Genome-Wide Identification and Evolutionary Analysis of Receptor-like Kinase Family Genes Provides Insights into Anthracnose Resistance of Dioscorea alata.

Dioscorea alata, commonly known as "greater yam", is a vital crop in tropical and subtropical regions of the world, yet it faces significant threats from anthracnose disease, mainly caused by Colletotrichum gloeosporioides. However, exploring disease resistance genes in this species has been challenging due to the difficulty of genetic mapping resulting from the loss of the flowering trait in many varieties. The receptor-like kinase (RLK) gene family represents essential immune receptors in plants. In this study, genomic analysis revealed 467 RLK genes in D. alata. The identified RLKs were distributed unevenly across chromosomes, likely due to tandem duplication events. However, a considerable number of ancient whole-genome or segmental duplications dating back over 100 million years contributed to the diversity of RLK genes. Phylogenetic analysis unveiled at least 356 ancient RLK lineages in the common ancestor of Dioscoreaceae, which differentially inherited and expanded to form the current RLK profiles of D. alata and its relatives. The analysis of cis-regulatory elements indicated the involvement of RLK genes in diverse stress responses. Transcriptome analysis identified RLKs that were up-regulated in response to C. gloeosporioides infection, suggesting their potential role in resisting anthracnose disease. These findings provide novel insights into the evolution of RLK genes in D. alata and their potential contribution to disease resistance.

Aqueous Developable and CO2-Sourced Chemical Amplification Photoresist with High Performance.

Seeking high-performance photoresist is an important item for semiconductor industry due to the continuous miniaturization and intelligentization of integrated circuits. Polymer resin containing carbonate group has many desirable properties, such as high transmittance, acid sensitivity and chemical formulation, thus serving as potential photoresist material. In this work, a series of aqueous developable CO2-sourced polycarbonate (CO2-PC) were produced via alternating copolymerization of CO2 and epoxides bearing acid-cleavable cyclic acetal groups in the presence of tetranuclear organoborane catalyst. The produced CO2-PCs were investigated as chemical amplification resists in deep ultraviolet (DUV) lithography. Under the catalysis of photoacid, the acetal (ketal) groups in CO2-PC were hydrolysed into two equivalents of hydroxyl groups, which changes the exposed areas from hydrophobicity to hydrophilicity, thus enabling the exposed regions to be developed in water. Through normalized remaining thickness analysis, the optimal CO2-derived resist achieved a remarkable sensitivity of 1.9 mJ/cm2, a contrast of 7.9, a favorable resolution (750 nm, half pitch), and etching resistance (38% higher than poly(tert-butyl acrylate)). Such performances outperforming commercial KrF and ArF chemical amplification resists (i.e., polyhydroxystyrene-derived and polymethacrylate-based resists), which endows broad application prospects in the field of DUV (248 nm and 193 nm) and extreme ultraviolet (EUV) lithography and nanomanufacturing.

A Lateral Flow-Recombinase Polymerase Amplification Method for Colletotrichum gloeosporioides Detection.

The greater yam (Dioscorea alata), a widely cultivated and nutritious food crop, suffers from widespread yield reduction due to anthracnose caused by Colletotrichum gloeosporioides. Latent infection often occurs before anthracnose phenotypes can be detected, making early prevention difficult and causing significant harm to agricultural production. Through comparative genomic analysis of 60 genomes of 38 species from the Colletotrichum genus, this study identified 17 orthologous gene groups (orthogroups) that were shared by all investigated C. gloeosporioides strains but absent from all other Colletotrichum species. Four of the 17 C. gloeosporioides-specific orthogroups were used as molecular markers for PCR primer designation and C. gloeosporioides detection. All of them can specifically detect C. gloeosporioides out of microbes within and beyond the Colletotrichum genus with different sensitivities. To establish a rapid, portable, and operable anthracnose diagnostic method suitable for field use, specific recombinase polymerase amplification (RPA) primer probe combinations were designed, and a lateral flow (LF)-RPA detection kit for C. gloeosporioides was developed, with the sensitivity reaching the picogram (pg) level. In conclusion, this study identified C. gloeosporioides-specific molecular markers and developed an efficient method for C. gloeosporioides detection, which can be applied to the prevention and control of yam anthracnose as well as anthracnose caused by C. gloeosporioides in other crops. The strategy adopted by this study also serves as a reference for the identification of molecular markers and diagnosis of other plant pathogens.

Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging.

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

Deep Learning-Assisted Spectrum-Structure Correlation: State-of-the-Art and Perspectives.

