGS test. RESULTS: Patient's condition improved rapidly after voriconazole treatment, and he was evaluated as a HIV-negative case of T. marneffei infection with normal immune function. This is a sporadic case of T. marneffei in non-endemic areas, and mNGS played a very important role in the treatment of the disease. The patient's immune function was relatively normal which was rare in clinical practice.
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Antifúngicos , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Talaromyces , Voriconazol , Humanos , Talaromyces/genética , Talaromyces/aislamiento & purificación , Masculino , Persona de Mediana Edad , Metagenómica/métodos , Voriconazol/uso terapéutico , Antifúngicos/uso terapéutico , Neumonía/microbiología , Neumonía/tratamiento farmacológico , Micosis/microbiología , Micosis/tratamiento farmacológico , Micosis/diagnóstico , Resultado del Tratamiento , InmunocompetenciaRESUMEN
We present analytical results of fundamental properties of one-dimensional (1D) Hubbard model with a repulsive interaction. New results of the model with arbitrary external fields include: I) Using the exact solutions of the Bethe Ansatz equations of the Hubbard model, we first rigorously calculate the gapless spin and charge excitations, exhibiting exotic features of fractionalized spinons and holons. We then investigate the gapped excitations in terms of the spin string and the $k-\Lambda$ string bound states at arbitrary driving fields, showing subtle differences of spin magnons and charge $\eta$-pair excitations. II) For a high density and high spin magnetization region, i.e. near the quadruple critical point, we further analytically obtain the thermodynamical properties, dimensionless ratios and scaling functions near quantum phase transitions. III) Importantly, we give the general scaling functions at quantum criticality for arbitrary filling and interaction strength. These can directly apply to other integrable models. IV) Based on the fractional excitations and the scaling laws, the spin-incoherent Luttinger liquid (SILL) with only the charge propagation mode is elucidated by the asymptotic of the two-point correlation functions with the help of the conformal field theory. We also for the first time obtain the analytical result of the thermodynamics for the SILL. V) Finally, in order to capture deeper insight into the Mott insulator and interaction-driven criticality, we further study the double occupancy and propose its associated Contact and Contact susceptibilities through which an adiabatic cooling scheme based upon quantum criticality is proposed. In this scenario, we build up general relations among arbitrary external and internal potential driven quantum phase transitions, providing a comprehensive understanding of quantum criticality. Our methods offer rich perspectives of quantum integrability and offer promising guidance to future experiments with interacting electrons and ultracold atoms both with and without a lattice.
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OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.
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Acuaporina 4 , Astrocitos , Biomarcadores , Proteína Ácida Fibrilar de la Glía , Inmunoglobulina G , Humanos , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/inmunología , Femenino , Masculino , Acuaporina 4/inmunología , Persona de Mediana Edad , Astrocitos/inmunología , Astrocitos/metabolismo , Astrocitos/patología , Estudios Retrospectivos , Adulto , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Anciano , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/sangre , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Proteínas de Neurofilamentos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. METHODS: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. RESULTS: During 2006-2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. CONCLUSIONS: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.
