Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer.

Patients with bladder cancer (BCa) frequently acquires resistance to platinum-based chemotherapy, particularly cisplatin. This study centered on the mechanism of cisplatin resistance in BCa and highlighted the pivotal role of lactylation in driving this phenomenon. Utilizing single-cell RNA sequencing, we delineated the single-cell landscape of Bca, pinpointing a distinctive subset of BCa cells that exhibit marked resistance to cisplatin with association with glycolysis metabolism. Notably, we observed that H3 lysine 18 lactylation (H3K18la) plays a crucial role in activating the transcription of target genes by enriching in their promoter regions. Targeted inhibition of H3K18la effectively restored cisplatin sensitivity in these cisplatin-resistant epithelial cells. Furthermore, H3K18la-driven key transcription factors YBX1 and YY1 promote cisplatin resistance in BCa. These findings enhance our understanding of the mechanisms underlying cisplatin resistance, offering valuable insights for identifying novel intervention targets to overcome drug resistance in Bca.

Regulation of cisplatin resistance in bladder cancer by epigenetic mechanisms.

Bladder cancer is one of the most common malignancies in the world. Cisplatin is one of the most potent and widely used anticancer drugs and has been employed in several malignancies. Cisplatin-based combination chemotherapies have become important adjuvant therapies for bladder cancer patients. Cisplatin-based treatment often results in the development of chemoresistance, leading to therapeutic failure and limiting its application and effectiveness in bladder cancer. To develop improved and more effective cancer therapy, research has been conducted to elucidate the underlying mechanism of cisplatin resistance. Epigenetic modifications have been demonstrated involved in drug resistance to chemotherapy, and epigenetic biomarkers, such as urine tumor DNA methylation assay, have been applied in patients screening or monitoring. Here, we provide a systematic description of epigenetic mechanisms, including DNA methylation, noncoding RNA regulation, m6A modification and posttranslational modifications, related to cisplatin resistance in bladder cancer.

An Adaptive Multi-Scale Network Based on Depth Information for Crowd Counting.

Crowd counting, as a basic computer vision task, plays an important role in many fields such as video surveillance, accident prediction, public security, and intelligent transportation. At present, crowd counting tasks face various challenges. Firstly, due to the diversity of crowd distribution and increasing population density, there is a phenomenon of large-scale crowd aggregation in public places, sports stadiums, and stations, resulting in very serious occlusion. Secondly, when annotating large-scale datasets, positioning errors can also easily affect training results. In addition, the size of human head targets in dense images is not consistent, making it difficult to identify both near and far targets using only one network simultaneously. The existing crowd counting methods mainly use density plot regression methods. However, this framework does not distinguish the features between distant and near targets and cannot adaptively respond to scale changes. Therefore, the detection performance in areas with sparse population distribution is not good. To solve such problems, we propose an adaptive multi-scale far and near distance network based on the convolutional neural network (CNN) framework for counting dense populations and achieving a good balance between accuracy, inference speed, and performance. However, on the feature level, in order to enable the model to distinguish the differences between near and far features, we use stacked convolution layers to deepen the depth of the network, allocate different receptive fields according to the distance between the target and the camera, and fuse the features between nearby targets to enhance the feature extraction ability of pedestrians under nearby targets. Secondly, depth information is used to distinguish distant and near targets of different scales and the original image is cut into four different patches to perform pixel-level adaptive modeling on the population. In addition, we add density normalized average precision (nAP) indicators to analyze the accuracy of our method in spatial positioning. This paper validates the effectiveness of NF-Net on three challenging benchmarks in Shanghai Tech Part A and B, UCF_ CC_50, and UCF-QNRF datasets. Compared with SOTA, it has more significant performance in various scenarios. In the UCF-QNRF dataset, it is further validated that our method effectively solves the interference of complex backgrounds.

Construction of vitamin D delivery system based on pine nut oil Pickering emulsion: effect of phenols.

