The effect of oropharyngeal colostrum administration on the clinical outcomes of premature infants: A meta-analysis.

BACKGROUND: Preterm complications are now the second leading cause of death in children under five years of age. Colostrum is essential to prevent infection and promote maturation in preterm infants. Guidelines recommend that preterm infants be fed colostrum by the oral and pharyngeal routes as early as possible after birth to provide immune protection; however, due to disease and an uncoordinated sucking and swallowing function, it is challenging to provide colostrum through the oropharyngeal route, which limits the immune protection it provides. OBJECTIVE: To update the existing meta-analysis, evaluate the effect of oropharyngeal colostrum administration on related outcomes in preterm infants and explore the optimal frequency and duration of oropharyngeal colostrum administration through subgroup analysis. METHODS: The Cochrane Library, PubMed, Web of Science, ScienceDirect, and Ovid databases were searched for randomized control trials (RCTs) of oropharyngeal colostrum administration for preterm infants. Two researchers screened the literature strictly according to the inclusion and exclusion criteria and evaluated the quality. Primary data and data from the included literature were extracted. Finally, the data were statistically analyzed by the Review Manager 5.3 software. RESULTS: A total of 1736 preterm infants were included in 16 RCTs. The meta-analysis showed that the incidence of necrotizing enterocolitis, late-onset sepsis, feeding intolerance, and death was lower, the time to full enteral feeding was shorter, and the day of recovery to birth weight was earlier in the intervention group (oropharyngeal colostrum administration group) than in the control group, and this difference was statistically significant. Subgroup analysis: Frequency of oropharyngeal colostrum administration: The incidence of necrotizing enterocolitis and late-onset sepsis in the once every 4 h group was lower than that in the control group, and the time to complete enteral feeding was shorter. Duration of oropharyngeal colostrum administration: In the 1-3 days group and 4-7 days group, the time to full enteral feeding in the intervention group was shorter. In the 8-10 days group, the incidence of necrotizing enterocolitis and late-onset sepsis was lower in the intervention group. CONCLUSIONS: Oropharyngeal colostrum administration can reduce the incidence of necrotizing enterocolitis, late-onset sepsis, feeding intolerance and mortality, shorten the time to full enteral feeding, and lead to a faster recovery to birth weight in preterm infants. The appropriate oropharyngeal colostrum administration frequency may be 4 h, and the optimal duration may be 8-10 days. Therefore, it is recommended that clinical medical staff implement oropharyngeal colostrum administration for premature infants based on existing evidence. TWEETABLE ABSTRACT: Oropharyngeal colostrum administration can reduce the incidence of complications in preterm infants and shorten the time to full enteral feeding.

Short-Chain Fatty Acids Alleviate Vancomycin-Caused Humoral Immunity Attenuation in Rabies-Vaccinated Mice by Promoting the Generation of Plasma Cells via Akt-mTOR Pathway.

Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host immunogenicity to vaccines. However, it remains unknown whether and how SCFAs improve the immunogenicity of the rabies vaccine. In this study, we investigated the effect of SCFAs on the immune response to rabies vaccine in vancomycin (Vanco)-treated mice and found that oral gavage with butyrate-producing bacteria (C. butyricum) and butyrate supplementation elevated RABV-specific IgM, IgG, and virus-neutralizing antibodies (VNAs) in Vanco-treated mice. Supplementation with butyrate expanded antigen-specific CD4+ T cells and IFN-γ-secreting cells, augmented germinal center (GC) B cell recruitment, promoted plasma cells (PCs) and RABV-specific antibody-secreting cells (ASCs) generation in Vanco-treated mice. Mechanistically, butyrate enhanced mitochondrial function and activated the Akt-mTOR pathway in primary B cells isolated from Vanco-treated mice, ultimately promoting B lymphocyte-induced maturation protein-1 (Blimp-1) expression and CD138+ PCs generation. These results highlight the important role of butyrate in alleviating Vanco-caused humoral immunity attenuation in rabies-vaccinated mice and maintaining host immune homeostasis. IMPORTANCE The gut microbiome plays many crucial roles in the maintenance of immune homeostasis. Alteration of the gut microbiome and metabolites has been shown to impact vaccine efficacy. SCFAs can act as an energy source for B-cells, thereby promoting both mucosal and systemic immunity in the host by inhibiting HDACs and activation of GPR receptors. This study investigates the impact of orally administered butyrate, an SCFA, on the immunogenicity of rabies vaccines in Vanco-treated mice. The results showed that butyrate ameliorated humoral immunity by facilitating the generation of plasma cells via the Akt-mTOR in Vanco-treated mice. These findings unveil the impact of SCFAs on the immune response of the rabies vaccine and confirm the crucial role of butyrate in regulating immunogenicity to rabies vaccines in antibiotic-treated mice. This study provides a fresh insight into the relationship of microbial metabolites and rabies vaccination.

