Esterase-Responsive Polymeric Micelles Containing Tetraphenylethene and Poly(ethylene glycol) Moieties for Efficient Doxorubicin Delivery and Tumor Therapy.

Enzyme-responsive drug delivery systems have drawn much attention in the field of cancer theranostics due to their high sensitivity and substrate specificity under mild conditions. In this study, an amphiphilic polymer T1 is reported, which contains a tetraphenylethene unit and a poly(ethylene glycol) chain linked by an esterase-responsive phenolic ester bond. In aqueous solution, T1 formed stable micelles via self-assembly, which showed an aggregation-induced emission enhancement of 32-fold at 532 nm and a critical micelle concentration of 0.53 µM as well as esterase-responsive activity. The hydrophobic drug doxorubicin (DOX) was efficiently encapsulated into the micelles with a drug loading of 21%. In the presence of the esterase, the selective decomposition of drug-loaded T1 micelles was observed, and DOX was subsequently released with a half-life of 5 h. In vitro antitumor studies showed that T1@DOX micelles exhibited good therapeutic effects on HeLa cells, while normal cells remained mostly intact. In vivo anticancer experiments revealed that T1@DOX micelles indeed suppressed tumor growth and had reduced side effects compared to DOX·HCl. The present work showed the potential clinical application of esterase-responsive drug delivery in cancer therapy.

Design of Fe3+-Rich, High-Conductivity Lignin Hydrogels for Supercapacitor and Sensor Applications.

Preparation of natural polymer-based highly conductive hydrogels with tunable mechanical properties for applications in flexible electronics is still challenging. Herein, we report a facile method to prepare lignin-based Fe3+-rich, high-conductivity hydrogels via the following two-step process: (1) lignin hydrogels are prepared by cross-linking sulfonated lignin with poly(ethylene glycol) diglycidyl ether (PEGDGE) and (2) Fe3+ ions are impregnated into the lignin hydrogel by simply soaking in FeCl3. Benefiting from Fe3+ ion complexation with catechol groups and other functional groups in lignin, the resultant hydrogels exhibit unique properties, such as high conductivity (as high as 6.69 S·m-1) and excellent mechanical and hydrophobic properties. As a strain sensor, the as-prepared lignin hydrogel shows high sensitivity when detecting various human motions. With the flow of moist air, the Fe3+-rich lignin hydrogel generates an output voltage of 162.8 mV. The assembled supercapacitor of the hydrogel electrolyte demonstrates a high specific capacitance of 301.8 F·g-1, with a maximum energy density of 26.73 Wh·kg-1, a power density of 2.38 kW·kg-1, and a capacitance retention of 94.1% after 10 000 consecutive charge-discharge cycles. These results support the conclusion that lignin-based Fe3+-rich, high-conductivity hydrogels have promising applications in different fields, including sensors and supercapacitors, rendering a new platform for the value-added utilization of lignin.

H2O2-Responsive amphiphilic polymer with aggregation-induced emission (AIE) for DOX delivery and tumor therapy.

Stimuli-responsive drug delivery systems (DDSs) based on amphiphilic polymers have attracted much attention. In this study, we reported an innovative H2O2-responsive amphiphilic polymer (TBP), bearing a H2O2-sensitive phenylboronic ester, AIE fluorophore tetraphenylethene (TPE) hydrophobic, and polyethylene glycol hydrophilic (PEG) moieties. TBP could self-assemble into micelles with an encapsulation efficiency as high as 74.9% for doxorubicin (DOX) in aqueous solution. In the presence of H2O2, TBP micelles was decomposed by oxidation, hydrolysis and rearrangement, leading to almost 80% DOX release from TBP@DOX micelles. TBP and the corresponding degradation products were biocompatible, while TBP@DOX micelles only displayed obvious toxicity toward cancer cells. Drug delivery process was clearly monitored by confocal laser scanning microscopic (CLSM) and flow cytometry (FCM) analysis. Moreover, in vivo anticancer study showed that TBP@DOX micelles were accumulated in tumor region of nude mice and effectively inhibited tumor growth. The results suggested that the reported H2O2-responsive amphiphilic polymer displayed great potential in drug delivery and tumor therapy.

Improving the Solubility and Bioavailability of Progesterone Cocrystals with Selected Carboxylic Acids.

