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.

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.

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.

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.

[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.

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.

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.

Mental health issues in parents of children with autism spectrum disorder: A multi-time-point study related to COVID-19 pandemic.

Given the unpredictability and challenges brought about by the 2019 novel coronavirus (COVID-19) pandemic, this study aimed to investigate the impact trend of the prolonged pandemic on the mental health of parents of children with autism spectrum disorder (ASD). The 8112 participants included parents of children with ASD and parents of typically developing (TD) children at two sites (Heilongjiang and Fujian province, China). The parents completed a set of self-report questionnaires covering demographic characteristics, influences related to COVID-19, COVID-19 concerns and perceived behaviors, as well as the Connor-Davidson resilience scale (CD-RISC), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) by means of an online survey platform. Data were collected by three cross-sectional surveys carried out in April 2020 (Time 1), October 2020 (Time 2), and October 2021 (Time 3). The results of quantitative and qualitative comparisons showed that: (i) parents of children with ASD had lower levels of resilience, and more symptoms of anxiety and depression than parents of TD children at each time point (all P < 0.05); and (ii) there were significant time-cumulative changes in resilience, anxiety, and depression among all participants (all P < 0.05). The logistic regression analyzes after adjusting for demographic characteristics revealed that the following factors were significantly associated with poor resilience and a higher rate of anxiety and depression in parents of children with ASD: time-point, the effect of COVID-19 on children's emotions and parents' emotions, changes in relationships, changes in physical exercise, changes in daily diet during the COVID-19 pandemic, and COVID-19-related psychological distress. In conclusions, the parents did not report improvements in resilience, anxiety, or depression symptoms from Time 1 to Time 2 or 3, indicating that cumulative mental health issues increased when, surprisingly, the COVID-19 restrictions were eased. The psychological harm resulting from the COVID-19 pandemic is far-reaching, especially among parents of children with ASD.

Three types of genes underlying the Gametophyte factor1 locus cause unilateral cross incompatibility in maize.

Unilateral cross incompatibility (UCI) occurs between popcorn and dent corn, and represents a critical step towards speciation. It has been reported that ZmGa1P, encoding a pectin methylesterase (PME), is a male determinant of the Ga1 locus. However, the female determinant and the genetic relationship between male and female determinants at this locus are unclear. Here, we report three different types, a total of seven linked genes underlying the Ga1 locus, which control UCI phenotype by independently affecting pollen tube growth in both antagonistic and synergistic manners. These include five pollen-expressed PME genes (ZmGa1Ps-m), a silk-expressed PME gene (ZmPME3), and another silk-expressed gene (ZmPRP3), encoding a pathogenesis-related (PR) proteins. ZmGa1Ps-m confer pollen compatibility. Presence of ZmPME3 causes silk to reject incompatible pollen. ZmPRP3 promotes incompatibility pollen tube growth and thereby breaks the blocking effect of ZmPME3. In addition, evolutionary genomics analyses suggest that the divergence of the Ga1 locus existed before maize domestication and continued during breeding improvement. The knowledge gained here deepen our understanding of the complex regulation of cross incompatibility.

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.

Electrophysiological and Proarrhythmic Effects of Hydroxychloroquine Challenge in Guinea-Pig Hearts.

Hydroxychloroquine (HCQ), clinically established in antimalarial and autoimmune therapy, recently raised cardiac arrhythmogenic concerns when used alone or with azithromycin (HCQ+AZM) in Covid-19. We report complementary, experimental, studies of its electrophysiological effects. In patch clamped HEK293 cells expressing human cardiac ion channels, HCQ inhibited IKr and IK1 at a therapeutic concentrations (IC50s: 10 ± 0.6 and 34 ± 5.0 µM). INa and ICaL showed higher IC50s; Ito and IKs were unaffected. AZM slightly inhibited INa, ICaL, IKs, and IKr, sparing IK1 and Ito. (HCQ+AZM) inhibited IKr and IK1 (IC50s: 7.7 ± 0.8 and 30.4 ± 3.0 µM), sparing INa, ICaL, and Ito. Molecular induced-fit docking modeling confirmed potential HCQ-hERG but weak AZM-hERG binding. Effects of µM-HCQ were studied in isolated perfused guinea-pig hearts by multielectrode, optical RH237 voltage, and Rhod-2 mapping. These revealed reversibly reduced left atrial and ventricular action potential (AP) conduction velocities increasing their heterogeneities, increased AP durations (APDs), and increased durations and dispersions of intracellular [Ca2+] transients, respectively. Hearts also became bradycardic with increased electrocardiographic PR and QRS durations. The (HCQ+AZM) combination accentuated these effects. Contrastingly, (HCQ+AZM) and not HCQ alone disrupted AP propagation, inducing alternans and torsadogenic-like episodes on voltage mapping during forced pacing. O'Hara-Rudy modeling showed that the observed IKr and IK1 effects explained the APD alterations and the consequently prolonged Ca2+ transients. The latter might then downregulate INa, reducing AP conduction velocity through recently reported INa downregulation by cytosolic [Ca2+] in a novel scheme for drug action. The findings may thus prompt future investigations of HCQ's cardiac safety under particular, chronic and acute, clinical situations.

Expression Level, Correlation, and Diagnostic Value of Serum miR-127 in Patients with Acute Respiratory Distress Syndrome.