Inhibitory Effect of Resveratrol on LPS-induced Glomerular Mesangial Cells Proliferation and TGF-ß1 Expression via Sphingosine Kinase 1 Pathway.

OBJECTIVE: To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-ß1 (TGF-ß1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs). METHODS: The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-ß1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016. RESULTS: LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-ß1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-II (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of -8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1. CONCLUSION: RSV inhibited LPS-induced GMCs proliferation and TGF-ß1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.

Alternative prey and farming system mediate predation of Colorado potato beetles by generalists.

BACKGROUND: Biological control by generalist predators can be mediated by the abundance and biodiversity of alternative prey. When alternative prey draw predator attacks away from the control target, they can weaken pest suppression. In other cases, a diverse prey base can promote predator abundance and biodiversity, reduce predator-predator interference, and benefit biocontrol. Here, we used molecular gut-content analysis to assess how community composition altered predation of Colorado potato beetle (Leptinotarsa decemlineata (Say)) by Nabis sp. and Geocoris sp. Predators were collected from organic or conventional potato (Solanum tuberosum L.) fields, encouraging differences in arthropod community composition. RESULTS: In organic fields, Nabis predation of potato beetles decreased with increasing arthropod richness and predator abundance. This is consistent with Nabis predators switching to other prey species when available and with growing predator-predator interference. In conventional fields these patterns were reversed, however, with potato beetle predation by Nabis increasing with greater arthropod richness and predator abundance. For Geocoris, Colorado potato beetle predation was more frequent in organic than in conventional fields. However, Geocoris predation of beetles was less frequent in fields with higher abundance of the detritus-feeding fly Scaptomyza pallida Zetterstedt, or of all arthropods, consistent with predators choosing other prey when available. CONCLUSION: Alternative prey generally dampened predation of potato beetles, suggesting these pests were less-preferred prey. Nabis and Geocoris differed in which alternative prey were most disruptive to feeding on potato beetles, and in the effects of farm management on predation, consistent with the two predator species occupying complementary feeding niches. © 2021 Society of Chemical Industry.

Behavior of iron and other heavy metals in passivated sediments and the coupling effect on phosphorus.

In situ passivation, which is easy to operate and affordable, is one of the most commonly used methods for sediment phosphorus (P) remediation. Understanding the behavior of iron and other heavy metals in passivated sediments is important for alleviating lake eutrophication and for ensuring drinking water safety. In this study, we investigated the behavior of P, Fe, Mn, Cd, Co, and Pb in lanthanum modified bentonite (LMB, Phoslock®) and polyaluminum chloride (PAC)-passivated sediments using intact sediment cores. Rhizon sampler and diffusive gradients in thin films technology (DGT) were respectively used to collect soluble and labile substances in sediment; a modified sequential selective extraction method was used to characterize metal forms. Results showed that LMB reduced soluble reactive phosphorus (SRP) at sediment depths of 0 ~ -15 mm and DGT-labile P flux at 0 ~ -50 mm. Correlation between DGT-labile P and Fe (R2 = 0.71) indicated that P mobility in the LMB group was affected by the behavior of Fe. PAC decreased SRP at sediment depths of 0, -5, -10, -15, -20, -25, and -50 mm with removal rates of 100%, 90%, 45%, 35%, 81%, 89%, and 100%, respectively. DGT-labile P flux was decreased by PAC at 0 ~ -10 mm and -50 ~ -110 mm, but increased at -10 ~ -50 mm; this is a result of synthetical effect by Al flocs adsorption and Fe(III) reductive dissolution. LMB decreased Cd, Co, and Pb in LMB layer in carbonate, reducible, and oxidizable forms. PAC decreased Cd mobility but caused the transformation of Co and Pb from reducible to other forms because of Fe(III) reductive dissolution. Those results indicate that sedimentary Fe plays an important role in in situ passivation. We suggest modifying passivators to Fe(II) adsorbents and increasing DO permeability of sediment to promote the formation of an Fe(III) passivation layer and hence the effectiveness of P control.

