Hybrid Surgery for Revascularization of Chronic Occlusion of Internal Carotid Artery.

OBJECTIVE: The aim of this study was to conclude the safety and effectiveness of hybrid surgery for revascularization of chronic occlusion of internal carotid artery (COICA). METHODS: A total of 56 COCIA patients underwent hybrid surgery (carotid endarterectomy+carotid artery stenting) from September 2017 to September 2021 in our department. The clinical material and radiology data (preoperation and postoperation) were retrospectively analyzed to conclude the safety and effectiveness of hybrid surgery for revascularization of COICA. RESULTS: All 56 patients underwent hybrid surgery got revascularization successfully (with a successful rate of 100%) and improved intracranial blood flow. The computed tomography perfusion results indicate that the postoperative cerebral blood flow perfusion of the patient is significantly improved compared with before surgery. In 1 patient, postoperative brain magnetic resonance imaging within 24 hours showed spotted fresh infarction with head magnetic resonance imaging, without any clinical symptoms; 3 patients developing symptoms of ipsilateral neural-functional defect (hypoglossal nerve, superior laryngeal nerve, and mandibular branch of facial nerve, respectively), 2 weeks later the symptoms were disappeared. Imaging study at 3 and 6 months during the follow-up showed no abnormalities. CONCLUSION: Hybrid surgery is safe and effective for revascularization of COICA.

ASSOCIATION OF ORAL MICROBIOTA AND PERIODONTAL DISEASE WITH LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Evidence of oral microbiota perturbations has been accumulated for lung cancers. This review focused on the oral microbiota alterations in population suffering from lung cancer. In addition, we also discussed conflicting data about the association between oral microbiota dysbiosis and risk of lung cancer. METHODS: A systematic search was conducted in Medline, Embase, PubMed, and Cochrane Library databases. The studies evaluated diversity and abundance of oral microbes in healthy and lung cancer individuals as well as association of periodontal disease and pathogens with lung cancer. Of 3559 studies, 28 included studies were performed in qualitative analysis, and 25 studies were used in meta-analyses for quantitative assessment. Heterogeneity was analyzed by using I² and chi-squared Q test statistics. Statistical analyses were performed by using the RevMan 5.4 software. RESULTS: Compared with the control, lung cancer patients had lower alpha diversity (Shannon: SMD = -0.54; 95% CI, -0.90 to -0.19; P < .01, I2 = 71%). In nested case-control studies, individuals with decreased alpha diversity tended to have an increased risk of lung cancer (observed species: HR = 0.90; 95% CI, 0.85-0.96; P < .01, I2 = 0%; Shannon: HR = 0.89; 95% CI, 0.83-0.95; P < .01, I2 = 0%). Overall, no strong evidence of association of relative abundance with specific oral microbes with lung cancers was found because of inconsistent data. No associations were found between periodontal pathogens and lung cancer risk (red complex: HR = 1.12, 95% CI: 0.42-3.02, P = .82, I2 = 62%; orange complex: HR =1.77, 95% CI: 0.78-3.98, P = .17, I2 = 36%), expect for Fusobacterium nucleatum (HR = 2.27, 95% CI: 1.13-4.58, P = .02, I2 = 0%). The positive association of periodontal disease with lung cancer risk was found (HR = 1.58, 95% CI: 1.25-2.00, P < .001, I2= 0%) with increase of periodontal diseases severity (HR = 2.39, 95% CI: 1.57-3.66, P < .001, I2 = 0%). However, such association was not found in never-smoker participants (HR = 1.00, 95% CI: 0.76-1.31, P = .37, I2= 7%). CONCLUSIONS: Lower alpha diversity of oral microbiome may be associated with a greater risk of lung cancer and might serve as a predictive signal of lung cancer risk. There was no strong evidence of relative abundance of oral microbial taxa and periodontal pathogens in lung cancer patients. Fusobacterium nucleatum might be a potential microbial candidate of biomarkers in lung cancer. Periodontal disease may be positively associated with lung cancer risk by confounding of smoking, but not an independent risk factor.

