Cold atmospheric plasma therapy for Malassezia folliculitis: Laboratory investigations and a randomized clinical trial.

BACKGROUND: Current treatment options for Malassezia folliculitis (MF) are limited. Recent research has demonstrated the inhibitory effect of cold atmospheric plasma (CAP) on the growth of Malassezia pachydermatis in vitro, suggesting CAP as a potential therapeutic approach for managing MF. OBJECTIVES: The objective of our study is to assess the in vitro antifungal susceptibility of Malassezia yeasts to CAP. Additionally, we aim to evaluate the efficacy and tolerability of CAP in treating patients with MF. METHODS: We initially studied the antifungal effect of CAP on planktonic and biofilm forms of Malassezia yeasts, using well-established techniques such as zone of inhibition, transmission electron microscopy, colony count assay and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt assay. Subsequently, a randomized (1:1 ratio), active comparator-controlled, observer-blind study was conducted comparing daily CAP therapy versus itraconazole 200 mg/day for 2 weeks in 50 patients with MF. Efficacy outcomes were measured by success rate, negative microscopy rate and changes in Dermatology Life Quality Index (DLQI) and Global Aesthetic Improvement Scale (GAIS) scores. Safety was assessed by monitoring adverse events (AEs) and local tolerability. RESULTS: In laboratory investigations, CAP time-dependently inhibited the growth of Malassezia yeasts in both planktonic and biofilm forms. Forty-nine patients completed the clinical study. At week 2, success was achieved by 40.0% of subjects in the CAP group versus 58.3% in the itraconazole group (p = 0.199). The negative direct microscopy rates of follicular samples were 56.0% in the CAP group versus 66.7% in the itraconazole group (p = 0.444). No significant differences were found in the proportion of subjects achieving DLQI scores of 0/1 (p = 0.456) or in the GAIS responder rates (p = 0.588) between the two groups. Three patients in the CAP group and one patient in the itraconazole group reported mild AEs. CONCLUSION: CAP demonstrated significant antifungal activity against Malassezia yeasts in vitro and exhibited comparable efficacy to itraconazole in treating MF patients. Without the associated adverse effects of oral antifungal drugs, CAP can be considered a promising and safe treatment modality for MF.

Mobile phone short video use negatively impacts attention functions: an EEG study.

The pervasive nature of short-form video platforms has seamlessly integrated into daily routines, yet it is important to recognize their potential adverse effects on both physical and mental health. Prior research has identified a detrimental impact of excessive short-form video consumption on attentional behavior, but the underlying neural mechanisms remain unexplored. In the current study, we aimed to investigate the effect of short-form video use on attentional functions, measured through the attention network test (ANT). A total of 48 participants, consisting of 35 females and 13 males, with a mean age of 21.8 years, were recruited. The mobile phone short video addiction tendency questionnaire (MPSVATQ) and self-control scale (SCS) were conducted to assess the short video usage behavior and self-control ability. Electroencephalogram (EEG) data were recorded during the completion of the ANT task. The correlation analysis showed a significant negative relationship between MPSVATQ and theta power index reflecting the executive control in the prefrontal region (r = -0.395, p = 0.007), this result was not observed by using theta power index of the resting-state EEG data. Furthermore, a significant negative correlation was identified between MPSVATQ and SCS outcomes (r = -0.320, p = 0.026). These results suggest that an increased tendency toward mobile phone short video addiction could negatively impact self-control and diminish executive control within the realm of attentional functions. This study sheds light on the adverse consequences stemming from short video consumption and underscores the importance of developing interventions to mitigate short video addiction.

The COVID-19 Vaccines Evaluation Program: Implementation, Management, and Experiences, 2021-2023.

