Polyphenols: Natural Food-Grade Biomolecules for the Treatment of Nervous System Diseases from a Multi-Target Perspective.

Polyphenols are the most prevalent naturally occurring phytochemicals in the human diet and range in complexity from simple molecules to high-molecular-weight polymers. They have a broad range of chemical structures and are generally categorized as "neuroprotective", "anti-inflammatory", and "antioxidant" given their main function of halting disease onset and promoting health. Research has shown that some polyphenols and their metabolites can penetrate the blood-brain barrier and hence increase neuroprotective signaling and neurohormonal effects to provide anti-inflammatory and antioxidant effects. Therefore, multi-targeted modulation of polyphenols may prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for difficult-to-treat neuropsychiatric disorders. Therefore, multi-target modulation of polyphenols has the potential to prevent the progression of neuropsychiatric disorders and provide a new practical therapeutic strategy for such nervous system diseases. Herein, we review the therapeutic benefits of polyphenols on autism-spectrum disorders, anxiety disorders, depression, and sleep disorders, along with in vitro and ex vivo experimental and clinical trials. Although their methods of action are still under investigation, polyphenols are still seldom employed directly as therapeutic agents for nervous system disorders. Comprehensive mechanistic investigations and large-scale multicenter randomized controlled trials are required to properly evaluate the safety, effectiveness, and side effects of polyphenols.

Exploring the Pathogenesis and Treatment of PSD from the Perspective of Gut Microbiota.

Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and treatment of PSD is still in the infancy stage. Patients with PSD often exhibit gastrointestinal symptoms; therefore the role of gut microbiota in the pathophysiology and potential treatment effects of PSD has become a hot topic of research. In this review, describe the research on the pathogenesis and therapy of PSD. We also describe how the gut microbiota influences neurotransmitters, the endocrine system, energy metabolism, and the immune system. It was proposed that the gut microbiota is involved in the pathogenesis and treatment of PSD through the regulation of neurotransmitter levels, vagal signaling, hypothalamic-pituitary-adrenal axis activation and inhibition, hormone secretion and release, in addition to immunity and inflammation.

Leaf diffusional capacity largely contributes to the reduced photosynthesis in rice plants under magnesium deficiency.

Numerous studies have clarified the impacts of magnesium (Mg) on leaf photosynthesis from the perspectives of protein synthesis, enzymes activation and carbohydrate partitioning. However, it still remains largely unknown how stomatal and mesophyll conductances (gs and gm, respectively) are regulated by Mg. In the present study, leaf gas exchanges, leaf hydraulic parameters, leaf structural traits and cell wall composition were examined in rice plants grown under high and low Mg treatments to elucidate the impacts of Mg on gs and gm. Our results showed that reduction of leaf photosynthesis under Mg deficiency was mainly caused by the decreased gm, followed by reduced leaf biochemical capacity and gs, and leaf outside-xylem hydraulic conductance (Kox) was the major factor restricting gs under Mg deficiency. Moreover, increased leaf hemicellulose, lignin and pectin contents and decreased cell wall effective porosity were observed in low Mg plants relative to high Mg plants. These results suggest that Kox and cell wall composition play important roles in regulating gs and gm, respectively, in rice plants under Mg shortages.

Nanomaterial-Based Drug Delivery Systems for Ischemic Stroke.

Ischemic stroke is a leading cause of death and disability in the world. At present, reperfusion therapy and neuroprotective therapy, as guidelines for identifying effective and adjuvant treatment methods, are limited by treatment time windows, drug bioavailability, and side effects. Nanomaterial-based drug delivery systems have the characteristics of extending half-life, increasing bioavailability, targeting drug delivery, controllable drug release, and low toxicity, thus being used in the treatment of ischemic stroke to increase the therapeutic effects of drugs. Therefore, this review provides a comprehensive overview of nanomaterial-based drug delivery systems from nanocarriers, targeting ligands and stimulus factors of drug release, aiming to find the best combination of nanomaterial-based drug delivery systems for ischemic stroke. Finally, future research areas on nanomaterial-based drug delivery systems in ischemic stroke and the implications of the current knowledge for the development of novel treatment for ischemic stroke were identified.