A trait-based framework for predicting foodborne pathogen risk from wild birds.

Recent foodborne illness outbreaks have heightened pressures on growers to deter wildlife from farms, jeopardizing conservation efforts. However, it remains unclear which species, particularly birds, pose the greatest risk to food safety. Using >11,000 pathogen tests and 1565 bird surveys covering 139 bird species from across the western United States, we examined the importance of 11 traits in mediating wild bird risk to food safety. We tested whether traits associated with pathogen exposure (e.g., habitat associations, movement, and foraging strategy) and pace-of-life (clutch size and generation length) mediated foodborne pathogen prevalence and proclivities to enter farm fields and defecate on crops. Campylobacter spp. were the most prevalent enteric pathogen (8.0%), while Salmonella and Shiga-toxin producing Escherichia coli (STEC) were rare (0.46% and 0.22% prevalence, respectively). We found that several traits related to pathogen exposure predicted pathogen prevalence. Specifically, Campylobacter and STEC-associated virulence genes were more often detected in species associated with cattle feedlots and bird feeders, respectively. Campylobacter was also more prevalent in species that consumed plants and had longer generation lengths. We found that species associated with feedlots were more likely to enter fields and defecate on crops. Our results indicated that canopy-foraging insectivores were less likely to deposit foodborne pathogens on crops, suggesting growers may be able to promote pest-eating birds and birds of conservation concern (e.g., via nest boxes) without necessarily compromising food safety. As such, promoting insectivorous birds may represent a win-win-win for bird conservation, crop production, and food safety. Collectively, our results suggest that separating crop production from livestock farming may be the best way to lower food safety risks from birds. More broadly, our trait-based framework suggests a path forward for co-managing wildlife conservation and food safety risks in farmlands by providing a strategy for holistically evaluating the food safety risks of wild animals, including under-studied species.

Colloidal Manganese Salt Improves the Efficacy of Rabies Vaccines in Mice, Cats, and Dogs.

Rabies, caused by rabies virus (RABV), remains a serious threat to public health in most countries worldwide. At present, the administration of rabies vaccines has been the most effective strategy to control rabies. Herein, we evaluate the effect of colloidal manganese salt (Mn jelly [MnJ]) as an adjuvant of rabies vaccine in mice, cats, and dogs. The results showed that MnJ promoted type I interferon (IFN-I) and cytokine production in vitro and the maturation of dendritic cells (DCs) in vitro and in vivo. Besides, MnJ serving as an adjuvant for rabies vaccines could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, plasma cells (PCs), and RABV-specific antibody-secreting cells (ASCs), consequently improve the immunogenicity of rabies vaccines, and provide better protection against virulent RABV challenge. Similarly, MnJ enhanced the humoral immune response in cats and dogs as well. Collectively, our results suggest that MnJ can facilitate the maturation of DCs during rabies vaccination, which can be a promising adjuvant candidate for rabies vaccines. IMPORTANCE Extending the humoral immune response by using adjuvants is an important strategy for vaccine development. In this study, a novel adjuvant, MnJ, supplemented in rabies vaccines was evaluated in mice, cats, and dogs. Our results in the mouse model revealed that MnJ increased the numbers of mature DCs, Tfh cells, GC B cells, PCs, and RABV-specific ASCs, resulting in enhanced immunogenicity and protection rate of rabies vaccines. We further found that MnJ had the same stimulative effect in cats and dogs. Our study provides the first evidence that MnJ serving as a novel adjuvant of rabies vaccines can boost the immune response in both a mouse and pet model.

