A chromosome-level genome assembly of the forestry pest Coronaproctus castanopsis.

As an important forestry pest, Coronaproctus castanopsis (Monophlebidae) has caused serious damage to the globally valuable Gutianshan ecosystem, China. In this study, we assembled the first chromosome-level genome of the female specimen of C. castanopsis by merging BGI reads, HiFi long reads and Hi-C data. The assembled genome size is 700.81 Mb, with a scaffold N50 size of 273.84 Mb and a contig N50 size of 12.37 Mb. Hi-C scaffolding assigned 98.32% (689.03 Mb) of C. Castanopsis genome to three chromosomes. The BUSCO analysis (n = 1,367) showed a completeness of 91.2%, comprising 89.2% of single-copy BUSCOs and 2.0% of multicopy BUSCOs. The mapping ratio of BGI, second-generation RNA, third-generation RNA and HiFi reads are 97.84%, 96.15%, 97.96%, and 99.33%, respectively. We also identified 64.97% (455.3 Mb) repetitive elements, 1,373 non-coding RNAs and 10,542 protein-coding genes. This study assembled a high-quality genome of C. castanopsis, which accumulated valuable molecular data for scale insects.

CDK13 promotes lipid deposition and prostate cancer progression by stimulating NSUN5-mediated m5C modification of ACC1 mRNA.

Cyclin-dependent kinases (CDKs) regulate cell cycle progression and the transcription of a number of genes, including lipid metabolism-related genes, and aberrant lipid metabolism is involved in prostate carcinogenesis. Previous studies have shown that CDK13 expression is upregulated and fatty acid synthesis is increased in prostate cancer (PCa). However, the molecular mechanisms linking CDK13 upregulation and aberrant lipid metabolism in PCa cells remain largely unknown. Here, we showed that upregulation of CDK13 in PCa cells increases the fatty acyl chains and lipid classes, leading to lipid deposition in the cells, which is positively correlated with the expression of acetyl-CoA carboxylase (ACC1), the first rate-limiting enzyme in fatty acid synthesis. Gain- and loss-of-function studies showed that ACC1 mediates CDK13-induced lipid accumulation and PCa progression by enhancing lipid synthesis. Mechanistically, CDK13 interacts with RNA-methyltransferase NSUN5 to promote its phosphorylation at Ser327. In turn, phosphorylated NSUN5 catalyzes the m5C modification of ACC1 mRNA, and then the m5C-modified ACC1 mRNA binds to ALYREF to enhance its stability and nuclear export, thereby contributing to an increase in ACC1 expression and lipid deposition in PCa cells. Overall, our results disclose a novel function of CDK13 in regulating the ACC1 expression and identify a previously unrecognized CDK13/NSUN5/ACC1 pathway that mediates fatty acid synthesis and lipid accumulation in PCa cells, and targeting this newly identified pathway may be a novel therapeutic option for the treatment of PCa.

[Research progress on anti-tumor effect of Chinese dragon's blood].

As a traditional Chinese medicine, Chinese dragon's blood has multiple effects, such as activating blood to remove blood stasis, softening and dispelling stagnation, astringent and hemostasis, clearing swelling and relieving pain, regulating menstruation and rectifying the blood, so it is called "an effective medicine of promoting blood circulation". It has been widely used clinically to treat a variety of diseases. With the further research on Chinese dragon's blood, its anti-tumor medicinal value is gradually emerging. Modern pharmacological studies have shown that Chinese dragon's blood exerts anti-tumor effects mainly by inhibiting cell proliferation, inducing apoptosis, inducing DNA damage and cell cycle arrest, inducing senescence and autophagy of tumor cells, inhibiting metastasis and angiogenesis, as well as reversing multidrug resistance. This article focuses on the research progress on anti-tumor effects of Chinese dragon's blood extract and its chemical components, with a view to provide new references for the in-depth research and reasonable utilization of Chinese dragon's blood.

[Effect of Huaier aqueous extract on growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms].

