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Electrocatalytic nitrogen reduction reaction (NRR) presents a sustainable alternative to the Haber-Bosch process for ammonia (NH3) production. However, developing efficient catalysts for NRR and deeply elucidating their catalytic mechanism remain daunting challenges. Herein, we pioneered the successful embedding of atomically dispersed (single/dual) W atoms into V2-x CT y via a self-capture method, and subsequently uncovered a quantifiable relationship between charge transfer and NRR performance. The prepared n-W/V2-x CT y shows an exceptional NH3 yield of 121.8 µg h-1 mg-1 and a high faradaic efficiency (FE) of 34.2% at -0.1 V (versus reversible hydrogen electrode (RHE)), creating a new record at this potential. Density functional theory (DFT) computations reveal that neighboring W atoms synergistically collaborate to significantly lower the energy barrier, achieving a remarkable limiting potential (U L) of 0.32 V. Notably, the calculated U L values for the constructed model show a well-defined linear relationship with integrated-crystal orbital Hamilton population (ICOHP) (y = 0.0934x + 1.0007, R 2 = 0.9889), providing a feasible activity descriptor. Furthermore, electronic property calculations suggest that the NRR activity is rooted in d-2π* coupling, which can be explained by the "donation and back-donation" hypothesis. This work not only designs efficient atomic catalysts for NRR, but also sheds new insights into the role of neighboring single atoms in improving reaction kinetics.
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Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency.
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The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ's metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (n = 44), the Atherosclerosis Risk in Communities (ARIC) study (n = 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (n = 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.
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Lesión Renal Aguda , Biomarcadores , COVID-19 , Osteopontina , Proteómica , Humanos , Lesión Renal Aguda/sangre , Proteómica/métodos , Masculino , Biomarcadores/sangre , Femenino , Persona de Mediana Edad , COVID-19/sangre , Osteopontina/sangre , Tenascina/sangre , Tenascina/genética , Tenascina/metabolismo , Túbulos Renales/metabolismo , Túbulos Renales/patología , Anciano , Adulto , SARS-CoV-2 , Análisis de la Célula Individual , Proteínas Sanguíneas/metabolismoRESUMEN
OBJECTIVE: Human T-cell leukemia virus type 1-associated myelopathy (HAM) is a chronic, progressive, inflammatory disease with unclear pathogenesis and no effective treatments. We aimed to investigate a novel mechanistic theory and treat HAM patients with rituximab, which can deplete CD20+ B lymphocytes in circulation. METHODS: Single-cell RNA sequencing (scRNA-seq) data was analyzed to identify HTLV-1-associated B cells and their effect on T cells. An observational analysis of our HAM cohort was conducted to elucidate changes in the immunological microenvironment of these patients. Peripheral blood mononuclear cells (PBMC) from HAM patients were isolated to explore the efficacy of B cell depletion in vitro. To assess the effect of B-cell depletion on HAM patients, eligible participants in our cohort received rituximab therapy (NCT04004819). RESULTS: ScRNA-seq results suggest a significant effect of HTLV-1-associated B cells on T cells. Additionally, HTLV-1 was found to infect B cells and depletion of B cells inhibited the proliferation of T cells. Number of B cells in HAM patients had positive correlation with the proviral load and infected cell counts. Depletion of B cells led to a reduction in HTLV-1 proviral load in vitro. Furthermore, in clinical trial, 14 HAM patients were enrolled. Three patients (21.4%) who received rituximab failed to achieve remission, compared to 24 (85.7%) patients received any other therapy that failed to achieve remission. With a low level of circulating B cells, the proportion of Ki67-positive cells in CD4+ T cells fell. INTERPRETATION: This study provided evidence that depleting B-lymphocytes is an innovative strategy for treating patients with HAM and broadens the understanding of the role of B cells in infectious immunity.