The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides and proteins in athletes.

Heavy training is associated with increased respiratory infection risk and antimicrobial proteins are important in defence against oral and respiratory tract infections. We examined the effect of 14 weeks of vitamin D3 supplementation (5000 IU/day) on the resting plasma cathelicidin concentration and the salivary secretion rates of secretory immunoglobulin A (SIgA), cathelicidin, lactoferrin and lysozyme in athletes during a winter training period. Blood and saliva were obtained at the start of the study from 39 healthy men who were randomly allocated to vitamin D3 supplement or placebo. Blood samples were also collected at the end of the study; saliva samples were collected after 7 and 14 weeks. Plasma total 25(OH)D concentration increased by 130% in the vitamin D3 group and decreased by 43% in the placebo group (both P = 0.001). The percentage change of plasma cathelicidin concentration in the vitamin D3 group was higher than in the placebo group (P = 0.025). Only in the vitamin D3 group, the saliva SIgA and cathelicidin secretion rates increased over time (both P = 0.03). A daily 5000 IU vitamin D3 supplement has a beneficial effect in up-regulating the expression of SIgA and cathelicidin in athletes during a winter training period, which could improve resistance to respiratory infections.

Sex differences in upper respiratory symptoms prevalence and oral-respiratory mucosal immunity in endurance athletes.

The purpose of this study was to examine sex differences in oral-respiratory mucosal immunity and the incidence, severity and duration of upper respiratory symptoms (URS) episodes in endurance athletes during a 16-week winter training period. Blood was collected from 210 subjects (147 men and 63 women) at the start and end of the study for determination of differential leukocyte counts. Timed collections of unstimulated saliva were obtained at the start and at 4-week intervals during the study period. Saliva samples were analysed for salivary antimicrobial peptides and proteins (AMPs). Weekly training and daily illness logs were kept using validated questionnaires. Training loads averaged 11 h/week of moderate-vigorous physical activity and were not different for males and females. The salivary concentration of lysozyme and lactoferrin (both P < 0.04) but not salivary immunoglobulin A (SIgA) or amylase were higher in males than females. Saliva flow rates were significantly higher in males than females (P < 0.03) and consequently so were the salivary secretion rates of lysozyme, lactoferrin and amylase (all P < 0.01) but not SIgA (P = 0.097). Total blood leukocyte, monocyte and lymphocyte counts were not different between the sexes but females had higher numbers of circulating neutrophils (P = 0.040). The average number of URS episodes was 0.6 +/- 0.8 (mean +/- SD) in males and 0.8 +/- 1.0 in females (P = 0.103) and the number of URS days was higher in females (4.7 vs 6.8 days, P < 0.02). The duration of URS episodes was longer in females (11.6 vs 15.5 days, P < 0.03). The findings of this study concur with recent reports of illness incidence at major competitive games indicating that female athletes may be more susceptible than their male counterparts to URS and that lower oral-respiratory mucosal immunity may, in part, account for this.

Synthesis of novel magnetic cellulose-chitosan composite microspheres and their application in laccase immobilization.

Novel magnetic cellulose-chitosan composite microspheres were prepared by sol-gel transition method using ionic liquids as solvent for dissolution and regeneration. Subsequently, the composite microspheres activated by glutaradehyde to immobilize enzyme. Which of their structure, properties and morphology were studied by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and vibrating-sample magnetometer showed Fe3O4 nanoparticles with mean size of -10 nm were successfully embedded in the composite microspheres. The microshpheres were examined to be with the mean size of 20 µm and good magnetic property with saturation magnetization of 30.1 emu g(-1). The effect of pH and temperature on the immobilization of laccase was also investigated. Compared with free laccase, the pH, thermal and operational stabilities of the immobilized laccase were improved and the activity recovery of immobilized laccase reached 80.6%. Immobilized laccase retained 88.9% activity after 12 reaction cycles. Therefore, the cellulose-chitosan composite microspheres were expected to be a novel support for enzyme immobilization.