In 2021, China's domestically produced coronavirus disease 2019 (COVID-19) vaccines received approval from regulatory bodies and were administered worldwide. Due to a low number of infections within China during that period, it became imperative to evaluate the vaccines' real-world effectiveness through international studies. To facilitate this, China CDC launched the COVID-19 Vaccines Evaluation Program (COVEP). This program formed research collaboration agreements with health institutes across five World Health Organization regions, addressing key questions about vaccine performance through ten cooperative agreements. The findings from COVEP projects reinforced confidence, both domestically and globally, in the effectiveness of the vaccines produced in China. Moreover, the outcomes observed internationally were frequently mirrored by later studies conducted within China. COVEP thus pioneered a novel approach for fostering cross-national research collaborations, addressing significant public health issues and exemplifying a framework for international cooperation. This approach is in line with the strategic objectives and other development efforts of China CDC's national disease control and prevention initiatives.

Nano-ZnO-modified hydroxyapatite whiskers with enhanced osteoinductivity for bone defect repair.

Hydroxyapatite (HA) whisker (HAw) represents a distinct form of HA characterized by its high aspect ratio, offering significant potential for enhancing the mechanical properties of bone tissue engineering scaffolds. However, the limited osteoinductivity of HAw hampers its widespread application. In this investigation, we observed HAw-punctured osteoblast membranes and infiltrated the cell body, resulting in mechanical damage to cells that adversely impacted osteoblast proliferation and differentiation. To address this challenge, we developed nano-zinc oxide particle-modified HAw (nano-ZnO/HAw). Acting as a reinforcing and toughening agent, nano-ZnO/HAw augmented the compressive strength and ductility of the matrix materials. At the same time, the surface modification with nano-ZnO particles improved osteoblast differentiation by reducing the mechanical damage from HAw to cells and releasing zinc ion, the two aspects collectively promoted the osteoinductivity of HAw. Encouragingly, the osteoinductive potential of 5% nano-ZnO/HAw and 10% nano-ZnO/HAw was validated in relevant rat models, demonstrating the efficacy of this approach in promoting new bone formation in vivo. Our findings underscore the role of nano-ZnO particle surface modification in enhancing the osteoinductivity of HAw from a physical standpoint, offering valuable insights into the development of bone substitutes with favorable osteoinductive properties while simultaneously bolstering matrix material strength and toughness.

An analysis combining proteomics and transcriptomics revealed a regulation target of sea cucumber autolysis.

Sea cucumber is a valuable seafood product and autolysis is the main concern for the aquaculture industry. This study employed proteomics and transcriptomics to investigate the autolysis mechanism of sea cucumbers. The fresh sea cucumber was exposed to UV light to induce autolysis. The body wall samples were cut off to analyze by proteomics and transcriptomics. The angiotensin-converting enzyme (ACE) inhibitor of teprotide and the activator of imatinib were gastric gavage to live sea cucumbers, respectively, to identify the regulation target. Autolysis occurrence was evaluated by appearance, soluble peptide, and hydroxyproline content. Four gene-protein pairs were ACE, AJAP10923, Heme-binding protein 2-like, and Ficolin-2-like. Only the ACE protein and gene changed synchronously and a significant down-regulation of ACE occurred in the autolysis sea cucumbers. Teprotide led to a 1.58-fold increase in the TCA-soluble protein content and a 1.57-fold increase in hydroxyproline content. No significant differences were observed between imatinib-treated sea cucumbers and fresh ones regarding TCA-soluble protein content or hydroxyproline levels (P > 0.05). ACE inhibitor accelerated the autolysis of sea cucumber, but ACE activator inhibited the autolysis. Therefore, ACE can serve as a regulatory target for autolysis in sea cucumbers.

Experimental study of the biological properties of nmHA-SiO2 fiber materials prepared by electrospinning technology.

To study the biocompatibility of nanohydroxyapatite (nmHA)-SiO2 fiber material and its efficacy in guided bone regeneration. ① The cytotoxicity of the nmHA-SiO2 fiber material to MC3T3-E1 cells was determined by CCK-8 assay. The adhesion of cells on the surface of the material was observed. ② Bone defects were prepared in the skull of three groups of New Zealand white rabbits. The following treatments were administered: implantation of nmHA-SiO2, implantation of Bio-Oss, and no treatment. The defects were then covered with nmHA-SiO2 membrane or Hai'ao oral repair membrane. Animal samples were analyzed by gross observation, micro-computed tomography, hematoxylin-eosin staining and Masson staining. The data were statistically analyzed by multivariate analysis of variance to evaluate the repair of bone defects. ① The nmHA-SiO2 fiber material has suitable biocompatibility. ② The nmHA-SiO2 fiber material performed more effectively as a barrier membrane than other bone substitute materials in GBR model rabbits.

