Analysis of the initial orbital MRI in aquaporin-4 antibody-positive optic neuritis (AQP4-ON): lesion location and lesion length can be predictive of visual prognosis.

PURPOSE: Despite mounting evidence indicating that aquaporin-4 antibody-positive optic neuritis (AQP4-ON) presents a less favorable prognosis than other types of optic neuritis, there exists substantial heterogeneity in the prognostic outcomes within the AQP4-ON cohort. Considering the persistent debate over the role of MRI in assessing the prognosis of optic neuritis, we aim to investigate the correlation between the MRI appearance and long-term visual prognosis in AQP4-ON patients. METHODS: We retrospectively reviewed the ophthalmological and imaging data of AQP4-ON patients admitted to our Neuro-ophthalmology Department from January 2015 to March 2018, with consecutive follow-up visits for a minimum of 3 years. RESULTS: A total of 51 AQP4-ON patients (59 eyes) meeting the criteria were enrolled in this research. After assessing the initial orbital MR images of each patient at the first onset, we observed the involvement of the canalicular segment (p < 0.001), intracranial segment (p = 0.004), optic chiasm (p = 0.009), and the presence of LEON (p = 0.002) were significantly different between recovery group and impairment group. For quantitative measurement, the length of the lesions is significantly higher in the impairment group (20.1 ± 9.3 mm) than in the recovery group (12.5 ± 5.3 mm) (p = 0.001). CONCLUSION: AQP4-ON patients with involvement of canalicular, intracranial segment and optic chiasm of the optic nerve, and the longer range of lesions threaten worse vision prognoses. Timely MR examination during the initial acute phase can not only exclude the intracranial or orbital mass lesions but also indicate visual prognosis in the long term.

[Syndrome differentiation and treatment of coronary heart disease combined with anxiety and depression from stages of phlegm, blood stasis, and toxic pathogen based on theory of "coexistence of diseases and depression syndromes"].

Depression syndromes(anxiety and depression), as typical psychological disorders, often coexist with and mutually influence coronary heart disease(CHD). They constitute a psycho-cardiology disease involving both the blood vessels of the heart and the spirit of the heart. Based on the theory of "coexistence of diseases and depression syndromes", it was proposed that CHD and depression syndromes coexisted independently and were causally related. The factors of depression syndromes go through the entire course of CHD and have different causal relationships at different stages, leading to a pathogenic process of "depression causing disease" or "disease causing depression". In the chronic latent period, phlegm predominates, with depression leading to the production of phlegm. Phlegm accumulation and Qi stagnation initiate a mutual damage process of psycho-cardiology, marking the onset of the disease. In the pathological development period, blood stasis becomes predominant. Depression leads to blood stasis, which further obstructs Qi circulation, accelerating disease progression. In the acute attack period, toxicity becomes crucial. Depression transforms into toxicity, damaging Qi and blood, disturbing the balance of the mind, and inducing a sudden and severe exacerbation of the disease. Based on this, the approach of treating phlegm and depression together, treating blood stasis and depression together, and treating toxicity and depression together by stages was established. Research has found that this approach can simultaneously improve organic damage and emotional disorders, and also has a regulating effect on micro-level syndrome indicators, achieving harmonization of psycho-cardiology in the treatment.

The genetic architecture of the dynamic changes in grain moisture in maize.

Low grain moisture at harvest is crucial for safe production, transport and storage, but the genetic architecture of this trait in maize (Zea mays) remains elusive. Here, we measured the dynamic changes in grain moisture content in an association-mapping panel of 513 diverse maize inbred lines at five successive stages across five geographical environments. Genome-wide association study (GWAS) revealed 71 quantitative trait loci (QTLs) that influence grain moisture in maize. Epistatic effects play vital roles in the variability in moisture levels, even outperforming main-effect QTLs during the early dry-down stages. Distinct QTL-environment interactions influence the spatio-temporal variability of maize grain moisture, which is primarily triggered at specific times. By combining genetic population analysis, transcriptomic profiling and gene editing, we identified GRMZM5G805627 and GRMZM2G137211 as candidate genes underlying major QTLs for grain moisture in maize. Our results provide insights into the genetic architecture of dynamic changes in grain moisture, which should facilitate maize breeding.