Progesterone (PROG) is a natural steroid hormone with low solubility and high permeability that belongs to biopharmaceutics classification system class II. In this study, novel pharmaceutical cocrystals of PROG were successfully prepared by solvent evaporation or a liquid-assisted grinding process aimed at enhancing its solubility and bioavailability. The cocrystal formers selected based on crystal engineering principles were carboxylic acids, namely, 4-formylbenzeneboronic acid (BBA), isophthalic acid (IPA), and 3-nitrophthalic acid (NPA). The cocrystal structures were characterized using multiple techniques. Single-crystal X-ray diffraction results showed that the carbonyl group, acting as a hydrogen bond acceptor, was pivotal in the cocrystal network formation, with C-H···O interactions further stabilizing the crystals. The cocrystals exhibited improved solubility and dissolution profiles in vitro, with no significant changes in hygroscopicity. The parallel artificial membrane permeability assay (PAMPA) models indicated that the cocrystals retained PROG's high permeability. Pharmacokinetic studies in Sprague-Dawley rats revealed that all cocrystals increased PROG exposure, with AUC(0~∞) values for PROG-BBA, PROG-IPA, and PROG-NPA being 742.59, 1201.72 and 442.67 h·ng·mL-1, respectively. These values are substantially higher compared to free PROG, which had an AUC(0~∞) of 301.48 h·ng·mL-1. Notably, PROG-IPA provided the highest AUC improvement, indicating a significant enhancement in bioavailability. Collectively, the study concludes that the cocrystal approach is a valuable strategy for optimizing the physicochemical properties and oral bioavailability of PROG, with potential implications for the development of other poor water-soluble drugs.

Di-aldehyde tunicate cellulose nanocrystal (D-tCNC) aerogels for drug delivery: Effect of D-tCNC composition on aerogel structure and release properties.

Aerogels as drug carriers have the characteristics of a large specific surface area, high porosity and an elastic skeleton structure. Compared with traditional drug carriers, the use of aerogels as drug carriers can avoid the complexity of drug delivery and improve the efficiency of drug loading. In this work, the oxidation of tunicate cellulose nanocrystals (tCNCs) with NaIO4 was used to prepare di-aldehyde tunicate cellulose nanocrystals (D-tCNCs). Tetracycline (TC) was used as a drug model and pH-responsive drug-loaded aerogels were prepared by the Schiff base reaction between TC and the aldehyde group on D-tCNCs. The chemical structure, crystallinity, morphology, compression properties, porosity, swelling rate and drug loading properties were investigated by FT-IR, XRD, SEM and universal testing machines. The results showed that the porosity and equilibrium swelling ratio of the D-tCNC-TC aerogels were 95.87 % and 17.52 g/g, respectively. The stress of the D-tCNC-TC aerogel at 15 % compression was 0.07 MPa. Moreover, the analysis of drug-loaded aerogels indicated that the drug loading and encapsulation rates of D-tCNC-TC aerogels were 16.86 % and 78.75 %, respectively. In in vitro release experiments, the cumulative release rate of drug-loaded aerogel at pH = 1.2 and pH = 7.4 was 87.5 % and 79.3 %, respectively. These results indicated that D-tCNC-TC aerogels have good drug loading capacity and are pH-responsive in the pH range of 1.2 to 7.4. The prepared D-tCNC-TC aerogels are expected to be applied in drug delivery systems.

Codelivery of CPT and siPHB1 with GSH/ROS Dual-Responsive Hybrid Nanoparticles Based on a [12]aneN3-Derived Lipid for Synergistic Lung Cancer Therapy.