Synthesis and biological evaluation of chrysin derivatives containing α-lipoic acid for the treatment of inflammatory bowel disease.

This study introduces newly discovered chrysin derivatives that show potential as candidate molecules for treating inflammatory bowel disease (IBD). Compound 4b, among the synthesized compounds, displayed significant inhibitory effects on monocyte adhesion to colon epithelium induced by TNF-α, with an IC50 value of 4.71 µM. Further mechanistic studies demonstrated that 4b inhibits the production of reactive oxygen species (ROS) and downregulates the expression of ICAM-1 and MCP-1, key molecules involved in monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. In vivo experiments have shown that compound 4b exhibits a dose-dependent inhibition of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, thereby validating its effectiveness as a colitis inhibitor in animal models. These results indicate that 4b shows considerable promise as a therapeutic agent for managing IBD.

Structural characterization of sphingomyelins from tissue using electron-induced dissociation.

RATIONALE: Sphingomyelins (SMs) and resulting metabolic products serve important functional and cell signaling roles and can act as potential biomarkers and therapeutic targets in many pathological disorders. SMs each contain a sphingoid base, an amide-linked fatty acyl chain, and a phosphocholine headgroup. Despite these simple building blocks, variations and modifications of both the sphingoid base and the fatty acyl chain result in a diverse array of structurally complicated SM compounds. Conventional tandem mass spectrometry (MS/MS) using the collision-induced dissociation (CID) method only provides limited structural information, necessitating other tools to unravel the structural complexity of these lipids. METHODS: We utilize electron-induced dissociation (EID) and sequential CID/EID approaches to elucidate detailed structural features of SMs. Integrating the CID/EID method into an imaging MS workflow enables accurate identification of SMs directly from kidney tissue. RESULTS: The application of EID enables identification of SMs at the molecular species level, identifying the sphingosine base and the amide-linked fatty acyl chains. Furthermore, removal of the phosphocholine headgroup via CID followed by sequential EID in an MS3 analysis (CID/EID) enhances the structural information obtained. CID/EID provides diagnostic fragmentation patterns revealing the hydroxylation site and double bond position in both the sphingosine base and amide-linked fatty acyl chains. CONCLUSIONS: Detailed structural information of SMs from synthetic standards and biological tissue samples is obtained using an alternative electron-based dissociation method. Accurate characterization of SMs promises to better inform studies of tissue biochemistry, lipid metabolism, and molecular pathology.

Light regulates nuclear detainment of intron-retained transcripts through COP1-spliceosome to modulate photomorphogenesis.

Intron retention (IR) is the most common alternative splicing event in Arabidopsis. An increasing number of studies have demonstrated the major role of IR in gene expression regulation. The impacts of IR on plant growth and development and response to environments remain underexplored. Here, we found that IR functions directly in gene expression regulation on a genome-wide scale through the detainment of intron-retained transcripts (IRTs) in the nucleus. Nuclear-retained IRTs can be kept away from translation through this mechanism. COP1-dependent light modulation of the IRTs of light signaling genes, such as PIF4, RVE1, and ABA3, contribute to seedling morphological development in response to changing light conditions. Furthermore, light-induced IR changes are under the control of the spliceosome, and in part through COP1-dependent ubiquitination and degradation of DCS1, a plant-specific spliceosomal component. Our data suggest that light regulates the activity of the spliceosome and the consequent IRT nucleus detainment to modulate photomorphogenesis through COP1.

Caching Policy in Low Earth Orbit Satellite Mega-Constellation Information-Centric Networking for Internet of Things.