BACKGROUND: The food industry has begun to develop foods fortified with unsaturated fatty acids; however, the susceptibility of pine nut oil to oxidation and other properties limits its use in food production. Researchers often inhibit the oxidation of oil by adding antioxidants. After the combination of polyphenols and proteins, the complex formed can improve or enhance the performance of the emulsion when it stabilizes the emulsion. Encapsulating, protecting, and controlling the release behavior of vitamin D (VD ) during digestion through an emulsion delivery system can effectively overcome limitations such as easy degradation during processing and storage. This research uses tannic acid, gallic acid, tea polyphenol, and vanillic acid to prepare Pickering emulsions, and the type of phenolic compound is explored by multi-dimensional characterization and the amount of emulsion. RESULTS: The influence of traits, microstructure, stability, VD load application, and effect on the emulsion matrix's encapsulation rate and bioaccessibility is studied. A method was investigated to enhance the oxidative stability of whey protein isolate-stabilized emulsions by introducing phenol. Pickering emulsions could be obtained in the presence of phenol, while the type of phenol played a relatively important role, probably because the mechanism involved interactions between particles. Viscosity and creaming stability of emulsions increased with crosslinking of phenol in emulsions. In addition, the presence of phenol in emulsions significantly increased the bioaccessibility of encapsulated VD after in vitro digestion. CONCLUSION: The method presented in this study was important for improving the oxidative stability of pine nut oil emulsions, expanding the application of pine nut oil in the food industry, and providing the theoretical and application basis of application and active substance emulsion delivery systems. © 2022 Society of Chemical Industry.

Evaluation of single-cell classifiers for single-cell RNA sequencing data sets.

Single-cell RNA sequencing (scRNA-seq) has been rapidly developing and widely applied in biological and medical research. Identification of cell types in scRNA-seq data sets is an essential step before in-depth investigations of their functional and pathological roles. However, the conventional workflow based on clustering and marker genes is not scalable for an increasingly large number of scRNA-seq data sets due to complicated procedures and manual annotation. Therefore, a number of tools have been developed recently to predict cell types in new data sets using reference data sets. These methods have not been generally adapted due to a lack of tool benchmarking and user guidance. In this article, we performed a comprehensive and impartial evaluation of nine classification software tools specifically designed for scRNA-seq data sets. Results showed that Seurat based on random forest, SingleR based on correlation analysis and CaSTLe based on XGBoost performed better than others. A simple ensemble voting of all tools can improve the predictive accuracy. Under nonideal situations, such as small-sized and class-imbalanced reference data sets, tools based on cluster-level similarities have superior performance. However, even with the function of assigning 'unassigned' labels, it is still challenging to catch novel cell types by solely using any of the single-cell classifiers. This article provides a guideline for researchers to select and apply suitable classification tools in their analysis workflows and sheds some lights on potential direction of future improvement on classification tools.

Effect of phenolic compounds and hydroxyl content on the physicochemical properties of pine nut oil Pickering emulsions.

BACKGROUND: For decades, pine nut oil Pickering emulsions have been stabilized using a covalent composite of two phenolic chemicals (tannic acid, TA; and gallic acid, GA) and whey protein isolate (WPI) following alkali treatment. Based on covalent composite particles being excellent sources of high-quality stabilizers, this research explored the influence of phenolic addition and hydroxyl content on stability, rheological parameters and characterization of Pickering emulsions. RESULTS: Tannic acid was more effective in reducing the average particle size of the emulsion, which decreased from 479.4 ± 2.1 nm without addition to between 187.6 ± 5.9 and 368.2 ± 16.8 nm (P < 0.05). The potential values of all the emulsions were between -30 and -50 mV (except for the gallic acid addition of 2.5 g kg-1 ). When the phenolic addition was 7.5 g kg-1 , emulsions demonstrated the best emulsification ability. Pickering emulsion stabilized by WPI-TA and WPI-GA particles were successfully generated, according to confocal laser scanning microscopy. Rheological results showed that the increase of phenolic addition contributed to larger elastic modulus (G'), viscosity modulus (G″) and viscosity of emulsions, which was beneficial to the stability of emulsions. CONCLUSION: Both phenolic compounds significantly improved the physicochemical stability of the emulsions (P < 0.05) and their oxidative stability. Covalently crosslinking phenolic compounds to proteins is a better method to prepare stable emulsions. It is more prominent that TA shows a more significant improvement in emulsion stability due to the number of hydroxyl groups it can provide. This research might serve as a theoretical foundation for enhancing the quality of pine nut oil-related products. © 2022 Society of Chemical Industry.