A holistic understanding of cobalt cycling and limiting roles in the eutrophic Lake Taihu.

Cobalt (Co) cycling is often dominated by its role as a micronutrient in marine, while little is known on its cycling in a shallow eutrophic lake. Monthly sampling was performed in eutrophic Meiliang Bay of Lake Taihu, combining two laboratory control experiments and in situ Co limitation bioassay experiments. The high-resolution dialysis and the diffusive gradients in thin films technique were used to detect dissolved and labile Co, respectively. The positive correlations between dissolved/labile Co and Mn in the sediments for 6 or 7 months demonstrated that the mobility of Co in the sediments was primarily controlled by Mn redox cycling in the field. However, it is unexpected that the dissolved and labile Co only showed a small change over one year irrespective of the significant fluctuation in dissolved/labile Mn, with the concentrations being as low as 1.08 ± 0.22 µg/L and 0.246 ± 0.091 µg/L for dissolved and labile Co in the surface 20 mm sediment, respectively. Cyanobacterial bloom simulation and aerobic-anaerobic-cyanobacterial addition experiments indicated that the level of Co in the sediment-overlying water system was strongly regulated by cyanobacterial uptake, followed by the degradation of Co-enriched cyanobacterial biomass, which offset the influence of Mn redox cycling on Co mobility in the sediment. The significant enhancement of Microcystis spp. biomass by Co addition further indicated that Co was the potential limiting nutrient for cyanobacterial blooms. This work provides new ideas for better management strategies of eutrophication in shallow lakes.

Laboratory investigation on calcium nitrate induced coupling reactions between nitrogen, phosphorus, sulfur, and metals in contaminated sediments.

In recent years, calcium nitrate addition has become a promising and usually used method for in situ sediment remediation. In this study, excess calcium nitrate was applied to column sediments to explore the coupling reactions of elements such as N, Fe, S, and P. Diffusive gradients in thin film (DGT) devices were used to collect labile substances at the sediment-water interface. Rhizon samplers were used to collect soluble substances in interstitial water. Results showed that nitrate addition turned the surface sediment into a more oxidized state, and mobile Fe, S, P, and As were removed in surface ~ 10-cm sediment. Due to different nitrate distributions in corresponding sediment depths, the consumption rates of NH3-N and soluble reactive P were faster in the surface sediment than that in deeper layers. Different from previous researches, the transient increase of soluble Fe was observed in this study, which was probably attributed to the solvation of FeS in the autotrophic denitrification process. According to our results, we suggest that a dosage of far less than 141 g N/m2 and slightly more than 45.3 g N/m2 can be used for the remediation of black and odorous sediment and control of internal P by calcium nitrate.

Therapeutic effects of hirsutella sinensis on the disease onset and progression of amyotrophic lateral sclerosis in SOD1G93A transgenic mouse model.

AIMS: Although the pathophysiology of amyotrophic lateral sclerosis (ALS) is still not completely understood, the deregulated microglia polarization and neuroinflammation have been shown to contribute to the pathogenesis and progression of this disease. In the present study, we aimed to determine whether hirsutella sinensis (HS) could reduce neuroinflammatory and pathological changes in the spinal cord of SOD1G93A model mice of ALS and consequently ameliorate disease onset and progression. METHODS: SOD1G93A mice were chronically treated with HS by gavage. Their lifespan was recorded, and motor behavior was evaluated by rotarod test. The pathological changes in skeletal muscles and motor neurons in spinal cords were assessed by immunofluorescent staining and hematoxylin-eosin staining. The microglia activation and neuroinflammation were determined by immunofluorescent staining and RT-PCR. RESULTS: Our data suggested that repeated HS administration prolonged the lifespan and extended disease duration of ALS mice without significant delay on disease onset. HS ameliorated the pathological changes in the motor neurons and gastrocnemius muscles. Moreover, HS promoted the transition of microglia from pro-inflammatory M1 to anti-inflammatory M2 phenotype in the spinal cord of ALS mice. CONCLUSION: All these findings indicate that HS may serve as a potential therapeutic candidate for the treatment of ALS.

