Lactobacillus acidophilus suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma through producing valeric acid.

BACKGROUND: Gut probiotic depletion is associated with non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). Here, we investigated the prophylactic potential of Lactobacillus acidophilus against NAFLD-HCC. METHODS: NAFLD-HCC conventional and germ-free mice were established by diethylnitrosamine (DEN) injection with feeding of high-fat high-cholesterol (HFHC) or choline-deficient high-fat (CDHF) diet. Orthotopic NAFLD-HCC allografts were established by intrahepatic injection of murine HCC cells with HFHC feeding. Metabolomic profiling was performed using liquid chromatography-mass spectrometry. Biological functions of L. acidophilus conditional medium (L.a CM) and metabolites were determined in NAFLD-HCC human cells and mouse organoids. FINDINGS: L. acidophilus supplementation suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice. This was confirmed in orthotopic allografts and germ-free tumourigenesis mice. L.a CM inhibited the growth of NAFLD-HCC human cells and mouse organoids. The protective function of L. acidophilus was attributed to its non-protein small molecules. By metabolomic profiling, valeric acid was the top enriched metabolite in L.a CM and its upregulation was verified in liver and portal vein of L. acidophilus-treated mice. The protective function of valeric acid was demonstrated in NAFLD-HCC human cells and mouse organoids. Valeric acid significantly suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice, accompanied by improved intestinal barrier integrity. This was confirmed in another NAFLD-HCC mouse model induced by CDHF diet and DEN. Mechanistically, valeric acid bound to hepatocytic surface receptor GPR41/43 to inhibit Rho-GTPase pathway, thereby ablating NAFLD-HCC. INTERPRETATION: L. acidophilus exhibits anti-tumourigenic effect in mice by secreting valeric acid. Probiotic supplementation is a potential prophylactic of NAFLD-HCC. FUNDING: Shown in Acknowledgments.

The genome of oil-Camellia and population genomics analysis provide insights into seed oil domestication.

BACKGROUND: As a perennial crop, oil-Camellia possesses a long domestication history and produces high-quality seed oil that is beneficial to human health. Camellia oleifera Abel. is a sister species to the tea plant, which is extensively cultivated for edible oil production. However, the molecular mechanism of the domestication of oil-Camellia is still limited due to the lack of sufficient genomic information. RESULTS: To elucidate the genetic and genomic basis of evolution and domestication, here we report a chromosome-scale reference genome of wild oil-Camellia (2.95 Gb), together with transcriptome sequencing data of 221 cultivars. The oil-Camellia genome, assembled by an integrative approach of multiple sequencing technologies, consists of a large proportion of repetitive elements (76.1%) and high heterozygosity (2.52%). We construct a genetic map of high-density corrected markers by sequencing the controlled-pollination hybrids. Genome-wide association studies reveal a subset of artificially selected genes that are involved in the oil biosynthesis and phytohormone pathways. Particularly, we identify the elite alleles of genes encoding sugar-dependent triacylglycerol lipase 1, ß-ketoacyl-acyl carrier protein synthase III, and stearoyl-acyl carrier protein desaturases; these alleles play important roles in enhancing the yield and quality of seed oil during oil-Camellia domestication. CONCLUSIONS: We generate a chromosome-scale reference genome for oil-Camellia plants and demonstrate that the artificial selection of elite alleles of genes involved in oil biosynthesis contributes to oil-Camellia domestication.

The incidence of psoriasis among smokers and/or former smokers inflammatory bowel diseases patients treated with tumor necrosis factor antagonist: A systematic review and meta-analysis.

BACKGROUND: Infliximab (IFX) and adalimumab (ADA) refer to the classic drugs to treat moderate-severe inflammatory bowel disease (IBD), which have been proven to be effective to control IBD. However, the side effects exerted by IFX and ADA should be monitored in therapies, especially the paradoxical reaction of the skin system (e.g., psoriasis). Psoriasis is recognized as the most common skin lesion, capable of significantly affecting the quality of patients' life. METHODS: This study searched literatures published in English language with the qualifications on PubMed, Embase, Web of Science, Google, and Geenmedical databases. Over 2 co-authors assessed the quality of the articles and extracted the data independently. The data acquired were statistically analyzed with the statistical software of Revman and Stata. RESULTS: The ADA Group achieved a higher incidence of psoriasis (odds ratio [OR] = 0.658, 95% confidence interval [CI] [0.471-0.919]); Females achieved a higher incidence of psoriasis than males (OR = 1.941, 95%CI [1.326-2.843], P < .05); Smoking up-regulated the incidence of psoriasis (OR = 1.679, 95%CI [1.237-2.279], P < .05); The interval of medication was over 1 year, and the interval of medication applying IFX was longer than that of the ADA Group; most cases could be relieved by using local hormone, phototherapy, or systemic hormone therapy under the strategy of biological agents. CONCLUSIONS: The frequency of reported in IBD exceeds those of other autoimmune diseases, and the ADA treatment for IBD is safer than IFX. Psoriasis is more common in females than in males. Smoking refers to one of risk factors of psoriasis.

