Biogeography and community assembly of soil fungi from alpine meadows in southwestern China show the importance of climatic selection.

Soil fungi are pivotal in alpine and arctic ecosystems that are vulnerable to climate changes. Previous studies have shown broad connections between soil fungi in the arctic and alpine regions, but most of these studies are mainly from Europe and North America, with more sporadic studies from East Asia. Currently, little is known about the biogeographic relationships between soil fungi in alpine meadows of southwestern China (AMSC) and other regions of the world. In addition, the regional-scale spatial patterns of fungal communities in the AMSC, as well as their driving factors and ecological processes, are also poorly understood. In this study, we collected roots and surrounding soils of two dominant ectomycorrhizal plants, Bistorta vivipara and B. macrophylla from the AMSC, and performed bioinformatic and statistical analyses based on high-throughput sequencing of ITS2 amplicons. We found that: (1) fungi from the AMSC were closely related with those from boreal forests and tundra, and saprotrophic fungi had higher dispersal potential than ectomycorrhizal fungi; (2) community compositions exhibited clear divergences among geographic regions and between root and soil samples; (3) climate was the predominant factor driving regional-scale spatial patterns but had less explanatory power for saprotrophic and total fungi from roots than those from soils; (4) homogeneous selection and drift were the key ecological processes governing community assembly, but in communities of saprotrophic and total fungi from soil samples, drift contributed less and its role was partially replaced by dispersal limitation. This study highlights the importance of climatic selection and stochastic processes on fungal community assembly in alpine regions, and emphasizes the significance of simultaneously investigating fungi with different trophic modes and from both roots and soils.

Chloroplast protein StFC-II was manipulated by a Phytophthora effector to enhance host susceptibility.

Oomycete secretes a range of RxLR effectors into host cells to manipulate plant immunity by targeting proteins from several organelles. In this study, we report that chloroplast protein StFC-II is hijacked by a pathogen effector to enhance susceptibility. Phytophthora infestans RxLR effector Pi22922 is activated during the early stages of P. infestans colonization. Stable overexpression of Pi22922 in plants suppresses flg22-triggered reactive oxygen species (ROS) burst and enhances leaf colonization by P. infestans. A potato ferrochelatase 2 (FC-II, a nuclear-encoded chloroplast-targeted protein), a key enzyme for heme biosynthesis in chloroplast, was identified as a target of Pi22922 in the cytoplasm. The pathogenicity of Pi22922 in plants is partially dependent on FC-II. Overexpression of StFC-II decreases resistance of potato and Nicotiana benthamiana against P. infestans, and silencing of NbFC-II in N. benthamiana reduces P. infestans colonization. Overexpression of StFC-II increases heme content and reduces chlorophyll content and photosynthetic efficiency in potato leaves. Moreover, ROS accumulation both in chloroplast and cytoplasm is attenuated and defense-related genes are down-regulated in StFC-II overexpression transgenic potato and N. benthamiana leaves. Pi22922 inhibits E3 ubiquitin ligase StCHIP-mediated StFC-II degradation in the cytoplasm and promotes its accumulation in chloroplasts. In summary, this study characterizes a new mechanism that an oomycete RxLR effector suppresses host defenses by promoting StFC-II accumulation in chloroplasts, thereby compromising the host immunity and promoting susceptibility.

Nontarget Analysis of Legacy and Emerging PFAS in a Lithium-Ion Power Battery Recycling Park and Their Possible Toxicity Measured Using High-Throughput Phenotype Screening.

Driven by the global popularity of electric vehicles and the shortage of critical raw materials for batteries, the spent lithium-ion power battery (LIPB) recycling industry has exhibited explosive growth in both quantity and scale. However, relatively little information is known about the environmental risks posed by LIPB recycling, in particular with regards to perfluoroalkyl and polyfluoroalkyl substances (PFAS). In this work, suspect screening and nontarget analysis were carried out to characterize PFAS in soil, dust, water and sediment from a LIPB recycling area. Twenty-five PFAS from nine classes were identified at confidence level 3 or above, including 13 legacy and 12 emerging PFAS, as well as two ultrashort-chain PFAS. Based on the target analysis of 16 PFAS, at least nine were detected in each environmental sample, indicating their widespread presence in a LIPB recycling area. Perfluorodecanoic acid, perfluorooctanesulfonic acid and trifluoromethanesulfonamide showed significant differences in the four phenotypic parameters (growth, movement, survival and fecundity) of Caenorhabditis elegans and were the most toxic substances in all target PFAS at an exposure concentration of 200 µM. Our project provides first-hand information on the existence and environmental risk of PFAS, facilitating the formulation of regulations and green development of the LIPB recycling industry.