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Rabia , Rabia/epidemiología , Rabia/prevención & control , Rabia/veterinaria , China/epidemiología , Humanos , Animales , Perros , Incidencia , Masculino , Femenino , Adolescente , Niño , Adulto , Persona de Mediana Edad , Estaciones del Año , Preescolar , Adulto Joven , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/virología , Enfermedades de los Perros/prevención & control , Lactante , Anciano , Profilaxis Posexposición , Vacunas Antirrábicas/administración & dosificaciónRESUMEN
Moxibustion, traditional Chinese medicine treatment, involves the warming of specific acupuncture points of the body using ignited herbal materials. Evidence suggests beneficial effects of moxibustion in several brain diseases including epilepsy, however, whether moxibustion pretreatment impacts on seizures and what are the underlying mechanisms remains to be established. Evidence has suggested the purinergic ATP-gated P2X7 receptor (P2X7R) to be involved in the actions of moxibustion. Moreover, P2X7R signalling is now well established to contribute to long-lasting brain hyperexcitability underlying epilepsy development. Whether P2X7R signalling is involved in the seizure-reducing actions of moxibustion has not been investigated to date. For our studies we used C57BL/6 male mice that received moxibustion pre-treatments at the acupoints Zusanli (ST36) and Dazhui (GV14) once daily for either 7, 14, or 21 days. This was followed by an intraperitoneal injection of kainic acid (KA, 30 mg/kg) to induce status epilepticus. Behavioral changes during KA-induced status epilepticus were analyzed according to the Racine scale. Changes in electrographic seizures were analyzed via cortical implanted electroencephalogram (EEG) electrodes. While no effect on seizure severity was observed following 7 days of moxibustion pre-treatment, moxibustion pre-treatment at both ST36 and GV14 for 14 or 21 days significantly reduced KA-induced behavior seizures at a similar rate. Cortical EEG recordings showed that 14 days of moxibustion pre-treatments also reduced electrographic seizures, confirming the anticonvulsant actions of moxibustion pre-treatment. To determine whether moxibustion impacts the pro-convulsant actions of P2X7R signaling, mice were treated with the P2X7R agonist BzATP or P2X7R antagonist A438079. While treatment with the P2X7R agonist BzATP exacerbated seizure severity, treatment with the P2X7R antagonist reduced seizure severity. We further found that moxibustion pre-treatment attenuated epileptic seizures by counteracting the effects of BzATP. These results suggest that moxibustion pre-treatment at the acupoints ST36 and GV14 for 14 days has anti-epileptic effects, which may counteract the proconvulsant functions of the P2X7R.
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Exploring nutrient limitation in forest soil holds significant implications for forest tending and management. However, current research on nutrient limitation status of microorganisms in Robinia pseudoacacia plantations within the Loess Plateau remains insufficient. To investigate soil microbial nutrient limitation of R. pseu-doacacia plantations on the Loess Plateau, we selected R. pseudoacacia plantations with different afforestation time series (15, 25, 35, and 45 years) and a pile of barren slope cropland (control) in Yongshou County, Shaanxi Province as the research objects. We analyzed the contents of soil organic matter, total nitrogen, and total phosphorus, and the activities of ß-1,4-glucosidase (BG), cellobiose hydrolase (CBH), leucine aminopeptidase (LAP), ß-1,4-N-acetylglucoside (NAG) and phosphatase (AP). We analyzed the soil nutrient limitation by stoichiometry and enzyme metrology. The results showed a shift in soil pH from alkaline to acidic during vegetation restoration process, and that total phosphorus exhibited a gradual decrease over the course of 0 to 25 years. Soil orga-nic matter, total nitrogen and enzyme activities exhibited an increasing trend during the same time frame. However, between 25 and 45 years of age, soil total phosphorus, soil organic matter, total nitrogen, AP and LAP gradually declined while NAG, BG, and CBH initially increased and then decreased. Notably, the values of (BG+CBH)/(LAP+NAG), (BG+CBH)/AP and (LAP+NAG)/AP in R. pseudoacacia plantations were higher than the global average throughout the process of vegetation restoration. In the study area, the vector length was less than 1 and gradually increased, indicating that a progressive increase in microbial carbon limitation during the process of vegetation restoration. The vector angle exceeded 45° and exhibited an overall decreasing trend, suggesting that soil microorganisms were constrained by phosphorus (P) with a gradual deceleration of P limitation, without any nitrogen (N) limitation. The restoration of R. pseudoacacia plantation resulted in significant change in soil physical and chemical properties, while the time series of afforestation also influenced nutrient limitation of soil microorganisms.
