EAF2 Downregulation Recruits Tumor-associated Macrophages in Prostate Cancer through Upregulation of MIF.

BACKGROUND: The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma. METHODS: A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization. RESULTS: Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout. CONCLUSIONS: Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF.

Additive partitioning of multispecies distributional aggregation of local assemblages.

The distribution of species is not random in space. At the finest-resolution spatial scale, that is, field sampling locations, distributional aggregation level of different species would be determined by various factors, for example spatial autocorrelation or environmental filtering. However, few studies have quantitatively measured the importance of these factors. In this study, inspired by the statistical properties of a Markov transition model, we propose a novel additive framework to partition local multispecies distributional aggregation levels for sequential sampling-derived field biodiversity data. The framework partitions the spatial distributional aggregation of different species into two independent components: regional abundance variability and the local spatial inertia effect. Empirical studies from field amphibian surveys through line-transect sampling in southwestern China (Minya Konka) and central-southern Vietnam showed that local spatial inertia was always the dominant mechanism structuring the local occurrence and distributional aggregation of amphibians in the two regions with a latitudinal gradient from 1200 to nearly 4000 m. However, regional abundance variability is still nonnegligible in highly diverse tropical regions (i.e. Vietnam) where the altitude is not higher than 2000 m. In summary, we propose a novel framework that shows that the multispecies distributional aggregation level can be structured by two additive components. The two partitioned components could be theoretically independent. These findings are expected to deepen our understanding of the local community structure from the perspective of both spatial distribution and regional diversity patterns. The partitioning framework might have potential applications in field ecology and macroecology research.

Clinical and Pathological Characteristics of Patients With Papillary Thyroid Carcinoma Coexisting With Hashimoto's Thyroiditis: A Retrospective Cohort Study.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma, and Hashimoto's thyroiditis (HT) has been postulated to have a relationship with PTC. This study aims to assess clinical and pathological characteristics of patients with papillary thyroid carcinoma coexisting with Hashimoto's thyroiditis. METHODS: A retrospective study was conducted in a cohort of patients with thyroid carcinoma at the Department of Surgery, Shanghai General Hospital from January 2017 to December 2018. Medical records of patients who had PTC with or without HT were reviewed and clinical and histopathological characteristics of these patients were analyzed. RESULTS: A total of 632 patients with thyroid carcinoma were identified. Among them, 614 (97.15%) had PTC and 120/614 (19.0%) harbored PTC together with HT. PTC was significantly associated with HT, as compared with other histological subtypes (P < .001). Patients with coexisting PTC and HT (PTC + HT group) were significantly younger than patients with PTC alone (PTC group) (P = .008). There were more women in the PTC + HT group than in the PTC group (88.3% vs. 73.1%, P < .001). TSH, TGAb, and TPOAb levels were significantly higher in the PTC + HT group than in the PTC group (P ≤ .001). In addition, tumor diameter was smaller in the PTC + HT group than in the PTC group (P = .034). The PTC + HT group showed a significant better recurrence-free survival than the PTC group. Furthermore, immunohistochemical analysis revealed that patients in the PTC + HT group had a higher positive rate and higher expression intensity of Ki67 than patients in the PTC group. CONCLUSIONS: Our study revealed that patients with coexisting PTC and HT were younger, had smaller tumor diameters, a better prognosis, and higher positive rates and expression intensity of Ki67, than did patients with PTC alone.

Preliminary exploration of the effects of environmental factors on the microsatellite status of BRAF-mutated colorectal cancer.

