Resistance development to one chemotherapeutic reagent leads frequently to acquired tolerance to other compounds, limiting the therapeutic options for cancer treatment. Herein, we find that ...overexpression of Rac1 is associated with multi-drug resistance to the neoadjuvant chemotherapy (NAC). Mechanistically, Rac1 activates aldolase A and ERK signaling which up-regulates glycolysis and especially the non-oxidative pentose phosphate pathway (PPP). This leads to increased nucleotides metabolism which protects breast cancer cells from chemotherapeutic-induced DNA damage. To translate this finding, we develop endosomal pH-responsive nanoparticles (NPs) which deliver Rac1-targeting siRNA together with cisplatin and effectively reverses NAC-chemoresistance in PDXs from NAC-resistant breast cancer patients. Altogether, our findings demonstrate that targeting Rac1 is a potential strategy to overcome acquired chemoresistance in breast cancer.
Standard plant DNA barcodes based on 2–3 plastid regions, and nrDNA ITS show variable levels of resolution, and fail to discriminate among species in many plant groups. Genome skimming to recover ...complete plastid genome sequences and nrDNA arrays has been proposed as a solution to address these resolution limitations. However, few studies have empirically tested what gains are achieved in practice. Of particular interest is whether adding substantially more plastid and nrDNA characters will lead to an increase in discriminatory power, or whether the resolution limitations of standard plant barcodes are fundamentally due to plastid genomes and nrDNA not tracking species boundaries. To address this, we used genome skimming to recover near‐complete plastid genomes and nuclear ribosomal DNA from Rhododendron species and compared discrimination success with standard plant barcodes. We sampled 218 individuals representing 145 species of this species‐rich and taxonomically difficult genus, focusing on the global biodiversity hotspots of the Himalaya‐Hengduan Mountains. Only 33% of species were distinguished using ITS+matK+rbcL+trnH‐psbA. In contrast, 55% of species were distinguished using plastid genome and nrDNA sequences. The vast majority of this increase is due to the additional plastid characters. Thus, despite previous studies showing an asymptote in discrimination success beyond 3–4 plastid regions, these results show that a demonstrable increase in discriminatory power is possible with extensive plastid genome data. However, despite these gains, many species remain unresolved, and these results also reinforce the need to access multiple unlinked nuclear loci to obtain transformative gains in species discrimination in plants.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To address the problems of uneven distribution and low coverage of wireless sensor network (WSN) nodes in random deployment, a node coverage optimization strategy with an improved COOT bird algorithm ...(COOTCLCO) is proposed. Firstly, the chaotic tent map is used to initialize the population, increase the diversity of the population, and lay the foundation for the global search for the optimal solutions. Secondly, the Lévy flight strategy is used to perturb the individual positions to improve the search range of the population. Thirdly, Cauchy mutation and an opposition-based learning strategy are fused to perturb the optimal solutions to generate new solutions and enhance the ability of the algorithm to jump out of the local optimum. Finally, the COOTCLCO algorithm is applied to WSN coverage optimization problems. Simulation results show that COOTCLCO has a faster convergence speed and better search accuracy than several other typical algorithms on 23 benchmark test functions; meanwhile, the coverage rate of the COOTCLCO algorithm is increased by 9.654%, 13.888%, 6.188%, 5.39%, 1.31%, and 2.012% compared to particle swarm optimization (PSO), butterfly optimization algorithm (BOA), seagull optimization algorithm (SOA), whale optimization algorithm (WOA), Harris hawks optimization (HHO), and bald eagle search (BES), respectively. This means that in terms of coverage optimization effect, COOTCLCO can obtain a higher coverage rate compared to these algorithms. The experimental results demonstrate that COOTCLCO can effectively improve the coverage rate of sensor nodes and improve the distribution of nodes in WSN coverage optimization problems.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In less than 6 months, COVID-19 spread rapidly around the world and became a global health concern. Hypertension is the most common chronic disease in COVID-19 patients, but its impact on these ...patients has not been well described. In this retrospective study, 82 patients diagnosed with COVID-19 were enrolled, and epidemiological, demographic, clinical, laboratory, radiological and therapy-related data were analyzed and compared between COVID-19 patients with (29 cases) or without (53 cases) hypertension. The median age of the included patients was 60.5 years, and the cohort included 49 women (59.8%) and 33 (40.2%) men. Hypertension (31 28.2%) was the most common chronic illness, followed by diabetes (16 19.5%) and cardiovascular disease (15 18.3%). The most common symptoms were fatigue (55 67.1%), dry cough (46 56.1%) and fever ≥ 37.3 °C (46 56.1%). The median time from illness onset to positive RT-PCR test was 13.0 days (range 3-25 days). There were 6 deaths (20.7%) in the hypertension group and 5 deaths (9.4%) in the nonhypertension group, and more hypertensive patients with COVID-19 (8 27.6%) than nonhypertensive patients (2 3.8%) (P = 0.002) had at least one comorbid disease. Compared with nonhypertensive patients, hypertensive patients exhibited higher neutrophil counts, serum amyloid A, C-reactive protein, and NT-proBNP and lower lymphocyte counts and eGFR. Dynamic observations indicated more severe disease and poorer outcomes after hospital admission in the hypertension group. COVID-19 patients with hypertension have increased risks of severe inflammatory reactions, serious internal organ injury, and disease progression and deterioration.
