High altitude retinopathy: An overview and new insights.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Analysis on dynamic changes of etizolam and its metabolites and exploration of its development prospect using UPLC-Q-exactive-MS.

As one of the most widely abused designer benzodiazepines in the world, etizolam has been found in many cases in many countries. In this study, UPLC-Q-Exactive-MS was used for the first time to establish a dynamic change model of etizolam and its metabolites in rats. Compared with previous studies, the detection sensitivity and reproducibility of the instrument were higher. In the experiment, we optimized the traditional pharmacokinetic model based on Gauss function. According to the significant difference of etizolam in the plasma elimination phase of rats, a new pharmacokinetic model based on Lorentz function was established to describe the dynamic changes of etizolam more rigorously, which made the error effects lower and the accuracy of the pharmacokinetic parameters was improved. At the same time, the pharmacokinetic parameters of etizolam were compared with four other designer benzodiazepines reported in previous studies in rats, and we found the direct reason for the popularity of etizolam in the NPS market and explored the future development of etizolam for the first time. In addition, 21 metabolites were found through rat experiments to effectively detect etizolam abuse for a long time, of which 4 metabolites had the longest detection window and could be used as long-acting metabolites for experiments, which greatly prolongs the detection window and extends the time range in which etizolam was detected in real cases. This study is the first to conduct a systematic and comprehensive study on the metabolism and pharmacokinetics of etizolam and find out the direct reason for the prevalence of etizolam abuse, and we also discuss the development trend of etizolam in the future market of new psychoactive substances, which is beneficial for forensic experts to assess the trend of drug abuse and can provide reference for relevant drug control and drug treatment.

Preparation and efficacy verification of three-dimensional printed partitioned multi-effect precision-care gel facial mask.

OBJECTIVE: A partition multi-effect precision-care gel facial mask conforming to facial skin characteristics was prepared using three-dimensional (3D) printing technology. METHODS: First, the hydrogel matrix and humectant of a 3D-printed gel for facial masks were screened, and three 3D-printed gels of arbutin, hexapeptide, and salicylic acid were prepared with whitening, wrinkle removal, and oil control functions, respectively. Skin irritation tests were performed on the gels. Physicochemical properties such as pH, heat and cold tolerance were evaluated. The efficacy of three 3D-printed gels was assessed by measuring melanin value, wrinkle depression score, and oil secretion. Finally, the facial mask model design and printing parameters were studied, and a partition multi-effect precision-care gel facial mask was printed in line with facial skin characteristics. RESULTS: For the 3D-printed facial mask, the gel prescription with 2% hydroxyethyl cellulose gel as matrix and 7% glycerol as humectant was the best. The prepared 3D-printed gel did not irritate the human skin, and its physicochemical properties met the Chinese facial mask industry standard (QB/T2872-2017). We showed that three types of 3D-printed gels containing arbutin, hexapeptide, and salicylic acid could be applied to the corresponding parts of the face to solve different problems, such as facial skin dullness, wrinkles, and oil secretion. Therefore, according to facial physiological characteristics, the facial mask model was designed for the forehead and nasolabial fold, which needs to be anti-wrinkled; the cheek, which needs to be whitened; and the nose and chin, which need oil control. The optimal printing parameters were 0.26 mm nozzle diameter, 90 mm/s printing speed, 30% filling density, 140% wire extrusion ratio, and 0.25 mm layer height. Different skin care effects can be achieved using a three-nozzle printer to print arbutin, hexapeptide, or salicylic acid gel on the mask's forehead and nasolabial fold, cheek, and nose and chin, respectively. CONCLUSION: The 3D-printed partition multi-effect care gel facial mask prepared according to the skin features of different parts of the face can overcome the problem of the single skincare effect of the mass-produced facial masks.