The relationship between 2019-nCoV and psychological distress among parents of children with autism spectrum disorder.

OBJECTIVES: The psychological distress caused by COVID-19 may be pronounced among the parents of children with autism spectrum disorder (ASD). This study aimed to investigate psychological distress among parents of children with ASD during the COVID-19 pandemic. METHODS: A total of 1764 parents of children with ASD and 4962 parents of typically developing (TD) children were recruited. The participants completed an online survey which contained demographic information, the impact due to COVID-19 crisis, resilience, coping styles, anxiety and depression. Hierarchical linear regression was used to assess the contributions of these variables to anxiety and depression. RESULTS: After adjusting for demographic variables, the following factors were associated with parents' anxiety and depression symptoms: (i) Whether or not the participants had a child with ASD; (ii) resilience; (iii) coping strategies, and; (iv) the impact due to COVID-19. Among these, the psychological stress caused by COVID-19 played the most important role in parental anxiety (ß = 0.353) and depression (ß = 0.242) symptoms. Parents of children with ASD had lower levels of resilience and positive coping, and used more negative coping strategies than parents of TD children. Among all participants, 8.0 and 24.2% of parents had symptoms of anxiety and depression, respectively. Compared to parents of TD children, more parents of children with ASD exhibited symptoms of anxiety and depression (12.2% vs. 6.6%; 31.0% vs. 21.7%, respectively). CONCLUSIONS: During the COVID-19 pandemic, parents experienced varying levels of anxiety and depression, particularly, parents of children with ASD. More specific attention should be paid to parental mental health and long-term effective intervention programs, that are targeted towards parents of children with ASD, and such programs should be promoted around China in the wake of the COVID-19 crisis.

Large-scale metabolite quantitative trait locus analysis provides new insights for high-quality maize improvement.

It is generally recognized that many favorable genes which were lost during domestication, including those related to both nutritional value and stress resistance, remain hidden in wild relatives. To uncover such genes in teosinte, an ancestor of maize, we conducted metabolite profiling in a BC2 F7 population generated from a cross between the maize wild relative (Zea mays ssp. mexicana) and maize inbred line Mo17. In total, 65 primary metabolites were quantified in four tissues (seedling-stage leaf, grouting-stage leaf, young kernel and mature kernel) with clear tissue-specific patterns emerging. Three hundred and fifty quantitative trait loci (QTLs) for these metabolites were obtained, which were distributed unevenly across the genome and included two QTL hotspots. Metabolite concentrations frequently increased in the presence of alleles from the teosinte genome while the opposite was observed for grain yield and shape trait QTLs. Combination of the multi-tissue transcriptome and metabolome data provided considerable insight into the metabolic variations between maize and its wild relatives. This study thus identifies favorable genes hidden in the wild relative which should allow us to balance high yield and quality in future modern crop breeding programs.

High-strength anaerobic digestion wastewater treatment by aerobic granular sludge in a step-by-step strategy.

To reduce the instability of aerobic granular sludge (AGS) caused by high-strength anaerobic digestion wastewater, a strategy of increasing proportion of anaerobic digestion wastewater step-by-step was adopted in this study. High-performance stable AGSs were successfully cultivated with sequencing batch reactors by this strategy, which could efficiently treat high-strength anaerobic digestion wastewater with an influent chemical oxygen demand (COD) up to 5090 mg⋅L-1. After six phases of stepwise increasing COD loads, the sludge sizes increased from 0.5 mm to 1.5 mm, with the final mixed liquor suspended solids increased to 13,814 mg⋅L-1, and the final sludge volume index decreased to 15 mL⋅g-1. The extracellular polymeric substance (EPS), which is crucial to keep the stability of AGS, increased continuously from 85.1 mg⋅g-1 SS to 307.8 mg⋅g-1 SS with the increase of COD loads. Moreover, the removal efficiency of COD and TN could reach 92% and 87% for real high-strength anaerobic digestion wastewater treatment. The bacterial community analysis revealed that the family Rhodocyclaceae, Flavobacteriaceae, and Xanthomonadaceae were the major microbes of AGS, and were responsible for COD and TN removal, as well as EPS secretion. These findings may provide novel information and enrich AGS treatment of high-strength real wastewater.