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Natural hybridization can influence the adaptive response to selection and accelerate species diversification. Understanding the composition and structure of hybrid zones may elucidate patterns of ...hybridization processes that are important to the formation and maintenance of species, especially for taxa that have experienced rapidly adaptive radiation. Here, we used morphological traits, ddRAD-seq and plastid DNA sequence data to investigate the structure of a Rhododendron hybrid zone and uncover the hybridization patterns among three sympatric and closely related species.
Our results show that the hybrid zone is complex, where bi-directional hybridization takes place among the three sympatric parental species: R. spinuliferum, R. scabrifolium, and R. spiciferum. Hybrids between R. spinuliferum and R. spiciferum (R. ×duclouxii) comprise multiple hybrid classes and a high proportion of F
generation hybrids, while a novel hybrid taxon between R. spinuliferum and R. scabrifolium dominated the F
generation, but no backcross individuals were detected. The hybrid zone showed basically coincident patterns of population structure between genomic and morphological data.
Natural hybridization exists among the three Rhododendron species in the hybrid zone, although patterns of hybrid formation vary between hybrid taxa, which may result in different evolutionary outcomes. This study represents a unique opportunity to dissect the ecological and evolutionary mechanisms associated with adaptive radiation of Rhododendron species in a biodiversity hotspot.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
One new alkaloid, picrasine A, two new quassinoids, picralactones A−B, together with eleven known compounds were isolated from Picrasma chinensis P.Y. Chen. The structures of these compounds were ...determined using 1D and 2D NMR, HR‐ESI‐MS, and IR spectroscopic data, and by comparison with published data. Some compounds were tested for tyrosinase inhibiting activity, however, none of them exhibited strong inhibitory effects.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Five unknown labdane diterpenoids Stevelins A–E (1–5), three known labdane diterpenoids (6–8) and three labdane norditerpenoids (9–11) were isolated from the Stevia rebaudiana. The structures were ...determined primarily via NMR spectroscopic data and HR‐ESI‐MS experiments. X‐ray crystallography using CuKα radiation was used to determine the absolute configurations of 1, and the absolute configurations of 2–5 were deduced by electronic circular dichroism (ECD) calculations. The potential anti‐atherosclerosis activities of all compounds were evaluated by measuring their inhibitory effects on the macrophage foam cell formation. As a result, most isolated compounds could significantly inhibit oxidized low‐density lipoprotein (ox‐LDL)‐induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment for atherosclerosis.
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•Volcanics erupted at 2574–2527Ma in Anshan–Benxi greenstone belt of the NCC.•The volcanic rock groups were derived from the dominant mantle wedge magmatism.•By the late Archean, ...Eastern Liaoning was a convergent plate margin environment.