Spectrum-structure correlation is playing an increasingly crucial role in spectral analysis and has undergone significant development in recent decades. With the advancement of spectrometers, the high-throughput detection triggers the explosive growth of spectral data, and the research extension from small molecules to biomolecules accompanies massive chemical space. Facing the evolving landscape of spectrum-structure correlation, conventional chemometrics becomes ill-equipped, and deep learning assisted chemometrics rapidly emerges as a flourishing approach with superior ability of extracting latent features and making precise predictions. In this review, the molecular and spectral representations and fundamental knowledge of deep learning are first introduced. We then summarize the development of how deep learning assist to establish the correlation between spectrum and molecular structure in the recent 5 years, by empowering spectral prediction (i.e., forward structure-spectrum correlation) and further enabling library matching and de novo molecular generation (i.e., inverse spectrum-structure correlation). Finally, we highlight the most important open issues persisted with corresponding potential solutions. With the fast development of deep learning, it is expected to see ultimate solution of establishing spectrum-structure correlation soon, which would trigger substantial development of various disciplines.

Unraveling the Molecular Basis of Color Variation in Dioscorea alata Tubers: Integrated Transcriptome and Metabolomics Analysis.

Dioscorea alata L. (Dioscoreaceae) is a widely cultivated tuber crop with variations in tuber color, offering potential value as health-promoting foods. This study focused on the comparison of D. alata tubers possessing two distinct colors, white and purple, to explore the underlying mechanisms of color variation. Flavonoids, a group of polyphenols known to influence plant color and exhibit antioxidant properties, were of particular interest. The total phenol and total flavonoid analyses revealed that purple tubers (PTs) have a significantly higher content of these metabolites than white tubers (WTs) and a higher antioxidant activity than WTs, suggesting potential health benefits of PT D. alata. The transcriptome analysis identified 108 differentially expressed genes associated with the flavonoid synthesis pathway, with 57 genes up-regulated in PTs, including CHS, CHI, DFR, FLS, F3H, F3'5'H, LAR, ANS, and ANR. The metabolomics analysis demonstrated that 424 metabolites, including 104 flavonoids and 8 tannins, accumulated differentially in PTs and WTs. Notably, five of the top ten up-regulated metabolites were flavonoids, including 6-hydroxykaempferol-7-O-glucoside, pinocembrin-7-O-(6″-O-malonyl)glucoside, 6-hydroxykaempferol-3,7,6-O-triglycoside, 6-hydroxykaempferol-7-O-triglycoside, and cyanidin-3-O-(6″-O-feruloyl)sophoroside-5-O-glucoside, with the latter being a precursor to anthocyanin synthesis. Integrating transcriptome and metabolomics data revealed that the 57 genes regulated 20 metabolites within the flavonoid synthesis pathway, potentially influencing the tubers' color variation. The high polyphenol content and antioxidant activity of PTs indicate their suitability as nutritious and health-promoting food sources. Taken together, the findings of this study provide insights into the molecular basis of tuber color variation in D. alata and underscore the potential applications of purple tubers in the food industry and human health promotion. The findings contribute to the understanding of flavonoid biosynthesis and pigment accumulation in D. alata tubers, opening avenues for future research on enhancing the nutritional quality of D. alata cultivars.

Patch-Based Convolutional Encoder: A Deep Learning Algorithm for Spectral Classification Balancing the Local and Global Information.

Molecular vibrational spectroscopies, including infrared absorption and Raman scattering, provide molecular fingerprint information and are powerful tools for qualitative and quantitative analysis. They benefit from the recent development of deep-learning-based algorithms to improve the spectral, spatial, and temporal resolutions. Although a variety of deep-learning-based algorithms, including those to simultaneously extract the global and local spectral features, have been developed for spectral classification, the classification accuracy is still far from satisfactory when the difference becomes very subtle. Here, we developed a lightweight algorithm named patch-based convolutional encoder (PACE), which effectively improved the accuracy of spectral classification by extracting spectral features while balancing local and global information. The local information was captured well by segmenting the spectrum into patches with an appropriate patch size. The global information was extracted by constructing the correlation between different patches with depthwise separable convolutions. In the five open-source spectral data sets, PACE achieved a state-of-the-art performance. The more difficult the classification, the better the performance of PACE, compared with that of residual neural network (ResNet), vision transformer (ViT), and other commonly used deep learning algorithms. PACE helped improve the accuracy to 92.1% in Raman identification of pathogen-derived extracellular vesicles at different physiological states, which is much better than those of ResNet (85.1%) and ViT (86.0%). In general, the precise recognition and extraction of subtle differences offered by PACE are expected to facilitate vibrational spectroscopy to be a powerful tool toward revealing the relevant chemical reaction mechanisms in surface science or realizing the early diagnosis in life science.