Characterization of the Hemolytic Activity of Mastoparan Family Peptides from Wasp Venoms.

Biologically active peptides have attracted increasing attention in research on the development of new drugs. Mastoparans, a group of wasp venom linear cationic α-helical peptides, have a variety of biological effects, including mast cell degranulation, activation of protein G, and antimicrobial and anticancer activities. However, the potential hemolytic activity of cationic α-helical peptides greatly limits the clinical applications of mastoparans. Here, we systematically and comprehensively studied the hemolytic activity of mastoparans based on our wasp venom mastoparan family peptide library. The results showed that among 55 mastoparans, 18 had strong hemolytic activity (EC50 ≤ 100 µM), 14 had modest hemolytic activity (100 µM < EC50 ≤ 400 µM) and 23 had little hemolytic activity (EC50 > 400 µM), suggesting functional variation in the molecular diversity of mastoparan family peptides from wasp venom. Based on these data, structure-function relationships were further explored, and, hydrophobicity, but not net charge and amphiphilicity, was found to play a critical role in the hemolytic activity of mastoparans. Combining the reported antimicrobial activity with the present hemolytic activity data, we found that four mastoparan peptides, Parapolybia-MP, Mastoparan-like peptide 12b, Dominulin A and Dominulin B, have promise for applications because of their high antimicrobial activity (MIC ≤ 10 µM) and low hemolytic activity (EC50 ≥ 400 µM). Our research not only identified new leads for the antimicrobial application of mastoparans but also provided a large chemical space to support the molecular design and optimization of mastoparan family peptides with low hemolytic activity regardless of net charge or amphiphilicity.

Micro gas chromatographic column with copper benzene-1,3,5-tricarboxylate modified by multilayer fluorinated graphene as a stationary phase.

A composite material was synthesized at room temperature by performing modification of the copper benzene-1,3,5-tricarboxylate (HKUST-1) metal-organic framework material by multilayer fluorinated graphene (FG). The FG-HKUST-1 composite was used as a stationary phase for a micro gas chromatography column (µGCC) fabricated using micro-electro-mechanical system (MEMS) technology. The separation results showed that the µGCC with the FG-HKUST-1 composite stationary phase achieved a baseline separation of C1-C4 in 8 min. The retention factors for C2-C4 were 2.13, 7.14, and 12.04, respectively. The maximum relative standard deviation (RSD) of the retention times was 0.14 %. The difference in the retention time between methane and ethane was 1.11 min, with a resolution of 9.2 for methane and ethane. The retention factor of ethane and the resolution of methane and ethane were increased by 166 % and 114 %. Therefore, this µGCC is promising for separating light hydrocarbons with widely differing concentrations.

Abnormal Fetal Lung of Hoxa1-/- Piglets Is Rescued by Maternal Feeding with All-Trans Retinoic Acid.

Neonatal Hoxa1-/- piglets were characterized by dyspnea owing to the Hoxa1 mutation, and maternal administration with ATRA alleviated the dyspnea of neonatal Hoxa1-/- piglets. The purpose of this experiment was to explore how maternal ATRA administration rescued the abnormal fetal lungs of Hoxa1-/- piglets. Samples of the lungs were collected from neonatal Hoxa1-/- and non-Hoxa1-/- piglets delivered by sows in the control group, and from neonatal Hoxa1-/- piglets born by sows administered with ATRA at 4 mg/kg body weight on dpc 12, 13, or 14, respectively. These were used for the analysis of ELISA, histological morphology, immunofluorescence staining, immunohistochemistry staining, and quantitative real-time PCR. The results indicate that the Hoxa1 mutation had adverse impacts on the development of the alveoli and pulmonary microvessels of Hoxa1-/- piglets. Maternal administration with ATRA at 4 mg/kg body weight on dpc 14 rescued the abnormal lung development of Hoxa1-/- piglets by increasing the IFN-γ concentration (p < 0.05), airspace area (p < 0.01) and pulmonary microvessel density (p < 0.01); increasing the expression of VEGFD (p < 0.01), PDGFD (p < 0.01), KDR (p < 0.01), ID1 (p < 0.01), and NEDD4 (p < 0.01); and decreasing the septal wall thickness (p < 0.01) and the expression of SFTPC (p < 0.01) and FOXO3 (p < 0.01). Maternal administration with ATRA plays a vital role in rescuing the abnormal development of lung of Hoxa1-/- fetal piglets.