BACKGROUND: To investigate the expression of EBV products and frequency of gallstone disease (GD) among different microsatellite status in colorectal cancer (CRC) with BRAFV600E mutation. METHODS: We collected 30 CRC patients with BRAFV600E mutation and 10 BRAF ( -) CRC patients as well as 54 healthy subjects. Tumor tissue samples were collected to detect the mutation of BRAF, KRAS, and TP53. Microsatellite status was determined by immunohistochemistry and PCR. EBER in situ hybridization was performed to detect EBV. In addition, we also collected clinical information about the patients. RESULTS: We found that although EBV products were detected in CRC, there were no significant differences in the EBV distribution between the different BRAF groups. Our study demonstrated that BRAFV600E mutation and BRAFV600E with MSI were significantly more frequent in the right CRC. Furthermore, the KRAS mutation rate in the BRAF-wild-type group was proved to be significantly higher than that in the BRAF mutation group. In addition, we revealed that BRAF mutation and MSI were independent risk factors of TNM stage. The frequency of GD was higher in CRC patients than in general population, and although there was no significant difference between CRC with or without BRAFV600E mutation, the highest frequency of GD was found in MSS CRC with BRAFV600E mutation. CONCLUSIONS: EBV plays a role in CRC, but is not a determinant of different microsatellite status in CRC with BRAFV600E mutation. The frequency of GD in MSS CRC with BRAFV600E mutation is significantly higher than that in the general population.

Boosting Reactive Oxygen Species Generation Using Inter-Facet Edge Rich WO3 Arrays for Photoelectrochemical Conversion.

Water oxidation reaction leaves room to be improved in the development of various solar fuel productions, because of the kinetically sluggish 4-electron transfer process of oxygen evolution reaction. In this work, we realize reactive oxygen species (ROS), H2 O2 and OH⋅, formations by water oxidation with total Faraday efficiencies of more than 90 % by using inter-facet edge (IFE) rich WO3 arrays in an electrolyte containing CO3 2- . Our results demonstrate that the IFE favors the adsorption of CO3 2- while reducing the adsorption energy of OH⋅, as well as suppresses surface hole accumulation by direct 1-electron and indirect 2-electron transfer pathways. Finally, we present selective oxidation of benzyl alcohol by in situ using the formed OH⋅, which delivers a benzaldehyde production rate of ≈768 µmol h-1 with near 100 % selectivity. This work offers a promising approach to tune or control the oxidation reaction in an aqueous solar fuel system towards high efficiency and value-added product.

Transcriptome profiling revealed potentially important roles of defensive gene expression in the divergence of insect biotypes: a case study with the cereal aphid Sitobion avenae.

BACKGROUND: Many insects can develop differential biotypes on variable host plants, but the underlying molecular factors and mechanisms are not well understood. To address this issue, transcriptome profiling analyses were conducted for two biotypes of the cereal aphid, Sitobion avenae (Fabricius), on both original and alternative plants. RESULTS: Comparisons between both biotypes generated 4174 differentially expressed unigenes (DEGs). In their response to host plant shift, 39 DEGs were shared by both biotypes, whereas 126 and 861 DEGs occurred only in biotypes 1 and 3, respectively. MMC (modulated modularity clustering) analyses showed that specific DEGs of biotypes 1 and 3 clustered into five and nine transcriptional modules, respectively. Among these DEGs, defense-related genes underwent intensive expression restructuring in both biotypes. However, biotype 3 was found to have relatively lower gene transcriptional plasticity than biotype 1. Gene enrichment analyses of the abovementioned modules showed functional divergence in defensive DEGs for the two biotypes in response to host transfer. The expression plasticity for some defense related genes was showed to be directly related to fecundity of S. avenae biotypes on both original and alternative plants, suggesting that expression plasticity of key defensive genes could have significant impacts on the adaptive potential and differentiation of S. avenae biotypes on different plants. CONCLUSIONS: The divergence patterns of transcriptional plasticity in defense related genes may play important roles in the phenotypic evolution and differentiation of S. avenae biotypes. Our results can provide insights into the role of gene expression plasticity in the divergence of insect biotypes and adaptive evolution of insect populations.

Heterogeneous components of lung adenocarcinomas confer distinct EGFR mutation and PD-L1 expression.

