Antiviral activity of porcine interferon omega 7 against foot-and-mouth disease virus in vitro.

Foot-and-mouth disease (FMD) is a disease of worldwide economic importance, and vaccines play an important role in preventing FMDV outbreaks. However, new control strategies are still needed since FMDV outbreaks still occur in some disease-free countries. Currently, interferon (IFN)-based strategies have been demonstrated to be an efficient biotherapeutic option against FMDV; however, interferon omega (IFN-ω) has not yet been assessed in this capacity. Thus, this study evaluated the antiviral activity of porcine IFN omega 7 (PoIFN-ω7) against FMDV. After the PoIFN-ω7 was expressed and purified, cell proliferation assays and quantitative real-time reverse transciption-polymerase chain reaction were used to evaluate the effective anti-cytopathic concentration of PoIFN-ω7 and its effectiveness pre- and post-infection with FMDV in swine kidney cells (IBRS-2). Results showed the rHis-PoIFN-ω7 fusion protein was considerably expressed using Escherichia coli BL21 (DE3) strain, and the recombinant protein exhibited significant in vitro protection against FMDV, including two strains belonging to type O and A FMDV, respectively. In addition, PoIFN-ω7 upregulated the transcription of Mx1, ISG15, OAS1, and PKR genes. These findings indicated that IFN-ω has the potential for serving as a useful therapeutic agent to prevent FMDV or other viral outbreaks in pigs.

Inhibitory effects of homoharringtonine on foot and mouth disease virus in vitro.

Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoof animals including cattle, swine, sheep, goats, and lots of wild species. Effectively control measures are urged needed. Here, we showed that homoharringtonine treatment exhibited a strong inhibitory effect against two different strains of FMDVs (O/MYA98/BY/2010 and A/GD/MM/2013) in swine kidney (IBRS-2) cells. Further experiments demonstrated that homoharringtonine did not affect virus attachment or entry. Using time-of-addition assays, we found that the antiviral activity of homoharringtonine occurred primarily during the early stage of infection. These results demonstrated that homoharringtonine might be an effective anti-FMDV drug. Further studies are required to explore the antiviral activity of homoharringtonine against FMDV replication in vivo.

A novel type I interferon, interferon alphaomega, shows antiviral activity against foot-and-mouth disease virus in vitro.

Recently, a novel type I interferon alphaomega (IFN-αω), also known as IFN-µ, was identified. However, the biological activity of IFN-αω remain poorly understood. In this study, the porcine IFN-αω (PoIFN-αω) was expressed, purified, and its antiviral activities assessed by its ability to inhibit the cytopathic effect caused by FMDV on IBRS-2 cells. In addition, q-PCR was used to evaluate the expression of IFN-stimulated genes induced by PoIFN-αω. It was found that PoIFN-αω exerted effective antiviral activity against FMDV pre- and post-infection. Additionally, PoIFN-αω induced the transcription of IFN-stimulated genes, including Mx1, ISG15, OAS1, and PKR genes. Our study reported a new indication of PoIFN-αω as an effective anti-FMDV agent for the first time.

Nitrogen-doped carbon nanodots prepared from polyethylenimine for fluorometric determination of salivary uric acid.

Stable and low-cost carbon dots (C-dots) were prepared from polyethylenimine (PEI) by a hydrothermal method. It is found that the fluorescence of the C-dots (best measured at excitation/emission wavelengths of 365/473 nm) is quenched by selective oxidation of surface PEI by periodate but recovers in the presence of uric acid (UA). It is assumed that this is due to the selective reduction of the nitrone groups to hydroxylamine groups by UA. The findings were used to design a fluorometric method for determination of UA that has a 2.3 nM detection limit. This is lower than that of reported fluorometric and enzymatic assays. The performance of the method has been validated by determination of UA in samples of human saliva. It is found that the results agree well with those obtained by a commercial UA assay. Graphical abstract Schematic presentation of the polyethylenimine (PEI) carbon nanodots (C-dots) as a fluorescent probe for uric acid. Their fluorescence is quenched by periodate (IO4-) due to oxidative formation of nitrone groups, an subsequently restored due to reduction by uric acid (UA).

Hyperbranched Aliphatic Polyester via Cross-Metathesis Polymerization: Synthesis and Postpolymerization Modification.