Characterization of the Molecular Diversity and Degranulation Activity of Mastoparan Family Peptides from Wasp Venoms.

Wasp stings have become an increasingly serious public health problem because of their high incidence and mortality rates in various countries and regions. Mastoparan family peptides are the most abundant natural peptides in hornet venoms and solitary wasp venom. However, there is a lack of systematic and comprehensive studies on mastoparan family peptides from wasp venoms. In our study, for the first time, we evaluated the molecular diversity of 55 wasp mastoparan family peptides from wasp venoms and divided them into four major subfamilies. Then, we established a wasp peptide library containing all 55 known mastoparan family peptides by chemical synthesis and C-terminal amidation modification, and we systematically evaluated their degranulation activities in two mast cell lines, namely the RBL-2H3 and P815 cell lines. The results showed that among the 55 mastoparans, 35 mastoparans could significantly induce mast cell degranulation, 7 mastoparans had modest mast cell degranulation activity, and 13 mastoparans had little mast cell degranulation activity, suggesting functional variation in mastoparan family peptides from wasp venoms. Structure-function relationship studies found that the composition of amino acids in the hydrophobic face and amidation in the C-terminal region are critical for the degranulation activity of mastoparan family peptides from wasp venoms. Our research will lay a theoretical foundation for studying the mechanism underlying the degranulation activity of wasp mastoparans and provide new evidence to support the molecular design and molecular optimization of natural mastoparan peptides from wasp venoms in the future.

Degradation of 1-alkyl-3-methylimidazolium tetrafluoroborate in an ultrasonic zero-valent zinc and activated carbon micro-electrolysis system.

Increased attention has been given to the removal of ionic liquids (ILs) from natural water environments. In this work, 5 kinds of 1-alkyl-3-methylimidazoliumtetrafluoroborate ([Cnmim][BF4] (n = 2, 4, 6, 8, 10)) ILs were degraded in an ultrasonic zero-valent zinc (ZVZ) and activated carbon (AC) micro-electrolysis system. Optimization of degradation conditions and the degradation levels were studied by high performance liquid chromatography, the surface morphology of the ZVZ and AC changed before and after the reaction were observed by scanning electron microscope. The degradation intermediates were detected by gas chromatography- mass spectrometry and ion chromatography, and inferred the degradation pathway. The degradation effect of [C4mim][BF4] was best with ultrasonic assistance, pH 3 and an AC/ZVZ ratio of 1:1. The degradation of [Cnmim][BF4] in aqueous solution exceeded 91.7% in 120 min, and the mineralization level exceeded 88.9%. The surface of smooth and dense ZVZ particles became loose flocculent and the porous surface of AC became larger and rougher after reaction. The degradation pathway suggested that the imidazolium ring was sulfurized or oxidized, and then the ring was opened to form N-alkyl formamide and N-methyl formamide. ZVZ/AC micro-electrolysis combined with ultrasonic irradiation is an effective method to remove ILs, which provides new insight into IL degradation.

A semi-packed gas chromatography column with high-density elliptic cylindrical posts.

Semi-packed columns are microfabricated gas chromatography columns which have a large surface area and high aspect ratio. In this paper, a new semi-packed column with high-density elliptic cylindrical posts (SCHECP) made by a micro-electro-mechanical system (MEMS) technique was reported. Compared to a semi-packed column with cylindrical posts (SCCP) under the same effective width, the surface area and aspect ratio of SCHECP were improved by 71.19% and 76.47%, respectively. To compare the performance of these two semi-packed columns, SCHECP and SCCP were fabricated. A 10-nm thick alumina film was deposited as the stationary phase by atomic layer deposition technique to ensure the uniformity and repeatability of the stationary-phase film. A contrast experiment was conducted, and the results showed that compared with SCCP, better separation performance was realized in SCHECP due to the increase in surface area and aspect ratio. The number of theoretical plates of nonane was increased by 541.84%, and the tailing factor was decreased by 54.31%.