Concurrent Ingestion of Alkaline Water and L-Glutamine Enhanced Salivary α-Amylase Activity and Testosterone Concentration in Boxing Athletes.

Athletes often take sport supplements to reduce fatigue and immune disturbances during or after training. This study evaluated the acute effects of concurrent ingestion of alkaline water and L-glutamine on the salivary immunity and hormone responses of boxers after training. Twelve male boxing athletes were recruited in this study. During regular training, the participants were randomly divided into three groups and asked to consume 400 mL of alkaline water (Group A), 0.15 g/kg body weight of L-glutamine with 400 mL of water (Group G), and 0.15 g/kg of L-glutamine with 400 mL of alkaline water (Group A+G) at the same time each day for three consecutive weeks. Before and immediately after the training, saliva, heart rates, and the rate of perceived exertion were investigated. The activity of α-amylase and concentrations of lactoferrin, immunoglobulin A (IgA), testosterone, and cortisol in saliva were measured. The results showed that the ratio of α-amylase activity/total protein (TP) significantly increased after training in Group A+G but not in Group A or G, whereas the ratios of lactoferrin/TP and IgA/TP were unaffected in all three groups. The concentrations of salivary testosterone after training increased significantly in Group A+G but not in Group A or G, whereas the salivary cortisol concentrations were unaltered in all groups. In conclusion, concurrent ingestion of 400 mL of alkaline water and 0.15 g/kg of L-glutamine before training enhanced the salivary α-amylase activity and testosterone concentration of boxers, which would be beneficial for post-exercise recovery.

Citrate Improves Biomimetic Mineralization Induced by Polyelectrolyte-Cation Complexes Using PAsp-Ca&Mg Complexes.

Magnesium ions are highly enriched in early stage of biological mineralization of hard tissues. Paradoxically, hydroxyapatite (HAp) crystallization is inhibited significantly by high concentration of magnesium ions. The mechanism to regulate magnesium-doped biomimetic mineralization of collagen fibrils has never been fully elucidated. Herein, it is revealed that citrate can bioinspire the magnesium-stabilized mineral precursors to generate magnesium-doped biomimetic mineralization as follows: Citrate can enhance the electronegativity of collagen fibrils by its absorption to fibrils via hydrogen bonds. Afterward, electronegative collagen fibrils can attract highly concentrated electropositive polyaspartic acid-Ca&Mg (PAsp-Ca&Mg) complexes followed by phosphate solution via strong electrostatic attraction. Meanwhile, citrate adsorbed in/on fibrils can eliminate mineralization inhibitory effects of magnesium ions by breaking hydration layer surrounding magnesium ions and thus reduce dehydration energy barrier for rapid fulfillment of biomimetic mineralization. The remineralized demineralized dentin with magnesium-doped HAp possesses antibacterial ability, and the mineralization mediums possess excellent biocompatibility via cytotoxicity and oral mucosa irritation tests. This strategy shall shed light on cationic ions-doped biomimetic mineralization with antibacterial ability via modifying collagen fibrils and eliminating mineralization inhibitory effects of some cationic ions, as well as can excite attention to the neglected multiple regulations of small biomolecules, such as citrate, during biomineralization process.

Influence of vitamin D status on respiratory infection incidence and immune function during 4 months of winter training in endurance sport athletes.