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Intervertebral disc degeneration (IDD) progresses owing to damage and depletion of nucleus pulposus (NP) cells. Cytoprotection mitigates oxidative stress, nutrient deprivation, and mechanical stress, which lead to cell damage and necrosis. We aimed to examine the protective effect of Raphanus sativus Linne (RSL), common radish, against oxidative stress by H2O2 in human NP cells and whether the RSL extracts can inhibit triggering receptor expressed on myeloid cells 2 (TREM2), an inducer of apoptosis and degeneration in NP cells. We administered hydrogen peroxide (H2O2) to cultured human NP cells treated with RSL extracts. We used immunoblotting and quantitative PCR to investigate expression of the apoptosis-associated proteins in cultured cells. RSL significantly enhanced cell survival by suppressing the activation of cleaved caspase-3 and Bax. In contrast, RSL extract increased Bcl2 concentration to downregulate apoptosis. Additionally, RSL treatment notably enhanced the mRNA levels of ACAN and Col2a1 while significantly reducing those of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, key genes involved in NP degeneration. While H2O2 elevated TREM2 expression, causing disc degeneration, RSL downregulated TREM2 expression. Thus, our findings imply that RSL supports human NP cells under oxidative stress and regulates the pathways underlying disc degeneration, particularly TREM2, and that RSL extracts may potentially prevent IDD.
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Aberrant inorganic phosphate (Pi) homeostasis causes brain calcification and aggravates neurodegeneration, but the underlying mechanism remains unclear. Here, we found that primary familial brain calcification (PFBC)-associated Pi transporter genes Pit2 and Xpr1 were highly expressed in astrocytes, with importer PiT2 distributed over the entire astrocyte processes and exporter XPR1 localized to astrocyte end-feet on blood vessels. This polarized PiT2 and XPR1 distribution endowed astrocyte with Pi transport capacity competent for brain Pi homeostasis, which was disrupted in mice with astrocyte-specific knockout (KO) of either Pit2 or Xpr1. Moreover, we found that Pi uptake by PiT2, and its facilitation by PFBC-associated galactosidase MYORG, were required for the high Pi transport capacity of astrocytes. Finally, brain calcification was suppressed by astrocyte-specific PiT2 re-expression in Pit2-KO mice. Thus, astrocyte-mediated Pi transport is pivotal for brain Pi homeostasis, and elevating astrocytic Pi transporter function represents a potential therapeutic strategy for reducing brain calcification.
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INTRODUCTION: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended in kidney disease and heart failure to reduce adverse clinical outcomes, but utilization can vary. To understand potential gaps in clinical practice and identify opportunities for improvement, we aimed to describe the prevalence and factors associated with SGLT2i prescription in patients with reduced kidney function hospitalized for fluid overload and/or heart failure. METHODS: Single-center observational study of patients with reduced kidney function (eGFR 20-59 mL/min/1.73 m2) hospitalized for fluid overload or heart failure between January 2022 and December 2023. Data were retrieved from electronic medical records. The outcome was SGLT2i prescription at discharge. Potential variables affecting SGLT2i prescription were identified during stakeholder engagement and evaluated using multivariable logistic regression. RESULTS: Among 2,543 patients, the median age was 79 (71, 86) years and admission eGFR was 38.7 (28.4, 49.4) mL/min/1.73 m2. SGLT2i was prescribed to 630 (24.8%) patients at discharge. SGLT2i prescription at discharge was independently associated with cardiovascular disease (OR 1.76, 95% CI: 1.31-2.35), diabetes (OR 1.59, 95% CI: 1.19-2.14), fluid overload or heart failure as the primary discharge diagnosis (OR 1.71, 95% CI: 1.29-2.28), SGLT2i pre-hospitalization (OR 104.91, 95% CI: 63.22-174.08), RAS blocker (OR 2.1, 95% CI: 1.65-2.89), and higher eGFR (OR 1.01, 95% CI: 1.003-1.02) at discharge; but inversely associated with older age (OR 0.97, 95% CI: 0.96-0.98). CONCLUSION: SGLT2i prescription at discharge was suboptimal among patients with reduced kidney function hospitalized for fluid overload and/or heart failure, especially in older age and more severe kidney disease. Additionally, cardiovascular disease, diabetes, primary discharge diagnosis of fluid overload or heart failure, prior SGLT2i use, and concurrent RAS blocker at discharge were independently associated with SGLT2i prescription at discharge. Interventions are needed to increase clinicians' knowledge and overcome clinical inertia to increase SGLT2i use in patients with fluid overload and heart failure.