The combination of small-interfering RNA (siRNA)-mediated gene silencing and chemotherapeutic agents for lung cancer treatment has attracted widespread attention in terms of a greater therapeutic effect, minimization of systemic toxicity, and inhibition of multiple drug resistance (MDR). In this work, three amphiphiles, CBN1-CBN3, were first designed and synthesized as a camptothecin (CPT) conjugate and gene condensation agents by the combination of CPT prodrugs and di(triazole-[12]aneN3) through the ROS-responsive phenylborate ester and different lengths of alkyl chains (with 6, 9, 12 carbon chains for CBN1-CBN3, respectively). CBN1-CBN3 were able to be self-assembled into liposomes with an average diameter in the range of 320-240 nm, showing the ability to effectively condense siRNA. Among them, CBN2, with a nine-carbon alkyl chain, displayed the best anticancer efficiency in A549 cells. In order to give nanomedicines a stealth property and PEGylation/dePEGylation transition, a GSH-responsive PEGylated TPE derivative containing a disulfide linkage (TSP) was further designed and prepared. A combination of CBN2/siRNA complexes and DOPE with TSP resulted in GSH/ROS dual-responsive lipid-polymer hybrid nanoparticles (CBN2-DP/siRNA NPs). In present GSH and H2O2, CBN2-DP/siRNA NPs were decomposed, resulting in the controlled release of CPT drug and siRNA. In vitro, CBN2-DP/siPHB1 NPs showed the best anticancer activity for suppression of about 75% of A549 cell proliferation in a serum medium. The stability of CBN2-DP/siRNA NPs was significantly prolonged in blood circulation, and they showed effective accumulation in the A549 tumor site through an enhanced permeability and retention (EPR) effect. In vivo, CBN2-DP/siPHB1 NPs demonstrated enhanced synergistic cancer therapy efficacy and tumor inhibition as high as 71.2%. This work provided a strategy for preparing lipid-polymer hybrid NPs with GSH/ROS dual-responsive properties and an intriguing method for lung cancer therapy.

Cold stress accentuates pressure overload-induced cardiac hypertrophy and contractile dysfunction: role of TRPV1/AMPK-mediated autophagy.

Severe cold exposure and pressure overload are both known to prompt oxidative stress and pathological alterations in the heart although the interplay between the two remains elusive. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated in response to a variety of exogenous and endogenous physical and chemical stimuli including heat and capsaicin. The aim of this study was to examine the impact of cold exposure on pressure overload-induced cardiac pathological changes and the mechanism involved. Adult male C57 mice were subjected to abdominal aortic constriction (AAC) prior to exposure to cold temperature (4 °C) for 4 weeks. Cardiac geometry and function, levels of TRPV1, mitochondrial, and autophagy-associated proteins including AMPK, mTOR, LC3B, and P62 were evaluated. Sustained cold stress triggered cardiac hypertrophy, compromised depressed myocardial contractile capacity including lessened fractional shortening, peak shortening, and maximal velocity of shortening/relengthening, enhanced ROS production, and mitochondrial injury, the effects of which were negated by the TRPV1 antagonist SB366791. Western blot analysis revealed upregulated TRPV1 level and AMPK phosphorylation, enhanced ratio of LC3II/LC3I, and downregulated P62 following cold exposure. Cold exposure significantly augmented AAC-induced changes in TRPV1, phosphorylation of AMPK, LC3 isoform switch, and p62, the effects of which were negated by SB366791. In summary, these data suggest that cold exposure accentuates pressure overload-induced cardiac hypertrophy and contractile defect possibly through a TRPV1 and autophagy-dependent mechanism.

Binary additives of polyamide epichlorohydrin-nanocellulose for effective valorization of used paper.

This paper presents a binary reinforcement system of polyamide polyamine epichlorohydrin with nanocellulose (PAE-NC) for effectively modification of the reclaimed fibres for paper production, and based on the improvement of physical and mechanical properties of cellulosic fibres together with PAE-NC self-crosslinking networks, the strengthening mechanisms of recycled papers are examined. The PAE-NC binary system was applied directly to old corrugated container (OCC) and softwood bleached kraft pulp (SWBKP), and handsheets are prepared with varying amounts of PAE/NC/PAE-NC, namely 0.05, 0.1, 0.3, 0.5, 0.75, 1.0, 1.5, 2.0 wt% (dry pulp). The results showed that the studied additives improved the performance of recycled fibres, whether SWBKP or OCC pulp, and handsheets in solely or combined mechanisms except for the air permeability of the handsheets. The treatment of PAE-NC combination was significantly more effective than those of PAE or NC alone for both OCC and SWBKP, although the combined PAE-NC treatment results in better performance enhancement for OCC than SWBKP handsheets, and the NC alone is more effective than PAE for SWBKP recycled paper and conversely for OCC recycled paper. SEM observations further confirmed that the combined PAE-NC addition treatment imparted a relatively uniform surface structure to the handsheet.

