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Ubiquitin-conjugating enzyme E2S (UBE2S), an important E2 enzyme in the process of ubiquitination, has exhibited oncogenic activities in various malignant tumors. However, it remains unknown whether UBE2S plays a role in urinary bladder cancer (UBC) development. In the current study, our data confirmed UBE2S upregulation in UBC. In vitro and in vivo experiments demonstrated that UBE2S knockdown resulted in attenuated proliferation and enhanced apoptosis, which was inverse to the phenotypes with UBE2S overexpression. Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, we discovered that this UBE2S-modulated carcinogenic mechanism was in the consequence of directly targeting tuberous sclerosis 1 (TSC1), which is the upstream inhibitor of mTOR signaling for ubiquitous degradation. Taken together, this study demonstrated that UBE2S is a carcinogen in UBC and promotes UBC progression by ubiquitously degrading TSC1. This consequently mediates the activation of the mTOR pathway, suggesting a potential therapeutic regimen for UBC by targeting the newly identified UBE2S/TSC1/mTOR axis.

A novel phosphoramidate salt fire retardant (FR) with high phosphorus–nitrogen (P–N) content, tris(2-aminoethyl)amine phosphoramidate salt (TAEAPA), was synthesized by a simple design philosophy. A three-arm star-like structure FR with a high level of P or N content was obtained. Phosphorus and nitrogen contents of TAEAPA increased up to 8.6 at% and 14.5 at%, respectively. Subsequently, TAEAPA was employed to finish lyocell fibers through the classical dip-dry-cure technique. Consequently, the thermal stability and fire retardancy of finished lyocell fibers were improved significantly, as evidenced by thermogravimetric and vertical flammability test. Finished lyocell fibers exhibited higher char residues (39.2 wt%) and lower degradation rate (0.6%/°C) under nitrogen atmosphere. Besides, lyocell fabrics finished by 300 g/L of TAEAPA finishing solution only had a char length of 53 mm when exposed to flame more than 60 s, and immediately extinguished after the removal of flame. Thermogravimetry-infrared and pyrolysis gas chromatography/mass spectrometry coupled techniques confirmed that the high contents of P and N included in TAEAPA played a good synergistic effect on both condensed and gaseous phase during the thermal pyrolysis process of lyocell fibers.

The identification of CN- in water, seeds and biological systems has, due to its high toxicity, attracted the increasing attention of many chemical industry researchers. In the work, a novel highly...

As an emerging tumor therapy, ideal oncolytic viruses preferentially replicate in malignant cells, reverse the immunosuppressive tumor microenvironment, and eventually can be eliminated by the patient. It is of great significance for cancer treatment to discover new excellent oncolytic viruses. Here, we found that WNV live attenuated vaccine WNV-poly(A) could be developed as a novel ideal oncolytic agent against several types of cancers. Mechanistically, due to its high sensitivity to type Ι interferon (IFN-Ι), WNV-poly(A) could specifically kill tumor cells rather than normal cells. At the same time, WNV-poly(A) could activate Dendritic cells (DCs) and trigger tumor antigen specific response mediated by CD8 + T cell, which contributed to inhibit the propagation of original and distal tumor cells. Like intratumoral injection, intravenous injection with WNV-poly(A) also markedly delays Huh7 hepatic carcinoma (HCC) transplanted tumor progression. Most importantly, in addition to an array of mouse xenograft tumor models, WNV-poly(A) also has a significant inhibitory effect on many different types of patient-derived tumor tissues and HCC patient-derived xenograft (PDX) tumor models. Our studies reveal that WNV-poly(A) is a potent and excellent oncolytic agent against many types of tumors and may have a role in metastatic and recurrent tumors.