BACKGROUND: Lung adenocarcinoma (LAC) is composed of lepidic, papillary, mucinous, micropapillary and solid components in its parenchyma. Complex responses to therapeutics result from intratumoral heterogeneity. However, it remains confused that what components in a mixed LAC tumor are responsible to the heterogeneous EGFR mutation and PD-L1 expression. METHODS: We investigated EGFR status via laser microdissection to capture spatially separated cancer cell subpopulations and digital droplet PCR to determine the abundance of EGFR sensitizing mutation and naïve T790M. Whilst, PD-L1 expression level via tumor proportion score (TPS) was evaluated by Ventana immunohistochemistry using SP263 antibody. PD-L1 expression levels were tiered in < 1, 1-49% and > =50% groups. RESULTS: EGFR mutation harbored in 154 (59%) of 261 LAC patients and more frequently occurred in papillary, lepidic and micropapillary constituents. Higher levels of PD-L1 were found in LACs at stage III and IV (68.3%) versus those at stage I and II (31.7%) (P = 0.04). Solid predominant LACs (41.3%) expressed PD-L1 with TPS > =50%, versus mucinous and lepidic LACs (P < 0.01). LACs with solid constituents also had more positive proportion of PD-L1 protein. Cut-offs < 1, 1-49% or > =50% were associated with patients' progression-free survival and longer in the < 1% group (22.9 month, 95% CI 17.6-28.2) (P < 0.05). LACs consisting of two constituents with PD-L1 TPS < 1% had a better prognosis than the groups with single component and more than two components (P < 0.05). Eighteen LACs (6.9%) had concomitantly deletion in exon 19 or L858R and naïve T790M mutation. The abundance of T790M varied diversely with sensitizing mutation. PD-L1 expression was not concordant in same components and usually negative in the EGFR-mutated constituents. Heterogeneous PD-L1 expression occurred in the vicinity of stromal tissues. 58.8, 29.4 and 11.8% in ALK positive LACs (N = 17) were found PD-L1 expression via cutoffs of < 1, 1-49% and > =50%, respectively (P > 0.05). CONCLUSION: Intratumoral genetic heterogeneity of LACs was demonstrated associated with histological patterns. Heterogeneous PD-L1 expression in higher level usually occurred in solid component both in EGFR mutated and EGFR wild-typed LACs. EGFR mutated LACs heterogeneously had sensitizing and resistant mutation and was accompanied with PD-L1 expression, but discordant among histological constituents. Immune checkpoint inhibitor combined with third generation EGFR tyrosine kinase inhibitor should be more effective to these LACs.

The Response in Air Quality to the Reduction of Chinese Economic Activities During the COVID-19 Outbreak.

During the COVID-19 outbreak that took place in early 2020, the economic activities in China were drastically reduced and accompanied by a strong reduction in the emission of primary air pollutants. On the basis of measurements made at the monitoring stations operated by the China National Environmental Monitoring Center, we quantify the reduction in surface PM2.5, NO2, CO, and SO2 concentrations in northern China during the lockdown, which started on 23 January 2020. We find that, on the average, the levels of surface PM2.5 and NO2 have decreased by approximately 35% and 60%, respectively, between the period 1 and 22 January 2020 and the period 23 January and 29 February 2020. At the same time, the mean ozone concentration has increased by a factor 1.5-2. In urban area of Wuhan, where drastic measures were adopted to limit the spread of the coronavirus, similar changes in the concentrations of PM2.5, NO2, and ozone are found.

A chemo- and regioselective C6-functionalization of 2,3-disubstituted indoles: highly efficient synthesis of diarylindol-6-ylmethanes.

An organocatalytic chemo- and regioselective C6-functionalization of 2,3-disubstituted indoles has been established via a reaction with ortho-hydroxybenzyl alcohols, which afforded biologically important diarylindol-6-ylmethanes in overall high yields (up to 99% yield). This protocol not only provides an efficient method for constructing biologically important diarylindol-6-ylmethane frameworks in an atom economical fashion, but also serves as a good example for the direct catalytic C6-functionalization of indoles, which have been rarely investigated. More importantly, the preliminary biological evaluation revealed that this new class of diarylindol-6-ylmethanes exhibited strong cytotoxicity to HeLa cell lines.

Life-history responses of insects to water-deficit stress: a case study with the aphid Sitobion avenae.