This study aims to investigate the effect of Huaier aqueous extract on the growth and metastasis of human non-small cell lung cancer NCI-H1299 cells and its underlying mechanisms. MTT assay was used to detect the effect of Huaier aqueous extract on the proliferation of NCI-H1299 cells. Flow cytometry was used to examine the effect of Huaier aqueous extract on the apoptosis, cell cycle, and ROS level of NCI-H1299 cells. Wound healing assay was used to evaluate the effect of Huaier aqueous extract on the migration ability of NCI-H1299 cells. Western blot was used to detect the levels of proteins involving apoptosis, epithelial-mesenchymal transition(EMT), and MAPK signaling pathway in NCI-H1299 cells exposed to Huaier aqueous extract. The results showed that Huaier aqueous extract inhibited the proliferation of NCI-H1299 cells, and induced cell-cycle arrest at the phase S. Huaier aqueous extract promoted the apoptosis of NCI-H1299 cells by down-regulating the expression of anti-apoptotic protein Bcl-2. Moreover, Huaier aqueous extract increased ROS level and induced ferroptosis in NCI-H1299 cells. EMT played a critical role in cancer metastasis. Huaier aqueous extract reduced the migration ability of NCI-H1299 cells by inhibiting EMT of NCI-H1299 cells. In addition, this study revealed that Huaier aqueous extract inhibited MAPK signaling pathway in human non-small cell lung cancer NCI-H1299 cells, which may be one of Huaier's mechanisms in inhibiting growth and metastasis of NCI-H1299 cells. This study provides a new theoretical basis for the clinical treatment of lung cancer with Huaier, and important reference significance for further studies on the anti-tumor mechanisms of Huaier.

Synergistically enhanced hydrogen evolution reaction by ruthenium nanoparticles dispersed on N-doped carbon hollow nanospheres.

Ultrafine Ru nanoparticles dispersed on 3D N-doped carbon hollow nanospheres were firstly prepared by a feasible templating strategy. Due to the synergistic effect of the unique composite and structure, the resulting nanocomposite as a HER catalyst shows extraordinary electrocatalytic performance, superior to that of commercial Pt-C and most previously reported electrocatalysts.

Kappa-carrageenan oligosaccharides retard the progression of protein and lipid oxidation in mackerel (Scomber japonicus) fillets during frozen storage.

The antioxidative effects of κ-carrageenan oligosaccharides (CO) on the stability of proteins and lipids in mackerel fillets were determined during frozen storage. Electronic nose analysis indicated that CO treatments maintained the stability of the overall volatile flavor profiles in frozen mackerel. Protein oxidation analysis suggested that the incorporation of CO significantly retarded the rapid decrease of Ca2+-ATPase activity and active sulphydryl (A-SH) contents while also effectively inhibiting the increases in carbonyl content and surface hydrophobicity of myofibrillar proteins (MPs) compared to the control treatments. Lipid stability results showed that the peroxide values (PVs), conjugated diene (CD) content, anisidine values (AVs), and thiobarbituric acid index (TBA-i) values of the extracted lipids were also clearly reduced by CO treatments during frozen storage. Fatty acid composition determinations further confirmed that the permeated CO molecules stabilized the polyunsaturated C22:6n3 (DHA) in the lipids, most likely due to their efficient free radical scavenging activities.

Ruthenium Nanoparticles Anchored on Graphene Hollow Nanospheres Superior to Platinum for the Hydrogen Evolution Reaction in Alkaline Media.

The design and construction of highly efficient and stable Pt-free catalysts for the electrocatalytic hydrogen evolution reaction (HER) in alkaline media is extremely desirable. Herein, a novel hybrid of ruthenium (Ru) nanoparticles anchored on graphene hollow nanospheres (GHSs) is synthesized by a template-assisted strategy. The combination of ultrafine Ru nanoparticles and hollow spherical support endows the resultant Ru/GHSs an extraordinary catalytic performance with a low overpotential of 24.4 mV at a current density of 10 mA cm-2, a small Tafel slope of 34.8 mV dec-1, as well as long-term stability in 1.0 M KOH solution, which is, to our knowledge, superior to commercial 20% Pt-C catalyst and most of the state-of-the-art HER electrocatalysts reported. Remarkably, this work provides a new route for the development of other metal-based HER electrocatalysts for energy-related applications.

