[Authenticity and adulteration identification of Bubali Cornu based on DNA fingerprints].

Whether adulteration exists is a difficult problem in the identification of traditional Chinese medicine(TCM). Bubali Cornu is mainly available in the medicinal material market in the form of buffalo horn silk or buffalo horn powder but lacks obvious identification characteristics, so there is a risk of adulteration. However, the method of identification of adulteration in Bubali Cornu is lacking at present. In order to ensure authenticity and identify adulteration of TCM Bubali Cornu, control the quality of TCM Bubali Cornu, and ensure the authenticity of clinical use, the DNA fingerprints of 43 batches of samples from pharmaceutical companies and medicinal material markets were identified, and the amplification primers of fluorescent DNA fingerprints of Bubali Cornu and Bovis Grunniens Cornu were screened. The DNA fingerprints of Bubali Cornu were obtained by fluorescent capillary typing. The identification effect of fluorescent capillary typing on different adulteration ratios was also tested. Two pairs of fluorescent STR typing primers, namely 16Sa and CRc, which can distinguish Bubali Cornu and Bovis Grunniens Cornu, were screened out, and a DNA fingerprint identification method was established. The 16Sa migration peaks of Bovis Grunniens Cornu and Bubali Cornu were 223.4-223.9 bp and 225.5-226.1 bp. The CRc migration peaks of Bovis Grunniens Cornu and Bubali Cornu were 518.8-524.8 bp and 535.9-542.5 bp. The peak height of the migration peak could be used for preliminary quantification of the adulterants with an adulteration ratio below 50%, and the quantitative results were similar to the adulteration ratio. In this study, a simple and quick universal DNA fingerprint method was established for the identification of Bubali Cornu and its adulterants, which could realize the identification of TCM Bubali Cornu and the semi-quantitative identification of the adulterants.

[Site-specific PCR identification of animal species and formula particles of Scorpio].

Scorpio, a commonly used animal medicine in China, is derived from Buthus martensii as recorded in the Chinese Pharmacopoeia. China harbors rich species of Scorpionida and adulterants exist in the raw medicinal material and deep-processed products of Scorpio. The microscopic characteristics of the deep-processed products may be incomplete or lost during processing, which makes the identification difficult. In this study, the maximum likelihood(ML) tree was constructed based on the morphology and cytochrome C oxidase subunit I(COⅠ) to identify the species of Scorpio products. The results showed that the main adulterant of Scorpio was Lychas mucronatus. According to the specific SNP sites in the COⅠ sequence of B. martensii, the stable primers were designed for the identification of the medicinal material and formula granules of Scorpio. The polymerase chain reaction(PCR) at the annealing temperature of 61 ℃ and 30 cycles produced bright specific bands at about 150 bp for both B. martensii and its formula particles and no band for adulterants. The adaptability of the method was investigated, which showed that the bands at about 150 bp were produced for Scorpio medicinal material, lyophilized powder, and formula granules, and commercially available formula granules. The results showed that the established method could be used to identify the adulterants of Scorpio and its formula granules, which could help to improve the quality control system and ensure the safe clinical application of Scorpio formula granules.

Surficial engineering of active hydroxyls for ambient formaldehyde oxidation via enhanced Lewis acidity over Zr-doped cryptomelane materials.

