Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency.

BACKGROUND AND AIMS: To investigate the clinical features, ALDH5A1 gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency. MATERIALS AND METHODS: This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023. RESULTS: Thirteen patients (seven male and six female patients; two sibling sisters) had the symptoms aged from 1 month to 1 year. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain magnetic resonance imaging (MRI) showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among the 12 novel variants, three (c.85_116del, c.206_222dup, c.762C > G) were pathogenic variants; five (c.427delA, c.515G > A, c.637C > T, c.755G > T, c.1274T > C) were likely pathogenic; and the remaining four (c.454G > C, c.479C > T, c.1480G > A, c.1501G > C) were variants of uncertain significance. The patients received drugs such as L-carnitine, vigabatrin, and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction. CONCLUSIONS: A cohort of 13 cases with early-onset SSADH deficiency was analyzed. Onset of symptoms occurred from 1 month to 1 year of age. Twelve novel variants of the ALDH5A1 gene were identified.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Targeting TGFß receptor-mediated snail and twist: WSG, a polysaccharide from Ganoderma lucidum, and it-based dissolvable microneedle patch suppress melanoma cells.

Cutaneous melanoma is a lethal skin cancer variant with pronounced aggressiveness and metastatic potential. However, few targeted medications inhibit the progression of melanoma. Ganoderma lucidum, which is a type of mushroom, is widely used as a non-toxic alternative adjunct therapy for cancer patients. This study determines the effect of WSG, which is a water-soluble glucan that is derived from G. lucidum, on melanoma cells. The results show that WSG inhibits cell viability and the mobility of melanoma cells. WSG induces changes in the expression of epithelial-to-mesenchymal transition (EMT)-related markers. WSG also downregulates EMT-related transcription factors, Snail and Twist. Signal transduction assays show that WSG reduces the protein levels in transforming growth factor ß receptors (TGFßRs) and consequently inhibits the phosphorylation of intracellular signaling molecules, such as FAK, ERK1/2 and Smad2. An In vivo study shows that WSG suppresses melanoma growth in B16F10-bearing mice. To enhance transdermal drug delivery and prevent oxidation, two highly biocompatible compounds, polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), are used to synthesize a dissolvable microneedle patch that is loaded with WSG (MN-WSG). A functional assay shows that MN-WSG has an effect that is comparable to that of WSG alone. These results show that WSG has significant potential as a therapeutic agent for melanoma treatment. MN-WSG may allow groundbreaking therapeutic approaches and offers a novel method for delivering this potent compound effectively.

Pericytes in Alzheimer's disease: Key players and therapeutic targets.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that leads to progressive cognitive decline and neuropathological changes. Pericytes, which are vessel mural cells on the basement membrane of capillaries, play a crucial role in regulating cerebrovascular functions and maintaining neurovascular unit integrity. Emerging research substantiates the involvement of pericytes in AD. This review provides a comprehensive overview of pericytes, including their structure, origin, and markers and various functions within the central nervous system. Emphatically, the review explores the intricate mechanisms through which pericytes contribute to AD, including their interactions with amyloid beta and apolipoprotein E, as well as various signaling pathways. The review also highlights potential for targeted pericyte therapy for AD, with a focus on stem cell therapy and drug treatments. Future research directions include the classification of pericyte subtypes, studies related to aging, and the role of pericytes in exosome-related mechanisms in AD pathology. In conclusion, this review consolidates current knowledge on the pivotal roles of pericytes in AD and their potential as therapeutic targets, providing valuable insights for future research and clinical interventions aimed at addressing the impact of AD on patients' lives.

Functional and structural investigation of a broadly neutralizing SARS-CoV-2 antibody.