The purpose of this study was to examine the influence of vitamin D status on mucosal and systemic immunity and the incidence, severity and duration of upper respiratory tract illness (URTI) episodes in endurance athletes during a 16-week winter training period. Blood was collected from 225 subjects at the start of the study and plasma was analysed for total 25-hydroxy vitamin D (25(OH)D) and cathelicidin concentration. Blood was also collected at the end of the study and analysed for 25(OH)D and antigen-stimulated cytokine production. Unstimulated saliva samples were obtained at the start and at 4-week intervals during the study period. Saliva samples were analysed for salivary antimicrobial peptides and proteins (AMPs). Weekly training and daily illness logs were kept. At the start and end of the study 38% and 55%, respectively, of the athlete cohort had inadequate (plasma 25(OH)D 30-50 nmol/L) or deficient (plasma 25(OH)D < 30 nmol/L) vitamin D status. There was a significantly higher proportion of subjects who presented with symptoms of URTI in the vitamin D deficient status group (initial plasma 25(OH)D < 30 nmol/L) during the study period than in the optimal vitamin D group (> 120 nmol/L) and the total number of URTI symptom days and the median symptom-severity score in the vitamin D deficient group was signifi- cantly higher than in the other groups. The plasma cathelicidin concentration positively correlated with the plasma 25(OH)D concentration and the saliva secretory immunoglobulin A (SIgA) secretion rate in the optimal vitamin D status group was significantly higher than in the other groups. Low vitamin D status was associated with lower pro-inflammatory cytokine production by monocytes and lymphocytes. Low vitamin D status could be an important determinant of URTI risk in endurance athletes and mucosal as well as systemic immunity may be modified via vitamin D-dependent mechanisms.

[Trans-extradural approach to resect trigeminal schwannomas involving the cavernous sinus region].

OBJECTIVE: To investigate the techniques and effect of extradural approach for the resection of trigeminal schwannomas involving the cavernous sinus. METHODS: Twenty-three patients (range 26-63 years, mean age 46.2 years) with trigeminal schwannomas involving the cavernous sinus treated by middle fossa extradural approach were retrospectively analyzed. Frontotemporal orbitozygomatic extradural approach was performed in 2 patients. Frontotemporal zygomatic extradural approach was carried out in 21 patients. The first follow-up visit was on the 3rd month after surgery, and if residual was observed on enhanced MRI, then the patient was followed up every 6 months; otherwise, the patient was followed up every 8-12 months. RESULTS: The length of hospital stay after surgery was 7-13 days (mean 8.5 days). Two tumors originated from the ophthalmic branch, 2 from the maxillary branch, 5 from the mandibular branch and 14 from the gasserian ganglion. Total resection was achieved in 21 of the 23 patients (91.3%) and subtotal resection in the other 2 patients. All the patients were followed up from 3 months to 4 years. Median follow-up time was 19 months. The most common symptom was facial hypoesthesia, occurring in 18 patients. This symptom improved in 10 patients and worsened in 8 patients after surgery. New postoperative facial hypoesthesia was observed in 2 patients. Facial pain was observed in 3 patients and subsided after surgery. Two patients had loss of hearing, this symptom improved in 1 patient and worsened in 1 patient after surgery. Diplopia was observed in 6 patients. In 1 of these 6 patients, diplopia resulted from palsy of the oculomotor nerve. In the other 5 patients, diplopia resulted from palsy of the abducens nerve. This symptom improved postoperatively in all these 6 patients. New postoperative atrophy of the temporalis muscle was observed in 3 patients. There was no operation-related mortality. Tumor recurrence was only found in 1 patient after 24 months and was treated by Gamma knife. CONCLUSIONS: The middle fossa extradural approach may be an ideal option for the resection of trigeminal schwannomas involving the cavernous sinus. This approach produces no further impairment, less complication, and is less likely to injured the trigeminal nerve, abducens nerve, trochlear nerve and internal carotid artery.

Chalcogen-bridged coordination polymer for the photocatalytic activation of aryl halides.

The ability to deliver electrons is vital for dye-based photocatalysts. Conventionally, the aromatic stacking-based charge-transfer complex increases photogenerated electron accessibility but decreases the energy of excited-state dyes. To circumvent this dilemma, here we show a strategy by tuning the stacking mode of dyes. By decorating naphthalene diimide with S-bearing branches, the S···S contact-linked naphthalene diimide string is created in coordination polymer, thereby enhancing electron mobility while simultaneously preserving competent excited-state reducing power. This benefit, along with in situ assembly between naphthalene diimide strings and exogenous reagent/reactant, improves the accessibility of short-lived excited states during consecutive photon excitation, resulting in greater efficiency in photoinduced electron-transfer activation of inert bonds in comparison to other coordination polymers with different dye-stacking modes. This heterogeneous approach is successfully applied in the photoreduction of inert aryl halides and the successive formation of CAr-C/S/P/B bonds with potential pharmaceutical applications.