Pogostemon cablin Benth (PCB) is a well-known traditional Chinese medicine that has been used for treatment of many ailments for several centuries. In presently, the chemical profiling and quality control study of PCB has mainly concentrated on the volatile fractions. However, the non-volatile chemical profile of PCB was still unclear. In this study, 73 non-volatile constituents (i.e., 33 flavonoids, 21 organic acids, 9 phenylpropanoids, 4 sesquiterpenes, 3 alkaloids, and 3 other types of compounds) were identified and characterized in PCB using high performance liquid chromatography coupled with quadruple time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS). Meanwhile, to assess PCB samples, an established HPLC-Q-TOF-MS fingerprint was combined with multivariate statistical analysis that included similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA). The PCB samples could be classified into two groups (herbal decoction pieces and processed medicinal materials), and acteoside, isoacteoside, 4',6-Dihydroxy-5,7-dimethoxyflavone, pachypodol and pogostone were screened as the potential chemical markers that attributed classification. In addition, nine representative components (pachypodol, vicenin-2, apigenin, rhamnocitrin, acteoside, isoacteoside, chlorogenic acid, azelaic acid and pogostone) in PCB were simultaneously determined by using an ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS). This study is the first to describe the chemical profile of PCB using liquid chromatography tandem mass spectrometry, which would improve our understanding of the substance basis of PCB and is helpful to the PCB further quality evaluation.

The genus Flavivirus comprises numerous emerging and re‐emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live‐attenuated vaccine (LAV), WNV‐poly(A), by replacing 5ʹ portion (corresponding to SL and DB domains in WNV) of 3ʹ‐UTR with internal poly(A) tract. WNV‐poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single‐dose vaccination elicited robust and long‐lasting immune responses, conferring full protection against WNV challenge. Such “poly(A)” vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses., West Nile virus (WNV) is one of the many members of the genus Flavivirus known to cause human diseases. Here we present a novel live attenuated WNV vaccine, WNV‐poly(A), that protects against WNV infections in a mouse model.

Omsk hemorrhagic fever virus (OHFV) is a tick-borne flavivirus classified as a biosafety level-4 (BSL4) pathogen. Studies of OHFV are restricted to be conducted within BSL4 laboratories. Currently, no commercial vaccines or antiviral drugs are available against OHFV infection. In this study, we recovered a replication-deficient OHFV with an NS1 deletion (OHFV-ΔNS1) and reporter virus replacing NS1 with the Gaussia luciferase (Gluc) (OHFV-ΔNS1-Gluc). Both the defective OHFV-ΔNS1 and OHFV-ΔNS1-Gluc virus could only replicate efficiently in the BHK21 cell line expressing NS1 (BHK21(NS1)) but not in naïve BHK21 cells. The Gluc reporter gene of OHFV-ΔNS1-Gluc virus was maintained stably after serial passaging of BHK21(NS1) cells and was used to surrogate the replication of OHFV. Using NITD008, OHFV-ΔNS1-Gluc virus was validated for antiviral screening, and high-throughput screening parameters were optimized in a 96-well plate format with a calculated Z′ value above 0.5. The OHFV-ΔNS1-Gluc reporter virus is a powerful tool for antiviral screening as well as viral replication and pathogenesis studies in BSL2 laboratories.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, which is highly pathogenic and classified as a biosafety level 3 (BSL-3) agent, has greatly threatened global health and efficacious antivirals are urgently needed. The high requirement of facilities to manipulate the live virus has limited the development of antiviral study. Here, we constructed a reporter replicon of SARS-CoV-2, which can be handled in a BSL-2 laboratory. The Renilla luciferase activity effectively reflected the transcription and replication levels of the replicon genome. We identified the suitability of the replicon in antiviral screening using the known inhibitors, and thus established the replicon-based high-throughput screening (HTS) assay for SARS-CoV-2. The application of the HTS assay was further validated using a few hit natural compounds, which were screened out in a SARS-CoV-2 induced cytopathic-effect-based HTS assay in our previous study. This replicon-based HTS assay will be a safe platform for SARS-CoV-2 antiviral screening in a BSL-2 laboratory without the live virus.

The miniature high-frequency monolithic crystal filter is developed according to the requirement of model. The main electrical performance of the monolithic crystal filter is better than that of technical specifications, and the parameters of passband bandwidth, insert loss, passband ripple, shape factor, parasitic suppression, stopband attenuation meet the requirements of users.

