Two new jatrophane diterpenoids from Euphorbia helioscopia with activity towards autophagic flux.

Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.

Cytotoxic glutarimide-containing polyketides isolated from Streptomyces sp. JCM 4793.

Glutarimide-containing polyketides usually exhibit anti-fungi activity, which was well exampled by cycloheximide. In our work, three new polyketide structures, 12-amidestreptimidone (1), 12-carboxylstreptimidone (2) and 3-(5S,8R)-(2-amino-2-oxoethyl-2'-methoxy-2'-oxoethyl)-8,10-dimethyl-7-oxododeca-5-hydroxy-9E,11-diolefin (3) were isolated from Streptomyces sp. JCM 4793. 3 without the glutarimide moiety is not active against fungi as expected, while 1 bearing the amide moiety is much more active than its carboxylic form 2. Here we report the isolation, structural elucidation, antifungal activity, and proposed biosynthesis pathway of 1-3.

Amundsen Sea Ice Loss Contributes to Australian Wildfires.

Wildfires in Australia have attracted extensive attention in recent years, especially for the devastating 2019-2020 fire season. Remote forcing, such as those from tropical oceans, plays an important role in driving the abnormal weather conditions associated with wildfires. However, whether high latitude climate change can impact Australian fires is largely unclear. In this study, we reveal a robust relationship between Antarctic sea ice concentration (SIC), primarily over the Amundsen Sea region, with Australian springtime fire activity, by using reanalysis data sets, AMIP simulation results, and a state-of-the-art climate model simulation. Specifically, a diminished Amundsen SIC leads to the formation of a high-pressure system above Australia as a result of the eastward propagation of Rossby waves. Meanwhile, two strengthened meridional cells originating from the tropic and polar regions also enhance subsiding airflow in Australia, resulting in prolonged arid and high-temperature conditions. This mechanism explains about 28% of the variability of Australian fire weather and contributed more than 40% to the 2019 extreme burning event, especially in the eastern hotspots. These findings contribute to our understanding of polar-low latitude climate teleconnection and have important implications for projecting Australian fires as well as the global environment.

Mapping land-use and land-cover changes through the integration of satellite and airborne remote sensing data.

An integrated, remotely sensed approach to assess land-use and land-cover change (LULCC) dynamics plays an important role in environmental monitoring, management, and policy development. In this study, we utilized the advantage of land-cover seasonality, canopy height, and spectral characteristics to develop a phenology-based classification model (PCM) for mapping the annual LULCC in our study areas. Monthly analysis of normalized difference vegetation index (NDVI) and near-infrared (NIR) values derived from SPOT images enabled the detection of temporal characteristics of each land type, serving as crucial indices for land type classification. The integration of normalized difference built-up index (NDBI) derived from Landsat images and airborne LiDAR canopy height into the PCM resulted in an overall performance of 0.85, slightly surpassing that of random forest analysis or principal component analysis. The development of PCM can reduce the time and effort required for manual classification and capture annual LULCC changes among five major land types: forests, built-up land, inland water, agriculture land, and grassland/shrubs. The gross change LULCC analysis for the Taoyuan Tableland demonstrated fluctuations in land types over the study period (2013 to 2022). A negative correlation (r = - 0.79) in area changes between grassland/shrubs and agricultural land and a positive correlation (r = 0.47) between irrigation ponds and agricultural land were found. Event-based LULCC analysis for Taipei City demonstrated a balance between urbanization and urban greening, with the number of urbanization events becoming comparable to urban greening events when the spatial extent of LULCC events exceeds 1000 m2. Besides, small-scale urban greening events are frequently discovered and distributed throughout the metropolitan area of Taipei City, emphasizing the localized nature of urban greening events.

Breast ultrasound image despeckling using multi-filtering DFrFT and adaptive fast BM3D.