Selective capture and determination of doxycycline in marine sediments by using magnetic imprinting dispersive solid-phase extraction coupled with high performance liquid chromatography.

Antibiotics are frequently used in aquaculture as feed additives and finally enter the marine environment that can pose potential threat to humans. In this study, magnetic molecularly imprinted nanocomposites were prepared by surface imprinting and applied as selective sorbents for specific capture of doxycycline. A multivariate approach based on response surface methodology with Box-Behnken design was adopted to optimize the dispersive solid-phase extraction of doxycycline from marine sediment. Three key parameters, including adsorbent amount and type of washing/eluting solvent, were screened. Under optimum conditions, the limit of detection was 0.03 µg g-1 with good linearity from 0.5 to 20 µg g-1 followed by HPLC detection. Finally, two sediment samples were analysed and satisfactory recoveries between 90.60 % and 93.76 % were obtained with acceptable relative standard deviations (≤4.12 %), suggesting a promising applicability of the developed method for efficient extraction and sensitive quantification of antibiotics in complex marine environmental matrix.

[Application of novel quantum dot-based molecularly imprinted fluorescence sensor in rapid detection].

A critical need in analytical chemistry is the efficient fabrication of selective and sensitive sensors to detect trace analytes in complicated samples. In recent years, fluorescence analysis has been widely used in environmental research and the life sciences due to its high sensitivity and simple operation. Quantum dots (QDs) are a new type of fluorescent nanomaterials. Owing to the quantum confinement effect, QDs possess excellent optical properties such as strong anti-bleaching ability, a narrow excitation and emission band, and tunable emission wavelength. As a hot labeling material, QDs are suitable for use in surface-modified analytical sensors employed in fields such as analytical chemistry, biology, and medicine. However, QD materials have a notable disadvantage, in that the actual sample matrix may contain some interferents with luminescent responses similar to those of the target; this decreases the selective ability of the fluorescence sensor. The surface modification of QDs via the molecular imprinting technique (MIT) is a promising solution to overcome this drawback. Molecularly imprinted polymers (MIPs) are a kind of "bionic" material that can carry out specific recognition and selective adsorption and hence, possess the unique properties of recognition specificity, structural predictability, good reproducibility, and excellent stability. Accordingly, MIPs have been widely employed in sensors as well as for drug delivery, catalysis, and solid phase extraction. Notably, QD-based molecularly imprinted fluorescence sensors combine the advantages of QDs and the MIT. Owing to their specific selectivity and high sensitivity, such sensors have been extensively developed for environmental monitoring, food detection, and biological analysis. However, there remain challenges associated with the preparation and application of the sensors: (i) single recognition: it is important to develop a composite sensor that can detect multiple target analytes from the actual samples at the same time during practical application; (ii) poor hydrophilicity: the actual sample is usually a liquid matrix; hence, it is imperative to determine an approach for improving the hydrophilicity of the sensor; (iii) the accuracy of fluorescence response and the resolution of visual detection need to be further improved; (iv) imprinting: it remains challenging to imprint biological macromolecules, viruses, and bacteria. Thus far, many researchers have made progress with regard to the preparation and application of the sensors. Accordingly, this work reviews approximately 20 papers published by the American Chemical Society, Elsevier, and other databases in the last five years to highlight progress in novel preparation methods and practical applications of QD-based molecularly imprinted fluorescence sensors for the sensitive analysis and rapid detection of trace substances. First, according to the different numbers of emission peaks in the fluorescence spectrum, three kinds of QD-based molecularly imprinted fluorescence sensors are introduced and the related recognition mechanisms are explained. Second, according to the different substances to be detected, this mini-review summarizes the latest research progress in sensors for the detection of ions, organic small molecules, biological macromolecules, as well as for the analysis of bacteria and viruses. Finally, existing challenges associated with the preparation and application of the sensors, as well as future development trends, are discussed.