Information-Centric Networking (ICN) is the emerging next-generation internet paradigm. The Low Earth Orbit (LEO) satellite mega-constellation based on ICN can achieve seamless global coverage and provide excellent support for Internet of Things (IoT) services. Additionally, in-network caching, typically characteristic of ICN, plays a paramount role in network performance. Therefore, the in-network caching policy is one of the hotspot problems. Especially, compared to caching traditional internet content, in-networking caching IoT content is more challenging, since the IoT content lifetime is small and transient. In this paper, firstly, the framework of the LEO satellite mega-constellation Information-Centric Networking for IoT (LEO-SMC-ICN-IoT) is proposed. Then, introducing the concept of "viscosity", the proposed Caching Algorithm based on the Random Forest (CARF) policy of satellite nodes combines both content popularity prediction and satellite nodes location prediction, for achieving good cache matching between the satellite nodes and content. And using the matching rule, the Random Forest (RF) algorithm is adopted to predict the matching relationship among satellite nodes and content for guiding the deployment of caches. Especially, the content is cached in advance at the future satellite to maintain communication with the current ground segment at the time of satellite switchover. Additionally, the policy considers both the IoT content lifetime and the freshness. Finally, a simulation platform with LEO satellite mega-constellation based on ICN is developed in Network Simulator 3 (NS-3). The simulation results show that the proposed caching policy compared with the Leave Copy Everywhere (LCE), the opportunistic (OPP), the Leave Copy down (LCD), and the probabilistic algorithm which caches each content with probability 0.5 (prob 0.5) yield a significant performance improvement, such as the average number of hops, i.e., delay, cache hit rate, and throughput.

Chemical composition and bioactivity variability of two-step extracts derived from traditional and "QiNan" agarwood (Aquilaria spp.).

One of the primary applications for agarwood lies in the extracts, instead, there are obvious differences in the demands for agarwood components with different application fields. To obtain the rough separation and clarify each part's activity, four extracts of essential oil, hydrolat, extractum, and ethanol precipitation from traditional agarwood (TraA) and "Qinan" agarwood (QinA) were obtained by steam-solvent multistage extraction and ethanol precipitation. We investigated the chemistry and biological activity of multistage extracts using gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), and in vitro activity testing. The results demonstrated that two kinds of agarwood essential oils contained mainly sesquiterpenoids, yet the sesquiterpene species were remarkably diverse in two kinds of agarwood essential oils. Then, the TraA and QinA hydrolat, all predominantly aromatic and sesquiterpene, but with differences from the essential oil ingredients. Additionally, the extractum chiefly contained chromones and the ethanol precipitation method worked well to separate the impurities in the TraA extract, however, it was ineffective for the QinA extract. Ultimately, essential oils and extractums all have antioxidant properties, with extractums outperforming essential oils. Moreover, both extractums and essential oils exhibited excellent broad-spectrum antimicrobial activity and anti-inflammatory activity. The findings pointed to the feasibility of separating the primary components from TraA and QinA using a multi-stage extraction technique, providing a scientific basis for the efficient utilization of all components of agarwood, as well as the functional product development and differentiated utilization of extract products in incense, fragrance, perfume, and daily chemicals.

Sequencing of Phosphopeptides Using a Sequential Charge Inversion Ion/Ion Reaction and Electron Capture Dissociation Workflow.

Protein phosphorylation, a common post-translational modification (PTM), is fundamental in a plethora of biological processes, most importantly in modulating cell signaling pathways. Matrix-assisted laser desorption/ionization (MALDI) coupled to tandem mass spectrometry (MS/MS) is an attractive method for phosphopeptide characterization due to its high speed, low limit of detection, and surface sampling capabilities. However, MALDI analysis of phosphopeptides is constrained by relatively low abundances in biological samples and poor relative ionization efficiencies in positive ion mode. Additionally, MALDI tends to produce singly charged ions, generally limiting the accessible MS/MS techniques that can be used for peptide sequencing. For example, collision induced dissociation (CID) is readily amendable to the analysis of singly charged ions, but results in facile loss of phosphoric acid, precluding the localization of the PTM. Electron-based dissociation methods (e.g., electron capture dissociation, ECD) are well suited for PTM localization, but require multiply charged peptide cations to avoid neutralization during ECD. Conversely, phosphopeptides are readily ionized using MALDI in negative ion mode. If the precursor ions are first formed in negative ion mode, a gas-phase charge inversion ion/ion reaction could then be used to transform the phosphopeptide anions produced via MALDI into multiply charged cations that are well-suited for ECD. Herein we demonstrate a multistep workflow combining a charge inversion ion/ion reaction that first transforms MALDI-generated phosphopeptide monoanions into multiply charged cations, and then subjects these multiply charged phosphopeptide cations to ECD for sequence determination and phosphate bond localization.