Improving the quality of breast ultrasound images is of great significance for clinical diagnosis which can greatly boost the diagnostic accuracy of ultrasonography. However, due to the influence of ultrasound imaging principles and acquisition equipment, the collected ultrasound images naturally contain a large amount of speckle noise, which leads to a decrease in image quality and affects clinical diagnosis. To overcome this problem, we propose an improved denoising algorithm combining multi-filter DFrFT (Discrete Fractional Fourier Transform) and the adaptive fast BM3D (Block Matching and 3D collaborative filtering) method. Firstly, we provide the multi-filtering DFrFT method for preprocessing the original breast ultrasound image so as to remove some speckle noise early in fractional transformation domain. Based on the fractional frequency spectrum characteristics of breast ultrasound images, three types of filters are designed correspondingly in low, medium, and high frequency domains. And by integrating filtered images, the enhanced images are obtained which not only remove some speckle noise in background but also preserve the details of breast lesions. Secondly, for further enhancing the image quality on the basis of multi-filter DFrFT, we propose the adaptive fast BM3D method by introducing the DBSCAN-based super pixel segmentation to block matching process, which utilizes super pixel segmentation labels to provide a reference on how similar it is between target block and retrieval blocks. It reduces the number of blocks to be retrieved and make the matched blocks with more similar features. At last, the local noise parameter estimation is also adopted in the hard threshold filtering process of traditional BM3D algorithm to achieve local adaptive filtering and further improving the denoising effect. The synthetic data and real breast ultrasound data examples show that this combined method can improve the speckle suppression level and keep the fidelity of structure effectively without increasing time cost.

Multifunctional In-MOF and Its S-Scheme Heterojunction toward Pollutant Decontamination via Fluorescence Detection, Physical Adsorption, and Photocatalytic REDOX.

A novel doubly interpenetrated indium-organic framework of 1 has been assembled by In3+ ions and highly conjugated biquinoline carboxylate-based bitopic connectors (H2L). The isolated 1 exhibits an anionic framework possessing channel-type apertures repleted with exposed quinoline N atoms and carboxyl O atoms. Owing to the unique architecture, 1 displays a durable photoluminescence effect and fluorescence quenching sensing toward CrO42-, Cr2O72-, and Cu2+ ions with reliable selectivity and anti-interference properties, fairly high detection sensitivity, and rather low detection limits. Ligand-to-ligand charge transition (LLCT) was identified as the essential cause of luminescence by modeling the ground state and excited states of 1 using DFT and TD-DFT. In addition, the negatively charged framework has the ability to rapidly capture single cationic MB, BR14, or BY24 and their mixture, including the talent to trap MB from the (MB + MO) system with high selectivity. Moreover, intrinsic light absorption capacity and band structure feature endow 1 with effective photocatalytic decomposition ability toward reactive dyes RR2 and RB13 under ultraviolet light. Notably, after further polishing the band structure state of 1 by constructing the S-scheme heterojunction of In2S3/1, highly efficient photocatalytic detoxification of Cr(VI) and degradation of reactive dyes have been fully achieved under visible light. This finding may open a new avenue for designing novel multifunctional MOF-based platforms to address some intractable environmental issues, i.e., detection of heavy metal ions, physical capture of pony-sized dyes, and photochemical decontamination of ultrastubborn reactive dyes and highly toxic Cr(VI) ions from water.

Genetic and prognostic analysis of blastoid and pleomorphic mantle cell lymphoma: a multicenter analysis in China.

Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.

Transition Metal Oxide-Decorated MXenes as Drugless Nanoarchitectonics for Enriched Nanocatalytic Chemodynamic Treatment.

