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Hybrid composite materials with hierarchical structures have attracted continuing attention for their enhanced features and various applications. The new hybrid composites XW9@PDA (XW9 means Na8H[α-PW9O34], Na10[α-SiW9O34] and Na10[α-GeW9O34]; PDA means polydopamine) have been synthesized for potential sensing applications. The effect of polyoxometalates on the formation of the hybrid composites was investigated. Scanning electron microscopy (SEM) supported the obtained XW9@PDA were hierarchical microsphere. By monitoring the reaction of classical peroxidase substrate o-phenylenediamine (OPD) to form yellow 2, 3-diaminophenazine (DAB) in the presence of H2O2, the peroxidase-like activity of XW9@PDA was calculated. The results showed that XW9@PDA still keep the peroxidase-like activity and have 505.98%, 208.58% and 582.78% enhancement in intrinsic catalytic activity for PW9@PDA, SiW9@PDA and GeW9@PDA. Among the three composites, PW9@PDA showed the highest peroxidase-like activity. Therefore, PW9@PDA was applicable to the colorimetric and electrochemical sensing for H2O2.

Background: Developing the high-efficiency and low-risk small-molecule greennematocide is the key of effective control of the nematodes. Paeonol, is a naturally occurring phenolic compound, isolated from the root bark of Paeonia suffruticosa and the whole plant of Cynanchum paniculatum. Due to its crucial phenolic ketone skeleton, modern biological science research has indicated that paeonol has a wide range of biological activities. The structural modification of paeonol into paeonol carbonyl hydrazone derivatives is a potential approach for the development of novel nematodes, which showed more toxicity than paeonol. However, there are no reports on the nematicidal activity of paeonol carbonyl hydrazone derivatives to control Heterodera glycines. Results: We always endeavor to discover and develop biorational natural products-based pesticidal agents, 4 significant intermediates and 21 novel 3/5(3,5)-(di)nitro/chloropaeonol carbonyl hydrazone derivatives were prepared, and their structures well characterized by 1H NMR, HRMS, MS, and mp. Due to the steric hindrance, the substituents on the C=N double bond of all hydrazine compounds adopted E configuration. Results of nematicidal activity revealed that, among all compounds, especially 5-nitropaeonol (5) and 3,5-dinitropaeonol (7) displayed the most potent nematicidal activity H. glycines in vivo with LC50 values of 0.0323 and 0.0367 mg/mL, respectively. Conclusion: It suggested that for the 3/5(3,5)-(di)nitro/chloropaeonol carbonyl hydrazone derivatives, a nitro group introduced at C5 position of 1 was necessary for obtaining the potent compound as nematicidal agents. These preliminary results will pave the way for further modification of paeonol in the development of potential new nematicides.

In this study, we conducted a 56-d feeding trial to investigate the effects of replacing the fish oil (FO) with palm oil (PO) on the performance, tissue fatty acid (FA) composition, and mRNA levels of genes related to hepatic lipid metabolism in grouper (Epinephelus coioides). Five isolipidic (13% crude lipid) and isonitrogenous (48% CP) diets were formulated by incrementally adding PO to the control diet (25% fish meal and 9% added FO) to replace FO in the control diets. Triplicate groups of 30 groupers (initial weight: 12.6 ± 0.1 g) were fed one of the diets twice daily, to apparent satiety. The replacement of FO with 50% PO revealed maximum growth without affecting the performance and whole-body proximate compositions, and replacing FO with 100% PO revealed a comparable (P > 0.05) growth with that of the control diet, suggesting PO as a suitable alternative to FO. The analysis of FA profiles in the dorsal muscle and liver though reflected the FA profile of the diet, PO substitutions above 50% could compromise (P

Iridoviruses are DNA virus and have caused huge economic losses in the aquaculture industry. The aim of this study was to establish a colorimetric loop-mediated isothermal amplification (LAMP) protocol for the on-site detection of Singapore grouper iridovirus (SGIV). The SGIV-VP61 gene was chosen as the target gene to develop a colorimetric LAMP assay. The optimized condition of the colorimetric LAMP assay was incubation at 63 °C for 1 h. Samples infected with SGIV could be detected with the color change from yellow into pink. The sensitivity of the developed assay is 5.66 copies/μL of the viral DNA template. This sensitivity was about 1000 times higher than that of conventional PCR while it was slightly lower than the one-step semi-nested PCR assay. A total of 60 DNA samples extracted from the fin tissue of the SGIV-infected Asian seabass were examined for SGIV by colorimetric LAMP, semi-nested PCR and conventional PCR. The results of the colorimetric LAMP assay showed 94.87 % agreement with the semi-nested PCR. In addition, the DNA extraction method using NaOH showed a better performance in the colorimetric LAMP assay. Taken together, the colorimetric LAMP established was a sensitive, rapid and specific method for the detection of SGIV. SGIV was not detected in samples randomly taken from a genetically improved line of the Asian seabass. However, some seabass obtained from the local markets were found to contain SGIV. Thus, the LAMP assay has the potential application in the diagnosis of iridovirus diseases in the aquaculture industry.