The Effects of swnH1 Gene Function of Endophytic Fungus Alternaria oxytropis OW 7.8 on Its Swainsonine Biosynthesis.

The swnH1 gene in the endophytic fungus Alternaria oxytropis OW 7.8 isolated from Oxytropis glabra was identified, and the gene knockout mutant ΔswnH1 was first constructed in this study. Compared with A. oxytropis OW 7.8, the ΔswnH1 mutant exhibited altered colony and mycelium morphology, slower growth rate, and no swainsonine (SW) in mycelia, indicating that the function of the swnH1 gene promoted SW biosynthesis. Five differential expressed genes (DEGs) closely associated with SW synthesis were identified by transcriptomic analysis of A. oxytropis OW 7.8 and ΔswnH1, with sac, swnR, swnK, swnN, and swnH2 down-regulating. Six differential metabolites (DEMs) closely associated with SW synthesis were identified by metabolomic analysis, with P450, PKS-NRPS, saccharopine, lipopolysaccharide kinase, L-PA, α-aminoadipic, and L-stachydrine down-regulated, while L-proline was up-regulated. The SW biosynthetic pathways in A. oxytropis OW 7.8 were predicted and refined. The results lay the foundation for in-depth exploration of the molecular mechanisms and metabolic pathways of SW synthesis in fungi and provide reference for future control of SW in locoweeds, which would benefit the development of animal husbandry and the sustainable use of grassland ecosystems.

Radiofrequency ablation therapy for knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study is to systematically analyze the safety and efficacy of radiofrequency ablation (RFA) therapy for the treatment of patients with knee osteoarthritis (KOA) and to assess the methodological quality of the published studies. METHODS: By searching the PubMed, Embase, and CENTRAL databases, we retrieved and collected relevant randomized controlled trials (RCTs) published up to June 26, 2023. RESULTS: We included 13 RCTs, involving a total of 865 patients. Compared with the control group, the RFA group had significantly reduced pain scores at 1-2 weeks, 4 weeks, 12 weeks, and 24 weeks post-treatment, with standardized mean differences of -1.24 (95% confidence interval [CI]: -1.99--0.49; p = 0.001; I2 = 91%), -0.76 (95% CI: -1.27--0.26; p = 0.003; I2 = 76%), -1.70 (95% CI: -2.56--0.83; p = 0.0001; I2 = 94%), and -2.26 (95% CI: -3.49--1.04; p = 0.0003; I2 = 95%). CONCLUSIONS: RFA, as an adjunctive treatment modality, demonstrates potential in the treatment of patients with KOA. This method may become a primary treatment strategy for these patients.

OBJETIVO: Analizar sistemáticamente la seguridad y la eficacia de la ablación por radiofrecuencia en pacientes con osteoartritis de rodilla y evaluar la calidad metodológica de los estudios publicados. MÉTODO: Mediante una búsqueda en las bases de datos PubMed, EMBASE y CENTRAL, recuperamos y recopilamos los ensayos aleatorizados controlados relevantes publicados hasta el 26 de junio de 2023. RESULTADOS: Se incluyeron 13 ensayos aleatorizados controlados que involucraron a 865 pacientes. En comparación con el grupo control, el grupo de ablación por radiofrecuencia registró una reducción significativa en la puntuación de dolor a 1-2 semanas, 4 semanas, 12 semanas y 24 semanas del tratamiento, con una diferencia media estandarizada de −1.24 (intervalo de confianza del 95% [IC95%]: −1.99 a −0.49; p = 0.001; I2 = 91%), de −0.76 (IC95%: −1.27 a −0.26; p = 0.003; I2 = 76%), de −1.70 (IC95%: −2.56 a − 0.83; p = 0.0001%; I2 = 2.94%) y de ­ 2.26 (IC95%: −3.49 a −1.04; p = 0.0003; I2 = 95%), respectivamente. CONCLUSIONES: La ablación por radiofrecuencia como tratamiento adyuvante muestra potencial en el tratamiento de pacientes con osteoartritis de rodilla. Este método puede convertirse en la principal estrategia terapéutica para estos pacientes.

Endophthalmitis Caused by Bacillus cereus: Clinical Characteristics, Outcomes and Antibiotic Susceptibility.