BACKGROUND: Drought may become one of the greatest challenges for cereal production under future warming scenarios, and its impact on insect pest outbreaks is still controversial. To address this issue, life-history responses of the English grain aphid, Sitobion avenae (Fabricius), from three areas of different drought levels were compared under three water treatments. RESULTS: Significant differences were identified in developmental time, fecundity and adult weight among S. avenae clones from moist, semiarid and arid areas under all the three water treatments. Semiarid and arid area clones tended to have higher heritability for test life-history traits than moist area clones. We identified significant selection of water-deficit on the developmental time of 1st instar nymphs and adult weight for both semiarid and arid area clones. The impact of intermediate and severe water-stress on S. avenae's fitness was neutral and negative (e.g., decreased fecundity and weight), respectively. Compared with arid-area clones, moist- and semiarid-area clones showed higher extents of adaptation to the water-deficit level of their respective source environment. Adult weight was identified as a good indicator for S. avenae's adaptation potential under different water-stress conditions. After their exposure to intermediate water-deficit stress for only five generations, adult weight and fecundity tended to decrease for moist- and semiarid-area clones, but increase for arid-area clones. CONCLUSIONS: It is evident from our study that S. avenae clones from moist, semiarid and arid areas have diverged under different water-deficit stress, and such divergence could have a genetic basis. The impact of drought on S. avenae's fitness showed a water-level dependent pattern. Clones of S. avenae were more likely to become adapted to intermediate water-deficit stress than severe water-deficit stress. After continuous water-deficit stress of only five generations, the adaptation potential of S. avenae tended to decrease for moist and semiarid area clones, but increase for arid area clones. The rapid shift of aphids' life-history traits and adaptation potential under drought could have significant implications for their evolutionary dynamics and outbreak risks in future climate change scenarios.

Cystathionine γ lyase-hydrogen sulfide increases peroxisome proliferator-activated receptor γ activity by sulfhydration at C139 site thereby promoting glucose uptake and lipid storage in adipocytes.

Adipocytes express the cystathionine γ lyase (CSE)-hydrogen sulfide (H2S) system. CSE-H2S promotes adipogenesis but ameliorates adipocyte insulin resistance. We investigated the mechanism of how CSE-H2S induces these paradoxical effects. First, we confirmed that an H2S donor or CSE overexpression promoted adipocyte differentiation. Second, we found that H2S donor inhibited but CSE inhibition increased phosphodiesterase (PDE) activity. H2S replacing isobutylmethylxanthine in the differentiation program induced adipocyte differentiation in part. Inhibiting PDE activity by H2S induced peroxisome proliferator activated receptor γ (PPARγ) protein and mRNA expression. Of note, H2S directly sulfhydrated PPARγ protein. Sulfhydrated PPARγ increased its nuclear accumulation, DNA binding activity and adipogenesis gene expression, thereby increasing glucose uptake and lipid storage, which were blocked by the desulfhydration reagent DTT. H2S induced PPARγ sulfhydration, which was blocked by mutation of the C139 site of PPARγ. In mice fed a high-fat diet (HFD) for 4 weeks, the CSE inhibitor decreased but H2S donor increased adipocyte numbers. In obese mice fed an HFD for 13 weeks, H2S treatment increased PPARγ sulfhydration in adipose tissues and attenuated insulin resistance but did not increase obesity. In conclusion, CSE-H2S increased PPARγ activity by direct sulfhydration at the C139 site, thereby changing glucose into triglyceride storage in adipocytes. CSE-H2S-mediated PPARγ activation might be a new therapeutic target for diabetes associated with obesity.

Correction: Zhao, J., et al. Podophyllotoxin-Loaded Nanostructured Lipid Carriers for Skin Targeting: In Vitro and In Vivo Studies. Molecules 2016, 21, 1549.

The authors wish to make the following correction to their paper [1].

Podophyllotoxin-Loaded Nanostructured Lipid Carriers for Skin Targeting: In Vitro and In Vivo Studies.