Effects of motor imagery training on gait performance in individuals after stroke: a systematic review and meta-analysis.

PURPOSE: This review systematically explores and summarise the effects of motor imagery training (MIT) compared to conventional therapy on gait performance in individuals after stroke. MATERIALS AND METHODS: Randomised controlled trials (RCTs) were systematically searched in five electronic databases (PubMed, EMBASE, PsycINFO, OVID Nursing and CINAHL) from inception to 30 December 2022. Studies investigating MITs, targeted at individuals after stroke were eligible. Data were extracted related to study and intervention characteristics. RESULTS: Sixteen studies were included. Compared with 'routine methods of treatment or training', the meta-analyses showed that MIT was more effective in improving cadence immediately post intervention (SMD: 1.22, 95% CI: 0.59, 1.85, p = 0.0001, I2 = 25%) and at 1- or 2-months post intervention (SMD: 0.78, 95% CI: 0.35, 1.20, p = 0.0004, I2 = 46%). The results also showed that MIT improves the step length of the affected side and the unaffected side at 1- or 2-months post intervention. Separate meta-analyses were also conducted on different tests of walking endurance (assessed by the 6-Minute Walk Test) and functional mobility (assessed by the Timed-Up-and-Go test). CONCLUSIONS: MIT effectively improved gait performance. The findings in individuals after stroke remain inconclusive due to significant heterogeneity in included studies.

Restoring gait performance and daily functional abilities is an important goal of post-stroke rehabilitation.Motor imagery training (MIT) may be a promising method to improve gait restoration and is expected to provide another option for the effective rehabilitation of stroke patients.This review highlights the limited research on MIT and thus the limited evidence to guide clinical rehabilitation.In the stroke rehabilitation, clinical specialists may consider incorporating MIT into the treatment programme to improve patients' gait performance and ensure effective early lower limb rehabilitation.

Hepatocyte-specific CCAAT/enhancer binding protein α restricts liver fibrosis progression.

Metabolic dysfunction-associated steatohepatitis (MASH) - previously described as nonalcoholic steatohepatitis (NASH) - is a major driver of liver fibrosis in humans, while liver fibrosis is a key determinant of all-cause mortality in liver disease independent of MASH occurrence. CCAAT/enhancer binding protein α (CEBPA), as a versatile ligand-independent transcriptional factor, has an important function in myeloid cells, and is under clinical evaluation for cancer therapy. CEBPA is also expressed in hepatocytes and regulates glucolipid homeostasis; however, the role of hepatocyte-specific CEBPA in modulating liver fibrosis progression is largely unknown. Here, hepatic CEBPA expression was found to be decreased during MASH progression both in humans and mice, and hepatic CEBPA mRNA was negatively correlated with MASH fibrosis in the human liver. CebpaΔHep mice had markedly enhanced liver fibrosis induced by a high-fat, high-cholesterol, high-fructose diet or carbon tetrachloride. Temporal and spatial hepatocyte-specific CEBPA loss at the progressive stage of MASH in CebpaΔHep,ERT2 mice functionally promoted liver fibrosis. Mechanistically, hepatocyte CEBPA directly repressed Spp1 transactivation to reduce the secretion of osteopontin, a fibrogenesis inducer of hepatic stellate cells. Forced hepatocyte-specific CEBPA expression reduced MASH-associated liver fibrosis. These results demonstrate an important role for hepatocyte-specific CEBPA in liver fibrosis progression, and may help guide the therapeutic discoveries targeting hepatocyte CEBPA for the treatment of liver fibrosis.