Preparation and characterization of highly conductive lignin aerogel based on tunicate nanocellulose framework.

The highly conductive and elastic three-dimensional mesh porous material is an ideal platform for the fabrication of high electrical conductivity conductive aerogels. Herein, a multifunctional aerogel that is lightweight, highly conductive and stable sensing properties is reported. Tunicate nanocellulose (TCNCs) with a high aspect ratio, high Young's modulus, high crystallinity, good biocompatibility and biodegradability was used as the basic skeleton to prepare aerogel by freeze-drying technique. Alkali lignin (AL) was used as the raw material, polyethylene glycol diglycidyl ether (PEGDGE) was used as the cross-linking agent, and polyaniline (PANI) was used as the conductive polymer. Preparation of aerogels by freeze-drying technique, in situ synthesis of PANI, and construction of highly conductive aerogel from lignin/TCNCs. The structure, morphology and crystallinity of the aerogel were characterized by FT-IR, SEM, and XRD. The results show that the aerogel has good conductivity (as high as 5.41 S/m) and excellent sensing performance. When the aerogel was assembled as a supercapacitor, the maximum specific capacitance can reach 772 mF/cm2 at 1 mA/cm2 current density, and maximum power and energy density can reach 59.4 µWh/cm2 and 3600 µW/cm2, respectively. It is expected the aerogel can be applied in the field of wearable devices and electronic skin.

Lignin-containing hydrogels with anti-freezing, excellent water retention and super-flexibility for sensor and supercapacitor applications.

We developed a highly conductive and flexible, anti-freezing sulfonated lignin (SL)-containing polyacrylic acid (PAA) (SL-g-PAA-Ni) hydrogel, with a high concentration of NiCl2. Ni2+ contributes multi-functions to the preparation of the hydrogel and its final properties, such as fast polymerization reaction as a result of the presence of redox pairs of Ni3+/Ni2+ and hydroquinone/quinone, and anti-freezing properties of the hydrogel due to the salt effects of NiCl2 so that at -20 °C the hydrogel shows similar properties to those at the room temperature. Thanks to the effective coordinations of Ni2+ with catecholic groups and carboxylic groups, as well as the rich hydrogen bonding capacity, the resultant hydrogel possesses excellent mechanical properties. High ionic conductivity (6.85 S·m-1) of the hydrogel is obtained due to the supply of high concentration of Ni2+. Moreover, the ionic solvation effect of NiCl2 in the hydrogel imparts excellent water retention ability, with water retention of ~93 % after 21-day storage. The SL-g-PAA-Ni hydrogel can accurately detect various human motions at -20 °C. The supercapacitor assembled from SL-g-PAA-Al hydrogel at -20 °C manifests a high specific capacitance of 252 F·g-1, with maximum energy density of 26.97 Wh·kg-1, power density of 2667 W·kg-1, and capacitance retention of 96.7 % after 3000 consecutive charge-discharge cycles.

High lignin containing hydrogels with excellent conducting, self-healing, antibacterial, dye adsorbing, sensing, moist-induced power generating and supercapacitance properties.

Herein, we design a dynamic redox system of using high contents of lignosulfonate (LS) and Al3+ to prepare poly acrylic acid (PAA) (LS-g-PAA-Al) hydrogels. The presence of high LS and Al3+ contents, in combination with the effective Al3+ complexes formed, renders the resultant hydrogel with some unique attributes, including excellent ionic conductivity (as high as 7.38 S·m-1) and antibacterial activity; furthermore, a very fast gelation (in 1 min) was obtained. As a flexible strain sensor, the LS-g-PAA-Al hydrogel with high conductivity demonstrates superior sensitivity in human movement detection. In addition, the rich anionic hydrophilic groups, such as sulfonic groups, phenolic hydroxyl groups, in the hydrogels impart the resultant hydrogels with excellent adsorption capacity for cationic dyes: when using Rhodamine B (RB) as a model cationic dye, the adsorption capacity of the resultant hydrogel reaches 334.64 mg·g-1; as a moist-induced power generator, it generates maximum 150.5 mV open circuit voltage with moist air flow. When the hydrogel electrolyte is assembled into a supercapacitor assembly, it shows high specific capacitance of 245.4 F·g-1, with the maximum energy density of 21.8 Wh·kg-1, power density of 2.37 kW·kg-1, and capacitance retention of 95.1% after 5000 consecutive charge-discharge cycles.