Phenolic constituents, pharmacological activities, quality control, and metabolism of Dracaena species: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Dragon's blood (Chinese name: Xuejie), which comprises red resins obtained from several plants (27 species from 4 families), is drawing worldwide interests in medicinal applications owing to its broad pharmacological spectrum such as promoting blood circulation, regenerating muscle, relieving swelling and pain, maintaining hemostasis, etc. AIM OF THE STUDY: This work aims to evaluate current research progress on phenolic constituents, pharmacological activities, quality control, and metabolism of six Dracaena plants, namely, Dracaena cochinchinensis (Lour.) S.C.Chen, D. cambodiana Pierre ex Gagnep., D. cinnabari Balf. f., D. draco (L.) L., D. loureiroi Gagnep., and D. schizantha Baker, figure out the shortcomings of existing studies, and provide meaningful guidelines for future investigations. METHODS: Extensive database retrieval, such as SciFinder, PubMed, CNKI, ChemSpider, etc., was performed by using the keywords "Dracaena," "dragon's blood," as well as the Latin names of the six Dracaena species. In addition, relevant textbooks, patents, reviews, and documents were also employed to ensure sufficient information is collected. RESULTS: Flavonoids and their oligomers are the primary chemical clusters distributed in Dracaena plants. Pharmacological activities including analgesic, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, and cytotoxic effects; bi-directional regulation effects on hemorheology; and cardiovascular and cerebrovascular effects have been disclosed by modern pharmacological evaluations. The chemical and metabolic profiles after oral administration of dragon's blood extract were preliminarily characterized. However, some of the pharmacological investigations reported only elementary methodologies and unreliable findings, and even worse, some important aspects were questionable or missing in these articles. CONCLUSIONS: Dragon's blood is a valuable source of bioactive compounds, mainly flavonoids and their oligomers. Its potential therapeutic effects on different diseases are attractive, such as the notable effect on cardiovascular diseases. In future studies, there is an urgent need to test the effect of this extract on appropriate cell lines and animal models to analyze its ethnopharmacological applications; moreover, "composition-effect correlation" methods and omics technologies are demanded for identifying the effective material basis and therapeutic mechanisms before entering into clinical trials. Moreover, attention should be paid to the chemical profiling and quality evaluation of this precious herbal medicine.

[Preparation, characterization and dissolution characteristics of dragon's blood extract nanosuspensions].

The single-factor test was used to optimize the high-pressure homogenization method to prepare the phenolic extract nanosuspensions(DBNs). The physicochemical properties of the obtained nanosuspensions were characterized and the cumulative release in vitro was evaluated. The results showed that the drug concentration was 0.5 g·L~(-1), the mass concentrations of PVPK30 and SDS were 0.5 and 0.25 g·L~(-1), respectively, the probe ultrasonic time was 5 min, the homogenization pressure was 900 bar, and the number of homogenization was 2 times. The prepared DBNs had an average particle size of(168.80±0.36) nm, polydispersity index(PDI) of 0.09±0.04, stability index(SI) of 0.85, and DBNs were stable for storage within 30 days. Scanning electron microscopy showed that the particle size of the dragon's blood extract was reduced and the uniformity was improved in the obtained nanosuspensions. X-ray diffraction pattern and differential scanning calorimetry showed that the phenolic extract of dragon's blood was still in an amorphous state after being prepared into nanosuspensions. The results of saturated solubility measurement showed that the solubility of DBNs lyophilized powder reached 6.25 g·L~(-1), while the solubility of DB raw powder was only 28.67 mg·L~(-1). The in vitro dissolution experiments showed that DBNs lyophilized powder accumulated in gastrointestinal fluid for 8 h. The release amount was 90%,the cumulative release of the raw powder in the gastrointestinal fluid for 24 h was less than 1%, and the solubility and dissolution rate of the DBNs lyophilized powder were significantly higher than the DB raw powder. The method is simple in process and convenient in operation, and can successfully prepare uniform and stable nanosuspensions to improve its solubility, and provides a research basis for solving the application limitation of dragon's blood extract.