A novel postpolymerization modification methodology is demonstrated to achieve selective functionalization of hyperbranched polymer (HBP). Terminal and internal acrylates of HBP derived from cross-metathesis polymerization (CMP) are functionalized in a chemoselective fashion using the thiol-Michael chemistries. Model reactions between different thiols (benzyl mercaptan and methyl thioglycolate) and acrylates (n-hexyl acrylate and ethyl trans-2-decenoate) by using dimethylphenylphosphine or amylamine as the catalyst are investigated to optimize the modification protocol for HBP. High-molecular-weight HBP P0 is generated through CMP of AB2 monomer 2, a compound containing one α-olefin and two acrylate metathetically polymerizable groups. CMP kinetics is monitored by NMR and gel permeation chromatography (GPC). Accordingly, microstructural analysis is conducted in detail, and CMP procedure is optimized. Postpolymerization modification of HBP P0 is performed via two distinguished strategies, namely one-step complete modification and sequential modification, to generate terminally and/or internally functionalized HBPs P1-P3 in a chemoselective fashion by using phosphine-initiated and/or base-catalyzed thiol-Michael chemistries. Finally, thermal stability and glass transition behaviors of HBPs P0-P3 are studied by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC), respectively.

Precision Aliphatic Polyesters via Segmer Assembly Polymerization.

Precise structure-property relation of a biodegradable polymer (e.g., aliphatic polyester) is anticipated only if monomer units and chiral centers are arranged in a defined primary sequence as a biomacromolecule. An emerging synthetic methodology, namely segmer assembly polymerization (SAP), is introduced in this paper to reveal the latest progress in polyester synthesis. Almost any periodic polyester envisioned can be synthesized via SAP using a programed linear or cyclic monomer. In this context, the macroscopic properties of a biodegradable polymer are fundamentally determined by microstructural information through a bottom-up approach. It can be highlighted that SAP ideally combines the precision of organic synthesis and the high efficiency of a polymerization reaction. Previously reported strategies including nucleophilic displacement, polyesterification, cross-metathesis polymerization (CMP), ring-opening polymerization (ROP), ring-opening metathesis polymerization (ROMP) and entropy-driven ring-opening metathesis polymerization (ED-ROMP) are critically reviewed in this paper to shed light on precision synthesis of aliphatic polyesters via SAP. Emerging yet challenging, SAP is a paradigm which reflects the convergence of organic and polymer chemistries and is also an efficient pathway to microstructural control. The current status, future challenges and promising trends in this realm are analyzed and discussed in this overview of the state-of-the-art.

Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro.

Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV-A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK-21 cell was dose-dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID50 ) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT-qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti-FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in-depth research in vivo.

Precision Aliphatic Polyesters with Alternating Microstructures via Cross-Metathesis Polymerization: An Event of Sequence Control.

Sequence-regulated polymerization is realized upon sequential cross-metathesis polymerization (CMP) and exhaustive hydrogenation to afford precision aliphatic polyesters with alternating sequences. This strategy is particularly suitable for the arrangement of well-known monomer units including glycolic acid, lactic acid, and caprolactic acid on polymer chain in a predetermined sequence. First of all, structurally asymmetric monomers bearing acrylate and α-olefin terminuses are generated in an efficient and straightforward fashion. Subsequently, cross-metathesis (co)polymerization of M1 and M2 using the Hoveyda-Grubbs second-generation catalyst (HG-II) furnishes P1-P3, respectively. Finally, hydrogenation yields the desired saturated polyesters HP1-HP3. It is noteworthy that the ε-caprolactone-derived unit is generated in situ rather than introduced to tailor-made monomers prior to CMP. NMR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) results verify the microstructural periodicity of these precision polyesters. Differential scanning calorimetry (DSC) results reflect that polyesters without methyl side groups exhibit crystallinity, and unsaturated polyester samples show higher glass transition temperatures than their hydrogenated counterparts owing to structural rigidity.

[Preparation of CD123 mono-antibody modified tanshinone â ¡A loaded immunoliposome and its in vitro evaluation].