Unveiling the role of HACE1 in cervical cancer: implications for human papillomavirus infection and prognosis.

Background: Cervical cancer, one of the prevalent malignancies among females, is closely associated with human papillomavirus (HPV) infection. Homologous to the E6-AP carboxyl terminus (HECT) domain and ankyrin repeat containing E3 ubiquitin-protein ligase 1 (HACE1) plays pivotal roles in various cancers. This study aimed to elucidate the expression of HACE1 in cervical cancer and its correlation with clinical features. Methods: From The Cancer Genome Atlas Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC) and Gene Expression Omnibus (GEO, GSE6791) datasets, we obtained RNA-Seq profiles and associated clinical information. Differential gene analysis was conducted using the R "limma" package. Implications for HPV infection and the overall survival (OS) of cervical cancer were determined by performing differential expression analysis and the Cox proportional hazards regression model. Immunohistochemical analyses were used to validate the expression in cervical cancer and normal cervical tissue. Further, nomogram was constructed to predict OS in cervical cancer. Whether the model was credible was evaluated according to receiver operating characteristic (ROC) curves and concordance curves. To further evaluate the potential functions of HACE1, we conducted functional enrichment analysis. Finally, we assessed methylation levels in HPV+ and HPV- patients in the TCGA-CESC dataset. Results: Utilizing TCGA and GSE6791 datasets, we observed significant upregulation of HACE1 in cervical cancer patients, particularly linked to HPV infection. Immunohistochemical staining revealed enhanced HACE1 expression in tumor tissues. Further analysis demonstrated a significant positive correlation between elevated HACE1 and HPV-associated proteins (E1, E6, and E7). Moreover, high HACE1 expression was associated with adverse prognosis in cervical cancer patients. Multivariate Cox analysis indicated that HACE1 could serve as an independent prognostic factor. We developed a prognostic model integrating HPV subtypes, the International Federation of Gynecology and Obstetrics (FIGO) staging, and HACE1, exhibiting strong predictive efficacy for cervical cancer prognosis. Gene enrichment analysis indicated HACE1's potential involvement in multiple signaling pathways during cervical cancer progression, while the demethylation of cg03002526 in HPV-positive patients might contribute to HACE1 upregulation. Conclusions: Our study reveals that HACE1 upregulation is associated with cervical cancer, particularly in HPV-positive patients. HACE1 emerges as an independent prognostic factor, linked to unfavorable outcomes.

Epithelium-derived exosomes promote silica nanoparticles-induced pulmonary fibroblast activation and collagen deposition via modulating fibrotic signaling pathways and their epigenetic regulations.

BACKGROUND: In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated. RESULTS: The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-ß/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-ß/BMPR2/Smad pathway. CONCLUSIONS: Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-ß/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Anti-MRSA mechanism of spirostane saponin in Rohdea pachynema F.T.Wang & tang.

ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.

Phylogenetic and taxonomic updates of Agaricales, with an emphasis on Tricholomopsis.

The order Agaricales was divided into eight suborders. However, the phylogenetic relationships among some suborders are largely unresolved, and the phylogenetic positions and delimitations of some taxa, such as Sarcomyxaceae and Tricholomopsis, remain unsettled. In this study, sequence data of 38 genomes were generated through genome skimming on an Illumina sequencing system. To anchor the systematic position of Sarcomyxaceae and Tricholomopsis, a phylogenetic analysis based on 555 single-copy orthologous genes from the aforementioned genomes and 126 publicly accessible genomes was performed. The results fully supported the clustering of Tricholomopsis with Phyllotopsis and Pleurocybella within Phyllotopsidaceae, which formed a divergent monophyletic major lineage together with Pterulaceae, Radulomycetaceae, and Macrotyphula in Agaricales. The analysis also revealed that Sarcomyxaceae formed a unique major clade. Therefore, two new suborders, Phyllotopsidineae and Sarcomyxineae, are proposed for the two major lineages. Analyses of 450 single-copy orthologous genes and four loci suggested that Tricholomopsis consisted of at least four clades. Tricholomopsis is subsequently subdivided into four distinct sections. Seventeen Tricholomopsis species in China, including six new species, are reported. Conoloma is established to accommodate T. mucronata. The substrate preference of Tricholomopsis species and the transitions of the pileate ornamentations among the species within the genus are discussed.