[LC-MS guided isolation of two anti-inflammatory cyclic dihydrochalcane trimers from Chinese dragon's blood].

As an important integral part of traditional Chinese medicine chemical biology( TCMCB),it is of great importance to rapid isolate,and reliably identify the chemical components in herbal medicines. Phytochemical studies on the anti-inflammatory active part of Chinese dragon's blood,the red resin of Dracaena cochinchinensis,resulted in the isolation of two compounds,nordracophane( 1) and dracophane( 2),using LC-MS and chromatographic techniques( Silica gel,ODS and preparative HPLC). The structures,cyclic dihydrochalcane trimers,were elucidated on the basis of 1 D and 2 D NMR,MS,IR and UV spectral analysis. Compound 1 is a new compound,and 2 is isolated from D. cochinchinensis for the first time. Both compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharides( LPS)-stimulated RAW264. 7 cells with IC50 values of( 14. 9±4. 50) and( 9. 0±0. 7) µmol·L-1.

[Anti-tumor activity of HIS-4,a biflavonoid from Resina draconis,on human hepatoma HepG2 and SK-HEP-1 cells].

The research of anti-hepatocellular carcinoma(HCC) drug has attracted more and more attention. Natural products are the important source of active compounds for cancer treatment. A biflavonoid HIS-4 was isolated from Resina draconis in our previous study. MTT assay, hoechst staining, and flow cytometry analysis were used to investigate the effects of HIS-4 on the proliferation and apoptosis of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, the effects of HIS-4 on the migration and invasion ability of HepG2 and SK-HEP-1 cells were evaluated by wound healing assay and Transwell assay. In addition, MTT assay, flow cytometry analyses, Hoechst staining, wound healing assay, Transwell assay, and tube formation assay were used to explore the anti-angiogenic activity of HIS-4 in human umbilical vein endothelial cells(HUVECs). Mechanistically, the HIS-4 regulatory of signal pathways in H9 epG2 and SK-HEP-1 cells were analyzed by Western blot. This results showed that HIS-4 suppressed the proliferation of human hepatoma HepG2 and SK-HEP-1 cells. Moreover HIS-4 induced their apoptosis of HepG2 and SK-HEP-1 cells. HIS-4 inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, HIS-4 exhibited angiogenesis effects. Mechanistically, up-regulation of MAPK signaling pathway and down-regulation of mTOR signaling pathway may be responsible for anti-hepatoma activity of HIS-4. Therefore, HIS-4 may be a promising candidate drug for HCC treatment.

Clampless and sutureless laparoscopic partial nephrectomy using monopolar coagulation with or without N-butyl-2-cyanoacrylate.

OBJECTIVE: To describe a novel technique for clampless and sutureless laparoscopic partial nephrectomy (LPN) using monopolar coagulation with or without N-butyl-2-cyanoacrylate (NBCA). METHODS: From February 2015 to October 2018, we performed clampless and sutureless LPN using monopolar coagulation with or without NBCA on 142 patients. The tumors were resected with cold scissor. The tumor beds were repeatedly coagulated with a monopolar hook in spray and fulgurate modes. NBCA was sprayed when bleeding was observed after coagulation in 98 patients. We compared outcomes in the NBCA and non-NBCA groups. RESULTS: Mean patient age was 55 years (range 20-86). Mean tumor size was 3.2 cm (range 1.0-10.6). Mean RENAL nephrometry score was 5 (range 4-8). Mean operative time was 120 min (range 40-200). Mean estimated blood loss was 100 ml (range 10-500). Mean eGFR changes were 2.3 ml/min. Two patients had positive surgical margins. Three patients received blood transfusions. No patients had urine leakage. Patients receiving NBCA had larger tumors (3.0 vs 2.0 cm, p < 0.001), higher RENAL nephrometry scores (5.59 vs 4.47, p = 0.004), and higher E item scores (p = 0.009). CONCLUSIONS: Use of monopolar coagulation with NBCA in clampless and sutureless LPN for renal tumors with low RENAL nephrometry scores is safe and effective. For patients with exophytic renal tumors less than 2 cm, NBCA is not necessary.