In the study, we developed a novel formulation, CD123 mono-antibody (mAb) modified tanshinone ⅡA loaded immunoliposome (CD123-TanⅡA-ILP) to achieve the targeted drug delivery for leukemia cells. Orthogonal test was used to optimize liposome preparation, and the TanⅡA-loaded PEGylated liposomes (TanⅡA-LP) of S100PC-Chol-(mPEG2000-DSPE)-TanⅡA at 19∶5∶1∶1 molar ratio were prepared by the thin film hydration-probe ultrasonic method. A post-insertion method was applied to prepare CD123-TanⅡA-ILP via thiolated mAb conjugated to the terminal of maleimide-PEG2000-DSPE. The cellular uptake assay was measured by flow cytometry, and the inhibitory effect of CD123-TanⅡA-ILP on NB4 cells proliferation was tested by using MTT assay. The results of cellular uptake assay showed that CD123-ILP could significantly increase the drug uptake of NB4 cells as compared with free drugs and LP. The IC50 values at 48 h incubation were 20.87, 11.71, 7.17 µmol•L⁻¹ respectively for TanⅡA，TanⅡA-LP and CD123-TanⅡA-ILP. CD123-ILP demonstrated a potential and promising targeted drug delivery strategy for acute myelogenous leukemia (AML) treatment.

Using PG-Liposome-Based System to Enhance Puerarin Liver-Targeted Therapy for Alcohol-Induced Liver Disease.

A critical issue for alcohol-induced liver disease (ALD) therapeutics is the lack of a highly efficient delivery system. In this study, a Puerarin-propylene glycol-liposome system was prepared for the purpose of targeting puerarin, an isoflavon, to the liver. Transmission electron microscope (TEM) results showed the liposomes to be spherical in shape with an average diameter of 182 nm with a polydispersity index of 0.239. The zeta potential of the particles was about -30 mV. The entrapment efficiency of puerarin was above 90%. MTT-based assay in HpeG2 cells showed no significant cytotoxicity in the presence of up to 25% concentration of the system containing 3% puerarin. In vivo performance of this system was studied in mice. Pharmacokinetics and distribution of puerarin-PG-liposome system was studied relative to puerarin solution at the same dose levels. The results show that puerarin-PG-liposome prolonged drug retention time and decreased elimination of puerarin in mice (AUC of liposome system and solution was 9.5 and 4.0 mg h L-1, respectively). Furthermore, propylene glycol (PG)-liposome system enhanced puerarin distribution into liver and spleen, while decreasing puerarin distribution in other tissues. Overall, the puerarin-PG-liposome system showed enhanced therapeutic effect in mice with ALD.

Adaptive laboratory evolution of ethanologenic Zymomonas mobilis strain tolerant to furfural and acetic acid inhibitors.

Furfural and acetic acid from lignocellulosic hydrolysates are the prevalent inhibitors to Zymomonas mobilis during cellulosic ethanol production. Developing a strain tolerant to furfural or acetic acid inhibitors is difficul by using rational engineering strategies due to poor understanding of their underlying molecular mechanisms. In this study, strategy of adaptive laboratory evolution (ALE) was used for development of a furfural and acetic acid-tolerant strain. After three round evolution, four evolved mutants (ZMA7-2, ZMA7-3, ZMF3-2, and ZMF3-3) that showed higher growth capacity were successfully obtained via ALE method. Based on the results of profiling of cell growth, glucose utilization, ethanol yield, and activity of key enzymes, two desired strains, ZMA7-2 and ZMF3-3, were achieved, which showed higher tolerance under 7 g/l acetic acid and 3 g/l furfural stress condition. Especially, it is the first report of Z. mobilis strain that could tolerate higher furfural. The best strain, Z. mobilis ZMF3-3, has showed 94.84% theoretical ethanol yield under 3-g/l furfural stress condition, and the theoretical ethanol yield of ZM4 is only 9.89%. Our study also demonstrated that ALE method might also be used as a powerful metabolic engineering tool for metabolic engineering in Z. mobilis. Furthermore, the two best strains could be used as novel host for further metabolic engineering in cellulosic ethanol or future biorefinery. Importantly, the two strains may also be used as novel-tolerant model organisms for the genetic mechanism on the "omics" level, which will provide some useful information for inverse metabolic engineering.

Co-delivery of dexamethasone and green tea polyphenols using electrospun ultrafine fibers for effective treatment of keloid.

PURPOSE: The electrospun polymer ultrafine fiber meshes wereused to co-deliver dexamethasone (DEX) and green tea polyphenols (GTP) in order to acquire a suitable balance between effective treament of keloid and safety to the skin. METHODS: This co-delivery system was prepared with a simple electrospinning technology. Keloid model was established on the back of athymic nude mice with the human keloid tissues and the formulated fiber meshes were applied onto keloids for an in vivo evaluation on their therapeutic effects. RESULTS: Unlike other therapeutic formulations, these fiber meshes as a new surgical dressing possess multiple useful functions, including the capabilities of maintaining a moist environment, resisting bacterial infection and controlling the drug release. Hydrophobic DEX molecules inside the fiber meshes can be released successfully from the channels formed by the early release of the hydrophilic GTP molecules and then transported across the skin. A distinctive result acquired from histological analysis shows that after 3-month treatment, the DEX/GTP-loaded fiber meshes significantly induce the degradation of collagen fibers in keloid on the back of nude mice compared to the traditional treatment. CONCLUSION: The dressing formulation based on nanofibers provides a promising platform for the treatment of keloid.