Preparation and characterization of super hydrophobic aerogels derived from tunicate cellulose nanocrystals.

First time aerogels composite with super hydrophobic properties were developed by using tunicate cellulose nanocrystals (TCNC), which expanded the application scope of animal cellulose resources. In this study, the TCNC was firstly cross-linked with silica and methyltrimethylsilane (MTMS), further coated with fluorodopa to form an aerogel with super hydrophobic properties. The aerogel was characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), and X-ray photoelectron spectroscopy (XPS). Results indicated that the contact angle of aerogel was 158.7°, which showed good hydrophobicity. The composite aerogel has superior stability in wide pH range, after 72 h immersion in pH = 0 and 12 solutions, the contact angle was still greater than 150°. The aerogel shows excellent oil-water separation ability and it can be repeatedly used more than 10 times. The separation efficiency can all reach more than 90% for different water-oil mixtures. This synthesized super hydrophobic aerogels derived from tunicate cellulose has greatly extended the application of marine animal celluloses.

Mother-to-infant transmission of hepatitis B virus: a Chinese experience.

Over 90% of infants infected with hepatitis B virus (HBV) caused by mother-to-infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg-positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother-to-infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother-to-infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother-to-infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow-up, all perinatal cases became HBsAg-negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine.

Establishment and characterization of a spontaneously immortalized trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone.

BACKGROUND: Most trophoblast cell lines currently available to study vertical transmission of hepatitis B virus (HBV) are immortalized by viral transformation. Our goal was to establish and characterize a spontaneously immortalized human first-trimester trophoblast cell line and its HBV-expressing clone. METHODS: Chorionic villi of Asian human first-trimester placentae were digested with trypsin and collagenase I to obtain the primary trophoblast cell culture. A spontaneously immortalized trophoblast cell line (HPT-8) was analyzed by scanning and transmission electron microscopy, cell cycle analysis, immunohistochemistry and immunofluorescence. HPT-8 cells were stably transfected with the adr subtype of HBV (HPT-8-HBV) and characterized by PCR and enzyme-linked immunosorbent assay. RESULTS: We obtained a clonal derivative of a spontaneously immortalized primary cell clone (HPT-8). HPT-8 cells were epithelioid and polygonal, and formed multinucleate, giant cells. They exhibited microvilli, distinct desmosomes between adjacent cells, abundant endoplasm, lipid inclusions and glycogen granules, which are all characteristic of cytotrophoblasts. HPT-8 cells expressed cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, estradiol, progesterone and hCG, and were positive for HLA-G, a marker of extravillous trophoblasts. HPT-8-HBV cells were positive for HBV relaxed-circular, covalently closed circular DNA and pre-S sequence. HPT-8-HBV cells also produced and secreted HBV surface antigen and HBV e antigen. CONCLUSIONS: We established a trophoblast cell line, HPT-8 and its HBV-expressing clone which could be valuable in exploring the mechanism of HBV viral integration in human trophoblasts during intrauterine infection.

High conservation of hepatitis B virus surface genes during maternal vertical transmission despite active and passive vaccination.

OBJECTIVE: Our purpose was to explore the relationship between hepatitis B virus (HBV) gene heterogeneity and maternal vertical transmission. METHODS: HBsAg-positive mothers and their neonates were selected and classified into a vertical infection neonate group (group N), a vertical infection mother group (group M) and a control group (group C). Serum HBsAg and HBeAg were examined. HBV gene fragments, including the pre-S1, and pre-S2 and S coding regions, were amplified and sequenced, and the genotype and serotype of the sequences were identified. Mutation sites and frequency of mutations were then compared between group N and group C. RESULTS: A total of 104 HBV clone sequences were obtained. All obtained sequences belonged to genotype C and serotype adr. Upon comparing sequences between group N and group C, 4 nonsynonymous mutations were found with significant difference in mutation frequency (p < 0.05). When the mothers were both HBsAg and HBeAg positive, 10 nonsynonymous mutations were found. The frequencies of these mutations were significantly lower in group N than in group C (p < 0.05). CONCLUSION: The 10 HBV mutations were negatively associated with vertical transmission when maternal HBeAg was positive. Furthermore, the species that were vertically transmitted to the fetus were mainly wild-type.