OBJECTIVE: To analyze the expression of miR-127 in the serum of patients with acute respiratory distress syndrome (ARDS) and to explore its correlation with the severity of ARDS patients and its value as a molecular marker for diagnosis of ARDS. METHODS: 70 patients with ARDS admitted to our hospital from September 2017 to September 2019 were selected as the observation group, and 60 healthy persons with physical examination were collected as the control group. RT-PCR was used to detect the serum miR-127 levels of all subjects, and the serum miR-127 levels of the observation group and control group were compared. The oxygenation index (PaO2/FiO2) of ARDS patients was recorded and divided into three subgroups: mild group, moderate group, and severe group. Serum miR-127 levels of patients in the mild group, moderate group, and severe group were compared. Pearson correlation was used to analyze the relationship between serum miR-127 levels and the severity of ARDS patients. The receiver operating characteristic curve (ROC) was drawn, and the area under the ROC curve (AUC) was used to evaluate the diagnostic value of miR-127 in patients with ARDS. RESULTS: The serum level of miR-127 (10.15 ± 1.03) in the observation group was significantly higher than that in the control group (3.09 ± 0.62). And in the three subgroups of mild, moderate, and severe, the serum miR-127 level in the moderate group (10.43 ± 0.71) and the severe group miR-127 level (11.05 ± 1.26) were significantly higher than those in the mild group level (9.38 ± 1.24). Pearson correlation analysis showed that the serum miR-127 level was negatively correlated with PaO2/FiO2 (r = -0.715, P < 0.05), that is, the serum miR-127 level was positively correlated with the severity of ARDS patients. The area under the curve (AUC) of the diagnostic value of serum miR-127 for ARDS was 0.732 (95% CI 0.607-0.858). When the optimal cutoff value was 0.380, the sensitivity was 59.1% and the specificity was 78.6%, which suggested that miR-127 can be used as a marker for ARDS diagnosis. CONCLUSION: There is an increase in miR-127 levels in the serum of ARDS patients. The serum miR-127 level is positively correlated with the severity of ARDS. The higher the level of miR-127, the worse the condition of ARDS, which is positively correlated with the severity of the condition. It suggests that the serum miR-127 level is an important indicator for evaluating the severity of ARDS patients. It can be used as a molecular marker for clinical diagnosis of ARDS.

Ursolic Acid and Related Analogues: Triterpenoids with Broad Health Benefits.

Ursolic acid (UA) is a well-studied natural pentacyclic triterpenoid found in herbs, fruit and a number of traditional Chinese medicinal plants. UA has a broad range of biological activities and numerous potential health benefits. In this review, we summarize the current data on the bioavailability and pharmacokinetics of UA and review the literature on the biological activities of UA and its closest analogues in the context of inflammation, metabolic diseases, including liver and kidney diseases, obesity and diabetes, cardiovascular diseases, cancer, and neurological disorders. We end with a brief overview of UA's main analogues with a special focus on a newly discovered naturally occurring analogue with intriguing biological properties and potential health benefits, 23-hydroxy ursolic acid.

Therapeutic Opportunities of Interleukin-33 in the Central Nervous System.

Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is involved in various diseases. IL-33 exerts its effects via its heterodimeric receptor complex, which comprises suppression of tumorigenicity 2 (ST2) and the IL-1 receptor accessory protein (IL-1RAP). Increasing evidence has demonstrated that IL-33/ST2 signaling plays diverse but crucial roles in the homeostasis of the central nervous system (CNS) and the pathogenesis of CNS diseases, including neurodegenerative diseases, cerebrovascular diseases, infection, trauma, and ischemic stroke. In the current review, we focus on the functional roles and cellular signaling mechanisms of IL-33 in the CNS and evaluate the potential for diagnostic and therapeutic applications.

Inhibition of myeloid HDAC2 upregulates glutaredoxin 1 expression, improves protein thiol redox state and protects against high-calorie diet-induced monocyte dysfunction and atherosclerosis.

BACKGROUND AND AIMS: The thiol transferase glutaredoxin 1 controls redox signaling and cellular functions by regulating the S-glutathionylation status of critical protein thiols. Here we tested the hypothesis that by derepressing the expression of glutaredoxin 1, inhibition of histone deacetylase 2 prevents nutrient stress-induced protein S-glutathionylation and monocyte dysfunction and protects against atherosclerosis. METHODS: Using both a pharmacological inhibitor and shRNA-mediated knockdown of histone deacetylase 2, we determine the role of this deacetylase on glutaredoxin 1 expression and nutrient stress-induced inactivation of mitogen-activated protein kinase phosphatase 1 activity and monocyte and macrophage dysfunction. To assess whether histone deacetylase 2 inhibition in myeloid cells protects against atherosclerosis, we fed eight-week-old female and male HDAC2-/-MyeloidLDLR-/- mice and age and sex-matched LysMcretg/wtLDLR-/- control mice a high-calorie diet for 12 weeks and assessed monocyte function and atherosclerotic lesion size. RESULTS: Myeloid histone deacetylase 2 deficiency in high-calorie diet-fed LDLR-/- mice reduced atherosclerosis in males by 39% without affecting plasma lipid and lipoprotein profiles or blood glucose levels but had no effect on atherogenesis in female mice. Macrophage content in plaques of male mice was reduced by 31%. Histone deacetylase 2-deficient blood monocytes from male mice showed increased acetylation on histone 3, and increased Grx1 expression, and was associated with increased MKP-1 activity and reduced recruitment of monocyte-derived macrophages, whereas in females, myeloid HDAC2 deficiency had no effect on Grx1 expression, did not prevent nutrient stress-induced loss of MKP-1 activity in monocytes and was not atheroprotective. CONCLUSIONS: Specific histone deacetylase 2 inhibitors may represent a potential novel therapeutic strategy for the prevention and treatment of atherosclerosis, but any benefits may be sexually dimorphic.

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.

Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder.

Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system-endogenous cannabinoids, their receptors and associated enzymes-in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg-1, which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD 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.