12. 76MHz discrete crystal filter adopts AT cut quartz resonator and differential bridge circuit design. The bandwith of 3dB passband is up to 60kHz at the operting temperature range of -20°c ∼ 60°C. The filter features advanced circuit design, reasonable component application, voltage standing wave ratio less than 2.0. The components are mounted and sealed with tin, and the whole structure is shielded and isolated. The successful development of this product provides a frequency selection device for electronic systems such as tactical mission and radar systems which require extremely high signal reception and transmission under severe conditions. The electrical performance test data and result analysis of the 12. 76MHz discrete crystal filter are given.

The first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib significantly improved the therapeutic effect in non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, the EGFR

Infections with zoonotic viruses, such as flaviviruses, influenza virus, and the SARS-CoV-2 pandemic coronavirus constitute an increasing global risk. Hence, an urgent need exists for the development of broad-spectrum antivirals to prevent such outbreaks. Here, we show that the maduramycin and CP-80,219 aglycone polyether ionophores exhibit effective broad-spectrum antiviral activity, against various viruses, including Japanese encephalitis virus (JEV), Dengue virus (DENV), Zika virus (ZIKV), and Chikungunya virus (CHIKV), while also exhibiting promising activity against PR8 influenza virus and SARS-CoV-2. Moreover, liposome-encapsulated maduramycin and CP-80,219 provide full protection for mice from infection with JEV in vivo. Mechanistic studies suggest that aglycone polyether ionophores primarily inhibit the viral replication step without blocking endosome acidification to promote the fusion between viral and cellular membranes. The successful application of liposomes containing aglycone polyether ionophores in JEV-infected mice offers hope to the development of broad-spectrum antiviral drugs like penicillin back to 1940s.

The emerging SARS-CoV-2 infection associated with the outbreak of viral pneumonia in China is ongoing worldwide. There are no approved antiviral therapies to treat this viral disease. Here we examined the antiviral abilities of three broad-spectrum antiviral compounds gemcitabine, lycorine and oxysophoridine against SARS-CoV-2 in cell culture. We found that all three tested compounds inhibited viral replication in Vero-E6 cells at noncytotoxic concentrations. The antiviral effect of gemcitabine was suppressed efficiently by the cytidine nucleosides. Additionally, combination of gemcitabine with oxysophoridine had an additive antiviral effect against SARS-CoV-2. Our results demonstrate that broad-spectrum antiviral compounds may have a priority for the screening of antiviral compounds against newly emerging viruses to control viral infection.

Mosquito-borne flaviviruses consist of a positive-sense genome RNA flanked by the untranslated regions (UTRs). There is a panel of highly complex RNA structures in the UTRs with critical functions. For instance, Xrn1-resistant RNAs (xrRNAs) halt Xrn1 digestion, leading to the production of subgenomic flaviviral RNA (sfRNA). Conserved short direct repeats (DRs), also known as conserved sequences (CS) and repeated conserved sequences (RCS), have been identified as being among the RNA elements locating downstream of xrRNAs, but their biological function remains unknown. In this study, we revealed that the specific DRs are involved in the production of specific sfRNAs in both mammalian and mosquito cells. Biochemical assays and structural remodeling demonstrate that the base pairings in the stem of these DRs control sfRNA formation by maintaining the binding affinity of the corresponding xrRNAs to Xrn1. On the basis of these findings, we propose that DRs functions like a bracket holding the Xrn1-xrRNA complex for sfRNA formation. IMPORTANCE Flaviviruses include many important human pathogens. The production of subgenomic flaviviral RNAs (sfRNAs) is important for viral pathogenicity as a common feature of flaviviruses. sfRNAs are formed through the incomplete degradation of viral genomic RNA by the cytoplasmic 5ʹ–3ʹ exoribonuclease Xrn1 halted at the Xrn1-resistant RNA (xrRNA) structures within the 3ʹ-UTR. The 3ʹ-UTRs of the flavivirus genome also contain distinct short direct repeats (DRs), such as RCS3, CS3, RCS2, and CS2. However, the biological functions of these ancient primary DR sequences remain largely unknown. Here, we found that DR sequences are involved in sfRNA formation and viral virulence and provide novel targets for the rational design of live attenuated flavivirus vaccine.