Enhancing robustness of aerobic granule sludge under low C/N ratios with addition of kitchen wastewater.

Aerobic granular sludge (AGS) is one of the most promising biotechnologies for wastewater treatment. However, the instability of AGS at low carbon to nitrogen (C/N) ratios limited its application. In this study, kitchen wastewater addition in the influent was found to improve the morphology, characteristics, and treatment performance of AGS at low C/N ratios of 10, 5 and 2, which strongly reduced the negative impact of low C/N ratios on the biomass concentration, settleability, EPS secretion, stability and performance of AGS. At C/N ratio of 2, sludge disintegration was observed in RA with synthetic wastewater as influent, while the sludge in RB was able to keep a compact microbial structure with particle size of 1.0-1.5 mm. When C/N ratio decreased from 20 to 2 (phase 1 to 4), the MLSS, SVI and EPS secretion in RB were negatively affected at the beginning of each phase, but recovered to 4800 mg L-1, 60 mL g-1, and 86 mg/g SS at the end of phase 4 (C/N ratio of 2), which were 1.3, 0.6 and 1.3 times of those in RA, respectively. Meanwhile, the removal efficiencies of COD, TN, TP and NH4+-N in RB were 90%, 73%, 53%, and 99% at the end of phase 4, which were 1.1, 1.2, 2.2 and 2.4 times of those in RA, respectively. Thus, high-performance AGS with enhanced robustness and high abundance of HN-AD functional bacteria Paracoccus was obtained. These findings provided a promising and cost-effective method to improve the long-term stability and performance of AGS dealing with wastewater of low C/N ratio.

The implication of neuronimmunoendocrine (NIE) modulatory network in the pathophysiologic process of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder implicitly marked by the substantia nigra dopaminergic neuron degeneration and explicitly characterized by the motor and non-motor symptom complexes. Apart from the nigrostriatal dopamine depletion, the immune and endocrine study findings are also frequently reported, which, in fact, have helped to broaden the symptom spectrum and better explain the pathogenesis and progression of PD. Nevertheless, based on the neural, immune, and endocrine findings presented above, it is still difficult to fully recapitulate the pathophysiologic process of PD. Therefore, here, in this review, we have proposed the neuroimmunoendocrine (NIE) modulatory network in PD, aiming to achieve a more comprehensive interpretation of the pathogenesis and progression of this disease. As a matter of fact, in addition to the classical motor symptoms, NIE modulatory network can also underlie the non-motor symptoms such as gastrointestinal, neuropsychiatric, circadian rhythm, and sleep disorders in PD. Moreover, the dopamine (DA)-melatonin imbalance in the retino-diencephalic/mesencephalic-pineal axis also provides an alternative explanation for the motor complications in the process of DA replacement therapy. In conclusion, the NIE network can be expected to deepen our understanding and facilitate the multi-dimensional management and therapy of PD in future clinical practice.

Analysis of aerobic granules under the toxic effect of ampicillin in sequencing batch reactors: Performance and microbial community.

To study the change of the aerobic granules' microbial community in the present of antibiotics, ampicillin (AMP) was selected as a model component. With acetate as carbon source, different concentrations of AMP (5, 10 and 15 mg L-1) were applied to the inflow intermittently and the results showed that the stability of the aerobic granules was maintained below 10 mg L-1 AMP. Simultaneously, under exposure to 5 and 10 mg L-1 AMP, the COD removal efficiency in the batch reactors remained at 86% and AMP was degraded almost completely with a removal efficiency of 97%. However, the EPS concentration and dehydrogenase activity decreased constantly with increasing AMP dosage. High-throughput sequencing analysis revealed that Proteobacteria was the most prominent phylum in the whole experiment and contributed to the degradation of AMP. The percentages of Azoarcus and Mycoplana increased at 10 mg L-1 AMP. In addition, Hydrogenophaga and Enterococcus played a key role in the microbial metabolism.

Role and influence of extracellular polymeric substances on the preparation of aerobic granular sludge.