Despite their unique characteristics, 2D MXenes with sole photothermal conversion ability are required to explore their superfluous abilities in biomedicine. The small-molecule-based chemotherapeutics suffer from various shortcomings of time-consuming and expensiveness concerning theoretical and performance (preclinical/clinical) checks. This study demonstrates the fabrication of Ti3C2 MXene nanosheets (TC-MX NSs) and subsequent decoration with transition metal oxides, that is, copper oxide (Cu2O/MX, CO-MX NCs) as drugless nanoarchitectonics for synergistic photothermal (PTT)-chemodynamic therapeutic (CDT) efficacies. Initially, the monolayer/few-layered TC-MX NSs are prepared using the chemical etching-assisted ultrasonic exfoliation method and then deposited with Cu2O nanoconstructs using the in situ reduction method. Further, the photothermal ablation under near-infrared (NIR)-II laser irradiation shows PTT effects of CO-MX NCs. The deposited Cu2O on TC-MX NSs facilitates the release of copper (Cu+) ions in the acidic microenvironment intracellularly for Fenton-like reaction-assisted CDT effects and enriched PTT effects synergistically. Mechanistically, these deadly free radicals intracellularly imbalance the glutathione (GSH) levels and result in mitochondrial dysfunction, inducing apoptosis of 4T1 cells. Finally, the in vivo investigations in BALB/c mice confirm the substantial ablation of breast carcinoma. Together, these findings demonstrate the potential synergistic PTT-CDT effects of the designed CO-MX NCs as drugless nanoarchitectonics against breast carcinoma.

Erratum: CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain: Erratum.

[This corrects the article DOI: 10.7150/thno.44364.].

Quassinoids from Twigs of Harrisonia perforata (Blanco) Merr and Their Anti-Parkinson's Disease Effect.

Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1-7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer-Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson's disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson's disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10-15% increase in cell viability of the model cells at 50 µM, while compounds 2 and 4 (100 µM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.

Terpenoids from Euphorbia helioscopia and Their Cytotoxic Activities against H1975 Cells.

Three previously undescribed diterpenoids, helioscopnoids A-C, and eight known compounds were isolated from the whole plants of Euphorbia helioscopia. Their structures were established by extensive analysis of spectra and data comparison with previous literatures. Among them, compound 4 was identified as 24,24-dimethoxy-25,26,27-trinoreuphan-3ß-ol with revised configurations of C-13, C-14, and C-17 (13R*, 14R*, 17R*). Cytotoxicity assays revealed that all compounds exhibited varying levels of cytotoxicity against H1975 cells, with compound 9 displaying the most potent activity, as indicated by cell viability rates of 18.13 % and 20.76 % at concentrations of 20 µM and 5 µM, respectively. This study expands the understanding of E. helioscopia terpenoids' structural diversity and biological activities, contributing to the exploration of potential therapeutic applications.

Increased aerosol scattering contributes to the recent monsoon rainfall decrease over the Gangetic Plain.

The climate effects of atmospheric aerosols remain highly uncertain. Part of the uncertainty arises from the fact that scattering and absorbing aerosols have distinct or even opposite effects. Thus their relative fraction is critical in determining the overall aerosol climate effect. This study combines observations and global model simulations to demonstrate that changes in the fraction of scattering and absorbing aerosols play an important role in driving the monsoon precipitation decrease over northern India since the 1980s, especially over the Gangetic Basin. Increased aerosol scattering, or decreased aerosol absorption, manifested as a significant increase of aerosol single scattering albedo (SSA), causes strong cooling in the upper atmosphere. This suppresses vertical convection and thus reduces precipitation. Further analysis of the Couple Model Intercomparison Project Phase 6 multi-model-mean historical simulation shows that failing to capture the SSA increase over northern India is likely an important cause of the simulated precipitation trend bias in this area.

Recent Advances in the Preparation and Application of Two-Dimensional Nanomaterials.

Two-dimensional nanomaterials (2D NMs), consisting of atoms or a near-atomic thickness with infinite transverse dimensions, possess unique structures, excellent physical properties, and tunable surface chemistry. They exhibit significant potential for development in the fields of sensing, renewable energy, and catalysis. This paper presents a comprehensive overview of the latest research findings on the preparation and application of 2D NMs. First, the article introduces the common synthesis methods of 2D NMs from both "top-down" and "bottom-up" perspectives, including mechanical exfoliation, ultrasonic-assisted liquid-phase exfoliation, ion intercalation, chemical vapor deposition, and hydrothermal techniques. In terms of the applications of 2D NMs, this study focuses on their potential in gas sensing, lithium-ion batteries, photodetection, electromagnetic wave absorption, photocatalysis, and electrocatalysis. Additionally, based on existing research, the article looks forward to the future development trends and possible challenges of 2D NMs. The significance of this work lies in its systematic summary of the recent advancements in the preparation methods and applications of 2D NMs.