Identification and characterization of two O-methyltransferases involved in biosynthesis of methylated 2-(2-phenethyl)chromones in agarwood.

The 2-(2-phenethyl)chromones (PECs) are the signature constituents responsible for the fragrance and pharmacological properties of agarwood. O-Methyltransferases (OMTs) are necessary for the biosynthesis of methylated PECs, but there is little known about OMTs in Aquilaria sinensis. In this study, we identified 29 OMT genes from the A. sinensis genome. Expression analysis showed they were differentially expressed in different tissues and responded to drill wounding. Comprehensive analysis of the gene expression and methylated PEC content revealed that AsOMT2, AsOMT8, AsOMT11, AsOMT16, and AsOMT28 could potentially be involved in methylated PECs biosynthesis. In vitro enzyme assays and functional analysis in Nicotiana benthamiana demonstrated that AsOMT11 and AsOMT16 could methylate 6-hydroxy-2-(2-phenylethyl)chromone to form 6-methoxy-2-(2-phenylethyl)chromone. A transient overexpression experiment in the variety 'Qi-Nan' revealed that AsOMT11 and AsOMT16 could significantly promote the accumulation of three major methylated PECs. Our results provide candidate genes for the mass production of methylated PECs using synthetic biology.

Salty treatment increased bioactive compounds accumulation during agarwood development in Aquilaria sinensis trees.

To compare the bioactive compounds in agarwood induced by different methods in Aquilaria sinensis(Lour.) Gilg trees, a two dimensional thin layer chromatograph(2D-TLC) combined with effect directive analysis(EDA) was developed. Three antioxidants were found by 2D-TLC-DPPH and further identified as 2-(2-phenylethyl) chromones(PECs) with LC-MS/MS. The 3 antioxidants decreased along agarwood formation and their compositions in drilling induced agarwood differed with those in microbe culture induced agarwood. Further study showed NaCl treatment promoted antioxidants accumulation in agarwood induced by drilling or hot drilling. Hot drilling combined with salty stimulation was most efficient in some chemicals accumulation, which were identified as PECs with antioxidant, tyrosinase or ß-glucosidase inhibiting activities by 2D-TLC-EDA-LC-MS/MS. This study provided a 2D-TLC-EDA-LC-MS/MS method for bioactive compounds screen and qualification of agarwood. Based on this method, non-conventional methods were found to accelerate the accumulation of some bioactive PECs in A. sinensis trees.

The protective effect of Enteromorpha prolifera polysaccharide on alcoholic liver injury in C57BL/6 mice.

An alcohol-induced liver injury model was induced in C57BL/6 mice to assess the protective efficacy of Enteromorpha prolifera polysaccharides (EP) against liver damage. Histological alterations in the liver were examined following hematoxylin-eosin (H&E) staining. Biochemical assay kits and ELISA kits were employed to analyze serum and liver biochemical parameters, as well as the activity of antioxidant enzymes and alcohol metabolism-related enzymes. The presence of oxidative stress-related proteins in the liver was detected using western blotting. Liquid chromatography and mass spectrometry were used to profile serum metabolites in mice. The findings demonstrated that EP-H (100 mg/Kg) reduced serum ALT and AST activity by 2.31-fold and 2.32-fold, respectively, when compared to the alcohol-induced liver injury group. H&E staining revealed a significant attenuation of microvesicular steatosis and ballooning pathology in the EP-H group compared to the model group. EP administration was found to enhance alcohol metabolism by regulating metabolite-related enzymes (ADH and ALDH) and decreasing CYP2E1 expression. EP also modulated the Nrf2/HO-1 signaling pathway to bolster hepatic antioxidant capacity. Furthermore, EP restored the levels of lipid metabolites (Glycine, Butanoyl-CoA, and Acetyl-CoA) to normalcy. In summary, EP confers protection to the liver through the regulation of antioxidant activity and lipid metabolites in the murine liver.

Bile salt hydrolase catalyses formation of amine-conjugated bile acids.

Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes1-6; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.