Convolutional neural network for hyperspectral data analysis and effective wavelengths selection.

Fusion of spectral and spatial information has been proved to be an effective approach to improve model performance in near-infrared hyperspectral data analysis. Regardless, most of the existing spectral-spatial classification methods require fairly complex pipelines and exact selection of parameters, which mainly depend on the investigator's experience and the object under test. Convolutional neural network (CNN) is a powerful tool for representing complicated data and usually works with few "hand-engineering", making it an appropriate candidate for developing a general and automatic approach. In this paper, a two-branch convolutional neural network (2B-CNN) was developed for spectral-spatial classification and effective wavelengths (EWs) selection. The proposed network was evaluated by three classification data sets, including herbal medicine, coffee bean and strawberry. The results showed that the 2B-CNN obtained the best classification accuracies (96.72% in average) when compared with support vector machine (92.60% in average), one dimensional CNN (92.58% in average), and grey level co-occurrence matrix based support vector machine (93.83% in average). Furthermore, the learned weights of the two-dimensional branch in 2B-CNN were adopted as the indicator of EWs and compared with the successive projections algorithm. The 2B-CNN models built with wavelengths selected by the weight indicator achieved the best accuracies (96.02% in average) among all the examined EWs models. Different from the conventional EWs selection method, the proposed algorithm works without any additional retraining and has the ability to comprehensively consider the discriminative power in spectral domain and spatial domain.

The drivers of bacterial community underlying biogeographical pattern in Mollisol area of China.

In order to better understand the composition and driving factors of the bacterial community in Mollisols, we selected 9 representative facility agricultural lands in Mollisol area of China for sampling, and described it on a larger spatial scale. Soil bacterial community structure in these 9 regions (determined by high-throughput sequencing analysis) showed significant differences at the genus level. The correlation between bacterial community composition and soil properties, contaminants and geographical latitude showed that the diversity of bacterial community was still strongly correlated with pH and SOM under the influence of phthalates (P < 0.05). Principal component Analysis (PCA) showed that soil properties (i.e. pH, organic matter, stacking density, the content of nitrogen, potassium, phosphorus) and PAEs level rather than geographic latitude were main drivers of differences in bacterial community structure. These factors account for 73.04% of the total variation of the bacterial community. Among them, PAEs act as a typical pollutant is the main factor driving the composition of bacterial community in facility agriculture Mollisols. This shows that PAEs is a potential pollution risk factor, which has important guiding significance for the sustainable and healthy development of agriculture in Mollisol area.

Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display.

BACKGROUND: Extracellular vesicles (EVs) and exosomes are nano-sized, membrane-bound vesicles shed by most eukaryotic cells studied to date. EVs play key signaling roles in cellular development, cancer metastasis, immune modulation and tissue regeneration. Attempts to modify exosomes to increase their targeting efficiency to specific tissue types are still in their infancy. Here we describe an EV membrane anchoring platform termed "cloaking" to directly embed tissue-specific antibodies or homing peptides on EV membrane surfaces ex vivo for enhanced vesicle uptake in cells of interest. The cloaking system consists of three components: DMPE phospholipid membrane anchor, polyethylene glycol spacer and a conjugated streptavidin platform molecule, to which any biotinylated molecule can be coupled for EV decoration. RESULTS: We demonstrate the utility of membrane surface engineering and biodistribution tracking with this technology along with targeting EVs for enhanced uptake in cardiac fibroblasts, myoblasts and ischemic myocardium using combinations of fluorescent tags, tissue-targeting antibodies and homing peptide surface cloaks. We compare cloaking to a complementary approach, surface display, in which parental cells are engineered to secrete EVs with fusion surface targeting proteins. CONCLUSIONS: EV targeting can be enhanced both by cloaking and by surface display; the former entails chemical modification of preformed EVs, while the latter requires genetic modification of the parent cells. Reduction to practice of the cloaking approach, using several different EV surface modifications to target distinct cells and tissues, supports the notion of cloaking as a platform technology.

Identifying the subfamilies of voltage-gated potassium channels using feature selection technique.