A review of the evidence to support electrical stimulation-induced vascularization in engineered tissue.

Tissue engineering presents a promising solution for regenerative medicine and the success depends on the supply of oxygen/nutrients to the cells by rapid vascularization. More and more technologies are being developed to facilitate vascularization of engineered tissues. In this review, we indicated that a regulatory system which influences all angiogenesis associated cells to achieve their desired functional state is ideal for the construction of vascularized engineered tissues in vitro. We presented the evidence that electrical stimulation (ES) enhances the synergistic promotion of co-cultured angiogenesis associated cells and its potential regulatory mechanisms, highlighted the potential advantages of a combination of mesenchymal stem cells (MSCs), endothelial cells (ECs) and ES to achieve tissue vascularization, with particular emphasis on the different biological pathways of ES-regulated ECs. Finally, we proposed the future direction of using ES to reconstruct engineered tissue blood vessels, pointed out the potential advantages and disadvantages of ES application on tissue vascularization.

The shift of decadal trend in Middle East dust activities attributed to North Tropical Atlantic variability.

The Middle East, as the world's second-largest dust source region, has dust emissions that significantly impact numerous populated areas, extending from North America to South Asia. Over the past two decades, dust activity in the Middle East has exhibited pronounced variability, with a notable trend shift from positive to negative around 2010. The underlying cause of this trend shift remains elusive. In this study, we employ multi-source datasets and global climate model simulations to demonstrate that the variability of Middle East dust activities is closely tied to changes in North Tropical Atlantic (NTA) sea surface temperature (SST). Specifically, a warm NTA SST anomaly generates an anomalous regional zonal cell characterized by ascending air motion above the NTA and descending air surrounding the Middle East. The associated surface high pressures around the Middle East subsequently induce hot and dry conditions accompanied by intensified Shamal winds in the north, which are favorable for dust emission and transport. The shift in SST trends from positive to negative in the NTA around 2010 is therefore responsible for the observed dust trend shift in the Middle East. This mechanism holds vital implications for predicting decadal dust variability over the Middle East region and further the project of global environment.

Euphejolkinolide A, a new ent-abietane lactone from Euphorbia peplus L. with promising biological activity in activating the autophagy-lysosomal pathway.

A new ent-abietane diterpenoid, named Euphejolkinolide A (1), was isolated from the whole plant of Euphorbia peplus L. Its structure, including absolute configurations, was determined by spectroscopic analyses and was corroborated by single-crystal X-ray diffraction analysis. This new compound was assessed for its activity to induce lysosome biogenesis through Lyso-Tracker Red staining, in which compound 1 could significantly induce lysosome biogenesis. In addition, quantitative real-time PCR (qRT-PCR) analysis demonstrated a direct correlation between the observed lysosome biogenesis and the transcriptional activation of the lysosomal genes after treatment with the compound 1. Moreover, compound 1 promoted autophagic flux by upregulating LC3-II and downregulating SQSTM1 in both human microglia cells and U251 cells, which is required for cellular homeostasis. Further results suggested 1 induced lysosome biogenesis and autophagy which was mediated by TFEB (transcription factor EB). The structure activity relationships (SAR) analysis suggested that the carbony1 at C-7 in 1 might be a key active group. Overall, the current data suggested that 1 could be a potential compound for lysosome disorder therapy by induction of autophagy.

Munronin V with 7/7/6 tricarbocyclic framework from Munronia henryi harms inhibits tau pathology by activating autophagy.