The pollution of aluminum (Al) in agricultural production and its wide application in food processing greatly increase the chance of human and animal exposure. Al can accumulate in bone and cause bone diseases by inducing oxidative stress. Mitophagy can maintain normal cell function by degrading damaged mitochondria and scavenging reactive oxygen species. However, the role of mitophagy in the bone impairment caused by Al is unknown. In this study, we demonstrated that PTEN induced putative kinase 1 (PINK1)/ E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy was activated in the bone impairment caused by Al in vivo. Then, the Al-induced mitophagy in Parkin-deficient mice and MC3T3-E1 cells were decreased. Meanwhile, Parkin deficiency exacerbated the bone impairment, mitochondrial damage, and oxidative stress under Al exposure, both in vivo and in vitro. In general, the results reveal that Al exposure can activate PINK1/Parkin-mediated mitophagy, and the PINK1/Parkin-mediated mitophagy plays a protective role in the bone impairment caused by Al.

Sarcoma is a rare and an extremely aggressive form of cancer that originates from mesenchymal cells. Pyroptosis exerts a dual effect on tumours by inhibiting tumour cell proliferation while creating a microenvironment suitable for tumour cell development and proliferation. However, the significance of pyroptosis-related gene (PRG) expression in sarcoma has not yet been evaluated. Here, we conduct a retrospective analysis to examine PRG expression in 256 sarcoma samples from The Cancer Genome Atlas database. We identified the PRGs that had a significant correlation with overall patient survival in sarcoma by performing a univariate Cox regression analysis. Subsequently, we conducted a LASSO regression analysis and created a risk model for a six-PRG signature. As indicated from the Kaplan–Meier analysis, this signature revealed a significant difference between high- and low-risk sarcoma patients. A receiver operating characteristic curve analysis confirmed that this signature could predict overall patient survival in sarcoma patients with high sensitivity and specificity. Gene ontology annotation and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses revealed that five independent PRGs were closely associated with increased immune activity. Moreover, we also deciphered that increased number of immune cells infiltrated the tumour microenvironment in sarcoma. In brief, the PRG signature can effectively act as novel prognostic biomarker for sarcoma patients and is associated with the tumour immune microenvironment.

The circRNAs, a new subclass of non-coding RNAs that are catalyzed by RNA-binding proteins (RBPs), have been reported to be associated with the progression of multiple types of cancer. We previously discovered that heterogeneous nuclear ribonucleoprotein L (HnRNP-L), a multi-functional RBP, is associated with pro-proliferation and anti-apoptosis activities in prostate tumor cells. In this study, we aim to establish the biological relevance of circCSPP1 (a newly discovered signature circRNA in prostate cancer [PCa]) and HnRNP-L to prostate cancer progression. First, we demonstrated that circCSPP1 expression was higher in prostate cancer tissues than in benign tissues and higher in prostate cancer cells than in benign cells. Then, the in vitro gain- and loss-of-function experiments showed that the circCSPP1 expression in prostate cancer cells was regulated by HnRNP-L, and the increased circCSPP1 significantly induced autophagy, which led to an enhanced potential in proliferation, migration, and invasion of prostate cancer cells. These results were consistent with the in vivo experiment where increased or decreased circCSPP1 was associated with higher or slower growth rate in grafted tumors. Finally, we demonstrated the potential competing endogenous RNA network, involving circCSPP1, miR-520h, and early growth response factor 1 (EGR1), in prostate cancer cells, which may play an important role in prostate cancer progression. Our study indicated that the increase in circCSPP1 in prostate cancer, which may be catalyzed by HnRNP-L, can induce cellular autophagy through the circCSPP1-miR-520h-EGR1 axis, leading to the progression of prostate tumor. This newly discovered circRNA biomarker may be used for clinical prognosis of prostate cancer as well as for development of novel therapy plans.

Soybean (Glycine max (L.) Merri) is a short-day, photoperiod-sensitive crop. The vegetative growth period (V), reproductive growth period (R), whole growth period (V + R) and the ratio of growth period structure (R/V) are photoperiod traits critical to adaptability and yield in soybean. To thoroughly dissect the genetic basis of these growth period traits and their correlations, a panel of 277 soybean accessions were genotyped with a single nucleotide polymorphisms (SNPs) chip and phenotyped at three field environments over three years. A genome-wide association study found 29 SNPs on fifteen chromosomes with 33 significant marker-trait associations, eleven, eight, four and ten for V, R, V + R and R/V, respectively. Two SNPs, Map-6077 and − 6502, showed pleiotropy in three and two traits, respectively. Map-6077, associated with V, R, and V + R, was a synonymous SNP of the GmMFT, a member of PEBP family that has been reported to inhibit seed germination and regulate oil content. These results provide candidate SNP markers and genes for further functional experiments to advance molecular marker-assisted breeding.