Aims: Endothelial dysfunction appears in early diabetes mellitus partially because of epidermal growth factor receptor (EGFR) abnormal activation and downstream oxidative stress. The aim of this study was to determine whether Y396, a synthesized analog of rhynchophylline, could protect against endothelial dysfunction in diabetes and the underlying molecular mechanism. Results: Y396 could directly target the EGFR and inhibit its phosphorylation induced by high glucose and EGF, downstream translocation to the nucleus of E2F1, and its transcriptional activity and expression of Nox4. Diabetes-induced endothelium malfunction was ameliorated by Y396 treatment through EGFR inhibition. Downstream oxidative stress was decreased by Y396 in the aortas of type 1 diabetes mellitus mice and primary rat aorta endothelial cells (RAECs). Y396 could also ameliorate tunicamycin-induced oxidative stress in the aorta and RAECs. In addition, we again determined the protective effects of Y396 on high-fat diet/streptozotocin-induced type 2 diabetes mellitus. Innovation: This is the first study to demonstrate that Y396, a novel rhynchophylline analog, suppressed high-glucose-induced endothelial malfunction both in vivo and in vitro by inhibiting abnormal phosphorylation of EGFR. Our work uncovered EGFR as a novel therapeutic target and Y396 as a potential therapy against diabetes-induced complication. Conclusion: Y396 could directly bind with EGFR, and inhibit its phosphorylation and downstream E2F1 transcriptional activity. It could also preserve tunicamycin-evoked endothelial dysfunction and oxidative stress. It could protect against diabetes-induced endothelium malfunction in vivo through EGFR inhibition and downstream oxidative stress. Antioxid. Redox Signal. 32, 743-765.

Cellulosic fibers are usually finished with flame retardant via repeated pad-dry-cure processes. The present contribution reports a simple, facile, and one-pot chemical treatment process to access durable flame retardant lyocell fibers by directly immersing the fibers into the solution of a flame retardant ester of 2,2-ethanolamine diphosphoric acid (EADP) and urea for a certain time without using catalyst and cross-linker. As demonstrated, the treated lyocell fibers with grafted EADP show excellent flame retardancy and durability, as evidenced by an increase of limiting oxygen index value up to 37.8% and still 25.6% after 40 washing cycles. The key to success is ascribed to the formation of three dimensional flame retardant structures with EADP. Various analytical techniques, including raman spectroscopy, scanning electron microscope, thermogravimetry, and TG-infrared coupled technique prove that the carbonaceous residue and non-combustion gases were preferably generated during thermal decomposition process of treated fibers. Microcombustion calorimetry results revealed a significant reduction in the peak of heat release rate. The results indicate that EADP is potential for using as an efficient durable flame retardant of lyocell fibers.

Aims Ischemic stroke is one of the leading causes of death worldwide. MicroRNAs (miRNAs) have been reported to be implicated in cerebral hypoxia injury and could serve as a therapeutic target. As the third gasotransmitter, hydrogen sulfide (H2S) plays a critical role in hypoxia-induced injury in the central nervous system. Cystathionine β-synthase (CBS) is the main enzyme catalyzing the production of H2S in brain. The objective of this study was to investigate the effect of miR-125b-5p on protecting against oxygen and glucose deprivation (OGD) injury in PC-12 cells by regulating CBS and H2S generation. Results The level of miR-125b-5p was increased in the rat MCAO model as well as OGD model in PC-12 cells. Meanwhile, CBS expression was remarkably downregulated. Overexpression of miR-125b-5p reduced CBS expression, decreased the H2S generation, and deteriorated OGD injury in PC-12 cells. On the contrary, silencing miR-125b-5p protected PC-12 cells from OGD injury by upregulated CBS and H2S levels. We found the protective effect of miR-125b-5p inhibition was associated with anti-oxidative and anti-apoptotic cell signaling through decreasing ROS level and reducing mitochondrial membrane potential (ΔΨm). Furthermore, the protective effect was absent when CBS was knockdown in PC-12 cells. Innovation and conclusion Our research discovered the regulation of CBS by miR-125b-5p. Besides, we provide the evidence for the therapeutic potential of miR-125b-5p inhibition for cerebral ischemia via CBS/H2S pathway.