Bacillus cereus endophthalmitis is a severe vision-threatening disease. This study aimed to analyze the clinical characteristics, antibiotic susceptibility, and risk factors for poor final visual acuity (VA) and enucleation or evisceration (ENEV) outcomes of B. cereus endophthalmitis patients. We retrospectively reviewed 52 cases (52 eyes) of culture-proven B. cereus endophthalmitis at Zhongshan Ophthalmic Center from January 2013 to December 2023. The mean age of the patients was 38.1 ± 20.1 years, and males composed the majority (90.4%) of the sample size; laborers (32.7%) and farmers (19.2%) were the primary occupations of the patients. All cases were caused by ocular trauma. Forty-one of 51 eyes (80.4%) had a final VA worse than the ability to count fingers (CFs), and 15 of the 52 total eyes (28.8%) underwent ENEV. Binary logistic forward (LR) regression analysis demonstrated that red eye (odds ratio [OR], 13.13; 95% confidence interval [CI], 1.58-108.80; p = 0.017), eye pain (OR, 22.87; 95% CI, 1.00-522.72; p = 0.050), and corneal edema/ulcer (OR, 13.13; 95% CI, 1.58-108.80; p = 0.017) were significant risk factors for poor VA outcomes. Conjunctival sac purulent discharge (OR, 10.08; 95% CI, 2.11-48.12, p = 0.004) and white blood cell (WBC) count (OR, 1.35; 95% CI, 1.06-1.72, p = 0.016) were significant risk factors for ENEV outcomes. B. cereus showed susceptibility rates of 100.0% to vancomycin and ofloxacin; 98.0% to levofloxacin; 93.3% to ciprofloxacin; 87.5% to imipenem; and 78.9% to tobramycin. The susceptibility to azithromycin and clindamycin was 66.7% and 50.0%, respectively. In contrast, B. cereus was resistant to penicillin (susceptibility at 3.8%), cefuroxime (5.6%), and cefoxitin (37.1%).

AKAP12 positive fibroblast determines immunosuppressive contexture and immunotherapy response in patients with TNBC by promoting macrophage M2 polarization.

BACKGROUND: Triple-negative breast cancer (TNBC) is a molecular subtype of breast cancer with high aggressiveness and poor prognosis. Cancer-associated fibroblasts (CAFs) are major components of the TNBC microenvironment and play an important role in tumor progression and treatment responses. Our goal is to identify specific CAFs subpopulations contributing to TNBC development. METHODS: Multiomics analyses were applied to identify the CAFs-specific genes related to immunotherapy response. The clinical significance of a CAFs subset with A-kinase anchoring protein 12 (AKAP12) positive was explored in 80 patients with TNBC through double-labeling immunofluorescence assay. Cytometry by time-of-flight and RNA sequencing were performed to elucidate the immune landscape of TNBC microenvironment and functional mechanism of AKAP12+ CAFs. RESULTS: Multiomics analyses identified an AKAP12+ CAFs subset associated with the immunotherapy response of TNBC, and a high population of these cells is correlated with poor prognosis in patients with TNBC. Intratumoral AKAP12+ CAFs promote formation of an immunosuppressive tumor microenvironment by spatially mediating macrophage M2 polarization via interleukin-34 (IL-34)/macrophage-colony stimulating factor receptor (CSF1R) signaling in TNBC. Single-cell RNA sequencing analyses revealed that AKAP12+ fibroblasts interact with macrophages through the PI3K/AKT/IL-34 axis. In addition, pharmacological blockade of the IL-34/CSF1R signaling enhances the efficacy of anti-programmed cell death protein-1 antibody in TNBC rodent models. CONCLUSIONS: AKAP12 is mainly expressed in fibroblasts in TNBC. AKAP12+ CAFs population is negatively associated with the prognosis of patients with TNBC. AKAP12+ CAFs shape the immunosuppressive TNBC microenvironment by releasing IL-34 to promote macrophage M2 polarization. Targeting IL-34 may boost the immunotherapeutic efficacy for TNBC.

Puerarin alleviates osteoporosis in rats by targeting the JAK2/STAT3 signaling pathway.

Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an effective treatment for OP. This study examined the effects and underlying mechanisms of Pue in treating postmenopausal osteoporosis (PMOP) in rats. Sprague-Dawley (SD) rats underwent bilateral ovariectomy to simulate PMOP and were then treated with subcutaneous injections of Pue. Bone mineral density (BMD) was measured using a bone densitometer. Micro-CT scans assessed femur bone structure and various parameters were calculated: bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone surface area-to-bone volume ratio (BS/BV). Hematoxylin-eosin (HE) staining was employed to observe femoral tissue pathology. Serum levels of bone formation metabolism-related markers-osteocalcin (OC), bone alkaline phosphatase (BALP), and procollagen type I N-terminal propeptide (PINP)-were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in bone tissue were evaluated using Western blotting assay. The results showed improved bone density and reduced bone loss in rats treated with Pue. There were also significant increases in serum levels of OC and BALP, indicating enhanced osteogenesis. Furthermore, there was a decrease in activation of the JAK2/STAT3 pathway in femoral tissue, suggesting a pathway inhibition. These findings indicate that Pue may combat osteoporosis by promoting osteogenesis and inhibiting activation of the JAK2/STAT3 pathway activation.

A systematic approach for authentication of medicinal Patrinia species using an integration of morphological, chemical and molecular methods.

Four common Patrinia species, including P. heterophylla, P. monandra, P. scabiosifolia and P. villosa, have been documented as herbal medicines with various clinical applications, such as anti-cancer, anti-diarrhea and sedative. However, the authentication of medicinal Patrinia species poses a problem, particularly with the processed herbal materials. This study aimed to systematically authenticate the four medicinal Patrinia species in the market using morphological and chemical characterization, as well as DNA markers. We found the species identity authenticated by traditional morphologies were in good agreement with both chemical and molecular results. The four species showed species-specific patterns in chromatographic profiles with distinct chemical markers. We also revealed the power of complete chloroplast genomes in species authentication. The sequences of targeted loci, namely atpB, petA, rpl2-rpl23 and psaI-ycf4, contained informative nucleotides for the species differentiation. Our results also facilitate authentication of medicinal Patrinia species using new DNA barcoding markers. To the best of our knowledge, this is the first report on the application of morphology, chemical fingerprinting, complete chloroplast genomes and species-specific Insertion-Deletions (InDels) in differentiating Patrinia species. This study reported on the power of a systematic, multidisciplinary approach in authenticating medicinal Patrinia species.

Distal clavicle fractures treated by anteroinferior plating with a single screw: Two case reports.

BACKGROUND: For the treatment of distal clavicle fractures, each treatment method has its own advantages and disadvantages, and there is no optimal surgical solution. CASE SUMMARY: Based on this, we report 2 cases of distal clavicle fractures treated utilizing an anterior inferior plate with a single screw placed in the distal, in anticipation of providing a better surgical approach to distal clavicle fracture treatment. Two patients were admitted to the hospital after trauma with a diagnosis of distal clavicle fracture, and were admitted to the hospital for internal fixation of clavicle fracture by incision and reduction, with good postoperative functional recovery. CONCLUSION: With solid postoperative fixation and satisfactory prognostic functional recovery, this technique has been shown to be simple, easy to perform and effective.

Synergistic ferroptosis-starvation therapy for bladder cancer based on hyaluronic acid modified metal-organic frameworks.

Bladder cancer (BCa) is one of the most common malignancies of the urinary tract. Metastasis and recurrence of BCa are the leading causes of poor prognosis, and only a few patients can benefit from current first-line treatments such as chemotherapy and immunotherapy. It is urgent to develop more effective therapeutic method with low side effects. Here, a cascade nanoreactor, ZIF-8/PdCuAu/GOx@HA (ZPG@H), is proposed for starvation therapy and ferroptosis of BCa. The ZPG@H nanoreactor was constructed by co-encapsulation of PdCuAu nanoparticles and glucose oxidase into zeolitic imidazolate framework-8 (ZIF-8) modified by hyaluronic acid. The vitro results indicated that ZPG@H enhanced intracellular reactive oxygen species levels and reduced mitochondrial depolarization in the tumor microenvironment. Therefore, the integrated advantages of starvation therapy and chemodynamic therapy endow ZPG@H with a perfect ferroptosis inducing ability. This effectiveness, combined with its excellent biocompatibility and biosafety, means that ZPG@H could make a critical contribution to the development of novel BCa treatments.