Gender-specific effects of polystyrene nanoplastic exposure on triclosan-induced reproductive toxicity in zebrafish (Danio rerio).

Nanoplastics (NPs) and triclosan (TCS) are ubiquitous emerging environmental contaminants detected in human samples. While the reproductive toxicity of TCS alone has been studied, its combined effects with NPs remain unclear. Herein, we employed Fourier transform infrared spectroscopy and dynamic light scattering to characterize the coexposure of polystyrene nanoplastics (PS-NPs, 50 nm) with TCS. Then, adult zebrafish were exposed to TCS at environmentally relevant concentrations (0.361-48.2 µg/L), with or without PS-NPs (1.0 mg/L) for 21 days. TCS biodistribution in zebrafish tissues was investigated using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. Reproductive toxicity was assessed through gonadal histopathology, fertility tests, changes in steroid hormone synthesis and gene expression within the hypothalamus-pituitary-gonad-liver (HPGL) axis. Transcriptomics and proteomics were applied to explore the underlying mechanisms. The results showed that PS-NPs could adsorb TCS, thus altering the PS-NPs' physical characteristics. Our observations revealed that coexposure with PS-NPs reduced TCS levels in the ovaries, livers, and brains of female zebrafish. Conversely, in males, coexposure with PS-NPs increased TCS levels in the testes and livers, while decreasing them in the brain. We found that co-exposure mitigated TCS-induced ovary development inhibition while exacerbated TCS-induced spermatogenesis suppression, resulting in increased embryonic mortality and larval malformations. This co-exposure influenced the expression of genes linked to steroid hormone synthesis (cyp11a1, hsd17ß, cyp19a1) and attenuated the TCS-decreased estradiol (E2) in females. Conversely, testosterone levels were suppressed, and E2 levels were elevated due to the upregulation of specific genes (cyp11a1, hsd3ß, cyp19a1) in males. Finally, the integrated analysis of transcriptomics and proteomics suggested that the aqp12-dctn2 pathway was involved in PS-NPs' attenuation of TCS-induced reproductive toxicity in females, while the pck2-katnal1 pathway played a role in PS-NPs' exacerbation of TCS-induced reproductive toxicity in males. Collectively, PS-NPs altered TCS-induced reproductive toxicity by disrupting the HPGL axis, with gender-specific effects.

Assessing the Impact of PM2.5-Bound Arsenic on Cardiovascular Risk among Workers in a Non-ferrous Metal Smelting Area: Insights from Chemical Speciation and Bioavailability.

Inhalation of fine particulate matter PM2.5-bound arsenic (PM2.5-As) may cause significant cardiovascular damage, due to its high concentration, long transmission range, and good absorption efficiency in organisms. However, both the contribution and the effect of the arsenic exposure pathway, with PM2.5 as the medium, on cardiovascular system damage in nonferrous smelting sites remain to be studied. In this work, a one-year site sample collection and analysis work showed that the annual concentration of PM2.5-As reached 0.74 µg/m3, which was 120 times the national standard. The predominant species in the PM2.5 samples were As (V) and As (III). A panel study among workers revealed that PM2.5-As exposure dominantly contributed to human absorption of As. After exposure of mice to PM2.5-As for 8 weeks, the accumulation of As in the high exposure group reached equilibrium, and its bioavailability was 24.5%. A series of animal experiments revealed that PM2.5-As exposure induced cardiac injury and dysfunction at the environmental relevant concentration and speciation. By integrating environmental and animal exposure assessments, more accurate health risk assessment models exposed to PM2.5-As were established for metal smelting areas. Therefore, our research provides an important scientific basis for relevant departments to formulate industry supervision, prevention and control policies.

Genetically predicted lipids mediate the association between intrahepatic cholestasis of pregnancy and cardiovascular disease.