Congruent audiovisual speech enhances auditory attention decoding with EEG.

OBJECTIVE: The auditory attention decoding (AAD) approach can be used to determine the identity of the attended speaker during an auditory selective attention task, by analyzing measurements of electroencephalography (EEG) data. The AAD approach has the potential to guide the design of speech enhancement algorithms in hearing aids, i.e. to identify the speech stream of listener's interest so that hearing aids algorithms can amplify the target speech and attenuate other distracting sounds. This would consequently result in improved speech understanding and communication and reduced cognitive load, etc. The present work aimed to investigate whether additional visual input (i.e. lipreading) would enhance the AAD performance for normal-hearing listeners. APPROACH: In a two-talker scenario, where auditory stimuli of audiobooks narrated by two speakers were presented, multi-channel EEG signals were recorded while participants were selectively attending to one speaker and ignoring the other one. Speakers' mouth movements were recorded during narrating for providing visual stimuli. Stimulus conditions included audio-only, visual input congruent with either (i.e. attended or unattended) speaker, and visual input incongruent with either speaker. The AAD approach was performed separately for each condition to evaluate the effect of additional visual input on AAD. MAIN RESULTS: Relative to the audio-only condition, the AAD performance was found improved by visual input only when it was congruent with the attended speech stream, and the improvement was about 14 percentage points on decoding accuracy. Cortical envelope tracking activities in both auditory and visual cortex were demonstrated stronger for the congruent audiovisual speech condition than other conditions. In addition, a higher AAD robustness was revealed for the congruent audiovisual condition, with reduced channel number and trial duration achieving higher accuracy than the audio-only condition. SIGNIFICANCE: The present work complements previous studies and further manifests the feasibility of the AAD-guided design of hearing aids in daily face-to-face conversations. The present work also has a directive significance for designing a low-density EEG setup for the AAD approach.

Brainstem encoding of frequency-modulated sweeps is relevant to Mandarin concurrent-vowels identification for normal-hearing and hearing-impaired listeners.

F0 contours convey the primary information of lexical Tones for Mandarin Chinese, and the processing of time-varying F0 contours is important for Mandarin concurrent-vowels identification (MCVI). In this work, we examined the relationship between frequency modulation (FM) detection of auditory system and MCVI in both normal-hearing (NH) and hearing-impaired (HI) listeners. Three experiments were conducted with the same subjects to measure their MCVI, FM detection limen (FMDL), and frequency following responses (FFRs) evoked by FM sweeps, respectively. To ensure that F0 contour was the primary cue utilized, mean F0s and durations were equalized among all test vowels in the MCVI experiment. To simulate the pattern of F0 contours of Mandarin vowels, linearly FM sweeps were used as stimuli in the FMDL and FFRs experiments. The results confirmed that the performance of HI listeners was significantly worse than that of NH listeners in all of the three measurements. Besides, FFRs evoked by FM sweeps had significantly lower tracking accuracy than those evoked by steady tones only for HI listeners. The correlation analysis further revealed that any two of the three measured indices were significantly correlated when the effects of age and absolute threshold were partialed out (|r| ≥ 0.502, p ≤ 0.017). These results suggested an association between the poor performance of HI listeners in the MCVI task and their degraded auditory function on FM detection, and such a behavioral degradation has emerged in the phase-locking activity at the brainstem level.

A Recombinant Rabies Virus Expressing Fms-like Tyrosine Kinase 3 Ligand (Flt3L) Induces Enhanced Immunogenicity in Mice.