Munronin V (1), isolated from Munronia henryi Harms, is the first example, to the best of our knowledge, of an unprecedented 7/7/6 tricarbocyclic framework featuring an unusual A,B-seco-limonoid ring. The structures of munronin V were established from extensive spectroscopic and electronic circular dichroism (ECD) analyses. The novel A,B-seco with two seven-membered lactones was formed as a result of Baeyer-Villiger oxidation. Compound 1 activated autophagy and inhibited Tau pathology as revealed by flow cytometric analyses, confocal imaging analysis and western blotting, and this effect was mediated by transcription factor EB (TFEB). These findings suggested that 1 might have potential as a compound for combating Alzheimer's disease.

Mechanism of antidepressant effect of Ansheng Buxin Liuwei pills based on network pharmacology / 中国药理学通报

Aim To apply network pharmacology, molecular docking, and in vitro experimental techniques to predict as well as verify the antidepressant pharmacological mechanisms of Mengyao Anshen Buxin Liuwei pills. Methods TCMSP database and literature mining were used to obtain the active ingredients of Anshen Buxin six flavor pills , Swiss Target Prediction was applied to predict the ingredient related target information, and Cytoscape was employed to construct a medicinal herb ingredient target network. Depression targets were retrieved through GeneCards , Drugbank , OMIM and other databases. STRING database was used to obtain protein interaction relationship network information. DAVID database was used for GO biological process enrichment analysis and KEGG signaling pathway enrichment analysis. Autodock vina software was applied for molecular docking validation. In vitro injury model was established in BV2 microglial cells, cell viability was assessed by CCK-8 assay, and the mRNA expression of relevant core targets was assessed by qPCR. Results A total of 34 active components of Anshen Buxin Liuwei pills were screened, involving 140 potential targets and 59 core targets, involving 99 signaling pathways. Molecular docking results showed that betulinic acid, stigmasterol p-stiosterol 10 active components such as sitosterol and quercetin had good binding ability with AKT1, APP, ALB, MAPK3, VE GFA and MAPK 1 targets. The re suits in vitro showed that the activity of BV2 cells increased significantly compared with the model group. Anshen Buxin Liuwei pills could regulate the mRNA expression of each core target. Conclusion Anshen Buxin Liuwei pills may play an antidepressant role mainly through serotonin synaptic and other signaling pathways and related core targets.

Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota / 中国中药杂志

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Changing trend of sickness absenteeism among students during 2010-2017 academic years and its correlation with the incidence of acute infectious diseases in Jiading District，Shanghai / 中国学校卫生

Objective@#To describe the sickness absenteeism among primary and secondary school students in Jiading District and to analyze its correlation with the incidence of infectious diseases and associated lead or lag times, so as,to provide a scientific basis for the health and education departments to take measures.@*Methods@#The regularity and symptom composition of school sickness absenteeism among primary and secondary school students in Jiading District from the 2010-2017 were described. The Joinpoint model was applied to analyze the changing trend of absenteeism. And the rate of school sickness absenteeism and incidences of 7 acute infectious diseases were compared through visual analysis. The time lagged correlation coefficients and Granger causality tests were applied to quantitatively analyze the correlation and lead/lag patterns.@*Results@#The average rate of school sickness absenteeism among primary and secondary school students in Jiading District, Shanghai was 0.27%. Since the 2012 academic year, the overall rate of sickness absenteeism has been on the rise. Fever was the most common symptom of absenteeism (47.49%). The trend of sickness absenteeism rate was mainly consistent with the incidence of influenza, and showed a one way Granger causality. The maximum time lagged correlation coefficient was obtained in the second semester of the 2017 academic year with a value of 0.43 (95% CI =0.25-0.58). The maximum time lagged correlation coefficient between the rate of sickness absenteeism with fever and other respiratory symptoms and the incidence of influenza was also obtained in the second semester of the 2017 academic year and the maximum correlation coefficient was 0.50(95% CI =0.33-0.65).@*Conclusion@#The sickness absenteeism rate in primary and secondary school students is correlated to influenza incidence, and it has potential application value in supplementing early warning of influenza activities in the community.