Lewis acids of solid catalysts have been featured for a pivotal role in promoting various reactions. Regarding the oxidation protocol to remove formaldehyde, the inherent drawback of the best-studied MnO2 materials in acidic sites has eventually caused deficiency of active hydroxyls to sustain low-temperature activity. Herein, the cryptomelane-type MnO2 was targeted and it was tuned via incorporation of Zr metal, exhibiting great advances in not only the complete HCHO-to-CO2 degradation but also cycling performance. Zr species were existent in doping state in the MnO2 lattice, rendering lower crystallinity and breaking the regular growth of MnO2 crystallites, which thereby tripled surface area and created larger volume of smaller mesopores. Meantime, the local electronic properties of Mn atoms were also changed by Zr doping, i.e., more low-valence Mn species were formed due to the electron transfer from Zr to Mn. The results of infrared studies demonstrate the higher possession of Lewis acid sites on ZrMn, and this high degree of electrophilic agents favored the production of hydroxyl species. Furthermore, the reactivity of surface hydroxyls, as investigated by CO temperature programmed reduction and temperature programmed desorption of adsorbed O2, was obviously improved as well after Zr modification. It is speculated jointly with the characterizations of the post-reaction catalysts that the accelerated production of active hydroxyls helped rapidly convert formaldehyde into key intermediate-formate, which was then degraded into CO2, avoiding the side reaction path with undesired intermediate-hydrocarbonate-over the pristine MnO2, where active sites were blocked and formaldehyde oxidation was inhibited. Additionally, Zr decoration could stabilize Lewis acidity to be more resistant to heat degeneration, and this merit brought about advantageous thermal recyclability for cycled application.

Regulating supramolecular interactions in dimeric macrocycles.

Supramolecular behavior is highly dependent on many factors, including complicated microenvironments and weak interactions. Herein, we describe tuning supramolecular architectures of rigid macrocycles by synergistic effects of their geometric configurations, sizes, and guests. Two paraphenylene-based macrocycles are anchored onto different positions in a triphenylene derivative, resulting in dimeric macrocycles with different shapes and configurations. Interestingly, these dimeric macrocycles show tunable supramolecular interactions with guests. In solid state, a 2 : 1 host-guest complex was observed between 1a and C60/C70, while an unusual 2 : 3 host-guest complex 3C60@(1b)2 can be observed between 1b and C60. This work expands the scope of the synthesis of novel rigid bismacrocycles and provides a new strategy to construct different supramolecular systems.

A new species of Otostigmus (Chilopoda, Scolopendromorpha, Scolopendridae) from China, with remarks on the phylogenetic relationships of Otostigmuspolitus Karsch, 1881.

Through a combination of morphological and DNA data, a new scolopendrid centipede from southern and southwestern China was revealed: O.tricarinatussp. nov. The species belong to the politus group but has three sharp tergal keels. Validation of phylogenetic status was performed through molecular analysis of the cytochrome c oxidase subunit I (COI), 16S rRNA, and 28S rRNA sequences from 16 Otostigmus species. Otostigmustricarinatussp. nov. was found to be two populations and varied in the number of spines on the ultimate prefemur, the sutures on a sternite, and a pore-free median longitudinal strip in the pore field. The Yunnan-Guizhou plateau population of O.tricarinatussp. nov. was sister to the clade O.polituspolitus + O.politusyunnanensis + Guangxi population of O.tricarinatussp. nov. with strong support from both BI (bayesian inference) and ML (maximum likelihood) analyses (PP = 1, BS = 97%).

Single Cell Sequencing Reveals Mechanisms of Persistent Truncus Arteriosus Formation after PDGFRα and PDGFRß Double Knockout in Cardiac Neural Crest Cells.

Persistent truncus arteriosus (PTA) is an uncommon and complex congenital cardiac malformation accounting for about 1.2% of all congenital heart diseases (CHDs), which is caused by a deficiency in the embryonic heart outflow tract's (OFT) septation and remodeling. PDGFRα and PDGFRß double knockout (DKO) in cardiac neural crest cells (CNCCs) has been reported to cause PTA, but the underlying mechanisms remain unclear. Here, we constructed a PTA mouse model with PDGFRα and PDGFRß double knockout in Pax3+ CNCCs and described the condensation failure into OFT septum of CNCC-derived cells due to disturbance of cell polarity in the DKO group. In addition, we further explored the mechanism with single-cell RNA sequencing. We found that two main cell differentiation trajectories into vascular smooth muscle cells (VSMCs) from cardiomyocytes (CMs) and mesenchymal cells (MSs), respectively, were interrupted in the DKO group. The process of CM differentiation into VSMC stagnated in a transitional CM I-like state, which contributed to the failure of OFT remodeling and muscular septum formation. On the other hand, a Penk+ transitional MS II cluster closely related to cell condensation into the OFT septum disappeared, which led to the OFT's septation absence directly. In conclusion, the disturbance of CNCC-derived cells caused by PDGFRα and PDGFRß knockout can lead to the OFT septation disorder and the occurrence of PTA.