OBJECTIF: Un masque facial de soin de précision en gel à effets multiples, adapté aux caractéristiques de la peau du visage, a été préparé à l'aide de la technologie d'impression tridimensionnelle (3D). MÉTHODES: Tout d'abord, la matrice d'hydrogel et l'humectant d'un gel imprimé en 3D pour les masques faciaux ont été sélectionnés, et trois gels imprimés en 3D d'arbutine, d'hexapeptide et d'acide salicylique ont été préparés avec des fonctions de blanchiment, d'élimination des rides et de contrôle du sébum, respectivement. Des tests d'irritation cutanée ont été réalisés sur les gels. Les propriétés physicochimiques telles que le pH et la tolérance à la chaleur et au froid ont été évaluées. L'efficacité des trois gels imprimés en 3D a été évaluée en mesurant la valeur de la mélanine, le score de dépression des rides et la sécrétion de sébum. Enfin, la conception du modèle de masque facial et les paramètres d'impression ont été étudiés, et un masque facial de gel de soin de précision à effets multiples a été imprimé en fonction des caractéristiques de la peau du visage. RÉSULTATS: Pour le masque facial imprimé en 3D, la prescription de gel avec 2 % de gel d'hydroxyéthylcellulose comme matrice et 7 % de glycérol comme humectant était la meilleure. Le gel imprimé en 3D n'a pas irrité la peau humaine et ses propriétés physicochimiques sont conformes à la norme industrielle chinoise relative aux masques faciaux (QB/T2872­2017). Nous avons montré que trois types de gels imprimés en 3D contenant de l'arbutine, de l'hexapeptide et de l'acide salicylique pouvaient être appliqués aux parties correspondantes du visage pour résoudre différents problèmes, tels que l'aspect terne de la peau du visage, les rides et la sécrétion de sébum. Par conséquent, en fonction des caractéristiques physiologiques du visage, le modèle de masque facial a été conçu pour le front et le sillon nasogénien, qui doivent être antirides, la joue, qui doit être blanchie, et le nez et le menton, qui ont besoin d'un contrôle du sébum. Les paramètres d'impression optimaux étaient les suivants : diamètre de buse de 0,26 mm, vitesse d'impression de 90 mm/s, densité de remplissage de 30 %, rapport d'extrusion du fil de 140 % et hauteur de couche de 0,25 mm. Différents effets de soin de la peau peuvent être obtenus en utilisant une imprimante à trois buses pour imprimer de l'arbutine, de l'hexapeptide ou du gel d'acide salicylique sur le front et le sillon nasogénien, la joue, le nez et le menton du masque, respectivement. CONCLUSION: Le masque facial en gel de soin à effets multiples imprimé en 3D et préparé en fonction des caractéristiques de la peau des différentes parties du visage peut résoudre le problème de l'effet de soin unique des masques faciaux produits en masse.

Individual sustainability competence development in engineering education: Community interaction open-source learning.

This empirical research creates and assesses a community interaction open-source learning framework. The framework established an efficient open-source learning environment for engineering courses to develop undergraduates' sustainability competencies. The teaching practice of the framework was designed into three stages: course preparation, theory lecture, and project practice. In the teaching practice, community interaction elements were embedded, including community/student two-way selection, systemic teaching and difficulty discussion, expert/student negotiation on teaching forms, teacher/expert coordination on teaching contents, and expert/student two-way feedback on schedules. The interaction elements between students, teachers, and experts enhanced the effectiveness of open-source learning in engineering courses. The experimental results showed that the students exhibited a positive attitude and high participation in the learning procedure and reported a sense of achievement in the project practice. The open-source learning framework significantly improved systemic thinking, conceptual understanding, interdisciplinary collaboration and professional skills. It enhanced students' key sustainability competencies and laid the foundation for them to become expertise-based innovators and open-source community contributors.

Research trends of worldwide ophthalmologic randomized controlled trials in the 21st century: A bibliometric study.