Administration of All-Trans Retinoic Acid to Pregnant Sows Alters Gut Bacterial Community of Neonatal Piglets With Different Hoxa1 Genotypes.

Administration of all-trans retinoic acid (ATRA) to pregnant sows improves developmental defects of Hoxa1-/- fetal pigs, and this study aimed to explore the influence of maternal ATRA administration during pregnancy on gut microbiota of neonatal piglets. Samples of jejunal and ileal meconium of neonatal piglets before suckling were collected including 5 Hoxa1-/- and 20 non-Hoxa1-/- (Hoxa1+/+ and Hoxa1+/-) neonatal piglets from the control group and 5 Hoxa1-/- and 7 non-Hoxa1-/- neonatal piglets from the experimental group. Results indicated that Hoxa1 mutation shaped the bacterial composition of the jejunum and ileum of neonatal piglets and Hoxa1-/- neonatal piglets had significantly higher diversity and species richness, higher relative abundance of phylum Bacteroidetes, lower relative abundances of phylum Firmicutes and genus Lactobacillus, and lower ratio of Firmicutes to Bacteroidetes than non-Hoxa1-/- neonatal piglets. After maternal ATRA administration, Hoxa1-/- neonatal piglets had significantly higher diversity and species richness, higher relative abundances of two bacterial phyla (Bacteroidetes and Proteobacteria), and lower relative abundances of phylum Firmicutes and genus Lactobacillus in the jejunum than non-Hoxa1-/- neonatal piglets. Hoxa1-/- neonatal piglets delivered by sows with maternal ATRA administration had lower diversity and species richness and higher relative abundance of phylum Firmicutes in the jejunum than Hoxa1-/- neonatal piglets born by sows with no maternal ATRA administration. Non-Hoxa1-/- neonatal piglets delivered by sows with maternal ATRA administration had higher diversity and species richness and significantly lower relative abundances of phyla Firmicutes and Actinobacteria and genus Lactobacillus in the ileum than non-Hoxa1-/- neonatal piglets born by sows with no maternal ATRA administration. Hoxa1 mutation decreased the expression of bacterial genes involved in ABC transporters, purine metabolism, and aminoacyl-tRNA biosynthesis and increased the expression of bacterial genes involved in two-component system, starch and sucrose metabolism, and arginine and proline metabolism. Maternal ATRA administration decreased the expression of bacterial genes involved in arginine and proline metabolism, peptidoglycan biosynthesis, and fatty acid biosynthesis. Hoxa1 mutation resulted in bacterial dysbiosis of the small intestine of Hoaxa1-/- neonatal piglets, and maternal ATRA administration restored the bacterial dysbiosis of Hoxa1-/- neonatal piglets and altered the bacterial composition of the small intestine of non-Hoxa1-/- neonatal piglets.

Construction of an index system for evaluating the effectiveness of transitional care in kidney transplant recipients.

BACKGROUND: Previous studies showed that transitional care reduces the complication rate and readmission rate and improves the quality of life in kidney transplant receipts, nevertheless, in fact there are no standard evaluation indexes and debatable scientific of existing indexes in kidney transplant recipients. Therefore, the aim of this study was to construct an evaluation index system to assess the effects of transitional care in kidney transplant recipients. METHODS: Based on Omaha system, an initial evaluation index system about the effects of transitional care in kidney transplant recipients was drafted by the literature review and semi-structured interview. Two rounds of correspondence were conducted in 19 experts and the analytic hierarchy process (AHP) was used to calculate the weights of all indexes. RESULTS: Five first-level indexes, sixteen second-level indexes, and forty-eight third-level indexes were selected in the initial evaluation index system. The authority coefficient of two-round expert consultations was 0.90 and coordination coefficients of indexes ranged from 0.24 to 0.34. CONCLUSION: The established evaluation index system for the effectiveness of transitional care for kidney transplant recipients was scientific and reliable. Furthermore, it would be a potential method to evaluate effects of transitional care in kidney transplant recipients after further examination.

In situ poly I:C released from living cell drug nanocarriers for macrophage-mediated antitumor immunotherapy.