ZIF-67-derived nanoframes as efficient bifunctional catalysts for overall water splitting in alkaline medium.

In order to lower energy consumption it is critical to develop highly efficient and stable non-precious metal bifunctional catalysts. In this study, we found that rational design of novel nanostructures is able to increase the number of active sites, conductivity and accelerate electron transfer, thus promoting enhanced performance of the catalyst. We successfully synthesized carbon nanotubes (CNTs) containing a hollow polyhedral (CNTHPs) structure through annealing, etching and phosphating. The unique hollow shape not only provides a stable structure but also facilitates mass and charge transfer. Thus, CoP/CNTHPs can catalyze the hydrogen and oxygen evolution reactions effectively with overpotentials of 147 and 238 mV at 10 mA cm-2. Simultaneously, CoP/CNTHPs only needs a voltage of 1.54 V to attain a current density of 10 mA cm-2 in the electrocatalytic water splitting process, demonstrating its bifunctional activity. Furthermore, the electrolytic catalytic performance does not weaken significantly after 12 hours of electrolysis, demonstrating excellent stability. Overall, this research offers useful insights into rational design of high-performance non-noble metal catalysts.

Construction of Fe-doped CoP with hybrid nanostructures as a bifunctional catalyst for overall water splitting.

Due to their open skeleton structures, adjustable active sites and homogeneous catalytic centers, PBA-based materials have promising applications in electrochemical water splitting. Herein, we report a PBA derived Fe0.25-CoP electrocatalyst with a hybrid nanostructure, which offered a large specific surface area and active sites for the HER and OER, respectively. The as-synthesized Fe0.25-CoP catalyst exhibits remarkable catalytic performance and durability at overpotentials of 262 mV for the OER and 111 mV for the HER, requiring a voltage of merely 1.57 V to achieve a current density of 10 mA cm-2 for the electrocatalytic water splitting process. The preeminent activity of Fe0.25-CoP was mainly ascribed to the framework structures of Co-PBA and appropriate doping of Fe3+ which regulated the electronic structures and morphology of Fe0.25-CoP. In addition, the partial phosphating strategy retained the active centers for the OER in Co-PBA, which were further enhanced by the catalysis of Fe3+. In short, the rational design and regulation of catalyst structures and compositions is a promising approach for the development of highly efficient water splitting catalysts.

[Research Progress of CD4+T Cells-mediated Regulation of Neuroinflammation Involved in Neurodegenerative Diseases].

Neurodegenerative diseases are associated with neuroinflammation,oxidative stress,and aging,which can lead to cognitive and motor dysfunctions.Recent studies suggest that the development of neurodegenerative diseases is related to adaptive immunity,in which CD4+T cells are involved as adaptive immune cells.Through different pathways,CD4+T cells differentiate into effector and regulatory subsets,which may have different effects on the progression of neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,and amyotrophic lateral sclerosis.Here,we review the role and research progress of CD4+T cells in neurodegenerative diseases.

Crizotinib and Doxorubicin Cooperatively Reduces Drug Resistance by Mitigating MDR1 to Increase Hepatocellular Carcinoma Cells Death.