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Nitrógeno , Fósforo , Robinia , Microbiología del Suelo , Suelo , Robinia/crecimiento & desarrollo , Robinia/metabolismo , Suelo/química , Fósforo/metabolismo , Fósforo/análisis , Nitrógeno/metabolismo , Nitrógeno/análisis , China , Leucil Aminopeptidasa/metabolismo , Bosques , Nutrientes/análisis , Nutrientes/metabolismo , Celulosa 1,4-beta-Celobiosidasa/metabolismo , EcosistemaRESUMEN
With an electron-deficient rigid planar structure and excellent π-π stacking ability, hexaazatriphenylene (HAT) and its derivatives are widely used as basic building blocks for constructing covalent organic frameworks (COFs), components of organic light-emitting diodes and solar cells, and electrode materials for lithium-ion batteries (LIBs). Here, a HAT derivative, hexaazatriphenylenehexacarbonitrile, is explored as an anode material for LIBs. The HAT anode exhibited high initial reversible capacities of 672 mA h g-1 at 100 mA g-1 and 550 mA h g-1 at 400 mA g-1 and stable cycling with a capacity of 503 mA h g-1 after 1000 cycles at 400 mA g-1 corresponding to a capacity retention of 91.5%. Furthermore, the lithium storage mechanism and the cause of the first irreversible capacity loss of the HAT anode were investigated by X-ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculations. We have carried out a series of analyses on the mechanism of initial capacity loss. This study provides new insight on initial capacity loss and provides valuable insights into the molecular design and the electrochemical properties of HAT-based anode materials.
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Improving the availability of soil phosphorus (P) and promoting tree growth through tree species selection and assembly are the critical issue. We conducted an afforestation experiment following randomized block experimental design with 1, 2, 4, and 6 tree species richness in south subtropics, including Pinus massoniana, Mytilaria laosensis, Erythrophleum fordii, Castanopsis hystrix, Michelia macclurei, Manglietia glauca, Aquilaria sinensis, and Dalbergia odorifera. We measured the bioavailable P components (CaCl2-P, citrate-P, enzyme-P and HCl-P) and examined the effects of different tree species assembly on bioavailable P components and tree growth. The results showed that, compared with non-nitrogen-fixing tree species, the mixing of nitrogen-fixing tree species (E. fordii and D. odorifera) effectively increased the contents of soil water, total nitrogen, total phosphorus, and microbial biomass P (MBP). The assembly of specific tree species improved the accumulation of bioavailable P. Mixing of nitrogen-fixing tree species significantly increased CaCl2-P content by 46.2% to 160.3%, the enzyme-P content produced by microbial mineralization by 69.3% to 688.2%, and HCl-P by 31.5% to 81.3%, increased MBP by 81.8% to 149.4%, and microbial biomass N (MBN) by 88.1% to 160.6%, respectively. Redundancy and correlation analysis results showed that MBP, available P, total phosphorus, L-leucine aminopeptidase, cellobiose, acid phosphatase, MBN and soil organic carbon were key factors driving the variation of rhizosphere soil bioavailable P. Mixing of nitrogen-fixing tree species increased enzyme-P and citrate-P, and the availability of which were positively correlated to tree basal area. In this study, mixing of nitrogen-fixing tree species increased the rhizosphere soil bioavailable P content, which facilitates tree growth.
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Fósforo , Rizosfera , Suelo , Árboles , Fósforo/metabolismo , Fósforo/análisis , Árboles/crecimiento & desarrollo , Árboles/metabolismo , Suelo/química , China , Clima Tropical , Nitrógeno/metabolismo , Nitrógeno/análisis , Pinus/crecimiento & desarrollo , Pinus/metabolismoRESUMEN
OBJECTIVE: This work aims to investigate whether RIP2 silencing in naive CD4+ T cells from lupus-prone mice impacts Th17 cell activity or differentiation in vitro. METHODS: Naive CD4+ T cells isolation from MRL/lpr mice's spleens. Three RNA interference target sequences of RIP2 were packaged with lentivirus and transfected into naive CD4+ T cells. The shRIP2 with the highest interference efficiency was selected and transfected into naive CD4+ T cells. Naive CD4+ T cells were cultured under conventional (TGF-ß1 and IL-6) and pathogenic (IL-6, IL-23, IL-1ß) differentiation environments, respectively. Then, RT-qPCR, Western blot or Flow Cytometry were used for measuring the amounts of