Identification of biological pathway and process regulators using sparse partial least squares and triple-gene mutual interaction.

Identification of biological process- and pathway-specific regulators is essential for advancing our understanding of regulation and formation of various phenotypic and complex traits. In this study, we applied two methods, triple-gene mutual interaction (TGMI) and Sparse Partial Least Squares (SPLS), to identify the regulators of multiple metabolic pathways in Arabidopsis thaliana and Populus trichocarpa using high-throughput gene expression data. We analyzed four pathways: (1) lignin biosynthesis pathway in A. thaliana and P. trichocarpa; (2) flavanones, flavonol and anthocyannin biosynthesis in A. thaliana; (3) light reaction pathway and Calvin cycle in A. thaliana. (4) light reaction pathway alone in A. thaliana. The efficiencies of two methods were evaluated by examining the positive known regulators captured, the receiver operating characteristic (ROC) curves and the area under ROC curves (AUROC). Our results showed that TGMI is in general more efficient than SPLS in identifying true pathway regulators and ranks them to the top of candidate regulatory gene lists, but the two methods are to some degree complementary because they could identify some different pathway regulators. This study identified many regulators that potentially regulate the above pathways in plants and are valuable for genetic engineering of these pathways.

Glutathione Liposomes Carrying Ceftriaxone, FK506, and Nilotinib to Control Overexpressed Dopamine Markers and Apoptotic Factors in Neurons.

Advances in liposomal formulation carrying multiple neuroprotective drugs, such as ceftriaxone (CEF), FK506, and nilotinib, can point toward an approach to obviating the difficulties in Parkinson's disease (PD) treatment. We prepared functionalized liposomes decorated with glutathione (GSH) to penetrate the blood-brain barrier (BBB) and cardiolipin (CL) to link up apoptotic neurons. Further, the effect of CEF-FK506-nilotinib-GSH-CL-liposomes on a PD model established by SH-SY5Y cells with 1-methyl-4-phenylpyridinium-induced neurotoxicity was investigated. An increment of the mole percentage of dihexadecyl phosphate and CL increased the particle size and the absolute value of ζ potential, improved the entrapment efficiency of CEF, FK506, and nilotinib, and reduced the drug-releasing rate. The toxicity studies revealed that CEF, FK506, and nilotinib-encapsulated liposomes could enhance the survival of SH-SY5Y cells. Western blot and immunofluorescence revealed that incorporation of CL in a lipid bilayer ameliorated the docking of CEF-FK506-nilotinib-GSH-CL-liposomes at α-synuclein (α-syn), indicating a better targeting capability of the liposomes to degenerated neurons. Treatment with CEF-FK506-nilotinib-GSH-CL-liposomes reduced the expression of Bax and α-syn and promoted the expression of Bcl-2, tyrosine hydroxylase, and the dopamine transporter. GSH- and CL-conjugated liposomes showed combined activity of targeting the BBB and α-syn and augmented the efficiency of the three drugs in rescuing dopaminergic neurons for neurodegenerative therapy.

Relationships among salivary immunoglobulin A, lactoferrin and cortisol in basketball players during a basketball season.

The aim of this study was to examine the changes and relationships of immune and stress parameters of basketball players during a basketball season. Eight members of National Taichung University basketball team volunteered to participate. Saliva samples were collected at rest and before the start of practice or competition at seven time points during the intense training, competition and recovery period. Salivary immunoglobulin A (sIgA), cortisol, and lactoferrin were measured during training and competition period and compared with those measured at the fourth recovery week. Relationships among immune and stress parameters were evaluated. Compared with those detected at the fourth recovery week, significant decreases in secretion rates and absolute concentrations of sIgA and lactoferrin were observed at times of intense training and competition. In addition, significant increases in secretion rates and absolute concentrations of salivary cortisol were observed during intense training and competition period and the first week of recovery. Moreover, a significant inverse correlation (r = -0.28; P < 0.05) that existed between secretion rates of sIgA and cortisol as well as a positive correlation (r = 0.32; P < 0.05) that existed between secretion rates of sIgA and lactoferrin was measured. Our results demonstrated that the secreted cortisol was induced and the mucosal immunity of the participants was suppressed during the basketball season. The inverse correlation existed between secretion rates of sIgA and cortisol may indicate a possible role of cortisol in the strenuous exercise-induced immunosuppression. Our results also suggest that a delicate balance may exist between mucosal innate and adaptive immune responses.