As the sixth most lethal cancers worldwide, hepatocellular carcinoma (HCC) has been treated with doxorubicin (Dox) for decades. However, chemotherapy resistance, especially for Dox is an even more prominent problem due to its high cardiotoxicity. To find a regimen to reduce Dox resistance, and identify the mechanisms behind it, we tried to identify combination of drugs that can overcome drug resistance by screening tyrosine kinase inhibitor(s) with Dox with various HCC cell lines in vitro and in vivo. We report here that combination of Crizo and Dox has a synergistic effect on inducing HCC cell death. Accordingly, Crizo plus Dox increases Dox accumulation in nucleus 3-16 times compared to Dox only; HCC cell death enhanced at least 50% in vitro and tumor weights reduced ranging from 35 to 65%. Combining these two drugs reduces multiple drug resistance 1 (MDR1) protein as a result of activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), which phosphorylates eIF2α, leading to protein translational repression. Additionally, PERK stimulation activates C-Jun terminal kinase (JNK), resulting in accumulation of unfused autophagosome to enhance autophagic cell death via Poly-ADP-ribosyltransferase (PARP-1) cleavage. When the activity of PERK or JNK is blocked, unfused autophagosome is diminished, cleaved PARP-1 is reduced, and cell death is abated. Therefore, Crizo plus Dox sensitize HCC drug resistance by engaging PERK-p- eIF2α-MDR1, and kill HCC cells by engaging PERK-JNK- autophagic cell death pathways. These newly discovered mechanisms of Crizo plus Dox not only provide a potential treatment for HCC but also point to an approach to overcome MDR1 related drug resistance in other cancers.

Ce-doped CoP nanoparticles embedded in carbon nanotubes as an efficient and durable catalyst for hydrogen evolution.

In this work, a cerium doped CoP nanoparticles (NPs) embedded in carbon nanotubes (CNTs) for efficient and durable hydrogen evolution was developed. The detailed preparation process was described as the followings. First, cerium was introduced into ZIF-67 to form Ce-doped ZIF-67 by a joint nucleation method. Then, the Ce-doped Co-CNTs was synthesized by carbonization of Ce-doped ZIF-67. During the process, the Co2+ was reduced to form Co NPs and the elegant nanostructure of CNTs was formed by the catalytic effect of Co NPs. Finally, by using Ce-doped Co-CNTs as the precursor, the target catalyst (Ce0.05-doped CoP CNTs) was obtained through a chemical vapour deposition (CVD) process in the presence of NaH2PO2. Results of the transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed that the target catalyst maintained the original rhombic dodecahedron morphology of ZIF-67 and the CoP NPs were embedded in CNTs and distributed uniformly throughout the catalyst. In electrochemical measurements, the catalyst showed the best performance for HER in 0.5 M H2SO4 solution. The onset potential, Tafel slope, electron transfer resistance (R ct) and double-layer capacitance (C dl) of the target catalyst was 49 mV, 78 mV dec-1, 19.2 Ω and 10.5 mF cm-2, respectively. Meanwhile, the catalyst yielded a current density of 10 mA cm-2 merely at an overpotential of 146 mV. Furthermore, it maintained 90% of the original current density in a chronoamperometry measurement and showed no obvious decay even after 2000 cycles scans in a long-term durability test.

Optimization on conditions of podophyllotoxin-loaded liposomes using response surface methodology and its activity on PC3 cells.

The purpose of this study was to optimize the preparation conditions of podophyllotoxin liposomes (PPT-Lips), and to investigate their effects on PC3 cells. PPT-Lips were prepared by using a thin-film dispersion method. In order to achieve maximum drug encapsulation efficiency (EE), the process and formulation variables were optimized by response surface methodology (RSM). The optimum preparation conditions were cholesterol to lecithin ratio of 3.6:40 (w/w), lipid to drug ratio of 15.8:1 (w/w), and the ultrasonic intensity of 35% (total power of 400 W). The experimental EE of PPT-Lips was 90.425%, which was consistent with the theoretically predicted value. The characterization studies showed that PPT-Lips were well-dispersible spherical particles with an average size of 106 nm and a zeta potential of -10.1 mV. A gradual and time-dependent pattern of PPT from liposomes was found in in vitro drug release with a cumulative release amount up to 70.3% in 24 h. Results of cell viability experiments on PC3 cells demonstrated that PPT-Lips exhibited more effective anticancer activity in comparison with free PPT. Therefore, PPT-Lips represent an efficient and promising drug delivery system for PPT.