RIP2 and IL-17 and the differentiation of Th17 cells in two settings. RESULTS: Under the conventional Th17 (cTh17) cell differentiation environment (TGF-ß1 and IL-6), RIP2 deficiency is linked to decreased IL-17A levels (1.00 ± 0.03 vs 0.80 ± 0.03) and attenuated cTh17 cell (2.46 ± 0.08 vs 0.78 ± 0.03) differentiation (all, P < 0.05). Under the pathogenic Th17 (pTh17) cell environment (IL-1ß, IL-23, IL-6), RIP2 deficiency is linked to elevated IL-17A levels (1.03 ± 0.05 vs 1.63 ± 0.07) and enhanced pTh17 cell (3.69 ± 0.19 vs 5.49 ± 0.10) differentiation (all, P < 0.05). CONCLUSION: Our data suggest that RIP2 inhibition induces preferential differentiation of naive CD4+ T cells to pathogenic Th17 cells, while being able to upregulate IL-17A levels in the context of pTh17 cell differentiation. Our study opens up new research areas to reveal the underlying mechanisms and potential therapeutic targets for the prevention and treatment of SLE patients. Key Points ⢠Silencing of RIP2 in naive CD4+ T cells from lupus-prone mice promotes pathogenic Th17 (pTh17) cell differentiation and IL-17A production under pTh17 cell (IL-1ß, IL-23, and IL-6) conditions. ⢠RIP2 deficiency in naive CD4+ T cells reduces conventional Th17 (cTh17) cell differentiation and IL-17A production under cTh17 cell (TGF-ß1 and IL-6) conditions. ⢠RIP2-deficient naive CD4+ T cells preferentially differentiate towards pTh17 cells rather than cTh17 cells in vitro. ⢠Inhibition of RIP2 may be involved in the development of SLE via effects on Th17/IL-17.
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AIMS: Succinate, a metabolite in the tricarboxylic acid cycle, is increasingly recognized to play essential roles in inflammation by functioning either as an intracellular or extracellular signaling molecule. However, the role and mechanisms of succinate in inflammation remain elusive. Here, we investigated the mechanism underlying the effects of succinate on neuroinflammation in intracerebral hemorrhage (ICH) models. RESULTS: We unexpectedly found that succinate robustly inhibited neuroinflammation and conferred protection following ICH. Mechanistically, oxidation of succinate by succinate dehydrogenase (SDH) drove reverse electron transport (RET) at mitochondrial complex I, leading to mitochondrial superoxide production in microglia. Complex I-derived superoxide, in turn, activated uncoupling protein 2 (UCP2). By using mice with specific deletion of UCP2 in microglia/macrophage, we showed that UCP2 was needed for succinate to inhibit neuroinflammation, confer protection, and activate downstream AMP-activated protein kinase (AMPK) following ICH. Moreover, knockdown of SDH, complex I or AMPK abolished the therapeutic effects of succinate following ICH. INNOVATION AND CONCLUSION: We provide evidence that driving complex I RET to activate UCP2 is a novel mechanism of succinate intracellular signaling and a mechanism underlying the inhibition of neuroinflammation by succinate. KEY WORDS: succinate; uncoupling protein 2; microglia; neuroinflammation; intracerebral hemorrhage.
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Kombucha, a fermented tea prepared with a symbiotic culture of bacteria and yeast (SCOBY), offers a unique and unpredictable home-brewed fermentation process. Therefore, the need for a controlled kombucha fermentation process has become evident, which requiring a thorough understanding of the microbial composition and its relationship with the metabolites produced. In this study, we investigated the dynamics of microbial communities and metabolites over a 12-day fermentation period of a conventional kombucha-making process. Our findings revealed similarities between the microbial communities in the early (0-2 days) and late (10-12 days) fermentation periods, supporting the principle of back-slopping fermentation. Untargeted metabolite analysis unveiled the presence of harmful biogenic amines in the produced kombucha, with concentrations increasing progressively throughout fermentation, albeit showing relatively lower abundance on days 8 and 12. Additionally, a contrasting trend between ethanol and caffeine content was observed. Canonical correspondence analysis highlighted strong positive correlations between specific bacterial/yeast strains and identified metabolites. In conclusion, our study sheds light on the microbial and metabolite dynamics of kombucha fermentation, emphasizing the importance of microbial control and quality assurance measures in the production process.