Due to the important role of the extracellular polymeric substances in the formation of aerobic granular sludge, the variation of the EPS contents in the process of cultivation and that in the one running cycle time were studied in this work. Aerobic granules with diameters between 0.8 and 1.1 mm were obtained within 30-35 days. The results suggested that the increase of EPS contents significantly contributed to the formation of aerobic granules. A linear relationship between the EPS and SVI was also developed, and it revealed that the aerobic granules had good settling property when the EPS exceeded 200 mg/g MLVSS. Two mainly components of EPS, protein (PN) and polysaccharides (PS), could act as the endogenous food for the microbes during the starvation period. The survival of the microbial population was jeopardized when the F/M ration was below 0.5 g COD/g SS d.

A 3-hour time interval may not be sufficient for delayed enhancement magnetic resonance imaging with intravenous gadoteridol injection based on 3d-real IR sequence of the inner ear in Meniere's disease patient.

BACKGROUND: Magnetic resonance imaging (MRI) can be applied to visualize endolymphatic hydrops (EH). AIMS/OBJECTIVES: To explore whether a 3-h time interval was feasible for clinical practice. MATERIALS AND METHODS: We prospectively enrolled 15 patients with unilateral Meniere's disease, each of whom underwent delayed enhancement MRI scan of the inner ear after intravenous gadoteridol injection at a 3-h interval. The ears of these patients were divided into two groups (group A: the affected ears; group B: the unaffected ears). Among the two groups, the signal intensity in perilymphatic area of the basal turn of cochlea, the results of visual evaluations in the vestibule, cochlea and semicircular canal and the detection results of EH were compared. RESULTS: Regarding the signal intensity, a difference was found between group A and group B (p = .016). Besides, no difference was found between the visual evaluations in the vestibule, cochlea and semicircular canal of the two groups. Regarding the detection results of EH, group A (6 vestibules were undiagnosable; 8 cochleae were undiagnosable); group B (9 vestibules were undiagnosable; 10 cochleae were undiagnosable). CONCLUSIONS AND SIGNIFICANCE: In the clinical application of gadoteridol for the inner ear, 3-h delayed MR imaging may not be sufficient.

Multiparametric MRI-based radiomics approach with deep transfer learning for preoperative prediction of Ki-67 status in sinonasal squamous cell carcinoma.

Purpose: Based on comparison of different machine learning (ML) models, we developed the model that integrates traditional hand-crafted (HC) features and ResNet50 network-based deep transfer learning (DTL) features from multiparametric MRI to predict Ki-67 status in sinonasal squamous cell carcinoma (SNSCC). Methods: Two hundred thirty-one SNSCC patients were retrospectively reviewed [training cohort (n = 185), test cohort (n = 46)]. Pathological grade, clinical, and MRI characteristics were analyzed to choose the independent predictor. HC and DTL radiomics features were extracted from fat-saturated T2-weighted imaging, contrast-enhanced T1-weighted imaging, and apparent diffusion coefficient map. Then, HC and DTL features were fused to formulate the deep learning-based radiomics (DLR) features. After feature selection and radiomics signature (RS) building, we compared the predictive ability of RS-HC, RS-DTL, and RS-DLR. Results: No independent predictors were found based on pathological, clinical, and MRI characteristics. After feature selection, 42 HC and 10 DTL radiomics features were retained. The support vector machine (SVM), LightGBM, and ExtraTrees (ET) were the best classifier for RS-HC, RS-DTL, and RS-DLR. In the training cohort, the predictive ability of RS-DLR was significantly better than those of RS-DTL and RS-HC (p< 0.050); in the test set, the area under curve (AUC) of RS-DLR (AUC = 0.817) was also the highest, but there was no significant difference of the performance between DLR-RS and HC-RS. Conclusions: Both the HC and DLR model showed favorable predictive efficacy for Ki-67 expression in patients with SNSCC. Especially, the RS-DLR model represented an opportunity to advance the prediction ability.

Biogenic volatile organic compounds in forest therapy base: A source of air pollutants or a healthcare function?