Voltage-gated K+ channel (VKC) plays important roles in biology procession, especially in nervous system. Different subfamilies of VKCs have different biological functions. Thus, knowing VKCs' subfamilies has become a meaningful job because it can guide the direction for the disease diagnosis and drug design. However, the traditional wet-experimental methods were costly and time-consuming. It is highly desirable to develop an effective and powerful computational tool for identifying different subfamilies of VKCs. In this study, a predictor, called iVKC-OTC, has been developed by incorporating the optimized tripeptide composition (OTC) generated by feature selection technique into the general form of pseudo-amino acid composition to identify six subfamilies of VKCs. One of the remarkable advantages of introducing the optimized tripeptide composition is being able to avoid the notorious dimension disaster or over fitting problems in statistical predictions. It was observed on a benchmark dataset, by using a jackknife test, that the overall accuracy achieved by iVKC-OTC reaches to 96.77% in identifying the six subfamilies of VKCs, indicating that the new predictor is promising or at least may become a complementary tool to the existing methods in this area. It has not escaped our notice that the optimized tripeptide composition can also be used to investigate other protein classification problems.

[Research of origin and ethnopharmacological uses of mineral medicine Halitum].

OBJECTIVE: To study the origin and ethnopharmacological uses of mineral medicine Halitum. METHOD: The historical literature and results of the modern researches were searched and on-the-spot investigation was also carried out. RESULT: The result showed that characteristics and function and uses of Halitum mentioned in historical literature and results of the modern researches were mostly coincident. However there were also some problems, which needed to explore further. CONCLUSION: With the development of mineral materials research and utilization, Halitum sources should be defined more clearly and scientifically.

[Study on expression of curcin gene cloned from Jatropha curcas in Escherichia coli].

OBJECTIVE: To construct mature protein curcin gene prokaryotic expression vectors in Escherichia coli and choose the optimal inducing condition of the recombinant strains. METHOD: The gene encoding of curcin was amplified from the genome of Jatropha curcas seeds by PCR and cloned into the expression vectors pQE-30 and pET-32 obtaining recombinant vectors pQE-R and pET-R respectively. The two vectors were transferred into E. coli BL21 (DE3) and the recombinant strains PRM and PRB were attained respectively. PRM and PRB were induced by different revulsants and under different temperature and time. RESULT: The gene encoding of mature protein curcin was amplified by PCR and the recombinant strains PRM and PRB were obtained. CONCLUSION: The results showed that PRB could not produce recombinant protein under such conditions. However, PRM could highly produce recombinant protein induced by 0.5 mmol x L(-1) IPTG at 28 degrees C for 6 h.

Expression, purification and anti-tumor activity of curcin.

Curcin, purified from the seeds of Jatropha curcas, can be used as a cell-killing agent. Understanding the anti-tumor activity of the recombinant protein of curcin is important for its application in clinical medicine. The segment encoding the mature protein of curcin was inserted into Escherichia coli strain M15, and the recombinant strain was induced to express by isopropyl-beta-D-thiogalactopyranoside at a concentration of 0.5 mM. The recombinant protein was expressed in the form of inclusion bodies and purified by Ni-NTA affinity chromatography. The target protein was incubated with the tumor cells at different concentrations for different times and the results demonstrated that the target protein could inhibit the growth of tumor cells (NCL-H446, SGC-7901 and S180) at 5 microg/ml.

Murine auditory brainstem evoked response: putative two-channel differentiation of peripheral and central neural pathways.

Standard noninvasive recordings of the auditory brainstem evoked response (ABR) from a single pair of obliquely oriented electrodes (typically midline vertex referenced to mastoid) confound inherently distinct signals propagating over peripheral and central neural pathways differing in location and spatial orientation. We describe here a technique for recording short-latency auditory evoked potentials that putatively differentiates peripheral and central neural activity in the mouse and rat. The technique involves recording from two orthogonally oriented electrode pairs using fast sample rates (100 k/s) to accurately measure differences in neural timing and waveform morphology. Electrodes oriented in a transverse plane (mastoid-to-mastoid) register an initial positive-going ABR peak (P1T) earlier than a series of peaks recorded from electrodes oriented along the midline (anterior and posterior to the inter-aural line). The absolute P1T latency is consistent with an origin in the primary auditory nerve, while the delayed midline latencies implicate activity farther along central neural pathways. Differences between these latencies (midline minus transverse) provide new and precise measures of central conduction time (CCT), which in one case is as brief as 0.10 ms. Results in wild type (WT) and knockout (KO) mice, as well as rats, show significant differences in absolute latencies as well as CCT.