The Experiences of Chinese Children 5- to 7-year-old during Cancer Treatment Reflected Through Interviews and Drawings.

Background: For children with cancer, the experience during treatment can be challenging. There is a limited number of studies on self-reported treatment experiences of younger Chinese children with cancer using qualitative methods. Objectives: This study aimed at exploring the experience of Chinese children aged 5 to 7 years during cancer treatment reflected through interviews and drawings. Methods: This study used a descriptive qualitative design with the technique of "draw-and-tell." Participants were enrolled from the pediatric oncology inpatient department of one national children's medical center in China. They were asked to draw a picture of "your feelings in the hospital." An inductive content analysis approach was used. Results: Twelve participants were enrolled (8 male, mean age 5.7 years). Four themes were established: (1) suffering from adverse treatment effects; (2) perceiving changed relationships; (3) being thankful for others; and (4) trying out coping strategies. Conclusion: Chinese children aged 5 to 7 years expressed multiple cancer treatment impacts. They appreciated others' support and had their own way to cope with treatment demands. The authors also extended the dynamic nature of using the "draw-and-tell" methodology. Study findings highlight the importance of inviting and hearing the voice of young children during their cancer treatment, with particular consideration of the influence of disease, treatment, child development, family dynamics, and culture.

A two-dimensional topological nodal-line material MgN4 with extremely large magnetoresistance.

Using first-principles calculations, we predict a stable two-dimensional atomically thin material MgN4. This material has a perfect intrinsic electron-hole compensation characteristic with high carrier mobility, making it a promising candidate material with extremely large magnetoresistance. As the magnetic field increases, the magnetoresistance of the monolayer MgN4 will show a quadratic dependence on the strength of the magnetic field without saturation. Furthermore, nontrivial topological properties are also found in this material. In the absence of spin-orbit coupling, the monolayer MgN4 belongs to a topological nodal-line material, in which the band crossings form a closed saddle-shape nodal-ring near the Fermi level in the Brillouin zone. Once the spin-orbit coupling is considered, a small local energy gap is opened along the nodal ring, resulting in a topological insulator defined on a curved Fermi surface with 2 = 1. The combination of two-dimensional single-atomic-layer thickness, an extremely large magnetoresistance effect, and topological non-trivial properties in the monolayer MgN4 makes it an excellent platform for designing novel multi-functional devices.

Phylogenomic analyses based on the plastid genome and concatenated nrDNA sequence data reveal cytonuclear discordance in genus Atractylodes (Asteraceae: Carduoideae).

Atractylodes species are widely distributed across East Asia and are cultivated as medicinal herbs in China, Japan, and Korea. Their unclear morphological characteristics and low levels of genetic divergence obscure the taxonomic relationships among these species. In this study, 24 plant samples were collected representing five species of Atractylodes located in China; of these, 23 belonged to members of the A. lancea complex. High-throughput sequencing was used to obtain the concatenated nrDNA sequences (18S-ITS1-5.8S-ITS2-28S) and plastid genomes. The concatenated nrDNA sequence lengths for all the Atractylodes species were 5,849 bp, and the GC content was 55%. The lengths of the whole plastid genome sequences ranged from 152,138 bp (A. chinensis) to 153,268 bp (A. lancea), while their insertion/deletion sites were mainly distributed in the intergenic regions. Furthermore, 33, 34, 36, 31, and 32 tandem repeat sequences, as well as 30, 30, 29, 30, and 30 SSR loci, were detected in A. chinensis, A. koreana, A. lancea, A. japonica, and A. macrocephala, respectively. In addition to these findings, a considerable number of heteroplasmic variations were detected in the plastid genomes, implying a complicated phylogenetic history for Atractylodes. The results of the phylogenetic analysis involving concatenated nrDNA sequences showed that A. lancea and A. japonica formed two separate clades, with A. chinensis and A. koreana constituting their sister clade, while A. lancea, A. koreana, A. chinensis, and A. japonica were found based on plastid datasets to represent a mixed clade on the phylogenetic tree. Phylogenetic network analysis suggested that A. lancea may have hybridized with the common ancestor of A. chinensis and A. japonica, while ABBA-BABA tests of SNPs in the plastid genomes showed that A. chinensis was more closely related to A. japonica than to A. lancea. This study reveals the extensive discordance and complexity of the relationships across the members of the A. lancea complex (A. lancea, A. chinensis, A. koreana, and A. japonica) according to cytonuclear genomic data; this may be caused by interspecific hybridization or gene introgression.