Air pollution poses a significant threat to public health, while biogenic volatile organic compounds (BVOCs) play a crucial role in both aspects. However, the unclear relationship between BVOCs and air pollutants in the under-canopy space limits the accuracy of air pollution control and the exploitation of forest healthcare functions. To clarify the variation of BVOCs in forest therapy bases, and their impacts on ozone (O3) and fine particulate matter (PM2.5) at nose height, total VOCs (TVOCs) in the forest were collected during typical sunny days, while air pollutants and meteorological factors were observed simultaneously. The results showed that the branch-level emissions of P. tabuliformis were dominated by healthcare-effective monoterpenoids, with only α-pinene having relative air concentrations of over 5 % in forest air samples. The correlation between concentrations of under-canopy TVOCs and emission rates of BVOCs from P. tabuliformis was weak (p > 0.09) in all seasons. However, the correlation between concentrations of TVOCs and the concentrations of O3 and PM2.5 showed clear seasonal differences. In spring, TVOCs only showed a significant negative correlation with PM2.5 in the forest (p < 0.01). In summer and autumn, TVOCs were significantly negatively correlated with both O3 (p < 0.001) and PM2.5 (p < 0.01). Specifically, the negative linear relationships were more pronounced for O3 and oxygenated VOCs in autumn (R2 = 0.40, p < 0.001) than for other relationships. The relationship between air pollutant concentrations inside and outside the forest also showed significant seasonal differences, generally characterized by a weaker correlation between them during seasons of strong emissions. Therefore, BVOCs in coniferous forests are health functions as they can provide healthcare effects and mitigate the concentration of air pollutants in the forest, and the establishment of forest therapy bases in rural areas with low NOx can be a sensible approach to promote good health, well-being, and sustainable development.

Sequence polymorphisms of rfbT among the Vibrio cholerae O1 strains in the Ogawa and Inaba serotype shifts.

BACKGROUND: Vibrio cholerae serogroup O1 has two major serotypes, Ogawa and Inaba, which may alternate among cholera epidemics. The rfbT gene is responsible for the conversion between the two serotypes. In this study, we surveyed the sequence variance of rfbT in the Ogawa and Inaba strains in China over a 48-year (1961-2008) period in which serotype shifts occurred among epidemic years. RESULTS: Various mutation events including single nucleotide, short fragment insertions/deletions and transposases insertions, were found in the rfbT gene of the Inaba strains. Ectopically introducing an intact rfbT could overcome the mutations by converting the Inaba serotype to the Ogawa serotype, suggesting the effects of these mutations on the function of RfbT. Characteristic rfbT mutations were recognized in the Inaba strains among Inaba serotype dominant epidemic years which were separate from the Ogawa dominant epidemics. Three distinguishable mutation sites in rfbT between the classical and the El Tor biotype strains were identified and could serve as biotype-specific biomarkers. CONCLUSIONS: Our results provide a comprehensive picture of the rfbT gene mutations among the V. cholerae O1 strains in different epidemic periods, which could be further used as the tracing markers in clonality analysis and dissemination surveillance of the epidemic strains.

A Chinese pedigree with Perry disease caused by the p.Y78H mutation in DCTN1: A 6-year clinical follow-up.

PURPOSE: Perry disease is a rare autosomal dominant neurodegenerative disorder with core features of parkinsonism, depression, apathy, weight loss, and central hyperventilation. To date, few cases of Perry disease have been reported worldwide, and they are all due to mutations in the DCTN1 gene. We report a case of a Chinese pedigree. METHODS: Clinical information was collected from a Chinese pedigree. Brain magnetic resonance imaging, pulmonary function tests, and arterial blood gas analysis were performed on both the proband and his youngest aunt. Genomic DNA from the proband's aunt was analyzed using whole-exome sequencing to detect genetic mutations. RESULTS: The family displayed an autosomal dominant mode of inheritance, and we identified a p.Y78H mutation in DCTN1. After 6 years of follow-up, the proband exhibited mood-related "on-off" phenomena, weight gain, and used a CPAP ventilator at night. The proband's aunt presented with weight loss and respiratory failure four years after disease onset. CONCLUSION: This study reports a Chinese family with Perry disease. The mutation of DCTN1 in this family is p.Y78H. We share the findings in this family, hoping to increase our understanding of Perry disease in clinical work. DATA AVAILABILITY STATEMENT: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Macrophage-restricted overexpression of glutaredoxin 1 protects against atherosclerosis by preventing nutrient stress-induced macrophage dysfunction and reprogramming.