Immunotherapy is one of the most promising approaches to inhibit tumor growth and metastasis by activating host immune functions. However, the arising problems such as low immune response caused by complex tumor microenvironment and extremely systemic immune storm still limit the clinical applications of immunotherapy. Here, we construct Poly I: C-encapsulated poly (lactic-co-glycolic acid) nanoparticles (PLP NPs) with a slow release profile. A biomimetic system (MPLP), which loads PLP NPs on the surface of bone marrow-derived macrophage (BMDM) via the maleimide-thiol conjugation, is synthesized to effectively deliver PLP, control drug release and activate the tumor-specific immune response in situ. The results show that PLP NPs loading does not affect the activity and function of BMDM. Then, BMDM acts as a living cell drug vehicle and promotes the accumulation of PLP NPs in tumors, where Poly I: C is released from PLP NPs and reprograms BMDM into tumoricidal M1 macrophage. Furthermore, MPLP triggers potent antitumor immune responses in vivo and effectively inhibits local and metastatic tumors without causing adverse pathological immune reactions. This study offers an inspiration to facilitate clinical translation through the delivery of drugs by living immune cells for future anticancer therapy.

The effect of a diet based on rice straw co-fermented with probiotics and enzymes versus a fresh corn Stover-based diet on the rumen bacterial community and metabolites of beef cattle.

Improvement of the food value of rice straw is urgently required in rice crop growing areas to mitigate pollution caused by rice straw burning and enhance the supply of high-quality forages for ruminants. The aims of the present study were to compare the effects of fresh corn Stover and rice straw co-fermented with probiotics and enzymes on rumen fermentation and establish the feasibility of increasing the rice straw content in ruminant diets and, by extension, reducing air pollution caused by burning rice straw. Twenty Simmental hybrid beef cattle were randomly allotted to two groups with ten cattle per group. They were fed diets based either on rice straw co-fermented with probiotics and enzymes or fresh corn Stover for 90 days. Rumen fluid was sampled with an esophageal tube vacuum pump device from each animal on the mornings of days 30, 60, and 90. Bacterial diversity was evaluated by sequencing the V4-V5 region of the 16S rRNA gene. Metabolomes were analyzed by gas chromatography/time-of-flight mass spectrometry (GC-TOF/MS). Compared to cattle fed fresh corn Stover, those fed rice straw co-fermented with probiotics and enzymes had higher (P < 0.05) levels of acetic acid and propionate in rumen liquid at d 60 and d 90 respectively, higher (P < 0.05) abundances of the phyla Bacteroidetes and Fibrobacteres and the genera Ruminococcus, Saccharofermentans, Pseudobutyrivibrio, Treponema, Lachnoclostridium, and Ruminobacter, and higher (P < 0.05) concentrations of metabolites involved in metabolisms of amino acid, carbohydrate, and cofactors and vitamins. Relative to fresh corn Stover, rice straw co-fermented with probiotics and enzymes resulted in higher VFA concentrations, numbers of complex carbohydrate-decomposing and H2-utilizing bacteria, and feed energy conversion efficiency in the rumen.

Smart gold nanocages for mild heat-triggered drug release and breaking chemoresistance.

Chemotherapy is an important modality available for cancer treatment. However, the present chemotherapy is still far from being satisfactory mainly owing to the severe side effects of the chemotherapeutic agents and drug resistance of cancer cells. Thus, reversing drug resistance by constructing an ideal chemotherapeutic strategy with the least side effects and the best efficacy is greatly needed. Here, we designed a smart nanosystem of thermo-sensitive liposome coated gold nanocages with doxorubicin (DOX) loading (LAD) for near-infrared (NIR)-triggered drug release and chemo-photothermal combination therapy. The biocompatible liposomes coating facilitated the cellular uptake of LAD and meanwhile avoided drug leakage during the circulation. More importantly, LAD exhibited controllable photothermal conversion property and produced mild heat under NIR irradiation, which not only triggered DOX release and transferred DOX from lysosome to nucleus, but also elicited the mild heat cell killing effect to improve the curative efficiency. Further mechanism study revealed that mild heat could reverse drug resistance by down-regulation of the chemoresistance-related markers (e.g., HSF-1, p53, P-gp), and inhibited DOX export and increased drug sensitiveness, thereby prominently increased the anticancer efficiency. This versatile nanoplatform with enhanced curative efficacy and lower side effect is promising to apply in the field of drug controlled release and combination tumor therapy.