Background: Randomized controlled trials (RCTs) are often considered the gold standard and the cornerstone for clinical practice. However, bibliometric studies on worldwide RCTs of ophthalmology published in the 21st century have not been reported in detail yet. This study aims to perform a bibliometric study and visualization analysis of worldwide ophthalmologic RCTs in the 21st century. Methods: Global ophthalmologic RCTs from 2000 to 2022 were searched in the Web of Science Core Collection. The number of publications, country/region, institution, author, journal, and research hotspots of RCTs were analyzed using HistCite, VOSviewer, CiteSpace, and Excel software. Results: 2366 institutions and 90 journals from 83 countries/regions participated in the publication of 1769 global ophthalmologic RCTs, with the United States leading in the number of volumes and research field, and the Moorfields Eye Hospital contributing to the most publications. Ophthalmology received the greatest number of publications and co-citations. Jeffrey S. Heier owned the most publications and Jost B. Jonas owned the most co-citations. The knowledge foundations of global ophthalmologic RCTs were mainly retinopathy, glaucoma, dry eye disease (DED), and cataracts, and anti-vascular endothelial growth factor (VEGF) therapy (ranibizumab), topical ocular hypotensive medication, laser trabeculoplasty. Anti-VEGF therapy for age-related macular degeneration (AMD), DME (diabetic macular edema), and DED, the use of new diagnostic tools, and myopia were the hottest research highlights. Anti-VEGF therapy, prompt laser, triamcinolone, and verteporfin photodynamic therapy for AMD, DME, and CNV (choroidal neovascularization), DED, myopia, and open-angle glaucoma were the research hotspots with the longest duration. The future research hotspots might be DED and the prevention and control of myopia. Conclusions: Overall, the number of global ophthalmologic RCTs in the 21st century was keeping growing, there was an imbalance between the regions and institutions, and more efforts are required to raise the quantity, quality, and global impact of high-quality clinical evidence in developing countries/regions.

Bitter Almond Albumin ACE-Inhibitory Peptides: Purification, Screening, and Characterization In Silico, Action Mechanisms, Antihypertensive Effect In Vivo, and Stability.

Almond expeller is an undeveloped reservoir of bioactive peptides. In the current study, a zinc ion ligand Arg-Pro-Pro-Ser-Glu-Asp-Glu-Asp-Gln-Glu (RPPSEDEDQE) offering a noncompetitive inhibitory effect on ACE (IC50: 205.50 µmol·L-1) was identified from almond albumin hydrolysates via papain and thermolysin hydrolysis, subsequent chromatographic separation, and UPLC-Q-TOF-MS/MS analysis. Molecular docking simulated the binding modes of RPPSEDEDQE to ACE and showed the formation of hydrogen bonds between RPPSEDEDQE and seven active residues of ACE. Moreover, RPPSEDEDQE could bind to fifteen active sites of ACE by hydrophobic interactions, and link with the His387 and zinc ions of the zinc tetrahedral coordination. Ultraviolet wavelength scanning and Fourier-transformed infrared spectroscopy analysis revealed that RPPSEDEDQE can provide multiple binding sites for zinc ions. However, RPPSEDEDQE cannot bind with any central pocket of ACE, which was evidenced by an inhibition kinetics experiment. Additionally, the zinc-chelating capacity and inhibiting ability against ACE of RPPSEDEDQE were both not significantly reduced by the hydrolysis of gastrointestinal enzymes. A moderate to high dose of RPPSEDEDQE (100-150 mg·kg bw-1) significantly reduced the systolic and diastolic blood pressure of spontaneous hypertensive rats, but chelation with zinc ions decreased its antihypertensive efficiency. These results indicate that bitter almond albumin peptides may be used for lowering blood pressure.

A longitudinal resource for population neuroscience of school-age children and adolescents in China.

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.

NAD+ metabolism and eye diseases: current status and future directions.

Currently, there are no truly effective treatments for a variety of eye diseases, such as glaucoma, age-related macular degeneration (AMD), and inherited retinal degenerations (IRDs). These conditions have a significant impact on patients' quality of life and can be a burden on society. However, these diseases share a common pathological process of NAD+ metabolism disorders. They are either associated with genetically induced primary NAD+ synthase deficiency, decreased NAD+ levels due to aging, or enhanced NAD+ consuming enzyme activity during disease pathology. In this discussion, we explore the role of NAD+ metabolic disorders in the development of associated ocular diseases and the potential advantages and disadvantages of various methods to increase NAD+ levels. It is essential to carefully evaluate the possible adverse effects of these methods and conduct a more comprehensive and objective assessment of their function before considering their use.

Phonemic mismatch negativity mediates the association between phoneme awareness and character reading ability in young Chinese children.

Poor phonological awareness is associated with greater risk for reading disability. The underlying neural mechanism of such association may lie in the brain processing of phonological information. Lower amplitude of auditory mismatch negativity (MMN) has been associated with poor phonological awareness and with the presence of reading disability. The current study recorded auditory MMN to phoneme and lexical tone contrast with odd-ball paradigm and examined whether auditory MMN mediated the associations between phonological awareness and character reading ability through a three-year longitudinal study in 78 native Mandarin-speaking kindergarten children. Hierarchical linear regression and mediation analyses showed that the effect of phoneme awareness on the character reading ability was mediated by the phonemic MMN in young Chinese children. Findings underscore the key role of phonemic MMN as the underlying neurodevelopmental mechanism linking phoneme awareness and reading ability.