BACKGROUND AND AIMS: Deficiency in the thiol transferase glutaredoxin 1 (Grx1) in aging mice promotes, in a sexually dimorphic manner, dysregulation of macrophages and atherogenesis. However, the underlying mechanisms are not known. Here we tested the hypothesis that macrophage-restricted overexpression of Grx1 protects atherosclerosis-prone mice against macrophage reprogramming and dysfunction induced by a high-calorie diet (HCD) and thereby reduces the severity of atherosclerosis. METHODS: We generated lentiviral vectors carrying cluster of differentiation 68 (CD68) promoter-driven enhanced green fluorescent protein (EGFP) or Grx1 constructs and conducted bone marrow (BM) transplantation studies to overexpress Grx1 in a macrophage-specific manner in male and female atherosclerosis-prone LDLR-/- mice, and fed these mice a HCD to induce atherogenesis. Atherosclerotic lesion size was determined in both the aortic root and the aorta. We isolated BM-derived macrophages (BMDM) to assess protein S-glutathionylation levels and loss of mitogen-activated protein kinase phosphatase 1 (MKP-1) activity as measures of HCD-induced thiol oxidative stress. We also conducted gene profiling on these BMDM to determine the impact of Grx1 activity on HCD-induced macrophage reprogramming. RESULTS: Overexpression of Grx1 protected macrophages against HCD-induced protein S-glutathionylation, reduced monocyte chemotaxis in vivo, limited macrophage recruitment into atherosclerotic lesions, and was sufficient to reduce the severity of atherogenesis in both male and female mice. Gene profiling revealed major sex differences in the transcriptional reprogramming of macrophages induced by HCD feeding, but Grx1 overexpression only partially reversed HCD-induced transcriptional reprogramming of macrophages. CONCLUSIONS: Macrophage Grx1 plays a major role in protecting mice atherosclerosis mainly by maintaining the thiol redox state of the macrophage proteome and preventing macrophage dysfunction.

Investigation of biogenic volatile organic compounds emissions in the Qinghai-Tibetan Plateau.

Biogenic volatile organic compounds (BVOCs), which are produced and emitted by plants, have significant chemical reactivity in the atmosphere and impacting climate change. Qinghai Province, a vital component of the plateau, has abundant vegetation resources, primarily grasslands and forests, yet BVOCs emissions and their impact on air quality remain understudied. In this study, the emissions rates and compositions of BVOCs from seven dominant vegetation types in Qinghai Province were sampled and analyzed using a closed-loop stripping dynamic headspace sampling approach combined with GC-MS, and the total emissions of BVOCs in Qinghai province in 2021 were estimated by using G95 model. At the same time, the emission characteristics of various vegetation types were also analyzed. The results showed that the emissions rates and compositions of BVOCs differed significantly among vegetation types, with monoterpenes being the dominant emission composition in coniferous forests, which accounted for >70 % of the total BVOCs emissions, while isoprene being the main composition in alpine meadow, accounting for 84.96 %. The emissions of three typical vegetation types, Picea asperata, alpine meadow and alpine steppe, were monitored daily, revealing significant diurnal and clear unimodal patterns. The study also found that the annual average BVOCs emissions from vegetation sources in Qinghai Province were estimated to be 1550.63 Gg yr-1, with isoprene contributing the highest proportion of emissions, accounting for 56.94 %. Grassland was the largest BVOCs emission source in Qinghai Province, with an annual average emission of 1438.52 Gg yr-1. Additionally, BVOCs emissions in Qinghai Province showed strong seasonal and daily variation patterns, with the highest emissions occurring in summer, with the peak in July. These findings provide the characteristics of BVOCs emissions from vegetation sources in the Tibetan Plateau, which will contribute to a better understanding of their impact on atmospheric chemistry and climate change.

Histone Deacetylase 4 Inhibition Reduces Rotenone-Induced Alpha-Synuclein Accumulation via Autophagy in SH-SY5Y Cells.