A novel subcritical water synergistic co-treatment of brominated epoxy resin and copper-based spent catalysts: debromination, phenol production, and copper recovery.

In this study, a high-efficiency co-treatment strategy for brominated epoxy resin (BER) and copper-based spent catalyst (CBSC) was developed by using subcritical water (SubCW) process. Multivalent species of copper released from CBSC could accelerate the electron transfer of the SubCW system and efficiently catalyze radical reactions to promote the debromination and decomposition of BER, and had an effect on the capture and binding of bromine species. Meanwhile, the formation of HBr by the BER debromination resulted in a decrease in the system pH and markedly enhanced the leaching/recovery of Cu from CBSC. The optimal conditions of the SubCW co-treatment process were as follows: reaction temperature of 350 °C, solid-to-liquid ratio of 1:30 g/mL, BER-to-CBSC mass ratio of 10:1 g/g, and reaction time of 60 min. Under the optimal conditions, 97.12 % of the Br could be removed from BER by the SubCW co-treatment process and a high-purity phenol (64.09 %) could be obtained in the oil phase product, and 86.44 % of Cu in the CBSC could be leached and recovered. The introduction of CBSC significantly changed the decomposition path of BER. Compared to the SubCW process without CBSC, bromine-free oils products could be obtained by the co-treatment process of BER and CBSC at low-temperature. This study provided a novel understanding of resource conversion mechanism of BER and CBSC in subcritical water medium via the synergistic effect between the two different waste streams to improve treatment efficiency and synchronously recover high-value products.

A low-temperature co-treatment of diethylhexyl phthalate-rich polyvinyl chloride and waste copper catalyst by subcritical water (hydrothermal treatment): Dechlorination, recovery of diethylhexyl phthalate and copper.

As one of the most widespread plastics in the world, the recycling of diethylhexyl phthalate-rich polyvinyl chloride (DEHP-rich PVC) faces great challenges because of the high levels of Cl and plasticizers. On the other hand, waste copper catalyst (WCC) discharged from various industrial processes is not effectively recycled. In this study, a significant synergistic effect between the DEHP-rich PVC and WCC was found in a subcritical water (SubCW) medium, and a co-treatment of the DEHP-rich PVC and WCC was developed by the SubCW process. The introduction of WCC significantly improved the dechlorination efficiency of the DEHP-rich PVC to 96.03 % at a low temperature of 250 °C. Under the optimal conditions, the leaching of copper from WCC reached a maximum of 81.08 %. Oil products included DEHP (55.7 %, GC peak area%), 3-methyl-3-heptene (37.3 %, GC peak area%), and 2-ethyl-1-hexanol (7.0 %, GC peak area%). The dechlorination pathways of the DEHP-rich PVC included hydroxyl substitution and direct dechlorination. HCl released from the DEHP-rich PVC led to a decrease in the pH of the system and significant copper leaching from the WCC. DEHP was decomposed by hydrolysis, dehydration, and rearrangement reaction by the SubCW co-treatment process. The enhancement mechanism of the WCC for the dechlorination of the DEHP-rich PVC was based on that the conversion of copper species in the SubCW promoted the formation of hydroxyl radicals and the hydroxyl substitution for chlorine in PVC molecular chain. The proposed SubCW low-temperature co-treatment could be a prospective strategy for the low-energy and synchronous recovery of the two different wastes of the DEHP-rich PVC and WCC.

Thermosensitive hydrogel from oligopeptide-containing amphiphilic block copolymer: effect of peptide functional group on self-assembly and gelation behavior.