Preparation of lignosulfonate ionic hydrogels for supercapacitors, sensors and dye adsorbent applications.

Lignin, an abundant natural polymer but presently under-utilized, has received much attention for its green/sustainable advantages. Herein, we report a facile method to fabricate lignosulfonate (LS) ionic hydrogels by simple crosslinking with poly (ethylene glycol) diglycidyl ether (PEGDGE). The as-obtained LS-PEGDGE hydrogels were comprehensively characterized by mechanical measurements, FT-IR, and SEM. The rich sulfonic and phenolic hydroxyl groups in LS hydrogels play key roles in imparting multifunctional smart properties, such as adhesiveness, conducting, sensing and dye adsorption, as well as superconductive behavior when increasing the moisture content. The hydrogels have a high adsorption capacity for cationic dyes, using methylene blue as a model, reaching 211 mg·g-1. As a moist-induced power generator, the maximum output voltage is 181 mV. The LS-PEGDGE hydrogel-based flexible strain sensors exhibit high sensitivity when detecting human movements. As the hydrogel electrolyte, the assembled supercapacitor shows high specific capacitance of 236.9 F·g-1, with the maximum energy density of 20.61 Wh·kg-1, power density of 2306.4 W·kg-1, and capacitance retention of 92.9% after 10,000 consecutive charge-discharge cycles. Therefore, this multifunctional LS hydrogels may have promising applications in various fields, providing a new platform for the value-added utilization of lignin from industrial waste.

Spatiotemporal distribution of malaria and the association between its epidemic and climate factors in Hainan, China.

BACKGROUND: Hainan is one of the provinces most severely affected by malaria epidemics in China. The distribution pattern and major determinant climate factors of malaria in this region have remained obscure, making it difficult to target countermeasures for malaria surveillance and control. This study detected the spatiotemporal distribution of malaria and explored the association between malaria epidemics and climate factors in Hainan. METHODS: The cumulative and annual malaria incidences of each county were calculated and mapped from 1995 to 2008 to show the spatial distribution of malaria in Hainan. The annual and monthly cumulative malaria incidences of the province between 1995 and 2008 were calculated and plotted to observe the annual and seasonal fluctuation. The Cochran-Armitage trend test was employed to explore the temporal trends in the annual malaria incidences. Cross correlation and autocorrelation analyses were performed to detect the lagged effect of climate factors on malaria transmission and the auto correlation of malaria incidence. A multivariate time series analysis was conducted to construct a model of climate factors to explore the association between malaria epidemics and climate factors. RESULTS: The highest malaria incidences were mainly distributed in the central-south counties of the province. A fluctuating but distinctly declining temporal trend of annual malaria incidences was identified (Cochran-Armitage trend test Z = -25.14, P < 0.05). The peak incidence period was May to October when nearly 70% of annual malaria cases were reported. The mean temperature of the previous month, of the previous two months and the number of cases during the previous month were included in the model. The model effectively explained the association between malaria epidemics and climate factors (F = 85.06, P < 0.05, adjusted R(2) = 0.81). The autocorrelations of the fitting residuals were not significant (P > 0.05), indicating that the model extracted information sufficiently. There was no significant difference between the monthly predicted value and the actual value (t = -1.91, P = 0.08). The R(2) for predicting was 0.70, and the autocorrelations of the predictive residuals were not significant (P > 0.05), indicating that the model had a good predictive ability. DISCUSSION: Public health resource allocations should focus on the areas and months with the highest malaria risk in Hainan. Malaria epidemics can be accurately predicted by monitoring the fluctuations of the mean temperature of the previous month and of the previous two months in the area. Therefore, targeted countermeasures can be taken ahead of time, which will make malaria surveillance and control in Hainan more effective and simpler. This model was constructed using relatively long-term data and had a good fit and predictive validity, making the results more reliable than the previous report. CONCLUSIONS: The spatiotemporal distribution of malaria in Hainan varied in different areas and during different years. The monthly trends in the malaria epidemics in Hainan could be predicted effectively by using the multivariate time series model. This model will make malaria surveillance simpler and the control of malaria more targeted in Hainan.