Nanostructured lipid carriers (NLC) exhibit high skin targeting efficiency and good safety. They are promising vehicles for topical drug delivery. This study aims to increase the skin distribution of podophyllotoxin (POD) by incorporating it into NLCs. Two kinds of POD-loaded NLCs (POD-NLCs)-POD-NLCformulation 1 and POD-NLCformulation 2-were prepared and characterized. Their skin targeting efficiencies were compared by conducting in vitro and in vivo experiments. Obviously smaller mean particle size was observed for POD-NLCformulation 1 (106 nm) than POD-NLCformulation 2 (219 nm), whereas relatively low POD loadings (less than 0.5%) were observed for both POD-NLCformulation 1 (0.33%) and POD-NLCformulation 2 (0.49%). Significantly higher in vitro and in vivo rat skin deposit amounts of POD (p ˂ 0.01) were detected after the topical application of POD-NLCformulation 1 compared to POD-NLCformulation 2. To visualize the skin distribution behavior of hydrophobic active pharmaceutical ingredients (APIs) when NLCs were used as carriers, POD was replaced with Nile red (NR-a hydrophobic fluorescent probe), and the distribution behavior of NR-NLCformulation 1 and NR-NLCformulation 2 in rat skin in vivo was observed using confocal laser scanning microscopy (CLSM). Higher fluorescent intensity was observed in rat skin after the topical application of NR-NLCformulation 1 than NR-NLCformulation 2, suggesting that higher skin targeting efficiency might be obtained when NLCs with smaller mean particle size were used as carriers for hydrophobic APIs. This result was in accordance with those of skin distribution evaluation experiments of POD-NLCs. Skin irritation property of POD-NLCformulation 1 was investigated and no irritation was observed in intact or damaged rabbit skin, suggesting it is safe for topical use. Our results validated the safety of NLCs when applied topically. More importantly, mean particle size might be an important parameter for formulation optimization when NLCs are used as carriers for hydrophobic APIs for topical application, considering that their loading is relatively low.

Impacts of Water Deficiency on Life History of Sitobion avenae Clones From Semi-arid and Moist Areas.

The climate warming trend appears to be evident with an increasing frequency of drought events in Shaanxi Province of China, which may have contributed to an increase in outbreaks of the English grain aphid, Sitobion avenae (Fabricius). To explore the potential effects of water-deficit stress on aphid outbreak risks, clones of S. avenae were collected from semi-arid and moist areas of Shaanxi. The life histories of collected clones were then compared on wheat under well-watered and moderately water-stressed conditions in the laboratory. Our results demonstrated that semi-arid area clones of S. avenae had longer developmental times, shorter reproductive times, lower fecundities, and lower net reproductive rates compared with moist area clones. Age-specific reproductive rates of moist area clones tended to be higher than those of semi-arid area clones. Significant differences between semi-arid and moist area clones were found for the survival functions when tested under water-stressed conditions, and semi-arid area clones tended to have a lower survival rate than moist area clones throughout their lives. "Population origin" (i.e., semi-arid and moist area clones) and "clone" together explained 62.74-96.56% of the total variance of tested life-history traits, suggesting the genetic basis for differentiation of clones from both areas. Significant differences in correlations, and selection differentials and gradients of life-history traits were also found between clones from both areas, providing further evidence of genetic basis for the life-history differentiation between them. Divergence between clones from both areas and its implications for S. avenae outbreaks are discussed.

Effect of hypoxia­HIF­1α­periostin axis in thyroid cancer.

The incidence of thyroid carcinoma (TC) has exhibited a rapid increase in recent years. A proportion of TCs exhibit aggressive behavior. The present study aimed to investigate the potential role of hypoxia­hypoxia inducible factor 1 subunit α (HIF­1α)­periostin axis in the progression of TC. The upregulation of periostin and HIF­1α expression levels was detected in 95 clinical TC tissues as compared with normal thyroid tissues. Hypoxia promoted the viability and invasion of TC cells and this effect was inhibited by the downregulation of periostin. Hypoxia also induced the Warburg effect in TC and this effect was inhibited by the silencing of periostin. Further investigations revealed that hypoxia activated HIF­1α, which in turn regulated the expression of periostin. Immunoprecipitation and dual luciferase reporter assays demonstrated that HIF­1α upregulated the expression of periostin by binding to the promoter of periostin. On the whole, these findings suggest the existence of a hypoxia­HIF­1α­periostin axis in TC and indicate the role of this axis in the progression of TC.