Since its emergence, SARS-CoV-2 has been continuously evolving, hampering the effectiveness of current vaccines against COVID-19. mAbs can be used to treat patients at risk of severe COVID-19. Thus, the development of broadly protective mAbs and an understanding of the underlying protective mechanisms are of great importance. Here, we isolated mAbs from donors with breakthrough infection with Omicron subvariants using a single-B cell screening platform. We identified a mAb, O5C2, which possesses broad-spectrum neutralization and antibody-dependent cell-mediated cytotoxic activities against SARS-CoV-2 variants, including EG.5.1. Single-particle analysis by cryo-electron microscopy revealed that O5C2 targeted an unusually large epitope within the receptor-binding domain of spike protein that overlapped with the angiotensin-converting enzyme 2 binding interface. Furthermore, O5C2 effectively protected against BA.5 Omicron infection in vivo by mediating changes in transcriptomes enriched in genes involved in apoptosis and interferon responses. Our findings provide insights into the development of pan-protective mAbs against SARS-CoV-2.

Dendrobium nobile Polysaccharide Attenuates Blue Light-Induced Injury in Retinal Cells and In Vivo in Drosophila.

Blue light is the higher-energy region of the visible spectrum. Excessive exposure to blue light is known to induce oxidative stress and is harmful to the eyes. The stems of Dendrobium nobile Lindl. (Orchidaceae), named Jinchaishihu, have long been used in traditional Chinese medicine (TCM) for nourishing yin, clearing heat, and brightening the eyes. The polysaccharide is one of the major components in D. nobile. However, the effect on ocular cells remains unclear. This study aimed to investigate whether the polysaccharide from D. nobile can protect the eyes from blue light-induced injury. A crude (DN-P) and a partially purified polysaccharide (DN-PP) from D. nobile were evaluated for their protective effects on blue light-induced damage in ARPE-19 and 661W cells. The in vivo study investigated the electroretinographic response and the expression of phototransduction-related genes in the retinas of a Drosophila model. The results showed that DN-P and DN-PP could improve blue light-induced damage in ARPE-19 and 661W cells, including cell viability, antioxidant activity, reactive oxygen species (ROS)/superoxide production, and reverse opsin 3 protein expression in a concentration-dependent manner. The in vivo study indicated that DN-P could alleviate eye damage and reverse the expression of phototransduction-related genes, including ninaE, norpA, Gαq, Gß76C, Gγ30A, TRP, and TRPL, in a dose-dependent manner in blue light-exposed Drosophila. In conclusion, this is the first report demonstrating that D. nobile polysaccharide pretreatment can protect retinal cells and retinal photoreceptors from blue light-induced damage. These results provide supporting evidence for the beneficial potential of D. nobile in preventing blue light-induced eye damage and improving eyesight.

Decoding the genome of bloodsucking midge Forcipomyia taiwana (Diptera: Ceratopogonidae): Insights into odorant receptor expansion.

Biting midges, notably those within the Ceratopogonidae family, have long been recognized for their epidemiological significance, both as nuisances and vectors for disease transmission in vertebrates. Despite their impact, genomic insights into these insects, particularly beyond the Culicoides genus, remain limited. In this study, we assembled the Forcipomyia taiwana (Shiraki) genome, comprising 113 scaffolds covering 130.4 Mbps-with the longest scaffold reaching 7.6 Mbps and an N50 value of 2.6 Mbps-marking a pivotal advancement in understanding the genetic architecture of ceratopogonid biting midges. Phylogenomic analyses reveal a shared ancestry between F. taiwana and Culicoides sonorensis Wirth & Jones, dating back approximately 124 million years, and highlight a dynamic history of gene family expansions and contractions within the Ceratopogonidae family. Notably, a substantial expansion of the odorant receptor (OR) gene family was observed, which is crucial for the chemosensory capabilities that govern biting midges' interactions with their environment, including host seeking and oviposition behaviors. The distribution of OR genes across the F. taiwana genome displays notable clusters on scaffolds, indicating localized tandem gene duplication events. Additionally, several collinear regions were identified, hinting at segmental duplications, inversions, and translocations, contributing to the olfactory system's evolutionary complexity. Among the 156 ORs identified in F. taiwana, 134 are biting midge-specific ORs, distributed across three distinct clades, each exhibiting unique motif features that distinguish them from the others. Through weighted gene co-expression network analysis, we correlated distinct gene modules with sex and reproductive status, laying the groundwork for future investigations into the interplay between gene expression and adaptive behaviors in F. taiwana. In conclusion, our study not only highlights the unique olfactory repertoire of ceratopogonid biting midges but also sets the stage for future studies into the genetic underpinnings of their unique biological traits and ecological strategies.