Zika virus (ZIKV) is an important emerging human pathogen associated with microcephaly, Guillain-Barre syndrome and meningoencephalitis. Developing rapid and reliable HTS assay is important for ZIKV drug discovery. Here, we constructed a dicistronic ZIKV replicon (ZIKV-Pac-Rluc-Rep) that contained the Renilla luciferase (Rluc) reporter gene separated from the puromycin N-acetyl-transferase (Pac) selectable marker by a short peptide cleavage site. A clonal replicon cell line stably expressing high level of ZIKV replicon was established by selection with puromycin. By optimizing cell number, compound concentration and incubation time, a robust replicon cell-based HTS assay was developed with a calculated Z' value of >0.5. The fully optimized assay was further validated using several known flavivirus replication inhibitors. Altogether, the replicon cell-based HTS assay developed in this study will facilitate the discovery of antiviral compounds against ZIKV.

The first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib significantly improved the therapeutic effect in non–small cell lung cancer (NSCLC) patients with EGFR mutation. However, the EGFRT790M mutation occurs and results in acquired resistance. Consequently, mutant selective third-generation EGFR TKIs represented by AZD9291 (Osimertinib) have been developed to offer more effective therapeutic treatment, but the clinical application is limited by the acquired resistance and the high costs. A series of 5-chloropyrimidine-2,4-diamine derivatives were synthesized and screened for in vitro antitumor activity on H1975 and A431 cells. XHL11 showed the strongest antineoplastic activity. Compared to AZD9291, XHL11 suppressed cellular proliferation and colony formation and induced apoptosis in H1975 cells with EGFRL858R/T790M mutation. In addition, XHL11 caused expression changes in EGFR and apoptosis-related pathways. Moreover, oral administration of XHL11 suppressed tumor progression in vivo in a H1975 subcutaneous xenograft model. These data demonstrated that XHL11 might be developed as a promising EGFR TKI for the therapeutic use of NSCLC patients.

As a renewable, abundant, and eco-friendly bio-based compound, phytic acid (PA) possesses high phosphorus content, which is a potential flame retardant for cellulosic fibers. Generally, PA is not efficient for cellulosic fibers due to strong acidity that results in greatly reduced strength and lack of soft hand. As proved elsewhere, the compounds with phosphorous and nitrogen was reported to be an efficient flame retardant and exhibited synergistic effect for cellulosic fibers. Therefore, PA was firstly reacted with urea to synthesize a novel green flame retardant containing a high level of phosphorus and nitrogen elements, i.e., phytic acid ammonium, then it was employed for lyocell fibers through pad-dry-cure finishing process. As expected, flame retardancy and durability of finished lyocell fabrics were considerably improved, as evidenced by an increase of limiting oxygen index value up to 39.2% and still 29.7% after 30 laundering cycles. TG–MS and TG–FTIR coupled techniques demonstrate that the formation of carbonaceous residue and non-combustion gases preferably generated during thermal pyrolysis process of finished lyocell fibers.

In this study, an in vitro ligation method was developed to assemble a full-length infectious cDNA clone of the Zika virus (ZIKV). Four contiguous cDNA subclones covering the complete ZIKV genome were constructed with unique BglI restriction sites at the ends of each fragment. The BglI restriction sites only allow in vitro ligation to happen between interconnecting restriction sites from adjacent cDNA fragments, resulting in an intact full-length cDNA of ZIKV. RNA transcripts derived from the full-length cDNA were infectious. The recombinant virus replicated as efficiently as the wild-type virus with similar growth kinetics and plaque morphologies in Vero and C6/36 cells. Both viruses were inhibited by NITD008 treatment. This in vitro ligation method will facilitate manipulation of the viral genome through genetic modifications of four separated subclones of ZIKV for the rapid and rational development of candidate vaccines and viral replication study.