3D Morphological Scanning and Environmental Correlates of Bufo gargarizans in the Yellow River Basin.

Morphology plays a crucial role in understanding the intricacies of biological forms. Traditional morphometric methods, focusing on one- or two-dimensional geometric levels, often fall short of accurately capturing the three-dimensional (3D) structure of organisms. The advent of 3D scanning techniques has revolutionized the study of organismal morphology, enabling comprehensive and accurate measurements. This study employs a 3D structured light scanning system to analyze the morphological variations in the Chinese toad (Bufo gargarizans Cantor, 1842) along the Yellow River Basin. The 3D digital model obtained from the scan was used to calculate various morphological parameters including body surface area, volume, fractal dimensions, and limb size. The research explores geographic variability patterns and identifies environmental drivers affecting the 3D phenotypic variation of B. gargarizans. Results reveal a bimodal pattern of variation in the toad population, with higher elevations exhibiting smaller body sizes, greater appendage proportions, and more complex body structures. Linear regression analyses highlight the influence of elevation and annual mean temperature on the morphological variation of B. gargarizans, with elevation playing a significant role. This study underscores the significance of 3D morphometric analysis in unraveling the intricacies of organismal morphology and understanding the adaptive strategies of species in diverse environments.

Identification of cytochrome P450 monooxygenase genes and their expression profiles in cyhalothrin-treated Colorado potato beetle, Leptinotarsa decemlineata.

Based on a Leptinotarsa decemlineata transcriptome dataset and the GenBank sequences, a total of 74 cytochrome P450 monooxygenase genes (Cyps) were identified. These genes fell into CYP2 clan, mitochondrial clan, CYP3 clan and CYP4 clan, and were classified into 19 families and 35 subfamilies according to standard nomenclature. Two new families were discovered in CYP4 clan, and were named CYP412 and CYP413 respectively. Four new families that were recently discovered in Tribolium castaneum, including mitochondrial family CYP353, CYP3 clan families CYP345 and CYP347, and CYP4 clan family CYP350, were also found in L. decemlineata. The phylogenetic trees of CYPs from L. decemlineata and other representative insect species were constructed, and these trees provided evolutionary insight for the genetic distance. Our results facilitate further researches to understand the functions and evolution of L. decemlineata Cyp genes. In order to find cyhalothrin-inducible Cyp genes, the expression levels of Cyps belonging to CYP12, CYP6, CYP9 and CYP4 families were determined by quantitative reverse transcriptase-PCR in cyhalothrin-treated and control fourth-instar larvae. Nine Cyp genes, i.e., Cyp12H2, Cyp6BH2, Cyp6BJ1, Cyp6BQ17, Cyp6EG1, Cyp6EH1, Cyp6EJ1 Cyp4BN13v1 and Cyp4BN15, were highly expressed in cyhalothrin-treated larvae. These CYPs are the candidates that are involved in cyhalothrin detoxification.

Habitat-specific conservation priorities of multidimensional diversity patterns of amphibians in China effectively contribute to the '3030' target.

Amphibia is the most threatened animal group among all land vertebrates in the context of anthropogenic global change. Filling the conservation gaps for this taxonomic group could help achieve the ambitious target of covering 30 % of the land by 2030 ('3030' target) set by the 15-th meeting of the Conference of the Parties (COP15). In this study, we compiled the most up-to-date occurrence records and corresponding species-specific traits and phylogenies of amphibians in China (particularly those newly described in the past decade) to explore the spatial distribution patterns of multidimensional diversity (including taxonomic, functional, and phylogenetic) for different species groups (including all, endemic and threatened). Additionally, a new conservation gap index (CGI) was proposed and applied to the analysis of multi-objective conservation strategies. The results showed that the spatial distribution of taxonomic, functional and phylogenetic diversity of amphibians in China is markedly geographically diverse, with common hotspots for all three concentrated in the humid mountainous regions of southern China. The CGI, which is independent of arbitrary threshold selection and grid cell size, showed that the conservation gap for amphibians in China is largest in biomes such as tropical and subtropical moist broadleaf forests and temperate broadleaf and mixed forests. The multi-objective conservation analysis revealed that the Yangtze River basin, Pearl River basin and Southeast Basin in China have pivotal roles in achieving the '3030' target due to their high taxonomic, phylogenetic and functional diversity, relatively high proportion of threatened and endemic species, and low coverage of existing nature reserves. Notably, sustainable management of less-protected habitats, including farmlands and grasslands, can reduce the area requirement of strict protection for reaching the '3030' conservation goal. This study provides practical strategies for guiding amphibian conservation by systematically integrating multidimensional biodiversity information, habitat features and the spatial distributions of the existing natural reserves.