Associations between single and multiple dietary vitamins and the risk of periodontitis: results from NHANES 2009-2014.

Background: Periodontitis is a prevalent inflammatory periodontal disease that has an impact on the overall quality of life. Although several studies have indicated an association between individual vitamin intake and periodontitis risk, the associations of the multivitamins with periodontitis risk remain unclear. Aim: This study aimed to explore the joint effect of multivitamins (including vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and vitamin K) on periodontitis. Methods: For this cross-sectional study, data were collected from participants aged ≥ 30 years in the National Health and Nutrition Examination Surveys 2009-2014 (n = 9,820). We employed weighted multivariate logistic regression models to evaluate the single association between individual vitamin intakes and periodontitis, and Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and quantile g-computation (qgcomp) models to assess the joint effect of nine vitamins on periodontitis. Results: The overall prevalence of periodontitis was approximately 35.97%. After adjustment of covariates, vitamin B6 [odds ratio (OR) = 0.82, 95% confidence interval (CI): 0.72-0.94] and vitamin E (OR = 0.79, 95%CI: 0.69-0.92) were negatively related to the likelihood of developing periodontitis, respectively. The result of three models indicated that, mixture of vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, and vitamin K had a significant negative combined effect on the risk of periodontitis. In the BKMR model, when all remaining vitamins were at their median levels, the periodontitis risk decreased with increased concentration levels of vitamin E and vitamin B2. WQS analysis indicated the highest weighted chemical was vitamin E, followed by vitamin B12 and vitamin D. In the qgcomp model, vitamin E received the highest negative weights for the periodontitis risk, followed by vitamin B2 and vitamin D, respectively. Conclusion: Both dietary vitamin B6 and vitamin E were associated with decreased odds of periodontitis. Additionally, the mixture-exposed analyses consistently showed the negative correlations between nine dietary vitamins mixtures and periodontitis.

Interferon-Alpha Induces Psoriatic Inflammation in Mice by Phosphorylating FOXO3.

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.

The accumulation of active ingredients of Polygonatum cyrtonema Hua is associated with soil characteristics and bacterial community.

Introduction: With the increasing demand for health products derived from Polygonati rhizoma (PR), people begin to artificially plant Polygonatum cyrtonema Hua (P. cyrtonema) in the middle and lower reaches of the Yangtze River. To promote P. cyrtonema cultivation and increase farmers' income, efforts are needed to understand the ways to obtain high-quality PR under artificial cultivation conditions. Methods: Rhizomes of artificial planting P. cyrtonema and rhizosphere soils were collected across five regions in Zhejiang Province, China. Subsequently, the contents of the main active ingredients of P. cyrtonema and soil properties were analyzed, and both rhizosphere and endophytic bacteria of P. cyrtonema were detected by 16S rDNA sequencing. The relationship between the active ingredients and soil properties, and the dominant bacteria were investigated by correlation analysis. Results: The content of active ingredients of P. cyrtonema from the five regions varied significantly, especially polysaccharides and saponins. High-throughput sequencing demonstrated that Proteobacteria was the dominant bacterial phylum in all samples, and Burkholderia-Caballeronia-Paraburkholderia was the main endophytic bacterial genus in rhizome. In addition, the bacterial diversity and richness of rhizosphere soil samples were higher than those of rhizome samples. Soil physicochemical properties and enzyme activities were significantly different across regions, leading to notable variations in the community structures of rhizosphere and endophytic bacteria. Redundancy analysis (RDA) displayed that pH and urease (UE) were the major factors altering shifting rhizosphere bacteria community structure. Moreover, the composition and diversity of rhizome endophytic bacteria were principally affected by both soil physicochemical properties and soil enzyme activities. Soil properties and bacteria from rhizosphere soil and rhizome had a considerable impact on certain active ingredients in P. cyrtonema under artificial cultivation conditions after Pearson correlation analysis. Polysaccharides were significantly correlated with nutrient-rich soil and endophytic bacteria, such as Burkholderia-Caballeronia-Paraburkholderia, Pseudomonas, Ralstonia, and Bacillus. However, flavonoids were associated with nutrient-poor soil. Saponins were positively correlated with OM and available phosphorous (AP) and were significantly negatively affected by rhizosphere bacterial communities. Conclusion: The study demonstrated that bacterial microorganisms were involved in the accumulation of active ingredients of P. cyrtonema together with soil physicochemical properties and enzyme activities, which provided a theoretical basis for the scientific and effective artificial cultivation of high-quality P. cyrtonema.