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Tasa de Filtración Glomerular , Insuficiencia Cardíaca , Hospitalización , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/complicaciones , Masculino , Anciano , Femenino , Anciano de 80 o más Años , Tasa de Filtración Glomerular/efectos de los fármacos , Hospitalización/estadística & datos numéricos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Desequilibrio Hidroelectrolítico/epidemiologíaRESUMEN
Duchenne muscular dystrophy (DMD) affecting 1 in 3500-5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient's DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.
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Adenina , Sistemas CRISPR-Cas , Modelos Animales de Enfermedad , Distrofina , Exones , Edición Génica , Distrofia Muscular de Duchenne , Animales , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Distrofina/genética , Distrofina/metabolismo , Exones/genética , Humanos , Masculino , Edición Génica/métodos , Ratones , Adenina/metabolismo , Músculo Esquelético/metabolismo , Dependovirus/genética , Terapia Genética/métodosRESUMEN
Purpose: Examine the alterations in antipsychotic concentrations following coronavirus disease-2019 (COVID-19) infection among hospitalized patients with mental disorders and conduct an analysis of the factors influencing these changes. Methods: Data were collected from inpatients at Beijing Huilongguan Hospital between December 12, 2022, and January 11, 2023, pre- and post-COVID-19. Based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 329 inpatients with mental disorders were included (3 with incomplete data excluded). Primary outcomes assessed changes in antipsychotic concentrations pre- and post-COVID-19, while secondary outcomes examined factors linked to concentration increases and antipsychotic dose adjustments. Results: Clozapine (P < 0.001), aripiprazole (P < 0.001), quetiapine (P = 0.005), olanzapine (P < 0.001), risperidone (P < 0.001), and paliperidone (P < 0.001) concentrations increased post-COVID-19 in patients with mental disorders. Notably, clozapine concentration surpassing pre-infection levels was highest. Clozapine users were more likely to adjust their dose (50.4%) compared to olanzapine (17.5%) and other antipsychotics. Moreover, traditional Chinese patent medicines and antibiotics during COVID-19 infection were associated with antipsychotic reduction or withdrawal (OR = 2.06, P = 0.0247; OR = 7.53, P = 0.0024, respectively). Conclusion: Antipsychotic concentrations in hospitalized patients with mental disorders increased after COVID-19 infection, that may be related not only to COVID-19, but also to the use of Chinese patent medicines during infection. The pre-infection concentration and types of antipsychotics, patient's gender, and combination of traditional Chinese medicine or antibiotics, were factors found to correlate with increased drug concentrations and necessitate dose adjustments.
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The prevalence of chicken coccidiosis in the poultry industry is a significant concern, further exacerbated by the emergence of drug-resistant coccidia resulting from the indiscriminate use of medications. Ethanamizuril, a novel triazine anti-coccidial compound, has been used to combat drug resistance. Currently, it is known that Ethanamizuril acts on the second-generation merozoites and early gametogenesis stages of Eimeria. Limited information exists regarding its impact on the early merozoites and exogenous stage of Eimeria. In the present study, the anti-coccidial properties of Ethanamizuril were evaluated both in vitro and in vivo. The in vitro experiments demonstrated that Ethanamizuril effectively inhibits the sporulation of E. tenella oocysts in a dose-dependent manner and significantly reduces the sporozoite excystation rate. Furthermore, in vivo tests revealed that treatment with 10 mg/L Ethanamizuril in drinking water significantly decreased the copy number of first-generation and secondary-generation merozoites in the chicken cecum, indicating that it can inhibit the development of whole schizonts development. Moreover, treatment with Ethanamizuril demonstrated excellent protective efficacy with an anti-coccidial index (ACI) of 180, which was manifested through higher body weight gains, lighter cecal lesion, lower fecal oocyst shedding score and reduced liver index. Collectively, this study suggests that Ethanamizuril effectively treats E. tenella infection by inhibiting both endogenous and exogenous stages development.