Laurencia undulata, as one of the most biologically active species in the genus Laurencia, is an edible folk herb red algae. Among them, d-isofloridoside (DIF, 940.68 Da) is isolated from Laurencia undulata, which has antioxidant and matrix metalloproteinases (MMP) inhibitory activities. However, its mechanism of action on tumor angiogenesis has not yet been reported. In this study, we have studied the mechanism of DIF on tumor metastasis and angiogenesis in HT1080 cell and human vascular endothelial cell (HUVEC). The results show that DIF can reduce the activity of MMP-2/9, and can inhibit the expression of hypoxia-inducible factor-1α (HIF-1α) by regulating the downstream PI3K/AKT and mitogen-activated protein kinases (MAPK) pathways, thereby down-regulating the production of vascular endothelial growth factor (VEGF) in CoCl2-induced HT1080 cell. In addition, DIF can inhibit the activation of VEGF receptor (VEGFR-2), regulate downstream PI3K/AKT, MAPK, nuclear factor-kappa B (NF-κB) signal pathways, activate apoptosis, and thus down-regulate the production of platelet-derived growth factor (PDGF) in VEGF-induced HUVEC. In conclusion, our research shows that DIF has the potential to develop into a tumor-preventing functional food and tumor angiogenesis inhibitor, and it can provide theoretical guidance for the high-value comprehensive utilization of edible red algae Laurencia undulata.

Background: Cadmium (Cd) is among the most toxic metals and is widely distributed in aquatic environments. Objective: Histopathological lesions and biochemical indices can be used to reflect the toxic effects of cadmium in fish target organs. Methods: In the present study, the common carp Cyprinus carpio was exposed to 0.5 mg/L of CdCl2 for 21 days. Histopathological analyses were performed in the spleen, liver, kidney, gills and head kidney tissues of C. carpio, and tissue sections were stained with hematoxylin-eosin (HE) and observed under an optical microscope. The acid phosphatase, alkaline phosphatase, and lysozyme activities were determined. Results: The results showed that there were various pathological changes in five major tissues of C. carpio. The kidney, gills, and liver were the most affected organs during cadmium exposure, and deformation and disorganization of epithelial cells, vacuolization formation, serious hemorrhages and necrosis were also observed. In addition, 0.5 mg/L cadmium exposure significantly increased serum lysozyme and acid phosphatase activities and inhibited alkaline phosphatase activity. The present study showed that cadmium stress causes significant pathological tissue changes and influences lysozyme, acid phosphatase and alkaline phosphatase activities in C. carpio. Acid phosphatase and lysozyme activities are sensitive to cadmium. Conclusion: In conclusion, the toxicity of cadmium caused varying degrees of pathological and biochemical changes in fish tissues in C. carpio.

Transcriptional downregulation is widely used for metabolic flux control. Here, marO, a cis-element of Escherichia coli mar operator, was explored to engineer promoters of Saccharomyces cerevisiae for downregulation. First, the ADH1 promoter (PADH1) and its enhanced variant PUADH1 were engineered by insertion of marO into different sites, which resulted in decrease in both gfp5 transcription and GFP fluorescence intensity to various degrees. Then, marO was applied to engineer the native ERG1 and ERG11 promoters due to their importance for accumulation of value-added intermediates squalene and lanosterol. Elevated squalene content (4.9-fold) or lanosterol content (4.8-fold) and 91 or 28% decrease in ergosterol content resulted from the marO-engineered promoter PERG1(M5) or PERG11(M3), respectively, indicating the validity of the marO-engineered promoters in metabolic flux control. Furthermore, squalene production of 3.53 g/L from cane molasses, a cheap and bulk substrate, suggested the cost-effective and promising potential for squalene production.