Spatiotemporal drivers of urban water pollution: Assessment of 102 cities across the Yangtze River Basin.

Effective management of large basins necessitates pinpointing the spatial and temporal drivers of primary index exceedances and urban risk factors, offering crucial insights for basin administrators. Yet, comprehensive examinations of multiple pollutants within the Yangtze River Basin remain scarce. Here we introduce a pollution inventory for urban clusters surrounding the Yangtze River Basin, analyzing water quality data from 102 cities during 2018-2019. We assessed the exceedance rates for six pivotal indicators: dissolved oxygen (DO), ammonia nitrogen (NH3-N), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total phosphorus (TP), and the permanganate index (CODMn) for each city. Employing random forest regression and SHapley Additive exPlanations (SHAP) analyses, we identified the spatiotemporal factors influencing these key indicators. Our results highlight agricultural activities as the primary contributors to the exceedance of all six indicators, thus pinpointing them as the leading pollution source in the basin. Additionally, forest coverage, livestock farming, chemical and pharmaceutical sectors, along with meteorological elements like precipitation and temperature, significantly impacted various indicators' exceedances. Furthermore, we delineate five core urban risk components through principal component analysis, which are (1) anthropogenic and industrial activities, (2) agricultural practices and forest extent, (3) climatic variables, (4) livestock rearing, and (5) principal polluting sectors. The cities were subsequently evaluated and categorized based on these risk components, incorporating policy interventions and administrative performance within each region. The comprehensive analysis advocates for a customized strategy in addressing the discerned risk factors, especially for cities presenting elevated risk levels.

Understanding Health Care Provider Burnout When Caring for Patients With Refractory Epilepsy in the United States.

Background and Objectives: Among health care providers (HCPs), neurologists have one of the highest rates of burnout in the United States, compromising the quality and accessibility of patient care. Patients with refractory epilepsy are especially challenging to treat. This study aims to understand the burnout level in neurologists treating patients with refractory epilepsy and identify key contributing factors. Methods: US board-certified pediatric/adult neurologists who devote ≥50% of their time to clinical practice and treat ≥10 unique patients with refractory epilepsy annually were invited to take a noninterventional quantitative survey, designed to capture key elements of the HCP's background, burnout level, current practice, burden domains, and satisfaction with current antiseizure medications (ASMs). Burnout in 3 domains (emotional exhaustion, depersonalization, and personal accomplishment) was assessed by the validated Maslach Burnout Inventory-Human Services Survey. Results: From March 11, 2022, to April 10, 2022, a total of 138 neurology-specialist HCPs participated in the survey, divided between adult epileptologists (n = 44), adult neurologists (n = 41), pediatric epileptologists (n = 36), and pediatric neurologists (n = 17). Of participating HCPs, 61% experienced at least some burnout (≥1 of 3 burnout domains categorized as high), and 4% experienced high burnout (3 of 3 burnout domains categorized as high). High burnout levels were driven by high pediatric and inpatient caseloads and unexpected pediatric patient reluctance to transition to adult care. HCPs with high burnout had a higher yearly caseload of patients with refractory epilepsy. Most HCPs (approximately 90%) indicated that patients with refractory epilepsy were more difficult to manage than those with nonrefractory epilepsy. The proportion of HCPs satisfied or extremely satisfied with ASMs was lower for patients with refractory epilepsy (20%) than that for patients with nonrefractory epilepsy (73%). Dissatisfaction was mostly due to workload and latency of the insurance approval process, out-of-pocket costs, and poor efficacy, safety, and tolerability. For 32% of HCPs, stopping practicing or moving to another practice within 5 years was probable or very probable. Discussion: Some burnout is common among HCPs who treat patients with refractory epilepsy. However, management of refractory epilepsy is challenging, and satisfaction with available ASMs is low. Thus, addressing these contributing factors may help to alleviate HCP burnout.