Acute Retinal Necrosis Possibly Triggered by Contra-Lateral Penetrating Trauma.

BACKGROUND: Acute retinal necrosis is a rare but devastating acute posterior uveitis caused by a member of the herpes virus family. We report an extremely rare ARN case following penetrating trauma in the contralateral eye. CASE PRESENTATION: A 61-year-old male was misdiagnosed as sympathetic ophthalmia due to a penetrating trauma history of the contralateral eye. The subsequent administration of high-dose IVMP therapy led to rapid progression of the retinal necrosis. ARN was strongly suspected base on the clinical examination and confirmed by the PCR aqueous testing. The patient finally got good visual outcomes by the effective and prompt antiviral treatment. CONCLUSION: Ophthalmologists should be alert to the possibility that penetrating injury can trigger the activation of latent viruses. If a patient experiences visual symptoms in the contralateral eye after an open-globe injury, it is recommended that a thorough peripheral retinal examination be performed to avoid missing ARN.

Chrysomycin A Regulates Proliferation and Apoptosis of Neuroglioma Cells via the Akt/GSK-3ß Signaling Pathway In Vivo and In Vitro.

Glioblastoma (GBM) is a major type of primary brain tumor without ideal prognosis and it is therefore necessary to develop a novel compound possessing therapeutic effects. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells through the Akt/GSK-3ß signaling pathway, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates the apoptosis of neuroglioma cells is unclear. The present study aims to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates the apoptosis of neuroglioma cells. Briefly, the anti-glioblastoma activity was assessed in human glioma U87 xenografted hairless mice. Chr-A-related targets were identified via RNA-sequencing. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed via flow cytometry. Apoptosis-related proteins and possible molecular mechanisms were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografted hairless mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathways were involved in the possible mechanisms. Chr-A increased the apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blotting revealed that Chr-A disturbed the balance between Bax and Bcl-2, activating a caspase cascade reaction and downregulating the expression of p-Akt and p-GSK-3ß, suggesting that Chr-A may contribute to glioblastoma regression modulating in the Akt/GSK-3ß signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.

Metabolic Profile Analysis of Designer Benzodiazepine Etizolam in Zebrafish and Human Liver Microsomes.

As one of the most widely abused designer benzodiazepines worldwide, Etizolam is characterized by its high addiction potential, low production cost, and difficulty in detection. Due to the rapid metabolism of Etizolam in the human body, the probability of detecting the Etizolam parent drug in actual case samples by forensic personnel is low. Therefore, without detecting the parent drug, analysis of Etizolam metabolites can help forensic personnel provide references and suggestions on whether the suspect has taken Etizolam. This study simulates the objective metabolic process of the human body. It establishes a zebrafish in vivo metabolism model and a human liver microsome in vitro metabolism model to analyze the metabolic characteristics of Etizolam. A total of 28 metabolites were detected in the experiment, including 13 produced in zebrafish, 28 produced in zebrafish urine and feces, and 17 produced in human liver microsomes. The UPLC-Q-Exactive-MS technology was used to analyze the structures and related metabolic pathways of Etizolam metabolites in zebrafish and human liver microsomes, and a total of 9 metabolic pathways were identified, including monohydroxylation, dihydroxylation, hydration, desaturation, methylation, oxidative deamination to alcohol, oxidation, reduction acetylation, and glucuronidation. Among them, metabolites involving hydroxylation reactions (including monohydroxylation and dihydroxylation) accounted for 57.1% of the total number of potential metabolites, indicating that hydroxylation may be the major metabolic pathway of Etizolam. Based on the response values of each metabolite, monohydroxylation (M1), desaturation (M19), and hydration (M16) were recommended as potential biomarkers for Etizolam metabolism. The experimental results provide reference and guidance for forensic personnel in identifying Etizolam use in suspects.

The essential role of N6-methyladenosine RNA methylation in complex eye diseases.