Rabies is a zoonotic disease that still causes 59,000 human deaths each year, and rabies vaccine is the most effective way to control the disease. Our previous studies suggested that the maturation of DC plays an important role in enhancing the immunogenicity of rabies vaccine. Flt3L has been reported to own the ability to accelerate the DC maturation, therefore, in this study, a recombinant rabies virus expressing mouse Flt3L, designated as LBNSE-Flt3L, was constructed, and its immunogenicity was characterized. It was found that LBNSE-Flt3L could enhance the maturation of DC both in vitro and in vivo, and significantly more TFH cells and Germinal Center B (GC B) cells were generated in mice immunized with LBNSE-Flt3L than those immunized with the parent virus LBNSE. Consequently, expressing of Flt3L could elevate the level of virus-neutralizing antibodies (VNA) in immunized mice which provides a better protection from a lethal rabies virus challenge. Taken together, our study extends the potential of Flt3L as a good adjuvant to develop novel rabies vaccine by enhancing the VNA production through activating the DC-TFH-GC B axis in immunized mice.

Fabrication and Characterization of Novel Water-Insoluble Protein Porous Materials Derived from Pickering High Internal-Phase Emulsions Stabilized by Gliadin-Chitosan-Complex Particles.

Pickering high internal-phase emulsions (HIPEs) and porous materials derived from the Pickering HIPEs have received increased attention in various research fields. Nevertheless, nondegradable inorganic and synthetic stabilizers present toxicity risks, thus greatly limiting their wider applications. In this work, we successfully developed nontoxic porous materials through the Pickering HIPE-templating process without chemical reactions. The obtained porous materials exhibited appreciable absorption capacity to corn oil and reached the state of saturated absorption within 3 min. The Pickering HIPE templates were stabilized by gliadin-chitosan complex particles (GCCPs), in which the volume fraction of the dispersed phase (90%) was the highest of all reported food-grade-particle-stabilized Pickering HIPEs so far, further contributing to the interconnected pore structure and high porosity (>90%) of porous materials. The interfacial particle barrier (Pickering mechanism) and three-dimensional network formed by the GCCPs in the continuous phase play crucial roles in stabilization of HIPEs with viscoelastic and self-supporting attributes and also facilitate the development of porous materials with designed pore structure. These materials, with favorable biocompatibility and biodegradability, possess excellent application prospects in foods, pharmaceuticals, materials, environmental applications, and so on.

Celastrol induces vincristine multidrug resistance oral cancer cell apoptosis by targeting JNK1/2 signaling pathway.

BACKGROUND: Oral cancers are one of the most aggressive malignancies, with high mortality rates globally. Patients with these cancers are treated using combination therapies including surgery, chemotherapy, and radiotherapy. HYPOTHESIS/PURPOSE: Traditional Chinese medicines and other herbal medicines have been used to treat various diseases in Asia. Celastrol is a pentacyclic triterpenoid isolated from the Chinese herbal medicine Trypterygium wilfordii, which has therapeutic potential in multiple diseases. The present study was to determine the effect of celastrol on vincristine-resistant cancer cell line and to illuminate the mechanism of celastrol-induced cell apoptosis. STUDY DESIGN: Celastrol was added to vincristine-resistant cancer cell and immunoreactive proteins were detected. METHODS AND RESULTS: Our study demonstrated that celastrol leads to apoptosis of head and neck cancer cells through mitochondria- and Fas-mediated pathways. However, whether this herbal medicine exhibits beneficial effects on vincristine-resistant oral cancer patients remains uncertain. Therefore, our study examined the apoptotic effect exerted by celastrol and the mechanism by this drug acts on a vincristine-resistant cancer cell line. The present study demonstrated that celastrol triggered apoptotic cell death by inducing cell cycle arrest at the G2/M phase via the intrinsic and extrinsic pathways (increased cleaved caspase-3, caspase-8, caspase-9, and PARP). Increased expression of tBid also indicated the presence of crosstalk between the two pathways. Celastrol mediated cell apoptosis through the downregulation of the expression of Bcl-2, not Bcl-xL. Moreover, JNK1/2 signaling was the main pathway of celastrol-induced apoptosis. CONCLUSION: Celastrol could become a useful agent for treating oral cancers with MDR.