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Viruses are dependent on the host factors for their replication and survival. Therefore, identification of host factors that druggable for antiviral development is crucial. The actin cytoskeleton plays an important role in the virus infection. The dynamics change of actin and its function are regulated by multiple actin-associated proteins (AAPs). However, the role and mechanism of various AAPs in the life cycle of virus are still enigmatic. In this study, we analyzed the roles of actin and AAPs in the replication of pseudorabies virus (PRV). Using a library of compounds targeting AAPs, our data found that multiple AAPs, such as Rho-GTPases, Rock, Myosin and Formin were involved in PRV infection. Besides, our result demonstrated that the actin-binding protein Drebrin was also participated in PRV infection. Further studies are necessary to elucidate the molecular mechanism of AAPs in the virus life cycle, in the hope of mining host factors for antiviral developments.
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BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of Ë 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.
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Anticuerpos Antinucleares , Anticuerpos Monoclonales Humanizados , ADN , Humanos , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , ADN/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Persona de Mediana Edad , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Artritis Reumatoide/sangre , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Adulto , Biomarcadores/sangreRESUMEN
BACKGROUND: This study aimed to assess the expression level of upstream stimulator 1 (USF1) in the bone marrow of newly diagnosed acute myeloid leukemia (AML) patients and investigate its clinical and prognostic significance. METHODS: Bone marrow samples from 60 newly diagnosed AML patients constituted the observation group, while 20 samples from healthy individuals formed the control group. Real-time quantitative PCR (qRT-PCR) was used to measure the USF1 expression in both groups and to analyze its correlation with clinicopathological features and prognosis in AML patients. Kaplan-Meier curves were utilized to assess the impact of USF1 on the overall survival (OS) in AML patients. The prognostic factors of AML were examined by using Cox regression analysis. RESULTS: A univariate analysis revealed a significantly higher USF1 expression in the AML patients compared to the control group (p < 0.001), with no difference in the clinicopathological features between the low-expression group and the control group. However, there was a significant difference between the high-expression group and the control group (p < 0.01). Moreover, the OS of the high USF1 expression group was notably shorter than of the low USF1 expression group (p < 0.0001). A multivariate analysis identified high USF1 expression and age ≥ 60 years as independent risk factors for a poor AML prognosis. CONCLUSIONS: High expression of USF1 is linked to a worse prognosis and shorter survival time in AML patients. USF1 may serve as an indicator of prognosis and survival in AML patients and could be a potential target for AML treatment.
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Leucemia Mieloide Aguda , Factores Estimuladores hacia 5' , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Factores Estimuladores hacia 5'/genética , Factores Estimuladores hacia 5'/metabolismo , Adulto , Anciano , Pronóstico , Adulto Joven , Estimación de Kaplan-Meier , Estudios de Casos y Controles , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Adolescente , Modelos de Riesgos Proporcionales , Médula Ósea/patología , Médula Ósea/metabolismo , Análisis Multivariante , Relevancia ClínicaRESUMEN
To develop a clean-up material suitable for high-fat food matrices for detecting mycotoxins in yak ghee, an octadecyl-bonded hectorite (Hectorite@NHCO(CH2)17CH3) was synthesized through multi-step chemical reactions. A modified QuEChERS-HPLC-MS/MS method for detecting ten mycotoxins in sesame oil in yak ghee was established using Hectorite@NHCO(CH2)17CH3 as clean-up agent. It involved extracting mycotoxin contaminants using acidified acetonitrile and employing the Hectorite@NHCO(CH2)17CH3 to remove interfering substances from the extract. The purified samples were then analyzed using HPLC-MS/MS. Within a linear range of 1.0-500 µg/kg, there was a good linear relationship between the quantification ion peak area of the target analytes and the corresponding concentrations (R2 ≥ 0.9991). The limit of detection (LOD) ranged from 0.10 µg/kg to 18.62 µg/kg and the limit of quantitation (LOQ) ranged 0.32-62.07 µg/kg. The recoveries at low, medium and high concentrations (25, 100 and 500 µg/kg) ranged from 72.2% to 113.9%, with relative standard deviations (RSD) between 3.2% and 17.5%. The intra-day and inter-day precision met experimental requirements. The proposed method was characterized by a high accuracy and precision, and it could cater to the current demand for detecting ten mycotoxins in yak ghee.