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OBJECTIVE: Most paroxysmal kinesigenic dyskinesia (PKD) cases are hereditary, yet approximately 60% of patients remain genetically undiagnosed. We undertook the present study to uncover the genetic basis for undiagnosed PKD patients. METHODS: Whole-exome sequencing was performed for 106 PRRT2-negative PKD probands. The functional impact of the genetic variants was investigated in HEK293T cells and Drosophila. RESULTS: Heterozygous variants in KCNJ10 were identified in 11 individuals from 8 unrelated families, which accounted for 7.5% (8/106) of the PRRT2-negative probands. Both co-segregation of the identified variants and the significantly higher frequency of rare KCNJ10 variants in PKD cases supported impacts from the detected KCNJ10 heterozygous variants on PKD pathogenesis. Moreover, a KCNJ10 mutation-carrying father from a typical EAST/SeSAME family was identified as a PKD patient. All patients manifested dystonia attacks triggered by sudden movement with a short episodic duration. Patch-clamp recordings in HEK293T cells revealed apparent reductions in K+ currents of the patient-derived variants, indicating a loss-of-function. In Drosophila, milder hyperexcitability phenotypes were observed in heterozygous Irk2 knock-in flies compared to homozygotes, supporting haploinsufficiency as the mechanism for the detected heterozygous variants. Electrophysiological recordings showed that excitatory neurons in Irk2 haploinsufficiency flies exhibited increased excitability, and glia-specific complementation with human Kir4.1 rescued the Irk2 mutant phenotypes. INTERPRETATION: Our study established haploinsufficiency resulting from heterozygous variants in KCNJ10 can be understood as a previously unrecognized genetic cause for PKD and provided evidence of glial involvement in the pathophysiology of PKD. ANN NEUROL 2024.
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An experimental and numerical study on the ejector pin's mechanics during automatic multistage cold forging (AMSCF) of an automobile wheel nut is conducted. The traditional, decoupled die structural analysis method (DDSM) of analyzing die structures as one of the post-processing functions is criticized, which uses the tractions exerting on the die parts predicted from the forging simulation under the rigid die assumption. To cope with the matter of the DDSM, a multibody treatment scheme (MBTS) is proposed to simulate the AMSCF process, emphasizing the ejector pin's mechanics, using an implicit elastoplastic finite element method. The experiments qualitatively validate the finite element predictions. It is shown that the asymmetric sheared material in AMSCF greatly influences the ejector pin's mechanics, which is characterized by its lateral and longitudinal displacements because of its structural flexibility. It is emphasized that the detailed understanding of the ejector pin's mechanics may not only give a helpful connection towards smart manufacturing because of its mechanical flexibility and sensitivity to the excitations and responses, but it also reveals the reason for the die's high-cycle fatigue (HCF) fracture of the critical die corner (CDC) near at the end of the ejector pin.