Mitochondrial dynamics dysfunction: Unraveling the hidden link to depression.

Depression is a common mental disorder and its pathogenesis is not fully understood. However, more and more evidence shows that mitochondrial dynamics dysfunction may play an important role in the occurrence and development of depression. Mitochondria are the centre of energy production in cells, and are also involved in important processes such as apoptosis and oxidative stress. Studies have found that there are abnormalities in mitochondrial function in patients with depression, including mitochondrial morphological changes, mitochondrial dynamics disorders, mitochondrial DNA damage, and impaired mitochondrial respiratory chain function. These abnormalities may cause excessive free radicals and oxidative stress in mitochondria, which further damage cells and affect the balance of neurotransmitters, causing or aggravating depressive symptoms. Studies have shown that mitochondrial dynamics dysfunction may participate in the occurrence and development of depression by affecting neuroplasticity, inflammation and neurotransmitters. This article reviews the effects of mitochondrial dynamics dysfunction on the pathogenesis of depression and its potential molecular pathway. The restorers for the treatment of depression by regulating the function of mitochondrial dynamics were summarized and the possibility of using mitochondrial dynamics as a biomarker of depression was discussed.

KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer's disease.

BACKGROUND: Epidemiological studies have revealed a correlation between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D). Insulin resistance in the brain is a common feature in patients with T2D and AD. KAT7 is a histone acetyltransferase that participates in the modulation of various genes. AIM: To determine the effects of KAT7 on insulin patients with AD. METHODS: APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes, respectively. An in vitro model of AD was established by Aß stimulation. Insulin resistance was induced by chronic stimulation with high insulin levels. The expression of microtubule-associated protein 2 (MAP2) was assessed using immunofluorescence. The protein levels of MAP2, Aß, dual-specificity tyrosine phosphorylation-regulated kinase-1A (DYRK1A), IRS-1, p-AKT, total AKT, p-GSK3ß, total GSK3ß, DYRK1A, and KAT7 were measured via western blotting. Accumulation of reactive oxygen species (ROS), malondialdehyde (MDA), and SOD activity was measured to determine cellular oxidative stress. Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation, respectively. Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR. A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A. RESULTS: KAT7 expression was suppressed in the AD mice. Overexpression of KAT7 decreased Aß accumulation and MAP2 expression in AD brains. KAT7 overexpression decreased ROS and MDA levels, elevated SOD activity in brain tissues and neurons, and simultaneously suppressed neuronal apoptosis. KAT7 upregulated levels of p-AKT and p-GSK3ß to alleviate insulin resistance, along with elevated expression of DYRK1A. KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A. HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion. CONCLUSION: We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation. Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.

Rh family C glycoprotein contributes to psoriatic inflammation through regulating the dysdifferentiation and cytokine secretion of keratinocytes.