Introduction: Intrahepatic cholestasis of pregnancy (ICP), the most prevalent liver disorder specific to pregnancy, affects approximately 1.5%-4% of pregnancies. However, the influence of ICP on cardiovascular disease (CVD), including hypertension (HTN) and coronary artery disease (CAD), has not been thoroughly investigated. Methods: This study explores the causal relationship between ICP and CVD (HTN, CAD) using Mendelian Randomization (MR). Utilizing summary-level data from Genome-Wide Association Studies (GWAS), we applied the inverse-variance weighted (IVW) method, supplemented by sensitivity and reverse MR analyses, to ascertain robustness. Results: Our findings reveal significant causal links, indicating ICP notably increases the risk of CVD (P = 0.001), hypertension (HTN, P = 0.024), and coronary artery disease (CAD, P = 0.039). A two-step MR analysis highlighted the mediation role of lipid profiles, with LDL, TC, and Apo-B contributing to increased CVD risk by 25.5%, 12.2%, and 21.3%, respectively. Additionally, HTN was identified as a mediator in the ICP-CAD association, accounting for a 14.5% mediation effect. Discussion: The results underscore the genetic predisposition of ICP to elevate CVD risk and the critical mediating role of lipid levels, emphasizing the need for vigilant lipid monitoring and early intervention in individuals with ICP.

Four New Species and One New Record of Thelephora from China.

Species of the genus Thelephora (Thelephorales, Thelephoraceae) are ectomycorrhizal symbionts of coniferous and broad-leaved plants, and some of them are well-known edible mushrooms, making it an exceptionally important group ecologically and economically. However, the diversity of the species from China has not been fully elucidated. In this study, we conducted a phylogenetic analysis based on the internal transcribed spacer (ITS) regions, using Maximum Likelihood and Bayesian analyses, along with morphological observations of this genus. Four new species from China are proposed, viz., T. dactyliophora, T. lacunosa, T. petaloides, and T. pinnatifida. In addition, T. sikkimensis originally described from India is reported for the first time from China. Thelephora dactyliophora, T. pinnatifida, and T. sikkimensis are distributed in subtropical forests and mainly associated with plants of the families Fagaceae and Pinaceae. Thelephora lacunosa and T. petaloides are distributed in tropical to subtropical forests. Thelephora lacunosa is mainly associated with plants of the families Fagaceae and Pinaceae, while T. petaloides is mainly associated with plants of the family Fagaceae. Line drawings of microstructures, color pictures of fresh basidiomes, and detailed descriptions of these five species are provided.

Sustained release gel based on CT image inspection for treatment of diabetes fundus macular lesions.

Currently, slow-release gel therapy is considered to be an effective treatment for fundus macular disease, but the lack of effective evaluation methods limits its clinical application. Therefore, the purpose of this study was to investigate the application and clinical effect of slow-release gel based on CT image examination in the treatment of diabetic fundus macular disease. CT images of fundus macular lesions were collected in a group of diabetic patients. Then the professional image processing software is used to process and analyze the image and extract the key parameters. A slow-release gel was designed and prepared, and applied to the treatment of diabetic fundus macular disease. CT images before and after treatment were compared and analyzed, and the effect of slow-release gel was evaluated. In a certain period of time after treatment, the lesion size and lesion degree of diabetic fundus macular disease were significantly improved by using slow-release gel therapy with CT image examination. No significant adverse reactions or complications were observed during the treatment. This indicates that the slow-release gel based on CT image examination is a safe, effective and feasible treatment method for diabetic fundus macular disease. This method can help improve the vision and quality of life of patients, and provide a new idea and plan for clinical treatment.

Molecular phylogeny and morphology of Sporodiniella sinensis sp. nov. (Syzygitaceae, Mucorales), an invertebrate-associated species from Yunnan, China.

During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62 % for internal transcribed spacer (ITS), 98.66-99.10 % for ribosomal small subunit (nrSSU), and 96.36-98.22 % for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.

Potato miR394 targets StA/N-INVE and StLCR to negatively regulate late blight resistance.