The aim of the present study was to compare the different effects of berberine (Ber) and Coptischinensis extract (CCE) on a rat model of type 2 diabetes mellitus (T2DM), and the islet Rin‑5f cell line was used to examine the differences between Ber and CCE and the underlying mechanisms. CCE was extracted and purified prior to analysis. Male Sprague‑Dawley rats were provided with a high‑fat diet to induce insulin resistance prior to injecting with streptozotocinto establish the T2DM model, the T2DM rats were treated with Ber and CCE, and blood samples and pancreatic tissues were obtained and compared to examine T2DM metabolic syndromes among the groups of rats, which included healthy rats, model rats, and model rats treated with Ber and CCE at different doses between 0 and 8 weeks. The protective effects of Ber and CCE on the Rin‑5f islet cell line were also evaluated. The effects on Rin‑5f cell proliferation and cell cycle, glucose‑stimulated insulin release test (GSIS), the anti‑apoptotic effects caused by fat induction, and protein expression levels of poly ADP‑ribose polymerase (PARP‑1) were evaluated. The results showed that the content of the prepared CCE was 96.07% for five alkaloids. When it was used for treatment of the T2DM rats, compared with Ber, metformin and rosiglitazone, the fasting blood glucose, glucosylated serum protein (GSP) and glucose infusion rate indicesin the fasting rats were ameliorated, compared with those in the T2MD rats, with no significant differences between treatment with Ber or CCE and metformin or rosiglitazone. The indices of mean optical density and fasting β‑cell function index (FBCI) were different following treatment with Ber and CCE, compared with those in the model rats, which may have stimulated the pancreatic secretion of insulin. When Ber and CCE were used to examine the protective effects on Rin‑5F cells, it was found that the Rin‑5f cell GSIS, cell cycle, lipotoxic islet cell proliferation and protein expression of PARP‑1 were altered and improved, which may have protected pancreatic islet β‑cells by improving islet β‑cell proliferation and the protein expression of PARP‑1. CCE and Ber exerted similar effects when used for the treatment of T2MD rats, and may have stimulated the pancreatic secretion of insulin through the protective effect on islet β‑cells via improving islet β‑cell proliferation and the protein expression of PARP‑1.

Ligands play a vital role in atom transfer radical polymerization (ATRP) in solubilizing the transition-metal salt and adjusting the redox potential of the metal center. In general, nitrogen ligands work particularly well for copper-mediated ATRP, while phosphorus-based ligands are rarely used due to less effectiveness. Therefore, this work aims to explore for the first time a facile, simple, and inexpensive ionic liquid (IL), 1-phenyl-3-methylimidazole diphenyl phosphate ([Phmim][Ph2PO4]), as an efficient phosphorus ligand for CuBr2-mediated reverse ATRP. The key to success is ascribed to stronger complexation of the IL ligand with the catalyst and higher solubility of the resulting complex. The polymerizations proceeded in a controlled/“living” fashion, as evidenced by first-order kinetics, linear evolution of molecular weights with monomer conversion, and narrow molecular weight distributions. Effects of various experimental parameters—solvent, reaction temperature, IL, and molar ratio of CuBr2/[Phmim][Ph2PO4]—on the polymerization were investigated in detail. Furthermore, 1H NMR analysis confirmed the halogen-containing chain-end functionality of the resultant polymer.