Study on the Anti-Biodegradation Property of Tunicate Cellulose.

Tunicate is a kind of marine animal, and its outer sheath consists of almost pure Iß crystalline cellulose. Due to its high aspect ratio, tunicate cellulose has excellent physical properties. It draws extensive attention in the construction of robust functional materials. However, there is little research on its biological activity. In this study, cellulose enzymatic hydrolysis was conducted on tunicate cellulose. During the hydrolysis, the crystalline behaviors, i.e., crystallinity index (CrI), crystalline size and degree of polymerization (DP), were analyzed on the tunicate cellulose. As comparisons, similar hydrolyses were performed on cellulose samples with relatively low CrI, namely α-cellulose and amorphous cellulose. The results showed that the CrI of tunicate cellulose and α-cellulose was 93.9% and 70.9%, respectively; and after 96 h of hydrolysis, the crystallinity, crystalline size and DP remained constant on the tunicate cellulose, and the cellulose conversion rate was below 7.8%. While the crystalline structure of α-cellulose was significantly damaged and the cellulose conversion rate exceeded 83.8% at the end of 72 h hydrolysis, the amorphous cellulose was completely converted to glucose after 7 h hydrolysis, and the DP decreased about 27.9%. In addition, tunicate cellulose has high anti-mold abilities, owing to its highly crystalized Iß lattice. It can be concluded that tunicate cellulose has significant resistance to enzymatic hydrolysis and could be potentially applied as anti-biodegradation materials.

Screening cellular proteins binding to the core region of hepatitis C virus RNA genome with digoxin-labeled nucleic acids.

OBJECTIVE: To screen and identify cellular proteins binding to the core region of hepatitis C virus (HCV) RNA genome. METHODS: The plasmid pHCV core was constructed to generate in vitro transcripts of the core region of HCV RNA genome. Ultraviolet (UV) cross-linking experiment and competition analysis were performed to screen HepG2 cellular proteins, which interact with digoxin-labeled transcripts of the core region of HCV RNA genome. RNA-binding proteins were separated by immunoprecipitation, analyzed by electrophoresis on SDS-PAGE and detected by immunoblotting with anti-digoxingenin-AP. After being excised from SDS-PAGE, the proteins bands were analyzed by MALDI-TOF-MS. RESULTS: Several cellular proteins of hepG2 cell specifically bound to the core region of HCV RNA genome. The binding of cellular proteins to digoxin-labeled HCV core RNA was competed out in proportion to the increasing amount of unlabeled RNA. One of the HCV RNA-binding proteins was the B (brain) isozyme of human phosphoglycerate mutase (PGAM-B) identified by MALDI-TOF-MS. CONCLUSION: PGAM-B could specifically bind to the core region of HCV RNA genome in vitro.

Prediction of functional outcome of ischemic stroke patients in northwest China.

OBJECTIVES: To identify the clinical factors which predicted the outcome of ischemic stroke patients in northwest China. PATIENTS AND METHODS: We retrospectively reviewed 489 consecutive patients with ischemic stroke admitted to the Neurology Department of Xijing Hospital. Demographic, clinical and laboratory data were recorded. Follow-up assessments were performed by telephone interviews or letters. The clinical outcome was assessed by using the modified Rankin Scale (mRS) and categorized as good (score 0-2) or poor (score 3-6) outcomes. Univariate and multivariate logistic regression analyses were performed to explore predictors of ischemic stroke. RESULTS: The follow-up period was up to 47 months (mean, 28.3 months). Fifty-five patients (11.2%) were lost. Among these 434 patients, 244 (56.2%) patients had good outcome and 190 (43.8%) had poor outcome. The poor outcome was associated with old age (OR: 3.505; CI 95%: 2.100-5.849), lower educational level (OR: 0.686; CI 95%: 0.570-0.825), having stroke history (OR: 2.481; CI 95%: 1.442-4.268), and higher NIHSS total score (OR: 2.619; CI 95%: 1.584-4.330). CONCLUSION: The results suggest that age, the educational level, stroke history, and NIHSS score are useful in the prediction of functional outcome of ischemic stroke in Chinese northwest area.