BACKGROUND: Keratinocyte dysdifferentiation and proinflammatory cytokine production play a central role in psoriatic inflammation. According to recent studies, the Rh family C glycoprotein (RHCG) enhances cell proliferation and disrupts cell differentiation. However, the specific role of RHCG psoriasis development remains unclear. OBJECTIVE: We here explored the effect of RHCG on keratinocytes under psoriatic inflammation. METHODS: The cell counting kit­8 assay was conducted to assess proliferation. RHCG protein expression was assessed through western blotting and enzyme-linked immunosorbent assays. The expression of proinflammatory cytokines and differentiation markers was analyzed through a quantitative reverse-transcription polymerase chain reaction. RESULTS: Both RHCG mRNA and protein levels increased in psoriatic skin. Notably, cultured keratinocytes treated with an M5 cocktail, which mimics psoriatic inflammation, exhibited higher RHCG expression. Furthermore, RHCG overexpression promoted keratinocyte proliferation, accompanied by an increase in the production of interleukin (IL)-1ß, IL-6, and IL-8, and tumor necrosis factor-α. RHCG overexpression also resulted in higher expression of keratin 17, a differentiation marker. Conversely, RHCG gene knockdown reduced keratinocyte proliferation and cytokine secretion. RHCG inhibition in cells recovered both keratin 1 and loricrin expression. Additionally, RHCG overexpression facilitated the phosphorylation of nuclear factor-kappa B and extracellular signal-regulated protein kinase signaling pathways. Importantly, when these signaling pathways were inhibited, the effect of RHCG on keratinocytes was attenuated. CONCLUSION: These findings support the substantial role of RHCG in psoriatic inflammation development and suggest that RHCG serves as a potential target for psoriasis treatment.

Effective separation of maslinic acid and oleanolic acid from olive pomace using high-speed shear off-line coupled with high-speed countercurrent chromatography and their antibacterial activity test.

In this work, a high-speed shear extraction off-line coupling high-speed countercurrent chromatography method was developed to separate maslinic acid and oleanolic acid from olive pomace. To improve extraction efficiency, the polar disparity between maslinic acid and oleanolic acid necessitated the concurrent utilization of both polar and non-polar solvents during high-speed shear extraction. Then, the high-speed shear extraction was directly feed to high-speed countercurrent chromatography for subsequently separation. A total of 250 min were needed to complete the extraction and separation process. This yielded two molecules from 3.3 g of defatted olive pomace: 7.2 mg of 93.8 % pure maslinic acid and 2.3 mg of 90.1 % pure oleanolic acid, both determined by HPLC at 210 nm. Furthermore, the compounds exhibited inhibitory activity against Escherichia coli and Staphylococcus aureus. At a concentration of 100 µg/mL, its efficacy in inhibiting hyaluronidase was comparable to that of the standard drug indomethacin. Compared with the conventional separation method, this coupled technique reduced the whole time due to the direct injection of sample extraction solution. This technique provides a useful approach for the separation of natural products with significant polarity differences.

Gene variants and clinical characteristics of children with sitosterolemia.

OBJECTIVE: To enhance the detection, management and monitoring of Chinese children afflicted with sitosterolemia by examining the physical characteristics and genetic makeup of pediatric patients. METHODS: In this group, 26 children were diagnosed with sitosterolemia, 24 of whom underwent genetic analysis. Patient family medical history, physical symptoms, tests for liver function, lipid levels, standard blood tests, phytosterol levels, cardiac/carotid artery ultrasounds, fundus examinations, and treatment were collected. RESULTS: The majority (19, 73.1%) of the 26 patients exhibited xanthomas as the most prevalent manifestation. The second most common symptoms were joint pain (7, 26.9%) and stunted growth (4, 15.4%). Among the 24 (92.3%) patients whose genetics were analyzed, 16 (66.7%) harbored ABCG5 variants (type 2 sitosterolemia), and nearly one-third (8, 33.3%) harbored ABCG8 variants (type 1 sitosterolemia). Additionally, the most common pathogenic ABCG5 variant was c.1166G > A (p.Arg389His), which was found in 10 patients (66.7%). Further analysis did not indicate any significant differences in pathological traits among those carrying ABCG5 and ABCG8 variations (P > 0.05). Interestingly, there was a greater abundance of nonsense variations in ABCG5 than in ABCG8 (P = 0.09), and a greater frequency of splicing variations in ABCG8 than ABCG5 (P = 0.01). Following a change in diet or a combination of ezetimibe, the levels of cholesterol and low-density lipoprotein were markedly decreased compared to the levels reported before treatment. CONCLUSION: Sitosterolemia should be considered for individuals presenting with xanthomas and increased cholesterol levels. Phytosterol testing and genetic analysis are important for early detection. Managing one's diet and taking ezetimibe can well control blood lipids.