Gastric Ulceration and Immune Suppression in Weaned Piglets Associated with Feed-Borne Bacillus cereus and Aspergillus fumigatus.

As a multifactorial cause, gastric ulceration-mediated diarrhea is widely prevalent in the weaned piglets, impairing pig health and economic benefits. With full implementation of antibiotic stewardship programs in China, Bacillus cereus (B. cereus) and Aspergillus fumigatus (A. fumigatus) were identified frequently in porcine feedstuffs and feeds of the animal industry. Association between feed-borne B. cereus and frequent diarrhea remains unclear. In the present study, we conducted a survey of B. cereus and A. fumigatus from feeds and feedstuffs in pig farms during hot season. Interestingly, B. cereus, B. subtilis, B. licheniformis and B. thuringinesis were isolated and identified from piglets' starter meals to sow feeds, accounting for 56.1%, 23.7%, 13.7% and 6.5%, respectively. Obviously, both B. cereus and B. subtili were dominant contaminants in the survey. In an in vitro study, Deoxynivalenol (DON) contents were determined in a dose-dependent manner post fermentation with B. cereus (405 and DawuC). Subsequently, 36 weaned piglets were randomly assigned to four groups and the piglets simultaneously received the combination of virulent B. cereus (Dawu C) and A. fumigatus while animals were inoculated with B. cereus (Dawu C), A. fumigatus or PBS as the control group. Clinically, piglets developed yellow diarrhea on day 5 and significant reductions of relative body weight were observed in the B. cereus group, and co-infection group. More importantly, IgG titers against Classical swine fever virus (CSFV) and Porcine epidemic diarrhea (PED) were reduced dramatically during 14-day observation in co-infection group, the B. cereus (Dawu C) group or the A. fumigatus group. However, lower Foot and mouth disease (FMD) -specific antibodies were reduced on day 7 compared to those of the control group. Additionally, lower lymphocyte proliferations were found in the B. cereus group and the co-infection group compared to the control group. Postmortem, higher lesions of gastric ulceration were observed in the B. cereus group and the co-infection group from day 7 to day 14 compared with those of the A. fumigatus group and the control group. Compared to the A. fumigatus group, higher DON contents were detected in the stomach inoculated with B. cereus and the co-infection with A. fumigatus. In conclusion, our data support the hypothesis that B. cereus might be associated with severe diarrhea by inducing gastric ulcerations and A. fumigatus might aggravate immune suppression, threating a sustainable swine industry. It is urgently needed to control feed-borne B. cereus contamination.

Recombinant ciliary neurotrophic factor promotes nerve regeneration and induces gene expression in silicon tube-bridged transected sciatic nerves in adult rats.

Sciatic nerves in adult male rats were transected and reunited via a silicone chamber. This was followed by a focal injection of recombinant ciliary neurotrophic factor (CNTF). To evaluate the effect of this therapeutic approach and to explore its possible mechanisms, nerve regeneration was traced by horseradish peroxidase retrograde labeling. Functional recovery was evaluated by functional assessment of the hind feet and the expression of a number of proteins was detected using immunohistochemistry. The results showed that a single administration of CNTF could promote regeneration of motor axons, with improved functional recovery in adult rats. Growth associated protein (GAP)-43, S100, CD68 and major histocompatibility complex class II immunoreactivity in the regenerative and distal nerves suggested that CNTF could promote axon regeneration, Schwann cell migration, monocyte infiltration and activation. CNTF might also indirectly promote axonal regeneration by further activating the JAK-STAT3 pathway and subsequently upregulating phosphotyrosine, GAP-43 and S100 expression to enhance proliferation, growth and migration of Schwann cells. CNTF has suggested important targets for pharmacological intervention in peripheral nerve disease and injury.