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Background: The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI). Methods: After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention. Results: EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum. Conclusion: The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.
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BACKGROUND: Acute immune rejection remains a challenge in the post-transplant period, with approximately 7.8% of renal transplant recipients experiencing rejection episodes within the first year. Genetic polymorphisms in the CYP3A5 gene, which influences tacrolimus metabolism, have garnered interest regarding their association with clinical outcomes in renal transplantation. METHODS: This retrospective correlation study analysed clinical data from kidney transplant patients who received tacrolimus treatment at our hospital from June 2015 to June 2023. The presence of CYP3A5 gene polymorphisms, tacrolimus trough levels, and demographic and clinical data were collected and analysed. RESULTS: A total of 105 kidney transplant patients were included. Patients were divided into acute immune rejection (n = 56) and non-acute immune rejection (n = 49) groups. The distribution of CYP3A5 gene polymorphisms differed significantly between the acute rejection and non-acute rejection groups (p = 0.037). The acute rejection group exhibited a higher frequency of CYP3A5 *1/*1 or *1/*3 genotypes than the non-acute rejection group. No statistically significant differences were found in the tacrolimus trough levels between the two groups. Correlation analysis revealed a statistically significant correlation between CYP3A5 gene polymorphism and post-transplant acute immune rejection (r = 0.223, p < 0.05). CONCLUSIONS: This study demonstrated a significant association between CYP3A5 gene polymorphism and the risk of post-transplant acute immune rejection in renal transplant recipients receiving tacrolimus therapy. These findings highlighted the importance of genetic variability in tacrolimus metabolism when managing immunosuppressive therapy in transplant recipients.
Asunto(s)
Citocromo P-450 CYP3A , Rechazo de Injerto , Inmunosupresores , Trasplante de Riñón , Polimorfismo Genético , Tacrolimus , Humanos , Tacrolimus/uso terapéutico , Citocromo P-450 CYP3A/genética , Rechazo de Injerto/genética , Masculino , Femenino , Estudios Retrospectivos , Inmunosupresores/uso terapéutico , Enfermedad Aguda , Persona de Mediana Edad , Adulto , Correlación de DatosRESUMEN
CLINICAL RELEVANCE: Constant technological improvements require practitioners to be open to adopting technologies such as telehealth for enhanced patient care. Understanding the barriers and facilitators of telehealth adoption will guide stakeholders in making decisions for safe and effective implementation of telehealth. BACKGROUND: Effective use of telehealth improves patient outcomes. It is unclear if optometry students feel supported in using and/or are accepting of telehealth. This study evaluated telehealth acceptance of optometry students, its association with their technology self-efficacy, and whether telehealth training alters this relationship. METHODS: Final-year optometry students at the University of Melbourne were invited to participate in a telehealth course. A 22-item online survey adapted from the Technology Proficiency Self-Assessment for twenty-first Century Learning was used to evaluate technology self-efficacy pre- and post-learning. Telehealth acceptance was evaluated using a 34-item survey according to the Unified Theory of Acceptance and Use of Technology-2. A 5-point Likert scale was used for each item, yielding two total scores. Respondent demographics, frequency of usage and number of devices were recorded. Descriptive statistics, ANOVA and Pearson correlation were used to analyse demographic variables and relationship between technology self-efficacy and telehealth acceptance. RESULTS: 58 (68%) and 49 (58%) students participated in the pre- and post-learning surveys. Majority were 20-29-year-old females. Students used between two and four devices for online activities, with 62% being online at least hourly. Technology self-efficacy scores (average ± SD) pre- and post-learning were 83.8% ± 8.2 and 87.8% ± 7.1. Telehealth acceptance scores pre- and post-learning were 66.1% ± 9.6 and 73.98% ± 9.9. There was no association with gender, number of devices and frequency of online use for all scores. Correlation between technology self-efficacy and telehealth acceptance was insignificant pre-learning (p = 0.3) but was significant post-learning (p = 0.04). CONCLUSION: Optometry students demonstrated high technology self-efficacy compared to telehealth acceptance. Telehealth training resulted in marked improvement in telehealth acceptance.