The Anshan–Benxi granite-greenstone belt (ABGB) in the Eastern Block of the North China Craton mainly comprises supracrustal rocks of amphibole plagioclase gneisses, plagioclase amphibolites, chlorite schists, biotite schists, quartzites and banded iron formations (BIFs), and intrusive monzogranitic to syenogranitic gneisses. Based on geology, spatial distributions, lithologies and zircon U-Pb geochronology, the metavolcanic rocks of the southern ABGB can be divided into the ∼2527Ma southern plagioclase gneiss group, ∼2536Ma southern amphibolite group, ∼2574 to 2560Ma northern chlorite schist group and northern amphibolite group from south to north. These rocks outcrop as stratified and stratoid beds, whereas some occur as enclaves within later intrusive K-rich granitic gneisses. The southern plagioclase gneiss group exhibits calc-alkaline andesite compositions with high MgO, Cr, and Ni, fractionated REE patterns and depletion in Nb–Ta, which resemble high magnesian andesite (HMA) and are derived from the partial melting of sub-arc mantle peridotite that was previously metasomatized by slab melts. The southern amphibolite group has tholeiitic basalt compositions with slight enrichment in LREEs and high Nb–Ti concentrations but low (Nb/La)PM ratios, which coincide with Nb-enriched basalt and are generated by the remelting of residues of sub-arc mantle after the extraction of HMA melts. The northern schist group shows high-K calc-alkaline andesite-dacite compositions and have highest silica and potassium, and obvious enrichment in LREEs and LILEs and depletion in Nb–Ta, which are comparable to the sanukitoid series rocks. These rocks probably formed by low-degree partial melting of a sub-arc mantle wedge that was metasomatized by slab-derived fluids. The northern amphibolite group exhibits tholeiite compositions with unfractionated REE patterns and low (Nb/La)PM ratios, which are consistent with back-arc basin basalts (BABB) and are produced by partial melting of depleted mantle.
Combined with lithological associations of the HMA, NEB, sanukitoid-like rocks and BABB-like rocks, the Anshan–Benxi granite-greenstone belt was produced under a convergent plate environment. Both the zircon εHf values and petrogenesis indicate that the four groups of the metamorphic volcanic rocks directly contributed to continental crustal growth. Integrating with the widespread ∼2.5Ga syenogranites and subordinate K-rich granitoids that were derived from reworking of ancient crust, we propose that the ABGB experienced a significant episode of continental growth dominated by a subduction-related lateral accretion accompanied with contemporaneously strong reworking of ancient crustal materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Nasopharyngeal carcinoma (NPC) is a tumor of epithelial origin with radiotherapy as its standard treatment. However, radioresistance remains a critical issue in the treatment of NPC. This study aimed ...to investigate the effect of berberine on the proliferation, cell cycle regulation, apoptosis, radioresistance of NPC cells and whether specificity protein 1 (Sp1) is a functional target of berberine. Our results showed that treatment with berberine reduced the proliferation and viability of CNE-2 cells in a dose- and time-dependent manner. Berberine induced cell cycle arrest in the G0/G1 phase and apoptosis. In CNE-2 cells exposed to gamma-ray irradiation, berberine reduced cell viability at various concentrations (25, 50, 75 and 100 µmol/l). Berberine significantly decreased mRNA and protein expression of Sp1 in the CNE-2 cells. Mithramycin A, a selective Sp1 inhibitor, enhanced the radiosensitivity and the rate of apoptosis in the CNE-2 cells. Berberine inhibited transforming growth factor-β (TGF-β)-induced tumor invasion and suppressed epithelial-to-mesenchymal transition (EMT) process, as evidenced by increased E-cadherin and decreased vimentin proteins. Sp1 may be required for the TGF-β1-induced invasion and EMT by berberine. In conclusion, berberine demonstrated the ability to suppress proliferation, induce cell cycle arrest and apoptosis, and enhance radiosensitivity of the CNE-2 NPC cells. Sp1 may be a target of berberine which is decreased during the radiosensitization of berberine.
A series of 4-aminoquinazoline derivatives were designed and synthesized as epidermal growth factor receptor (EGFR) inhibitors in our group. The bioassay results showed all the target compounds ...possessed potential anti-tumor activities against on A549 and H1975 cell lines. The IC50 values of 8.35 (for A549) and 19.18 μM (for H1975) exhibited remarkable inhibitory activity of compound 7d, which were better compared to the positive control Afatinib (IC50 = 10.41 μM for A549, IC50 = 24.96 μM for H1975). In addition, the molecular docking and ADME prediction of compound 7d was carried out. The experimental results show the compound 7d is worth to further research and discuss.
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