MicroRNAs (miRNAs) are small noncoding RNAs in eukaryotes. Plant endogenous miRNAs play pivotal roles in regulating plant development and defense responses. MicroRNA394 (miR394) has been reported to regulate plant development, abiotic stresses and defense responses. Previous reports showed that miR394 responded to P. infestans inoculation in potato, indicating that miR394 may be involved in defense responses. In this study, we further investigated its role in potato defense against P. infestans. Stable expression of miR394 in tobacco and potato enhances the susceptibility to P. infestans, which is accompanied with the reduced accumulation of ROS and down-regulation of the PTI (pattern-triggered immunity) marker genes. Besides well-known target StLCR, miR394 also targets StA/N-INVE, which encodes a chloroplast Alkaline/Neutral Invertases (A/N-INVE). Both StLCR and StA/N-INVE positively regulate late blight resistance, while miR394 degrades them. Interestingly, StA/N-INVE is located in the chloroplast, indicating that miR394 may manipulate chloroplast immunity. Degradation of StA/N-INVE may affect the chloroplast function and hence lead to the compromised ROS (reactive oxygen species) burst and reduced retrograde signaling from the chloroplast to the nucleus and cytoplasm. In summary, this study provides new information that miR394 targets and degrades StA/N-INVE and StLCR, which are positive regulators, to enhance potato susceptibility to P. infestans.

Generation of sulfones utilizing ß-sulfinyl esters as masked aryl sulfinates under redox-neutral conditions.

A method for generation of SVI sulfones from ß-sulfinyl esters (SIV) under transition-metal-free non-oxidative mild conditions is presented. Various sulfones have been achieved with moderate to excellent yields. The advantage of using ß-sulfinyl esters as masked aryl sulfinates has also been exemplified using brominated substrates. Oxygen isotope-labeling experiments indicated that the oxygen atoms incorporated into the sulfone product come from the sulfoxide of the ß-sulfinyl ester. Successive ß-elimination/O-addition/sulfinate esterification/ß-elimination processes are proposed for the mechanism of generating SVI from SIV.

Polymer-DNA assembled nanoflower for targeted delivery of dolastatin-derived microtubule inhibitors.

Dolastatin derivatives possess excellent anticancer activity and have been translated into clinical trials for cancer therapy. Drug delivery systems enable dolastatin derivatives to break the limitation of instability during blood circulation and ineffective cell internalization in the application. Nevertheless, their potential has not been thoroughly established because of the limited loading efficacy and complicated chemical modification. Herein, we rationally propose a rolling circle amplification-based polymer-DNA assembled nanoflower for targeted and efficient delivery of dolastatin-derived drugs to achieve efficient anticancer therapy. The polymer-DNA assembled nanoflower with targeted aptamer conjugate is widely applicable for loading dolastatin-derived drugs with high encapsulation efficiency. The developed monomethyl auristatin E (MMAE) loaded PN@M exhibited increased cellular uptake and enhanced inhibitory effect, especially in multidrug-resistant tumor cells. The results of in vivo anticancer effects indicate that nanoflower as a dolastatin derivatives delivery system holds considerable potential for the treatment of malignant cancer.

Molecular phylogeny and morphology reveal two new entomopathogenic species of Ophiocordyceps (Ophiocordycipitaceae, Hypocreales) parasitic on termites from China.

Two new termite-pathogenic species, Ophiocordycepsglobiperitheciata and O.longistipes, are described from Yunnan Province, China. Six-locus (ITS, nrSSU, nrLSU, tef-1α, rpb1 and rpb2) phylogenetic analyses in combination with morphological observations were employed to characterize these two species. Phylogenetically, O.globiperitheciata is most closely related to Hirsutellacryptosclerotium and O.communis, whereas O.longistipes shares a sister relationship with O.fusiformis. However, O.globiperitheciata differs from H.cryptosclerotium by parasitizing Blattodea and producing clavate, unbifurcated stromata. Ophiocordycepsglobiperitheciata is distinguished from O.communis by multiple stromata, shorter asci and ascospores. Ophiocordycepslongistipes differs from O.fusiformis in producing larger stromata, perithecia, asci and ascospores, as well as smaller citriform or oval conidia. Morphological descriptions of the two new species and a dichotomous key to the 19 termite-pathogenic Ophiocordyceps species are presented.

Biomimetic Total Synthesis of Bimagnolignan: A Natural Anti-Breast Cancer Agent.

A short scalable biomimetic route to bioactive natural product bimagnolignan (1) was accomplished. Compound 1 was successfully prepared through a three-step metal-free synthesis from honokiol (2). Alternatively, 1 was also synthesized by biomimetic transformations that mimic tyrosinase in four steps. The key reactions feature a regioselective acetylation, a highly efficient C(sp2)-H oxidation, a cascade aerobic oxidative cyclization/coupling, and a Cu-catalyzed direct oxidative coupling. In addition, cell-based assays validate that 1 is a promising natural lead for HER2-positive breast cancer treatment.