[Identification of active components in Longxue Tongluo Capsules against ischemic brain injury based on component-activity relationship].

Ten fractions(A-J) were prepared by separation of Longxue Tongluo Capsules(LTC) by using silica gel column chromatography and orthogonal experimental design,showing similar chemical profiles with different abundances of peaks.These ten samples were assessed with UHPLC-QE OrbitrapHRMS for 97 common peaks.For the pharmacological activity experiment,three kinds of in vitro cell models including lipopolysaccharide(LPS)-induced BV-2 microglial cells NO release model,oxygen-glucose deprivation/reoxygenation(OGD/R)-treated HUVEC vascular endothelial cells injury model,and OGD/R-treated PC-12 nerve cells injury model were employed to evaluated the bioactivity of each fraction.Based on the contribution of each identified component,grey relation analysis and partial least squares(PLS) analysis were performed to establish component-activity relationship of LTC,identify the potential active components.After that,validation of the potential active components in LTC was carried out by using the same models.The results indicated that 4 phenolic compounds including 7,4'-dihydroxyhomoisoflavanone,loureirin C,4,4'-dihydroxy-2,6-dimethoxydihydrochalcone,and homoisosocotrin-4'-ol,might be the active components for anti-neuroinflammation effect;five phenolic compounds such as 3,5,7,4'-tetrahydroxyhomoisoflavanone,loureirin D,7,4'-dihydroxyhomoisoflavane,and 5,7-dihydroxy-4'-methoxy-8-methyflavane,might have positive effects on the vascular endothelial injury;three phenolic compounds including 5,7,4'-trihydroxyflavanone,7,4'-dihydroxy-5-methoxyhomoisoflavane,and loureirin D,might be the active components in LTC against neuronal injury.

Two new polyketides from the fungus Penicillium oxalicum MHZ153.

Two new polyketides, penicilloxalones A (1) and B (2), together with 13 known compounds (3-15), were isolated from the ethyl acetate extract of the solid substrate fermentation cultures of the fungus Penicillium oxalicum MHZ153. The structures of the isolates were determined by spectroscopic analysis and comparison of their spectroscopic and physicochemical data with the literature values. Compounds 7 and 11 showed inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 values of 0.9 ± 0.2 µM and 87.9 ± 0.7 µM, respectively.

LC-MS-guided isolation of anti-inflammatory 2-(2-phenylethyl)chromone dimers from Chinese agarwood (Aquilaria sinensis).

Fifteen previously undescribed 2-(2-phenylethyl)chromone dimers, along with two known analogues were isolated from Chinese agarwood (Aquilaria sinensis) by a LC-MS-guided fractionation procedure. Their structures were elucidated on the basis of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The isolated compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values in the range 0.6-37.1 µM.

[Phenylpropanoid amides from whole plants of Corydalis edulis].

Ten phenylpropanoid amides were isolated from the whole plants of Corydalis edulis Maxim. by various of column chromatographies including silica gel, Sephadex LH-20, and ODS. Their structures were identified on the basis of physicochemical properties, MS, NMR, and IR spectroscopic data. These compounds were identified as N-trans-sinapoyl-3-methoxytyramine-4'-O-ß-glucoside(1), N-trans-sinapoyl-3-methoxytyramine(2), N-trans-sinapoyltyramine(3), N-trans-p-coumaroyltyramine(4), N-trans-sinapoyl-7-hydroxytyramine(5), N-cis-feruloyltyramine(6), N-cis-p-coumaroyltyramine(7), N-trans-feruloyltyramine(8), N-trans-feruloyl-3-methoxytyramine(9), and N-trans-feruloyl-7-hydroxytyramine(10). Compound 1 is a new compound. Compounds 2-7 are obtained from the plants of Papaveraceae for the first time, while compounds 8-10 are firstly isolated from C. edulis.