The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.

The protective effect of vagus nerve stimulation against myocardial ischemia/reperfusion injury: pooled review from preclinical studies.

Aims: Myocardial ischemia-reperfusion (I/R) injury markedly undermines the protective benefits of revascularization, contributing to ventricular dysfunction and mortality. Due to complex mechanisms, no efficient ways exist to prevent cardiomyocyte reperfusion damage. Vagus nerve stimulation (VNS) appears as a potential therapeutic intervention to alleviate myocardial I/R injury. Hence, this meta-analysis intends to elucidate the potential cellular and molecular mechanisms underpinning the beneficial impact of VNS, along with its prospective clinical implications. Methods and Results: A literature search of MEDLINE, PubMed, Embase, and Cochrane Database yielded 10 articles that satisfied the inclusion criteria. VNS was significantly correlated with a reduced infarct size following myocardial I/R injury [Weighed mean difference (WMD): 25.24, 95% confidence interval (CI): 32.24 to 18.23, p < 0.001] when compared to the control group. Despite high heterogeneity (I2 = 95.3%, p < 0.001), sensitivity and subgroup analyses corroborated the robust efficacy of VNS in limiting infarct expansion. Moreover, meta-regression failed to identify significant influences of pre-specified covariates (i.e., stimulation type or site, VNS duration, condition, and species) on the primary estimates. Notably, VNS considerably impeded ventricular remodeling and cardiac dysfunction, as evidenced by improved left ventricular ejection fraction (LVEF) (WMD: 10.12, 95% CI: 4.28; 15.97, p = 0.001) and end-diastolic pressure (EDP) (WMD: 5.79, 95% CI: 9.84; -1.74, p = 0.005) during the reperfusion phase. Conclusion: VNS offers a protective role against myocardial I/R injury and emerges as a promising therapeutic strategy for future clinical application.

1D Gradient-Weighted Class Activation Mapping, Visualizing Decision Process of Convolutional Neural Network-Based Models in Spectroscopy Analysis.

Being characterized by the self-adaption and high accuracy, the deep learning-based models have been widely applied in the 1D spectroscopy-related field. However, the "black-box" operation and "end-to-end" working style of the deep learning normally bring the low interpretability, where a reliable visualization is highly demanded. Although there are some well-developed visualization methods, such as Class Activation Mapping (CAM) and Gradient-weighted Class Activation Mapping (Grad-CAM), for the 2D image data, they cannot correctly reflect the weights of the model when being applied to the 1D spectral data, where the importance of position information is not considered. Here, aiming at the visualization of Convolutional Neural Network-based models toward the qualitative and quantitative analysis of 1D spectroscopy, we developed a novel visualization algorithm (1D Grad-CAM) to more accurately display the decision-making process of the CNN-based models. Different from the classical Grad-CAM, with the removal of the gradient averaging (GAP) and the ReLU operations, a significantly improved correlation between the gradient and the spectral location and a more comprehensive spectral feature capture were realized for 1D Grad-CAM. Furthermore, the introduction of difference (purity or linearity) and feature contribute in the CNN output in 1D Grad-CAM achieved a reliable evaluation of the qualitative accuracy and quantitative precision of CNN-based models. Facing the qualitative and adulteration quantitative analysis of vegetable oils by the combination of Raman spectroscopy and ResNet, the visualization by 1D Grad-CAM well reflected the origin of the high accuracy and precision brought by ResNet. In general, 1D Grad-CAM provides a clear vision about the judgment criterion of CNN and paves the way for CNN to a broad application in the field of 1D spectroscopy.

Responses of microbial community and antibiotic resistance genes to co-existence of chloramphenicol and salinity.

In recent years, the risk from environmental pollution caused by chloramphenicol (CAP) has emerged as a serious concern worldwide, especially for the co-selection of antibiotic resistance microorganisms simultaneously exposed to CAP and salts. In this study, the multistage contact oxidation reactor (MCOR) was employed for the first time to treat the CAP wastewater under the co-existence of CAP (10-80 mg/L) and salinity (0-30 g/L NaCl). The CAP removal efficiency reached 91.7% under the co-existence of 30 mg/L CAP and 10 g/L NaCl in the influent, but it fluctuated around 60% with the increase of CAP concentration and salinity. Trichococcus and Lactococcus were the major contributors to the CAP and salinity shock loads. Furthermore, the elevated CAP and salinity selection pressures inhibited the spread of CAP efflux pump genes, including cmlA, tetC, and floR, and significantly affected the composition and abundance of antibiotic resistance genes (ARGs). As the potential hosts of CAP resistance genes, Acinetobacter, Enterococcus, and unclassified_d_Bacteria developed resistance against high osmotic pressure and antibiotic environment using the efflux pump mechanism. The results also revealed that shifting of potential host bacteria significantly contributed to the change in ARGs. Overall, the co-existence of CAP and salinity promoted the enrichment of core genera Trichococcus and Lactococcus; however, they inhibited the proliferation of ARGs. KEY POINTS: • Trichococcus and Lactococcus were the core bacteria related to CAP biodegradation • Co-existence of CAP and salinity inhibited proliferation of cmlA, tetC, and floR • The microorganism resisted the CAP using the efflux pump mechanism.