There are many complex eye diseases which are the leading causes of blindness, however, the pathogenesis of the complex eye diseases is not fully understood, especially the underlying molecular mechanisms of N6-methyladenosine (m6A) RNA methylation in the eye diseases have not been extensive clarified. Our review summarizes the latest advances in the studies of m6A modification in the pathogenesis of the complex eye diseases, including cornea disease, cataract, diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy, Graves' disease, uveal melanoma, retinoblastoma, and traumatic optic neuropathy. We further discuss the possibility of developing m6A modification signatures as biomarkers for the diagnosis of the eye diseases, as well as potential therapeutic approaches.

Determination of 5 synthetic cannabinoids in hair by Segmental analysis using UHPLC-MS/MS and its application to eight polydrug abuse cases.

In recent years, an increasing number of new synthetic cannabinoids (SCs) have appeared in the drug trade market. A UPLC-MS/MS method was developed to simultaneously identify five synthetic cannabinoids in 1 cm segment hair samples. The method was fully validated and confirmed to have good selectivity, accuracy, and precision, as well as satisfactory linearity within the calibrated range. The limit of quantification (LOD) was 0.5 pg/mg, and the lower limit of quantitation (LLOQ) was 1 pg/mg, with intraday and interday accuracies (bias) ranging from - 9.6-13.7%. The validated method was successfully used for qualitative and quantitative analysis of five SCs in authentic hair samples of eight SC abusers. SCs were detected in 8 cases at concentrations ranging from 1.5 to 632.9 pg/mg.

Sohlh2 Regulates the Stemness and Differentiation of Colon Cancer Stem Cells by Downregulating LncRNA-H19 Transcription.

Colon cancer stem cells (CSC) are tumor-initiating cells that drive tumorigenesis and progression through self-renewal and various differentiation potency. Therefore, the identification of factors critical for colon CSC function is vital for the development of therapies. Sohlh2 belongs to the superfamily of bhlh transcription factors and serves as a tumor suppressor in several tumors. The role of Sohlh2 in CSCs remains unknown. Here we demonstrated that Sohlh2 was related to the inhibition of LncRNA-H19/miR-141/ß-catenin signaling and led to the consequent suppression of colon CSC stemness and the promotion of colon CSC differentiation in vitro and in vivo. Moreover, Sohlh2 could directly bind to the promoter of LncRNA-H19 and repress its transcription activity. LncRNA-H19 mediated the effects of Sohlh2 on colon CSC stemness and differentiation. Clinically, we observed a significant inverse correlation between Sohlh2 and LncRNA-H19, ß-catenin, Lgr5, CD133 expression levels, and positive correlation between Sohlh2 and MUC2, TFF2 expression in colon cancer tissues. Collectively, our findings suggest an important role of the Sohlh2/LncRNA-H19/miR-141/ß-catenin pathway in regulating colon CSC stemness and differentiation, suggesting potential therapeutic targets for colon cancer. IMPLICATIONS: This study identifies that Sohlh2 directly manipulates LncRNA-H19 transcription and suppresses the ß-catenin signaling pathway and the Sohlh2/LncRNA-H19/miR-141/ß-catenin signaling pathway plays an essential role in the stemness of colon CSCs.

JAK/STAT3 Signaling Activation Related to Distinct Clinicopathologic Features in Systemic ALK - Anaplastic Large Cell Lymphomas : New Insights into Their Heterogeneity.

Systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a group of heterogenous CD30 + T-cell non-Hodgkin lymphomas. Previous studies have highlighted the importance of JAK/STAT3 signaling activation in the molecular pathogenesis of ALK - ALCLs. In the present study, we aimed to establish a potential relationship between JAK/STAT3 signaling activation and clinicopathologic features in ALK - ALCLs, and further recognize the heterogenous nature of these neoplasms. Immunohistochemistry staining of the phosphorylated-STAT3 (p-STAT3) and dual-specificity protein phosphatase 22 ( DUSP22 ) gene rearrangement analysis were performed. Forty-five cases of ALK - ALCL were divided into 3 groups, including 9 DUSP22 -rearranged ALCLs, 21 p-STAT3 + double-negative (DN) ALCLs (both ALK and DUSP22 rearrangement negative), and 15 p-STAT3 - DN-ALCLs. Morphologically, p-STAT3 + DN-ALCLs exhibited sheet-like neoplastic cells and sometimes showed large pleomorphic cells scattered in a lymphocyte-rich background more frequently than those in other ALK - ALCLs subtypes. Phenotypically, the p-STAT3 + DN-ALCLs frequently expressed cytotoxic molecules, epithelial membrane antigen, and programmed death-ligand 1, whereas CD3 and CD5 expression was not observed. Clinically, patients with p-STAT3 + DN-ALCLs had a better prognosis than those with p-STAT3 - DN-ALCLs. These observations suggest that p-STAT3 + DN-ALCLs represent a distinct subtype of ALK - ALCLs. Identifying ALK - ALCL subtypes by using p-STAT3 staining and DUSP22 rearrangement is a promising approach that may contribute to risk stratification and better treatment decisions in the future clinical practice.