We reveal that a slight change in the functional group of the oligopeptide block incorporated into the poloxamer led to drastically different hierarchical assembly behavior and rheological properties in aqueous media. An oligo(L-Ala-co-L-Phe-co-ß-benzyl L-Asp)-poloxamer-oligo(ß-benzyl-L-Asp-co-L-Phe-co-L-Ala) block copolymer (OAF-(OAsp(Bzyl))-PLX-(OAsp(Bzyl))-OAF, denoted as polymer 1), which possessed benzyl group on the aspartate moiety of the peptide block, was synthesized through ring-opening polymerization. The benzyl group on aspartate was then converted to carboxylic acid to yield oligo(L-Ala-co-L-Phe-co-L-Asp)-poloxamer-oligo(L-Asp-co-L-Phe-co-L-Ala) (OAF-(OAsp)-PLX-(OAsp)-OAF, denoted as polymer 2). Characterization of the peptide secondary structure in aqueous media by circular dichroism revealed that the oligopeptide block in polymer 1 exhibited mainly an α-helix conformation, whereas that in polymer 2 adopted predominantly a ß-sheet conformation at room temperature. The segmental dynamics of the PEG in polymer 1 remained essentially unperturbed upon heating from 10 to 50 °C; by contrast, the PEG segmental motion in polymer 2 became more constrained above ca. 35 °C, indicating an obvious change in the chemical environment of the block chains. Meanwhile, the storage modulus of the polymer 2 solution underwent an abrupt increase across this temperature, and the solution turned into a gel. Wet-cell TEM observation revealed that polymer 1 self-organized to form microgel particles of several hundred nanometers in size. The microgel particle was retained as the characteristic morphological entity such that the PEG chains did not experience a significant change of their chemical environment upon heating. The hydrogel formed by polymer 2 was found to contain networks of nanofibrils, suggesting that the hydrogen bonding between the carboxylic acid groups led to an extensive stacking of the ß sheets along the fibril axis at elevated temperature. The in vitro cytotoxicity of the polymer 2 aqueous solution was found to be low in human retinal pigment epithelial cells. The low cytotoxicity coupled with the sol-gel transition makes the corresponding hydrogel a good candidate for biomedical applications.

[Changes in Th17 and CD4+CD25+ Treg cells and their significance among children with hand, foot and mouth disease].

OBJECTIVE: To investigate the changes in peripheral blood Th17 and CD4(+)CD25(+) regulatory T (Treg) cells and their significance among children with hand, foot and mouth disease (HFMD). METHODS: Eighty-nine children with HFMD, including 55 cases of common HFMD and 34 cases of severe HFMD, were included in the study; and 30 healthy children were selected as the control group. The percentages of Th17 and CD4(+)CD25(+) Treg cells in CD4(+) T cells in peripheral blood were determined by flow cytometry. The expression levels of interleukin (IL)-10, transforming growth factor-ß (TGF-ß), and IL-17 were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the cases of common HFMD and severe HFMD had significantly increased levels of Th17 cells and IL-17 (P<0.05) but significantly decreased levels of CD4(+)CD25(+) Treg cells, IL-10, and TGF-ß (P<0.05). The severity of the HFMD was positively correlated with the levels of Th17 cells and IL-17 in peripheral blood but negatively correlated with the levels of CD4(+)CD25(+) Treg cells, IL-10, and TGF-ß. CONCLUSIONS: Children with HFMD have increased response of Th17 cells but decreased response of CD4(+)CD25(+) Treg cells in peripheral blood. Th17/CD4(+)CD25(+) Treg cell imbalance may play an important role in the pathogenesis of HFMD.

Treatment of DEHP-rich PVC waste in subcritical urine wastewater: Efficient dechlorination, denitrification, plasticizer decomposition, and preparation of high-purity phthalic acid crystals.

It is difficult to dispose diethylhexyl phthalate-rich polyvinyl chloride (DEHP-rich PVC) waste due to the high level of chlorine and plasticizer. On the other hand, the denitrification of urine wastewater with high nitrogen content also faces great challenges. In this study, a synergistic treatment strategy was developed for the DEHP-rich PVC waste and urine wastewater by a subcritical water process. Subcritical urine wastewater (SUW) was used as a reaction medium in the synergistic treatment. PVC dechlorination, DEHP decomposition, and denitrification of urine wastewater were synchronously achieved in the one pot SUW. Under the optimal conditions (300 °C, 15 min, 1:5 g/mL), the PVC dechlorination ratio, urine wastewater denitrification ratio and DEHP decomposition ratio could reach 98.4%, 64.9%, and 99.2%, respectively. The decomposition of DEHP mainly included hydrolysis, nucleophilic substitution, and acylation. DEHP could be converted into phthalic acid crystal at 220 °C with a yield of 66.25% due to the efficient hydrolysis action of SUW. All the removed Cl was transferred from PVC matrix to aqueous phase. Hydroxyl nucleophilic substitution is the principal dechlorination path of PVC. The reactions between N-containing species and DEHP in SUW resulted in the high-efficiency denitrification of urine wastewater, and the N element was fixed in solid residue or transferred to oil phase as amides compounds. It is believed that the proposed SUW process is a promising technology for the synergistic treatment of DEHP-rich PVC waste and urine wastewater.