Effect of short-term nitrogen deposition on dry-wet seasonal variation of soil respiration in degraded Poa pratensis alpine meadow of the Napahai, Yunnan, China.

To explore the coupling of dry-wet seasonal variations of soil respiration with their environmental factors in the alpine meadow under the background of increasing nitrogen (N) deposition, we conducted an experiment in the typical degraded Poa pratensis meadow in the Napahai, Yunnan. There were four treatments, i.e., control (0 g·m-2·a-1), low (5 g·m-2·a-1), medium (10 g·m-2·a-1), and high (15 g·m-2·a-1) levels. We examined the effects of aboveground biomass, plant diversity, and soil physicochemical properties on soil respiration. The results showed that N deposition significantly promoted soil respiration. Compared with that in the control, soil respiration rates increased by 21.9%-53.9% and 27.3%-51.2% in dry and wet seasons, respectively. The maximum value of soil respiration rate was recorded in the medium N treatment. N deposition dramatically elevated aboveground biomass (52.2%-66.4%). Plant diversity declined with increasing N addition levels, with the maximum value (13.5%-24.2%) being recorded in high treatment in wet season. The values of ammonium nitrogen, organic matter, microbial biomass carbon and nitrogen, temperature and moisture in the three N treatments were elevated by 14.3%-333.5% compared with the control, while those of soil pH were decreased by 9.0%-34.6%. Results of the structural equation modelling showed that plant biomass, Shannon diversity, microbial biomass, soil temperature, and moisture showed a positive effect on soil respiration, while bulk density had a negative effect. Soil nitrogen pool and pH were main factors driving soil CO2 emissions, accounting for 55.7% and 45.1% of the variations, respectively. Therefore, short-term atmospheric N deposition stimulated soil respiration primarily via altering soil pH and nitrogen pool components in the degraded alpine meadow.

Dual regulation of cytochrome P450 gene expression by two distinct small RNAs, a novel tasiRNA and miRNA, in Marchantia polymorpha.

The miR390-derived TAS3 trans-acting short-interfering RNAs (tasiRNAs) module represents a conserved RNA silencing pathway in the plant kingdom; however, its characterization in the bryophyte Marchantia polymorpha is limited. This study elucidated that MpDCL4 processes MpTAS3 double-stranded RNA (dsRNA) to generate tasiRNAs, primarily from the 5'- and 3'-ends of dsRNA. Notably, we discovered a novel tasiRNA, tasi78A, can negatively regulate a cytochrome P450 gene, MpCYP78A101. Additionally, tasi78A was abundant in MpAGO1, and transient expression assays underscored the role of tasi78A in repressing MpCYP78A101. A microRNA, miR11700, also regulates MpCYP78A101 expression. This coordinate regulation suggests a role in modulating auxin signaling at apical notches of gemma, influencing the growth and sexual organ development of M. polymorpha and emphasizing the significance of RNA silencing in MpCYP78A101 regulation. However, phylogenetic analysis identified another paralog of the CYP78 family, Mp1g14150, which may have a redundant role with MpCYP78A101, explaining the absence of noticeable morphological changes in loss-of-function plants. Taken together, our findings provide new insights into the combined regulatory roles of miR390/MpTAS3/miR11700 in controlling MpCYP78A101 and expand our knowledge about the biogenesis and regulation of tasiRNAs in M. polymorpha.