Steric Effect of Antioxidant Diels-Alder-Type Adducts: A Comparison of Sanggenon C with Sanggenon D.

Sanggenons C and D are two Diels-Alder-type adducts from Chinese crude drug Sang-bai-pi. Structurally, both sanggenons construct stereoisomers. In the study, they were comparatively determined using four antioxidant assays, including ferric ion reducing antioxidant power (FRAP) assay, Cu2+-reducing assay, 1,1-diphenyl-2-picryl-hydrazl (DPPH•)-scavenging assay, and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid radical (ABTS•⁺)-scavenging assay. Their Fe2+-binding reactions were explored using UV-Vis spectra. Finally, their cytoprotective effects were evaluated using flow cytometry. In electron transfer (ET)-based FRAP and Cu2+-reducing assays, sanggenon D was found to have lower IC50 values than sanggenon C; however, in multi-pathway-based DPPH•-scavenging and ABTS•⁺-scavenging assays, sanggenon C possessed lower IC50 values than sanggenon D. UV-Vis spectra suggested that sanggenon C generated a bathochromic-shift (286 nm → 302 nm) and displayed stronger UV absorption than sanggenon D. In flow cytometry, sanggenon C and sanggenon D, respectively, exhibited 31.1% and 42.0% early apoptosis-percentages towards oxidative-stressed mesenchymal stem cells (MSCs). In conclusion, both sanggenons may undergo multiple pathways (e.g., ET and Fe2+-binding) to protect MSCs against oxidative stress. In the mere ET aspect, sanggenon D possesses a higher level than sanggenon C, while in multi-pathway-based radical-scavenging, Fe2+-binding, and cytoprotection aspects, sanggenon C is more active than sanggenon D. These discrepancies can conclusively be attributed to the steric effect.

Fabrication of Zein/Pectin Hybrid Particle-Stabilized Pickering High Internal Phase Emulsions with Robust and Ordered Interface Architecture.

Diets containing partially hydrogenated oils (PHOs) expose the human body to trans fatty acids, thus endangering cardiovascular health. Pickering high internal phase emulsions (HIPEs) is a promising alternative of PHOs. This work attempted to construct stable Pickering HIPEs by engineering interface architecture through manipulating the interfacial, self-assembly, and packing behavior of zein particles using the interaction between protein and pectin. Partially wettable zein/pectin hybrid particles (ZPHPs) with three-phase contact angles ranging from 84° to 87° were developed successfully. ZPHPs were irreversibly anchored at the oil-water interface, resulting in robust and ordered interfacial structure, evidenced by the combination of LB-SEM and CLSM. This situation helped to hold a percolating 3D oil droplet network, which facilitated the formation of Pickering HIPEs with viscoelasticity, excellent thixotropy (>91.0%), and storage stability. Curcumin in HIPEs was well protected from UV-induced degradation and endowed HIPEs with ideal oxidant stability. Fabricated Pickering HIPEs possess a charming application prospect in foods and the pharmaceutical industry.

[Analysis of acne animal model based on Chinese and western medicine clinical symptoms characteristic].

This paper aimed to analyze the existing acne animal model based on the characteristics of acne clinical symptoms between Chinese and western medicine, in order to provide reference for the establishment of the rational acne animal model. Relevant literatures at home and abroad in recent years were reviewed to summarize the research progress of diagnostic criteria and drug treatment of acne with Chinese and western medicine, and analyze the existing acne animal model. The animal acne models were pathological models, and mainly reflected the clinical indicators of western medicine. Their evaluation was based on western medicine standard, with the standard of Chinese medicine for reference. More improved ideas and methods to establish acne animal models based on clinical study were put forward, so as to establish the reasonable quantitative standard for acne animal model. Furthermore, the animal model based on the combination of disease and syndrome was formed to provide a reliable experimental method for further study of acne. Rational acne animal model shall be selected according to the pathogenesis of acne, in order to improve the consistency between animal model and clinical symptoms, and lay a foundation for further study of acne.