Pharmacokinetics of Panax notoginseng Saponins in Adhesive and Normal Preparation of Fufang Danshen.

BACKGROUND AND OBJECTIVE: Fufang Danshen formula, a famous Chinese patent medicine containing Salvia miltiorrhiza, Panax notoginseng and borneol, has been widely used in the treatment of coronary heart disease. The application is restricted by low bioavailability partly due to Panax notoginseng saponins (PNS) instability and low in vivo absorption. Thus, adhesive pellets were developed to improve bioavailability. The objectives of the present study were to evaluate the adhesive preparation by describing PNS's plasma pharmacokinetics in vivo and compare adhesive micro pills with normal preparation. METHOD: LC-MS/MS method was established to analyze five ingredients, notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), ginsenoside Rb1 (Rb1), ginsenoside Re (Re), and ginsenoside Rd (Rd), in rats' plasma to describe the pharmacokinetic parameters of PNS. RESULTS: The pharmacokinetic parameters were significantly different after oral administration three formulations. The results show adhesive formulations are superior to Fufang Danshen tablet (FDT); there are differences between the two adhesive, but not obvious. CONCLUSIONS: It was found that the modification with adhesive materials improved PNS bioavailability in Fufang Danshen formula. These findings provide a way for further in vivo evaluation of different formulations.

Extensive diversity and evolution of hepadnaviruses in bats in China.

To better understand the evolution of hepadnaviruses, we sampled bats from Guizhou, Henan and Zhejiang provinces, China, and rodents from Zhejiang province. Genetically diverse hepadnaviruses were identified in a broad range of bat species, with an overall prevalence of 13.3%. In contrast, no rodent hepadnaviruses were identified. The newly discovered bat hepadnaviruses fell into two distinct phylogenetic groups. The viruses within the first group exhibited high diversity, with some closely related to viruses previously identified in Yunnan province. Strikingly, the newly discovered viruses sampled from Jiyuan city in the second phylogenetic group were most closely related to those found in bats from West Africa, suggestive of a long-term association between bats and hepadnaviruses. A co-phylogenetic analysis revealed frequent cross-species transmission among bats from different species, genera, and families. Overall, these data suggest that there are likely few barriers to the cross-species transmission of bat hepadnaviruses.

[Optimize ethanol-extraction procedure of Shenlian granules by orthogonal design with pharmacodynamics index].

To optimize the ethanol extraction process for Shenlian formula. On the basis of the pharmacodynamics index for different extraction process routes, the contents of salvianolic acid B, tanshinone ⅡA and berberine, as well as the extraction ratio in different experimental schemes were used as the ethanol extraction examining indexes, and multi-criterion synthesizing grading method was used for data analysis to optimize and verify the ethanol-extraction process conditions in orthogonal experiment. The optimum ethanol extraction process was as follows: adding 60% ethanol, 10 times amount, extracting for 2.0 h each time for a total of 2 times. This extraction process showed good stability and availability.

[Bio-adhesive drug delivery system and its application in traditional Chinese medicine].

Bio-adhesive drug delivery system (BDDS) is a novel drug delivery system, which can prolong the retention time of the preparation, improve the stability of the drug, and improve the mucosa absorption and the targeting of the drug. With the development of polymer materials over the past 30 years, BDDS made a great progress. This paper reviews the muco-adhesion theory, adhesive materials, and methods to evaluate muco-adhesive properties and applications in traditional Chinese medicine according to domestic and foreign literatures, in order to provide new ideas for further studies.