(1) Background: Parkinson's disease (PD) is the most common movement disorder. Imbalanced protein homeostasis and α-syn aggregation are involved in PD pathogenesis. Autophagy is related to the occurrence and development of PD and can be regulated by histone deacetylases (HDACs). Various inhibitors of HDACs exert neuroprotective effects within in vitro and in vivo models of PD. HDAC4, a class Ⅱ HDAC, colocalizes with α-synuclein and ubiquitin in Lewy bodies and also accumulates in the nuclei of dopaminergic neurons in PD models. (2) Methods: In the present study, the gene expression profile of HDACs from two previously reported datasets in the GEO database was analyzed, and the RNA levels of HDAC4 in brain tissues were compared between PD patients and healthy controls. In vitro, SH-SY5Y cells transfected with HDAC4 shRNA or pretreated with mc1568 were treated with 1 µM of rotenone for 24 h. Then, the levels of α-syn, LC3, and p62 were detected using Western blot analysis and immunofluorescent staining, and cell viabilities were detected using Cell Counting Kit-8 (CCK-8). (3) Results: HDAC4 was highly expressed in PD substantia nigra and locus coeruleus. Mc1568, an inhibitor of HDAC4, decreased α-synuclein levels in rotenone-treated SH-SY5Y cells in a concentration-dependent manner and activated autophagy, which was impaired by rotenone. The knockdown of HDAC4 reversed rotenone-induced α-syn accumulation in SH-SY5Y cells and protected the neurons by enhancing autophagy. (4) Conclusions: HDAC4 is a potential therapeutic target for PD. The inhibition of HDAC4 by mc1568 or a gene block can reduce α-syn levels by regulating the autophagy process in PD. Mc1568 is a promising therapeutic agent for PD and other disorders related to α-syn accumulation.

Current Strategies in Treating Cytokine Release Syndrome Triggered by Coronavirus SARS-CoV-2.

Since the beginning of the SARS-CoV-2 pandemic, the treatments and management of the deadly COVID-19 disease have made great progress. The strategies for developing novel treatments against COVID-19 include antiviral small molecule drugs, cell and gene therapies, immunomodulators, neutralizing antibodies, and combination therapies. Among them, immunomodulators are the most studied treatments. The small molecule antiviral drugs and immunoregulators are expected to be effective against viral variants of SARS-CoV-2 as these drugs target either conservative parts of the virus or common pathways of inflammation. Although the immunoregulators have shown benefits in reducing mortality of cytokine release syndrome (CRS) triggered by SARS-CoV-2 infections, extensive investigations on this class of treatment to launch novel therapies that substantially improve efficacy and reduce side effects are still warranted. Moreover, great challenges have emerged as the SARS-CoV-2 virus quickly, frequently, and continuously evolved. This review provides an update and summarizes the recent advances in the treatment of COVID-19 and in particular emphasized the strategies in managing CRS triggered by SARS-CoV-2. A brief perspective in the battle against the deadly disease was also provided.

Glutaredoxin 1 controls monocyte reprogramming during nutrient stress and protects mice against obesity and atherosclerosis in a sex-specific manner.

High-calorie diet-induced nutrient stress promotes thiol oxidative stress and the reprogramming of blood monocytes, giving rise to dysregulated, obesogenic, proatherogenic monocyte-derived macrophages. We report that in chow-fed, reproductively senescent female mice but not in age-matched male mice, deficiency in the thiol transferase glutaredoxin 1 (Grx1) promotes dysregulated macrophage phenotypes as well as rapid weight gain and atherogenesis. Grx1 deficiency derepresses distinct expression patterns of reactive oxygen species and reactive nitrogen species generators in male versus female macrophages, poising female but not male macrophages for increased peroxynitrate production. Hematopoietic Grx1 deficiency recapitulates this sexual dimorphism in high-calorie diet-fed LDLR-/- mice, whereas macrophage-restricted overexpression of Grx1 eliminates the sex differences unmasked by high-calorie diet-feeding and protects both males and females against atherogenesis. We conclude that loss of monocytic Grx1 activity disrupts the immunometabolic balance in mice and derepresses sexually dimorphic oxidative stress responses in macrophages. This mechanism may contribute to the sex differences reported in cardiovascular disease and obesity in humans.