NIK­ and IKKß­binding protein contributes to gastric cancer chemoresistance by promoting epithelial­mesenchymal transition through the NF­κB signaling pathway.

Systematic chemotherapy is indispensable for gastric cancer patients with advanced stage disease, but the occurrence of chemoresistance drastically limits treatment effectiveness. There is a tremendous need for identifying the underlying mechanism of chemoresistance. NIK­ and IKKß­binding protein (NIBP) (also known as TRAPPC9, trafficking protein particle complex 9) is a regulator of the cytokine­induced NF­κB signaling pathway which has been proven to play pivotal roles in the progression of various malignancies. Nevertheless, it is still ambiguous whether NIBP is involved in the chemoresistance of gastric cancer. The aim of the present study was to investigate the effect of NIBP on chemotherapy resistance of gastric cancer (GC) and to research the mechanisms of Ginkgo biloba extract 761 (EGb 761®) on reversing chemoresistence which has been confirmed in our previous study. In the present study, the results of immumohistochemisty revealed that the positive staining rates of NIBP, NF­κB p65 and NF­κB p­p65 in gastric cancer tissues were obviously higher than those in normal tissues. Furthermore, a close correlation was found to exist between the expression of NIBP and NF­κB p65 (p­p65) in gastric cancer tissues. Moreover, the overexpression of NIBP was closely related to tumor differentiation, depth of invasion, clinical stage and lymphatic metastasis in gastric cancer. Western blot analysis, real­time PCR, MTT assay and flow cytometric analysis were performed and the results demonstrated that compared with the gastric cancer SGC­7901 cells, the expression of NIBP, NF­κB p65, NF­κB p­p65 and mesenchymal marker vimentin were significantly increased in gastric cancer multidrug­resistant SGC­7901/CDDP cells, and the epithelial cell marker ZO­1 was significantly decreased. Meanwhile, it was found that SGC­7901/CDDP cells were accompanied by spindle­like mesenchymal appearance and upregulation of stem cell marker CD133 which has been verified to be an upstream regulatory gene of epithelial­mesenchymal transition (EMT). Further research confirmed that downregulation of NIBP by Ginkgo biloba extract (EGb) 761 EGb 761 suppressed the cis­diamminedichloroplatinum(II) (CDDP)­induced NF­κB signaling pathway, EMT and the expression of CD133 in SGC­7901 and SGC­7901/CDDP cells. Altogether, these data indicate that the NIBP­regulated NF­κB signaling pathway plays a pivotal role in the chemoresistance of gastric cancer by promoting CD133­induced EMT.

Using NextRAD sequencing to infer movement of herbivores among host plants.

Herbivores often move among spatially interspersed host plants, tracking high-quality resources through space and time. This dispersal is of particular interest for vectors of plant pathogens. Existing molecular tools to track such movement have yielded important insights, but often provide insufficient genetic resolution to infer spread at finer spatiotemporal scales. Here, we explore the use of Nextera-tagmented reductively-amplified DNA (NextRAD) sequencing to infer movement of a highly-mobile winged insect, the potato psyllid (Bactericera cockerelli), among host plants. The psyllid vectors the pathogen that causes zebra chip disease in potato (Solanum tuberosum), but understanding and managing the spread of this pathogen is limited by uncertainty about the insect's host plant(s) outside of the growing season. We identified 1,978 polymorphic loci among psyllids separated spatiotemporally on potato or in patches of bittersweet nightshade (S. dulcumara), a weedy plant proposed to be the source of potato-colonizing psyllids. A subset of the psyllids on potato exhibited genetic similarity to insects on nightshade, consistent with regular movement between these two host plants. However, a second subset of potato-collected psyllids was genetically distinct from those collected on bittersweet nightshade; this suggests that a currently unrecognized source, i.e., other nightshade patches or a third host-plant species, could be contributing to psyllid populations in potato. Oftentimes, dispersal of vectors of pathogens must be tracked at a fine scale in order to understand, predict, and manage disease spread. We demonstrate that emerging sequencing technologies that detect genome-wide SNPs of a vector can be used to infer such localized movement.