Using pre-operative radiomics to predict microvascular invasion of hepatocellular carcinoma based on Gd-EOB-DTPA enhanced MRI.

OBJECTIVES: We aimed to investigate the value of performing gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) radiomics for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) based on multiple sequences. METHODS: We randomly allocated 165 patients with HCC who underwent partial hepatectomy to training and validation sets. Stepwise regression and the least absolute shrinkage and selection operator algorithm were used to select significant variables. A clinicoradiological model, radiomics model, and combined model were constructed using multivariate logistic regression. The performance of the models was evaluated, and a nomogram risk-prediction model was built based on the combined model. A concordance index and calibration curve were used to evaluate the discrimination and calibration of the nomogram model. RESULTS: The tumour margin, peritumoural hypointensity, and seven radiomics features were selected to build the combined model. The combined model outperformed the radiomics model and the clinicoradiological model and had the highest sensitivity (90.89%) in the validation set. The areas under the receiver operating characteristic curve were 0.826, 0.755, and 0.708 for the combined, radiomics, and clinicoradiological models, respectively. The nomogram model based on the combined model exhibited good discrimination (concordance index = 0.79) and calibration. CONCLUSIONS: The combined model based on radiomics features of Gd-EOB-DTPA enhanced MRI, tumour margin, and peritumoural hypointensity was valuable for predicting HCC microvascular invasion. The nomogram based on the combined model can intuitively show the probabilities of MVI.

Deep Learning-Enabled Raman Spectroscopic Identification of Pathogen-Derived Extracellular Vesicles and the Biogenesis Process.

Pathogenic bacterial infections, exacerbated by increasing antimicrobial resistance, pose a major threat to human health worldwide. Extracellular vesicles (EVs), secreted by bacteria and acting as their "long-distance weapons", play an important role in the occurrence and development of infectious diseases. However, no efficient methods to rapidly detect and identify EVs of different bacterial origins are available. Here, label-free Raman spectroscopy in combination with a new deep learning model of the attentional neural network (aNN) was developed to identify pathogen-derived EVs at Gram±, species, strain, and even down to physiological levels. By training the aNN model with a large Raman data set from six typical pathogen-derived EVs, we achieved the identification of EVs with high accuracies at all levels: exceeding 96% at the Gram and species levels, 93% at the antibiotic-resistant and sensitive strain levels, and still above 87% at the physiological level. aNN enabled Raman spectroscopy to interrogate the bacterial origin of EVs to a much higher level than previous methods. Moreover, spectral markers underpinning EV discrimination were uncovered from subtly different EV spectra via an interpretation algorithm of the integrated gradient. A further comparative analysis of the rich Raman biochemical signatures of EVs and parental pathogens clearly revealed the biogenesis process of EVs, including the selective encapsulation of biocomponents and distinct membrane compositions from the original bacteria. This developed platform provides an accurate and versatile means to identify pathogen-derived EVs, spectral markers, and the biogenesis process. It will promote rapid diagnosis and allow the timely treatment of bacterial infections.

Corrigendum: Combination therapy with fingolimod and neural stem cells promotes functional myelination in vivo through a non-immunomodulatory mechanism.

[This corrects the article DOI: 10.3389/fncel.2019.00014.].

Granular cell tumor of the vulva: Case report and systematic review of the literature.

RATIONALE: Granular cell tumor (GCT) of the vulva is an exceptionally rare female genital tract tumor. The majority of these are benign and there are no standardized surgical techniques for the special site to reduce tension of the wound. PATIENT CONCERNS: A 47-years-old Chinese woman experienced a nodule on her right vulva with itch sometimes in late 2018. DIAGNOSES: Magnetic resonance imaging showed a high possibility of vulvar cancer. While Chest X-ray, abdominal sonography, and cystoscopy examination were unremarkable. INTERVENTIONS: The patient underwent local complete resection of vulvar tumor under general anesthesia on March 24, 2022. The resection scope was approximately 4 cm × 3 cm × 3 cm. Due to the large surgical incision, Z-plasty was performed to achieve the primary closure for decreasing wound tension and improving aesthetic reduction. OUTCOMES: The final pathological diagnosis was benign GCT of the vulva and surgical margins were uninvolved. At 8 months follow-up, no new lesions were detected. LESSONS: Surgery with negative resection margins is the mainstay for benign GCT of the vulva, while Z-plasty is appropriate for decreasing the tension of the wound and improving aesthetic reduction.

Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism.

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

Precisely Alternating Copolymerization of Episulfides and Isothiocyanates: A Practical Route to Construct Sulfur-Rich Polymers.

The development of a controlled and reliable method to construct well-defined sulfur-containing polymers has sparked great interest in polymer science. Herein, we present the trial on the copolymerization of isothiocyanates with episulfides in the presence of organic onium salts, which provides direct access to a class of sulfur-rich polymers. This methodology has combined advantages of simple operation, no metals, mild conditions (25-100 °C), controlled polymerization performance (Mn > 105 g mol-1, D < 1.3), and high reactivity (turnover frequency over 1000 h-1). The metal-free feature and versatility of the easily accessible monomers, along with fine adjustment of the final properties enable this strategy to be a feasible approach to produce sulfur-rich polymers (16 examples).

[Effects of tetrandrine on proliferation, migration, and invasion of glioblastoma cells].

Glioblastoma is the most common intracranial primary malignant tumor, which leads to the poor quality of life of patients and has a high recurrence rate. Chemotherapy is a vital part in the treatment of this disease. Tetrandrine(Tet) is an active ingredient extracted from the root of the Chinese medicinal plant Stephania tetrandra, which has been proved with a wide range of pharmacological effects including anti-tumor. However, there are few studies regarding the effect of Tet on glioma. In this study, MTT and BrdU assays were employed to detect the effect of Tet on the proliferation of LN229 glioblastoma cells; flow cytometry was used to analyze the cycle distribution and apoptosis; plate cloning assay and soft agar colony formation assay were performed to study the colony formation ability of LN229 cells exposed to Tet; scratch assay and Transwell assay were conducted to detect the ability of migration and invasion; Western blot was adopted to the exploration of the molecular mechanism. The MTT and BrdU assays showed that Tet inhibited the proliferation of LN229 cells in a time-and dose-dependent manner. The plate cloning assay and soft agar colony formation assay showed that Tet weakened the colony formation of LN229 cells in vitro; cytometry assay showed that Tet blocked cells in the G_1 phase and promoted cell apoptosis; scratch and Transwell assays proved that Tet inhibited the migration and invasion of LN229 cells; Western blot results showed that Tet down-regulated the expression levels of CDK2, CDK6, cyclin D1, cyclin E1, snail, slug, vimentin, and N-cadherin, while up-regulated the level of E-cadherin. The results indicate that Tet has a certain inhibitory effect on the proliferation, migration, and invasion of LN229 glioblastoma cells, and such effect may be related to the participation of Tet in the regulation of c-Myc/p27 axis and snail signaling pathway.

Coagulation-flocculation: a potential application for mosquito Larval Source Management (LSM).

Larval mosquitoes have a more limited home range and lower resistance to adverse environment than adults, thus can be ideal targets for vector control in some cases. Coagulation-flocculation technology, which could be used for water treatment in breeding sites of several vector mosquito species, can significantly change both the distribution of organic particles and surface sediment characteristics in water environment. The aim of this study was to explore the effect, principle and possibility of using coagulation-flocculation technology in immature mosquitoes killing. In this study, dechlorinated water was treated with Poly Aluminum Chloride (PACl, sewage treatment using), and we observed the impacts of PACl treatment on the development and survival of immature Culex pipiens pallens mosquitoes. When exposed to PACl treatment, physical effect is believed to be a main reason of coagulation-flocculation caused high larvae mortality: Ⅰ) alum floc layer increases the difficulty of larvae foraging, leads larvae starving to death; (Ⅱ) the little floc particles could attach to the lateral hair of larvae, which impede floatation process and then surface respiration by larval mosquitoes. The alum floc layer had a good killing effect on the mosquito larvae, presented the half lethal time (LT50) of 2d, the 90% lethal time (LT90) of 8.7±7.3 ∼ 14±4.5 d, and the pupation rate of 0 ∼ (6.5±0.5)%, respectively. Our results indicates alum floc, produced by PACl coagulation-flocculation, was shown to be highly active against 1st∼2nd instar larvae, the high mortality rate of immature mosquitoes as a result of physical effect. The observations suggest that coagulation-flocculation technology offers a novel potential approach to a sustainable and low-impact mosquito control method.

Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota.

Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.