Efficacy and safety of QL0911 in adult patients with chronic primary immune thrombocytopenia: A multicenter, randomized, double-blind, placebo-controlled, phase III trial.

Objective: QL0911, a recombinant human thrombopoietin mimetic peptide-Fc fusion protein, is a romiplostim (Nplate®) biosimilar used to treat primary immune thrombocytopenia (ITP). This phase III study aimed to assess the efficacy and safety of QL0911 in adult patients with chronic primary ITP over a 24-week treatment period. Methods: We conducted a double-blind, placebo-controlled, phase III study in patients diagnosed with primary ITP for at least 12 months who had received at least one first-line ITP treatment with no response or recurrence after treatment, or who relapsed after splenectomy at 44 sites in China. Patients were randomly allocated (2:1 ratio) to QL0911 or placebo injection subcutaneously once weekly at an initial dose of 1 µg/kg for 24 weeks. The doses were adjusted to maintain the target platelet counts from 50 × 109/L to 200 × 109/L. Patients and investigators were blinded to the assignment. The primary endpoints were the proportion of patients who achieved a durable platelet response at week 24 (platelet count, ≥ 50 × 109/L during 6 of the last 8 weeks of treatment) and safety. The study was registered at ClinicalTrials.gov (NCT05621330). Results: Between October 2019 and December 2021, 216 patients were randomly assigned (QL0911,144; placebo,72). A durable platelet response was achieved by significantly more patients in the QL0911 group (61.8%, 95% CI: 53.3-69.8; P < 0.0001) than in the placebo group (0%). The mean duration of platelet responses was 15.9 (SE: 0.43) weeks with QL0911, and 1.9 (SE:0.26) week with placebo. Consistent results were achieved in subgroup analyses categorized by baseline splenectomy status (yes/no), concomitant ITP treatment (yes/no), and baseline platelet count (≤ 10 × 109/L, > 10 × 109/L, ≤ 20 × 109/L, > 20 × 109/L, and < 30 × 109/L). The incidence of TEAEs was comparable between the QL0911 and the placebo groups (91.7% and 88.9%, respectively). The most common adverse events overall were ecchymosis (28.5% for QL0911 vs. 37.5% for placebo), upper respiratory tract infections respiratory tract infections (31.9% for QL0911 vs. 27.8% for placebo), and gingival bleeding (17.4% for QL0911 vs. 26.4% for placebo). Conclusion: QL0911 was well-tolerated and increased and maintained platelet counts in adults with ITP. QL0911, a biosimilar to romiplostim (Nplate®), may be a novel treatment option for patients with ITP who have failed or relapsed from first-line treatment in China. Ongoing studies will provide further data on long-term efficacy and safety in such patient populations.

Pulsatile drug release from PLGA hollow microspheres by controlling the permeability of their walls with a magnetic field.

Pulsatile release: When a high-frequency magnetic field is applied, heat will be generated by coupling to the iron oxide nanoparticles encapsulated in the shells of PLGA hollow microspheres. As the temperature approaches the T(g) of PLGA, the polymer chains become more mobile, subsequently increasing the free volume of PLGA matrix and significantly enhancing the diffusion of drug molecules.

Transcriptome profiling of Zymomonas mobilis under furfural stress.

Furfural from lignocellulosic hydrolysates is the prevalent inhibitor to microorganisms during cellulosic ethanol production, but the molecular mechanisms of tolerance to this inhibitor in Zymomonas mobilis are still unclear. In this study, genome-wide transcriptional responses to furfural were investigated in Z. mobilis using microarray analysis. We found that 433 genes were differentially expressed in response to furfural. Furfural up- or down-regulated genes related to cell wall/membrane biogenesis, metabolism, and transcription. However, furfural has a subtle negative effect on Entner-Doudoroff pathway mRNAs. Our results revealed that furfural had effects on multiple aspects of cellular metabolism at the transcriptional level and that membrane might play important roles in response to furfural. This research has provided insights into the molecular response to furfural in Z. mobilis, and it will be helpful to construct more furfural-resistant strains for cellulosic ethanol production.