Flame-Retardant Foamed Material Based on Modified Corn Straw Using Two Nitrogenous Layers.

Foamed materials based on a biopolymer of crop straws are environmentally friendly, but ignitability limits their application. In this study, two nitrogenous layers were introduced onto corn straw by esterification and grafting for flame-retardant purposes. The inner thin nitrogenous layer consisted of imidazole rings, and the outer thick nitrogenous layer consisted of grafted acrylamide by a free-radical polymerization. The outer nitrogenous layer was simultaneously introduced into the system with a foaming process at 150 °C. Azodiisobutyronitrile acted both as initiator of the polymerization and the main foaming agent, and deionized water acted both as a plasticizing agent and an auxiliary foaming agent, which simplified the process and formula. It was found that cavities of two different sizes were formed. The nonuniformity of the foamed material was ascribed to the heterogeneous foaming precursor consisting of a rigid core and a soft shell. Its excellent flame-retard rating of UL-94 V-0 was ascribed to the two nitrogenous layers, which provides a sufficient nitrogen source for non-combustible gases. A relatively high compression strength of 17.7 MPa was partly due to the fiber of corn straw.

Total alkaloid fraction of Leonurus japonicus Houtt. Promotes angiogenesis and wound healing through SRC/MEK/ERK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt., also known as motherwort, is a traditional Chinese medicine that was first identified in Shennong Bencao Jing, the first and essential pharmacy monograph in China. L. japonicus has been regarded as a good gynecological medicine since ancient times. It has been widely used in clinical settings for treatment of gynecological diseases and postnatal rehabilitation with good efficacy and low adverse effects. AIM OF THE STUDY: The main purpose of this study was to determine the angiogenic and wound healing effects of total alkaloid fraction from L. japonicus Houtt. (TALH) in vivo and in vitro. In addition, the main bioactive components of total alkaloids were to be identified and analyzed in this study. MATERIALS AND METHODS: First, the UHPLC/Q-TOF-MS method was used to identify and quantify the major components in the TALH extract. The wound healing activity was evaluated in vivo using a rat full-thickness cutaneous wound model. Histological study of wound healing in rat model was performed via immunohistochemistry and immunofluorescence. Cell proliferation was determined by MTT assay. Wound healing and transwell assays were used for detection of cell migration. The effect on tube formation was determined by tube formation assay in HUVECs. Western blot and RT-PCR were used to detect the expressions of relative proteins and genes respectively. Knock-down of SRC by siRNA was done to verify the crucial role of SRC in promotion of angiogenesis induced by TALH. RESULTS: Seven characteristic peaks were recognized in the UHPLC/Q-TOF-MS spectrum, while four of the main components were quantified. The wound model in rats showed that treatment of TALH promoted wound healing by stimulating cellular proliferation and collagen deposition. In vitro experiments showed that co-treatment of TALH and VEGF increased cell proliferation, migration and tube formation in HUVECs. Mechanistic studies suggested that the co-treatment increased gene expressions of SRC, MEK1/2 and ERK1/2, as well as the phosphorylation levels of these proteins. Furthermore, the effect of co-treatment was attenuated after SRC knockdown, suggesting that SRC plays an important role in angiogenesis and wound healing induced by TALH and VEGF co-treatment. CONCLUSION: Our results showed that TALH was one of the main active components of L. japonicus that promoted angiogenesis and wound healing by regulating the SRC/MEK/ERK pathway. Our study provided scientific basis for better clinical application of L. japonicas.