Tumor-targeted nanoplatform for in situ oxygenation-boosted immunogenic phototherapy of colorectal cancer.

Advanced colorectal cancer has a high mortality rate since conventional treatments have limited therapeutic effects and poor prognosis with high risks of metastasis and recurrence. Photodynamic therapy (PDT) is a promising treatment modality for the eradication of colorectal cancer, but its curative efficacy is severely affected by tumor hypoxia. Herein, we developed a core-shell gold nanocage coated with manganese dioxide and hyaluronic acid (AMH) for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic phototherapy in situ. The AMH nanoparticles can generate abundant oxygen from mild acidic/H2O2 medium, which can further enhance the PDT efficacy of AMH itself under near infrared (NIR) irradiation. Meanwhile, AMH-based PDT induced immunogenic cell death (ICD) of tumor cells with damage-associated molecular patterns (DAMPs) release and facilitated the dendritic cells (DCs) maturation to further potentiate the systematic antitumor immunity against advanced tumors. In vivo experiment results exhibited that AMH nanoparticles not only had the ability of targeting tumor but also in situ produced sufficient oxygen to relieve the tumor hypoxia. Furthermore, AMH-mediated oxygen-boosted immunogenic PDT effectively inhibited the tumor growth and recurrence. Thus, this work provides a potent targeted delivery nanoplatform for enhanced immunogenic PDT against advanced cancers. STATEMENT OF SIGNIFICANCE: Local hypoxic tumor microenvironment not only greatly limits the photodynamic therapy (PDT) efficacy, but also has an association with tumor invasiveness and metastasis. This study provides an AMH nanoparticle for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic PDT in situ. AMH nanoparticle exhibits a good tumor-targeted ability to in situ produce abundant oxygen to relieve the tumor hypoxia, and initiates the potent oxygen-boosted immunogenic PDT effect under NIR irradiation to effectively inhibit the growth and recurrence of colorectal tumor. This oxygen-boosted immunogenic PDT nanosystem can be a promising candidate for advanced tumor treatment.

Administration of All-Trans Retinoic Acid to Pregnant Sows Improves the Developmental Defects of Hoxa1-/- Fetal Pigs.

Hoxa1 mutation adversely affect fetal pig development, but whether all-trans retinoic acid (ATRA) administration to Hoxa1+/- pregnant sows can improve Hoxa1-/- fetal pig development defects has not been reported. A total of 24 healthy Hoxa1+/- sows were mated with a healthy Hoxa1+/- boar and randomly assigned to one control group and nine experiment groups. ATRA was orally administered to pregnant sows at the doses of 0, 4, 5, or 6 mg/kg maternal body weight on 12, 13, and 14 days post coitum (dpc), respectively, and a total of 146 live piglets were delivered including 37 Hoxa1-/- piglets and 109 non-Hoxa1-/- piglets. Results indicated that Hoxa1-/- piglets delivered by sows in control group had bilateral microtia, canal atresia and ear's internal defects, and had lower birth liveweight and external ear score than non-Hoxa1-/- neonatal piglets (P < 0.05). Maternal administration with ATRA can effectively correct the development defects of Hoxa1-/- fetal pigs, Hoxa1-/- neonatal piglets delivered by sows administered ATRA at a dose of 4 mg/kg body weight on 14 dpc had higher birth liveweight (P > 0.05) and higher scores of external ear (P < 0.05) compared to Hoxa1-/- neonatal piglets from the control group, but had no significantly difference in terms of birth liveweight and external ear integrity than non-Hoxa1-/- piglets from the control group (P > 0.05). The time of ATRA administration significantly affected Hoxa1-/- fetal development (P < 0.05). Administration of ATRA to Hoxa1+/- pregnant sows at 4 mg/kg body weight on 14 dpc can effectively improve the birth liveweight and ear defects of Hoxa1-/- piglets.

Bioorthogonal Metabolic Labeling Utilizing Protein Biosynthesis for Dynamic Visualization of Nonenveloped Enterovirus 71 Infection.