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The operation of the Cansolv tail gas treatment device in natural gas plants generates acidic and alkaline wastewater from the venturi unit and amine purification unit (APU), respectively. The APU wastewater is complex in composition and contains hard-to-degrade organic matter, which can adversely impact the normal functioning of the water treatment system. This study assesses the efficacy of three ozone-based advanced oxidation processes (ozone (O3), ozone/hydrogen peroxide (O3/H2O2), and ozone/Fenton (O3/Fenton)) for treating Cansolv wastewater, with chemical oxygen demand (COD) and total organic carbon (TOC) serving as indicators of organic degradation. The findings demonstrate that all three processes effectively eliminate coloration and reducible sulfur, with O3/Fenton exhibiting superior performance in removing organic substances. The treated wastewater has a clarified light-yellow appearance with residual COD levels at 43 mg L-1. Under the optimum Fenton oxidation conditions (initial pH 5, H2O2 dosage 97.8 mmol L-1, FeSO4·7H2O dosage 550 mg L-1), average TOC and COD removal rates reached 50% and 97%, respectively. After a treatment duration of 60 minutes, the wastewater demonstrated an enhanced membrane-specific flux, confirming the effectiveness of the O3/Fenton oxidation process in mitigating membrane fouling while ensuring the stable operation of the wastewater treatment system.
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Introduction: To investigate the impact of interpersonal sensitivity on the subjective well-being of accompanying children of migrant workers and the role of perception of exclusion and peer support in the process. Methods: A questionnaire survey was conducted among 304 migrant workers' accompanying children and 501 urban children in grades 4-9 in seven schools in Jiangxi Province, China. Hierarchical regression and bootstrap analysis were used. Results: Interpersonal sensitivity not only had a significant direct negative effect on the subjective well-being of migrant workers' accompanying children (ß= -0.27, 95% CI = [-0.37, -0.17]), but also had an indirect effect through perception of exclusion (ß= -0.06, 95% CI = [-0.11, -0.03]). Peer support negatively moderated the relationship between interpersonal sensitivity and perception of exclusion (ß= -0.18, 95% CI = [-0.28, -0.08]) and the mediating effect of perceptions of exclusion between interpersonal sensitivity and subjective well-being (ß = 0.06, CI = [0.02, 0.11]). Conclusion: The subjective well-being of migrant children is indeed lower than that of urban children, and one of the most important reasons is their higher interpersonal sensitivity. Interpersonal sensitivity not only directly reduces their subjective well-being, but also reduces it by triggering their perception of exclusion, while peer support can effectively mitigate this negative effect. Therefore, one way to improve the subjective well-being of these children is to reduce their excessive interpersonal sensitivity. Their parents should help them to adapt to urban life, to develop correct professional values and to deal correctly with "occupational stigma", to overcome feelings of inferiority, while communities can create specialized activity centers to provide more social opportunities and psychological counseling services for these children.
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The choice of treatment for lumbar spinal stenosis (LSS) depends on symptom severity. When severe motor issues with urinary dysfunction are not present, conservative treatment is often considered to be the priority. One such conservative treatment is epidural injection, which is effective in alleviating inflammation and the pain caused by LSS-affected nerves. In this study, Shinbaro2 (Sh2), pharmacopuncture using natural herbal medicines for patients with disc diseases, is introduced as an epidural to treat LSS in a rat model. The treatment of primary sensory neurons from the rats' dorsal root ganglion (DRG) neurons with Sh2 at various concentrations (0.5, 1, and 2 mg/mL) was found to be safe and non-toxic. Furthermore, it remarkably stimulated axonal outgrowth even under H2O2-treated conditions, indicating its potential for stimulating nerve regeneration. When LSS rats received epidural injections of two different concentrations of Sh2 (1 and 2 mg/kg) once daily for 4 weeks, a significant reduction was seen in ED1+ macrophages surrounding the silicone block used for LSS induction. Moreover, epidural injection of Sh2 in the DRG led to a significant suppression of pain-related factors. Notably, Sh2 treatment resulted in improved locomotor recovery, as evaluated by the Basso, Beattie, and Bresnahan scale and the horizontal ladder test. Additionally, hind paw hypersensitivity, assessed using the Von Frey test, was reduced, and normal gait was restored. Our findings demonstrate that epidural Sh2 injection not only reduced inflammation but also improved locomotor function and pain in LSS model rats. Thus, Sh2 delivery via epidural injection has potential as an effective treatment option for LSS.