High-throughput metabolomic method based on liquid chromatography: high resolution mass spectrometry with chemometrics for metabolic biomarkers and pathway analysis to reveal the protective effects of baicalin on thyroid cancer.

Cell metabonomics focuses on discovering metabolic biomarkers and pathway changes in cells from biological systems to obtain the cell properties and functional information under different conditions. Baicalin possesses various pharmacological activities, and plays a vital role in the oncology research field. However, the detailed mechanism of its action is still unclear. In this work, we employed ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based non-targeted metabolomics method associated with chemometrics analysis to explore metabolic pathways and biomarkers for investigating the efficacy and pharmacological targets of baicalin against thyroid cancer cells. In addition, morphological observation, parameter calculation of cell proliferation and apoptosis were carried out, which assisted in elucidation of pharmacological activity of baicalin on the human thyroid cancer cells. The results showed that baicalin possesses an intense stimulative apoptosis and inhibits proliferation activity on SW579 human thyroid cancer cells, and partially reversed the cell metabolite abnormalities. A total of nineteen differentiated metabolites in SW579 cells were identified and deemed as potential biomarkers after the baicalin treatment, involving nine metabolic pathways, such as taurine and hypotaurine metabolism, pyrimidine metabolism, fructose and mannose metabolism, steroid hormone biosynthesis and sphingolipid metabolism. High-throughput non-targeted metabolomics provide an insight into specialized mechanism of baicalin against thyroid cancer and contributes to novel drug discovery and thyroid cancer management in clinical practice.

DNMHMM: An approach to identify the differential nucleosome regions in multiple cell types based on a Hidden Markov Model.

Nucleosome occupancy changes across cell types and environmental conditions and such changes often have profound influence in transcription. It's of importance to identify the differential nucleosome regions (DNRs) where the nucleosome occupancy level differs across cell types. Here we developed DNMHMM, a Hidden Markov Model (HMM) based algorithm, to detect the DNRs with nucleosomal DNA sequenced dataset. The performance evaluation indicates that DNMHMM is advisable for multi-cell type comparison. Upon testing this model in yeast mutants, where the modifiable histone residues were mutated into alanine, we found that DNA sequences of the dynamic nucleosomes lack 10-11 bp periodicities and harbor binding motifs of the nucleosome remodelling complex. Moreover, the highly expressed genes have more dynamic nucleosomes at promoters. We further compared nucleosome occupancy between resting and activated human CD4+ T cells with this model. It was revealed that during the activation of CD4+ T cells, dynamic nucleosomes are enriched at regulatory sites, hence, up to some extent can affect the gene expression level. Taken together, DNMHMM offers the possibility to access precise nucleosome dynamics among multiple cell types and also can describe the closer association between nucleosome and transcription.

Rapid and robust authentication of deer antler velvet product by fast PCR-RFLP analysis.

Deer antler velvet is widely used as a vitalizing, tonifying, haemopoietic and strengthening agent for debilitated persons in East Asia. To develop a rapid and sensitive method for the identification of the biological source or origin in antler velvet products, a molecular approach was applied using PCR-restriction fragment length polymorphism analysis. The cytochrome b gene sequences of nine cervidae species were analyzed, and a Dde I restriction endonuclease recognition site was found only in sika deer and red deer, the official origin of deer velvet in Chinese pharmacopoeia. A specific primer was designed, and rapid PCR amplified products were subjected to restriction digestion using a fast RFLP procedure. Sika deer and red deer showed two bands of 161 and 102 bp, in contrast to the undigested state of 263 from other antlers. The established PCR-RFLP method was applied in commercial velvet products, and a high frequency of substitution (50%) was revealed in collected commercial samples. The method was successful in detecting contaminated and adulterated antler products in Chinese patent drugs, and the whole detection process was accomplished within 1-1.5 h.