Bioorthogonal metabolic labeling through the endogenous cellular metabolic pathways (e.g., phospholipid and sugar) is a promising approach for effectively labeling live viruses. However, it remains a big challenge to label nonenveloped viruses due to lack of host-derived envelopes. Herein, a novel bioorthogonal labeling strategy is developed utilizing protein synthesis pathway to label and trace nonenveloped viruses. The results show that l-azidohomoalanine (Aha), an azido derivative of methionine, is more effective than azido sugars to introduce azido motifs into viral capsid proteins by substituting methionine residues during viral protein biosynthesis and assembly. The azide-modified EV71 (N3-EV71) particles are then effectively labeled with dibenzocyclooctyl (DBCO)-functionalized fluorescence probes through an in situ bioorthogonal reaction with well-preserved viral infectivity. Dual-labeled imaging clearly clarifies that EV71 virions primarily bind to scavenger receptors and are internalized through clathrin-mediated endocytosis. The viral particles are then transported into early and late endosomes where viral RNA is released in a low-pH dependent manner at about 70 min postinfection. These results first reveal viral trafficking and uncoating mechanisms, which may shed light on the pathogenesis of EV71 infection and contribute to antiviral drug discovery.

Cost-effectiveness of antiosteoporosis strategies for postmenopausal women with osteoporosis in China.

OBJECTIVE: Osteoporosis has become an important public health problem in China, especially among elderly postmenopausal women. Massive amounts of medical and health resources have been devoted to patients with osteoporosis and osteoporosis-related fractures. This study estimated the cost-effectiveness of alendronate, zoledronate, raloxifene, teriparatide, and calcium/vitamin D as treatments for osteoporosis in elderly postmenopausal women in China from the medical system perspective. METHODS: A Markov model was constructed by using TreeAge Pro 2015 software. This model simulated the disease process over 40 years in response to the five investigated therapeutic strategies. Each cycle lasted for 1 year. The model parameters included Chinese epidemiological data, clinical effectiveness, cost, and utility. Total treatment costs and quality-adjusted life-years (QALYs) were estimated, and incremental cost-effectiveness analysis was performed. Univariate and probabilistic sensitivity analyses were conducted to verify the model. RESULTS: The calcium/vitamin D strategy, zoledronate, alendronate, teriparatide, and raloxifene offered patients 10.24, 10.83, 10.70, 10.88, and 10.54 QALYs at the cost of $3,799.72, $8,425.61, $9,849.89, $34,843.72, and $13,353.33 for over 40 years, respectively. The alendronate and raloxifene strategies were eliminated because they were less effective and more expensive than the other strategies. The base-case analysis revealed that the incremental cost-effectiveness ratios (ICERs) of the zoledronate strategy relative to those of the calcium/vitamin D strategy were $7,864.59/QALY. This result indicated that the zoledronate strategy was more cost-effective than other strategies and was within the willingness-to-pay threshold of China ($28,624/QALY). The ICERs of the teriparatide versus zoledronate strategies were $4,70,797.08/QALY, which exceeded the threshold. CONCLUSION: From the perspective of the Chinese medical system, zoledronate is more cost-effective than the calcium/vitamin D strategy, alendronate, raloxifene, and teriparatide for the treatment of osteoporosis in elderly postmenopausal women. Not factoring the parameters of adherence and persistence in, and consequent variability in treatment effectiveness relative risks, seems like a major limitation, but it can be speculated that it would not change the conclusion that zoledronate is the most economical strategy.

A Fatal Case of Acute Arsenic Poisoning.

This manuscript reported a case of fatal arsenic poisoning. A woman with schizophrenia took arsenic-containing "pills," which consisted of arsenic trioxide and realgar (arsenic (II) sulfide) and wrapped with gauze. The victim consumed 1.09 and 0.819 g arsenic on two occasions, respectively, with the interval between the two doses of 3 days. The woman died on the sixth day after the first dose without any treatment. In this case, pathological examination revealed fat degeneration of the liver rather than hepatomegaly, a rare finding in acute arsenic poisoning. Arsenic in tissue samples was measured, the total arsenic and inorganic arsenic in blood, liver, and gastric wall was 10.2 µg/mL (9.61 µg/mL), 23.1 µg/g (20.7 µg/g), and 32.3 µg/g (28.6 µg/g), respectively.