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BACKGROUND Papillary fibroelastoma is the most common type of benign primary cardiac tumor and is usually asymptomatic. However, tumor fragments or surface thrombus can embolize and cause transient ischemic attacks, strokes, or myocardial infarction. This report describes a 76-year-old woman who presented with dysarthria and right-sided weakness due to a stroke associated with a left atrial papillary fibroelastoma. CASE REPORT A 76-year-old woman visited the Emergency Department because she had right-sided weakness and dysarthria from 12 h ago. Brain magnetic resonance image was done at the Emergency Department, showing multiple small embolic, acute infarction in left basal ganglia and fronto-temporo-parietal lobes. Transthoracic and transesophageal echocardiogram showed a hypermobile echogenic mass (0.8×1.5 cm) with villous surface on the orifice of left atrial appendage. Twenty-four-hour Holter monitoring was performed to evaluate the cause of cerebral infarction, and there was no paroxysmal atrial fibrillation. Thoracic computed tomography angiography also showed a sea anemone-shaped mass around the left atrial appendage. Cardiac tumor excision was done via a lower partial sternotomy. Histopathologic analysis showed multiple delicate fronds, and the avascular fibroelastic cores were lined by a single layer of CD31-positive endothelial cells. Histopathologic findings were consistent with papillary fibroelastoma. The patient was discharged without any other complications on day 30 of hospitalization. CONCLUSIONS This case highlights the importance of cardiac imaging in patients with acute stroke, including transthoracic and transesophageal echocardiography, which can show the typical imaging features of papillary fibroelastoma and other intracardiac sources of embolus.
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Fibroelastoma Papilar Cardíaco , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Accidente Cerebrovascular/etiología , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Atrios Cardíacos , Ecocardiografía TransesofágicaRESUMEN
BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.
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Factores de Crecimiento de Fibroblastos , Humanos , Masculino , Femenino , Factores de Crecimiento de Fibroblastos/genética , Persona de Mediana Edad , Adulto , Imagen por Resonancia Magnética , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/patología , Anciano , Linaje , Expansión de Repetición de Trinucleótido/genética , Secuencias Repetidas en Tándem/genética , Degeneraciones EspinocerebelosasRESUMEN
Positron emission tomography (PET), a cornerstone in cancer diagnosis and treatment monitoring, relies on the enhanced uptake of fluorodeoxyglucose ([18F]FDG) by cancer cells to highlight tumors and other malignancies. While instrumental in the clinical setting, the accuracy of [18F]FDG-PET is susceptible to metabolic changes introduced by radiation therapy. Specifically, radiation induces the formation of giant cells, whose metabolic characteristics and [18F]FDG uptake patterns are not fully understood. Through a novel single-cell gamma counting methodology, we characterized the [18F]FDG uptake of giant A549 and H1299 lung cancer cells that were induced by radiation, and found it to be considerably higher than that of their non-giant counterparts. This observation was further validated in tumor-bearing mice, which similarly demonstrated increased [18F]FDG uptake in radiation-induced giant cells. These findings underscore the metabolic implications of radiation-induced giant cells, as their enhanced [18F]FDG uptake could potentially obfuscate the interpretation of [18F]FDG-PET scans in patients who have recently undergone radiation therapy.
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In adverse foggy weather conditions, images captured are adversely affected by natural environmental factors, resulting in reduced image contrast and diminished visibility. Traditional image dehazing methods typically rely on prior knowledge, but their efficacy diminishes in practical, complex environments. Deep learning methods have shown promise in single-image dehazing tasks, but often struggle to fully leverage depth and edge information, leading to blurred edges and incomplete dehazing effects. To address these challenges, this paper proposes a deep-guided bilateral grid feature fusion dehazing network. This network extracts depth information through a dedicated module, derives bilateral grid features via Unet, employs depth information to guide the sampling of bilateral grid features, reconstructs features using a dedicated module, and finally estimates dehazed images through two layers of convolutional layers and residual connections with the original images. The experimental results demonstrate the effectiveness of the proposed method on public datasets, successfully removing fog while preserving image details.