Rosmarinic acid- and curcumin-loaded polyacrylamide-cardiolipin-poly(lactide-co-glycolide) nanoparticles with conjugated 83-14 monoclonal antibody to protect ß-amyloid-insulted neurons.

Polymeric nanoparticles (NPs) combined with lipids can have profound effects on treatment efficacy in patients with neurological disorders such as Alzheimer's disease (AD). We developed polyacrylamide (PAAM)-cardiolipin (CL)-poly(lactide-co-glycolide) (PLGA) NPs grafted with surface 83-14 monoclonal antibody (MAb) to carry rosmarinic acid (RA) and curcumin (CUR). This drug delivery system was used to cross the blood-brain barrier (BBB) and enhance the viability of SK-N-MC cells insulted with ß-amyloid (Aß) deposits. Experimental evidence revealed that an increase in the concentration of 83-14 MAb enhanced the permeability coefficient of RA and CUR using the nanocarriers. The levels of phosphorylated p38 and phosphorylated tau protein at serine 202 in degenerated SK-N-MC cells were in the order: Aß > (Aß + RA-CUR) > (Aß + 83-14 MAb-RA-CUR-PAAM-PLGA NPs) > (Aß + 83-14 MAb-RA-CUR-PAAM-CL-PLGA NPs) ≈ control. The viability of SK-N-MC cells reduced with time and CL in 83-14 MAb-RA-CUR-PAAM-CL-PLGA NPs advantaged Aß-targeted delivery of RA-CUR. These results evidenced that the current 83-14 MAb-RA-CUR-PAAM-CL-PLGA NPs can be a promising pharmacotherapy to permeate the BBB and reduce the fibrillar Aß-induced neurotoxicity.

Rapid detection of foot-and-mouth disease virus using reverse transcription recombinase polymerase amplification combined with a lateral flow dipstick.

Foot-and-mouth disease caused by foot-and-mouth disease virus (FMDV) is one of the most highly contagious diseases of domestic animals, and leads to enormous economic loss. Currently there are two main prevention and control strategies for the disease: eradication of the infected animals in FMDV free countries, and vaccination of the susceptible animals in countries with endemic FMDV infection. Early discovery and diagnosis of the source of infection is therefore integral to the containment of FMDV. In this study, a two-step reverse transcription recombinase polymerase amplification assay combined with lateral flow detection (RPA-LFD) was developed to detect FMDV. With incubation at 38 °C, a region of the 2B gene on the FMDV genome was successfully amplified within 20 min using specific primers and a probe. The amplified RPA product can be visualized on a lateral flow dipstick. The RPA-LFD assay was highly sensitive, detecting down to 10 copies of plasmid DNA. There was no cross-reactivity with other pathogens causing vesicular lesions. In addition, 143 clinical samples were used to compare RPA-LFD with real-time PCR, with 98.6% concordance between the assays. Therefore, the developed RPA-LFD assay provides a rapid, simple, highly promising approach to be used as point-of-care diagnostics in the field.

The synthesis of amphiphilic polyethyleneimine/calcium phosphate composites for bispecific T-cell engager based immunogene therapy.

Bispecific T-cell engagers (BiTEs) are single chain variable fragments with specific structures, which could connect the surface antigen on cancer cells and CD3 ligands on T cells, and then engage the T cells for cancer immunotherapy. In this report, a novel organic-inorganic hybrid gene delivery system composed of stearic acid modified polyethyleneimine (stPEI) and calcium phosphate (CaP) was used to deliver MC.DNA into cells to express BiTE antibodies. This gene delivery system exhibits high transfection efficiency, long-term effects and low cytotoxicity in vitro. Furthermore, the gene production, anti-IGF1R/CD3 bispecific T-cell engager, exhibited a rapid redirection activity in T cells to induce cancer cell apoptosis. In summary, the results confirmed that stPEI-CaP could be an efficient gene delivery system for BiTE encoding MC.DNA based gene immunotherapy.