Over the past few years, ionic liquids (ILs) have been widely reported as reaction media for reverse atom transfer radical polymerization (ATRP). In particular, almost all the ILs with the structure [Hmim][RCOO] (R represents an alkyl group) have been used as ligands for a reverse ATRP system. However, the facile, simple and low-cost ILs, 1-alkyl-3-methylimidazole chloride ([Rmim][Cl]), have rarely been employed as ligands for reverse ATRP. In this article, a [Rmim][Cl] was successfully employed as a ligand for the reverse ATRP of methyl methacrylate with Fe(III) as catalyst and 2,2′-azobisisobutyronitrile as initiator. The key to success is to adjust the FeCl3/[Rmim][Cl] molar ratio value to 1 : 1. The results indicated that the polymerization with [Rmim][Cl] as a ligand proceeded in a controlled/“living” fashion, as evidenced by the first-order kinetic plot, low polydispersity index values, and increase in polymer molecular weight with monomer conversion. The effects of various experimental parameters, including different catalysts, reaction temperatures, solvents, and molar ratios of FeCl3/[Rmim][Cl], on the polymerization were investigated in detail. Furthermore, 1H NMR and gel permeation chromatography analyses confirmed the halogen-containing chain-end functionality of the resultant polymer.

Reverse atom transfer radical polymerization (R-ATRP) and ring-opening polymerization (ROP) are the two representative processes of the most promising living/controlled polymerization techniques. Herein, a facile and stable metal catalyst, Cu(S(SC)(N–CH3)CH2CH2OH)2, containing a hydroxyl group was first designed with an aim to prepare block copolymers of vinyl monomer and cyclic ester monomer via a combination of R-ATRP and ROP. The vinyl polymer chain end attached with a hydroxyl functionality obtained from R-ATRP was directly used as a macroinitiator to prepare the block copolymers via ROP of e-caprolactone. 1H NMR and GPC analyses as well as ROP chain-extension reaction confirmed that the vinyl polymers possessed very high chain end functionality, and the block copolymers of the vinyl monomer and cyclic ester monomer were successfully synthesized.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes epidemics of debilitating disease worldwide. Currently, there are no licensed vaccines or antivirals available against CHIKV infection. In this study, we generated a novel live attenuated vaccine (LAV) candidate for CHIKV with a complete deficiency of capsid (ΔC-CHIKV). It could propagate in BHK-21 cells, and had antigenic properties similar to those of native CHIKV. Vaccination of either immunocompromised IFNAR(−/−) mice or immunocompetent C57BL/6 mice with a single dose of ΔC-CHIKV conferred complete protection upon challenge with wild-type (WT) CHIKV. Taken together, this vaccine candidate appeared to be safe and efficacious, representing a novel strategy for CHIKV vaccine design. IMPORTANCE Currently, there is no licensed vaccine against CHIKV infection. An ideal CHIKV vaccine should generate an optimal balance between efficacy and safety. Live attenuated vaccines that can elicit strong immune responses often involve a trade-off of reduced safety. Here, a novel live attenuated vaccine candidate for CHIKV lacking the entire capsid gene, ΔC-CHIKV, was developed. It was demonstrated to be genetically stable, highly attenuated, immunogenic, and able to confer complete protection against lethal CHIKV challenge after a single dose of immunization. Such an infectious vaccine candidate devoid of capsid provides a novel strategy for the development of a live attenuated CHIKV vaccine.

Leonurine, also named SCM-198, which was extracted from Herba leonuri, displayed a protective effect on various cardiovascular and brain diseases, like ischemic stroke. Ischemic stroke which is the leading cause of morbidity and mortality, ultimately caused irreversible neuron damage. This study is aimed at exploring the possible therapeutic potential of SCM-198 in the protection against postischemic neuronal injury and possible underlying mechanisms. A transient middle cerebral artery occlusion (tMCAO) rat model was utilized to measure the protective effect of SCM-198 on neurons. TEM was used to determine neuron ultrastructural changes. The brain slices were stained with Nissl staining solution for Nissl bodies. Fluoro-Jade B (FJB) was used for staining the degenerating neurons. In the oxygen-glucose deprivation and re-oxygenation (OGD/R) model of bEnd.3 cells treated with SCM-198 (0.1, 1, 10 μM). Then, the bEnd.3 cells were cocultured with SH-SY5Y cells. Cell viability, MDA level, CAT activity, and apoptosis were examined to evaluate the cytotoxicity of these treatments. Western blot and immunofluorescent assays were used to examine the expression of protein related to the p-STAT3/NOX4/Bcl-2 signaling pathway. Coimmunoprecipitation was performed to determine the interaction between p-STAT3 and NOX4. In the transient middle cerebral artery occlusion (tMCAO) rat model, we found that treatment with SCM-198 could ameliorate neuron morphology and reduce the degenerating cell and neuron loss. In the in vitro model of bEnd.3 cell oxygen-glucose deprivation and reoxygenation (OGD/R), treatment with SCM-198 restored the activity of catalase (CAT), improved the expression of Cu-Zn superoxide dismutase (SOD1), and decreased the malondialdehyde (MDA) production. SCM-198 treatment prevented OGD/R-induced cell apoptosis as indicated by increased cell viability and decreased the number of TUNEL-positive cells, accompanied with upregulation of Bcl-2 and Bcl-xl protein and downregulation Bax protein. The results were consistent with SH-SY5Y cells which coculture with bEnd.3 cells. The forthcoming study revealed that SCM-198 activated the p-STAT3/NOX4/Bcl-2 signaling pathway. All the data indicated that SCM-198 protected against oxidative stress and neuronal damage in in vivo and in vitro injury models via the p-STAT3/NOX4/Bcl-2 signaling pathway. Our results suggested that SCM-198 could be the potential drug for neuroprotective effect through stabilizing endothelial cell function.