Acorane sesquiterpenes from the deep-sea derived Penicillium bilaiae fungus with anti-neuroinflammatory effects.

Acorane-type sesquiterpenes comprise a unique class of natural products with a range of pharmaceutical effects. Genome sequencing and gene annotation, along with qRT-PCR detection, demonstrate that the deep-sea derived Penicillium bilaiae F-28 fungus shows potential to produce acorane sesquiterpenes. Chromatographic manipulation resulted in the isolation of 20 acorane sesquiterpenes from the large-scale fermented fungal strain. Their structures were established by the interpretation of spectroscopic data, together with X-ray diffraction, chemical conversion, and ECD data for configurational assignments. A total of 18 new sesquiterpenes, namely, bilaiaeacorenols A-R (1-18), were identified. Bilaiaeacorenols A and B represent structurally unique tricyclic acoranes. Compound 18 exhibited efficient reduction against NO production in LPS-induced BV-2 macrophages in a dose-dependent manner, and it abolished LPS-induced NF-κB in the nucleus of BV-2 microglial cells. In addition, marked reductions of iNOS and COX-2 in protein and mRNA levels were observed. This study extends the chemical diversity of acorane-type sesquiterpenoids and suggests that compound 18 is a promising lead for anti-neuroinflammation.

Guideline for the treatment of no light perception eyes induced by mechanical ocular trauma.

Severe mechanical ocular trauma with no light perception (NLP) predicts a poor prognosis of visual acuity and enucleation of the eyeball. Since the innovative treatment concept of exploratory vitreoretinal surgery has developed and treatment technology has advanced, the outcomes of severe ocular trauma treatment in NLP patients have greatly improved. However, there remains a lack of unified standards for the determination, surgical indication, and timing of vitrectomy in NLP eye treatment. To address these problems, we aimed to create evidence-based medical guidelines for the diagnosis, treatment, and prognosis of mechanical ocular trauma with NLP. Sixteen relevant recommendations for mechanical ocular trauma with NLP were obtained, and a consensus was reached. Each recommendation was explained in detail to guide the treatment of mechanical ocular trauma associated with NLP.

Metabolic profiles and screening tactics for MDMB-4en-PINACA in human urine and serum samples.

MDMB-4en-PINACA (Methyl 3,3-dimethyl-2-[1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido] butanoate) is a potent agonist of the CB1 receptor. In 2021, it was one of the most common synthetic cannabinoid receptor agonists (SCRAs) seized by the Beijing Drug Control Agency. MDMB-4en-PINACA can be hard to detect in biological specimens because of ester hydrolysis. In this work, a highly sensitive liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was developed for the detection of MDMB-4en-PINACA metabolites in urine, serum, and hair samples. Metabolites from authentic samples were compared with those from human liver microsomes (HLMs) in vitro and in zebrafish in vivo. A total of 75 metabolites, including 44 previously unreported metabolites, were identified from urine samples. We found that 11 metabolic pathways were involved in MDMB-4en-PINACA metabolism, including acetylation, a novel metabolic pathway for SCRAs. Our results revealed that ester hydrolysis and hydroxylation were to the major metabolic pathways involved in MDMB-4en-PINACA metabolism. Using serum samples, we detected 9 metabolites along with the parent drug. Only the parent drug was detected using hair samples. The existence of ADB-4en-PINACA makes the currently used biomarkers for MDMB-4enPINACA not very specific for the intake of MDMB-4en-PINACA. Therefore, based on the identified metabolites and their structural features, we propose more sensitive screening tactics for MDMB-4en-PINACA using urine and serum samples.