Cerasus humilis is a species of small, perennial, drought-resistant and multipurpose deciduous shrub grown in arid and semi-arid conditions in northern China. In this study, an efficient protocol for the rapid micropropagation of C. humilis has been standardized using stem and/or leaf explants. Direct multiple shoot induction was observed when the stem explants were cultured on Murashige and Skoog (MS) medium supplemented with different plant growth regulators. The highest shoot induction was obtained when stem explants from adult trees were cultured on MS medium supplemented with 2.0 mg L−1 6-benzyladenine (6-BA) and 0.9 mg L−1 α-naphthaleneacetic acid (NAA). The leaf and stem explants cultured on MS medium with 1.0 mg L−1 6-BA and 0.6 mg L−1 NAA, and 0.5 mg L−1 6-BA and 0.8 mg L−1 NAA, respectively, produced the highest induction frequency of callus. Maximum proliferation of callus was observed on MS medium containing a combination of 0.5 mg L−1 6-BA with 0.6 mg L−1 2,4-dichlorophenoxyacetic aci...

A case of congenital renal arteriovenous fistula (AVF) complicating pregnancy with gross hematuria was managed successfully by superselective embolization with metallic coils. The patient was in the first trimester of her pregnancy at 12 weeks of gestation. The AVF was detected by color Doppler sonography and confirmed by renal arteriography. Because of its easy accessibility and absence of irradiation, ultrasound is the first choice for pregnant patients. Color Doppler ultrasound is effective in diagnosing AVF, and it is also helpful in the long-term followup after treatment. The cirsoid-type renal congenital arteriovenous fistula has a characteristic sonographic appearance with a cluster of tubular anechoic structures in the kidney, which produce continuous turbulent high-velocity flow signals and a burr-like boundary flow spectrum. When the sonographic features are present, the diagnosis of renal AVF should be made, after which renal arteriography can be performed to confirm it. Selective embolization provided a safe and effective treatment with minimal damage to the parenchyma and without compromising renal function.

In the present study, our bioinformatics analysis first reveals the existence of a conserved guanine-rich sequence within the Zaire ebolavirus L gene. Using various methods, we show that this sequence tends to fold into G-quadruplex RNA. TMPyP4 treatment evidently inhibits L gene expression at the RNA level. Moreover, the mini-replicon assay demonstrates that TMPyP4 effectively inhibits the artificial Zaire ebolavirus mini-genome and is a more potent inhibitor than ribavirin. Although TMPyP4 treatment reduced the replication of the mutant mini-genome when G-quadruplex formation was abolished in the L gene, its inhibitory effect was significantly alleviated compared with wild-type. Our findings thus provide the first evidence that G-quadruplex RNA is present in a negative-sense RNA virus. Finally, G-quadruplex RNA stabilization may represent a new therapeutic strategy against Ebola virus disease.