Optineurin (OPTN) has important functions in diverse biological processes and diseases, but its effect on dendritic cell (DC) differentiation and functionality remains elusive. Here we show that OPTN is upregulated in human and mouse DC maturation, and that deletion of Optn in mice via CD11c-Cre attenuates DC maturation and impairs the priming of CD4+ T cells, thus ameliorating autoimmune symptoms such as experimental autoimmune encephalomyelitis (EAE). Mechanistically, OPTN binds to the JH1 domain of JAK2 and inhibits JAK2 dimerization and phosphorylation, thereby preventing JAK2-STAT3 interaction and inhibiting STAT3 phosphorylation to suppress downstream transcription of IL-10. Without such a negative regulation, Optn-deficient DCs eventually induce an IL-10/JAK2/STAT3/IL-10 positive feedback loop to suppress DC maturation. Finally, the natural product, Saikosaponin D, is identified as an OPTN inhibitor, effectively inhibiting the immune-stimulatory function of DCs and the disease progression of EAE in mice. Our findings thus highlight a pivotal function of OPTN for the regulation of DC functions and autoimmune disorders., Optineurin (OPTN) has been implicated in various biological processes, but its function in dendritic cells (DC) maturation is still unclear. Here the authors show, by characterizing Optn-conditional knockout mice, that the loss of OPTN induces Jak2/Stat3 activation and IL-10 production to suppress DC maturation and function, thereby ameliorating autoimmune responses in mice.

To evaluate the protective role of lycopene (LYC) against aflatoxin B1 (AFB1)-induced erythrocyte dysfunction and oxidative stress, male kunming mice were treated with LYC (5 mg/kg) and/or AFB1 (0.75 mg/kg) by intragastric administration for 30 d. Hematological indices were detected to assess erythrocyte function. The erythrocytes C3b receptor rate (E-C3bRR) and erythrocytes C3b immune complex rosette rate (E-ICRR) were detected to assess erythrocyte immune function. Hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents and superoxide dismutase (SOD) and catalase (CAT) activities were determined to evaluate erythrocyte oxidative stress. The results showed that LYC administration significantly relieved AFB1-induced erythrocyte dysfunction by increasing the levels of red blood cell count (RBC), hemoglobin (HGB) and hematocrit (HCT), as well as reducing red blood cell volume distribution width (RDW) level, while the levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and mean platelet volume (MPV) had no significant differences among the four groups. Besides, LYC ameliorated AFB1-induced erythrocyte immune dysfunction by increasing E-C3bRR and decreasing E-ICRR. Furthermore, LYC also alleviated AFB1-induced erythrocyte oxidative stress by decreasing H2O2 and MDA contents and increasing SOD and CAT activities. These results indicated that LYC protected against AFB1-induced erythrocyte dysfunction and oxidative stress in mice. The findings could lead a possible therapeutics for the management of AFB1-induced erythrocyte toxicity.

Escherichia coli infections can result in lung injury, which may be closely linked to the induction of interferon secretion. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is one of most important pathways that regulate interferon production. Thus, the present study aimed to dissect whether E. coli infections can regulate interferon production and the underlying mechanisms. For this aim, two lung cell lines, a human bronchial epithelial cell line transformed with Ad12-SV40 2B (BEAS-2b) and a human fetal lung fibroblast (HFL1) cell line, were used. The effects of E. coli infections on interferon production were studied using qRT-PCR, Western blot, and siRNA knockdown assays. E. coli infections remarkably promoted the expression levels of IFN-α, IFN-β, and ISGs. Major components of the JAK/STAT pathway, including JAK1, STAT1, and STAT2, were demonstrated to be regulated by E. coli infections. Importantly, knockdown of JAK1, STAT1, and STAT2 abolished the induction of IFN-α, IFN-β, and ISGs by E. coli. Therefore, experiments in the present study demonstrated that E. coli infections remarkably promoted interferon production in lung cells, which was closely regulated by the JAK/STAT signaling pathway. The findings in the present study are useful for further understanding the pathogenesis of E. coli infections in the lung and finding novel therapies to treat E. coli-induced lung injury.

BackgroundThis study aimed to explore the potential regulatory mechanisms of brain metastasis and to identify novel underlying targets of lung cancer with brain metastasis.MethodsExosomes were isolated from the plasma of lung cancer patients with or without brain metastasis and low or high metastatic lung cancer cells, and small RNA from plasma-derived exosomes were sequenced. Differentially expressed miRNAs (DE-miRNAs) were identified. Human brain microvascular endothelial cells (HBMECs) were transfected with miR-550a-3-5p mimics or inhibitors and exosomes. Cell viability, migration, and apoptosis/cycle were determined using Cell Counting Kit-8 (CCK-8), Transwell, and flow cytometry, respectively. Western blotting was used to measure the expression of the associated proteins. Finally, a dual-luciferase reporter gene assay was performed to confirm the miR-550a-3-5p target.ResultsTransmission electron microscopy, NanoSight, and western blotting showed that exosomes were successfully isolated and cell-derived exosomes could be taken up by HBMECs. Sequencing identified 22 DE-miRNAs which were enriched in the MAPK, chemokine, PPAR, and Wnt signaling pathways. MiR-550a-3-5p was significantly enriched in brain metastatic exosomes. Cellular experiments showed that miR-550a-3-5p and exosome enrichment significantly inhibited cell viability and migration, promoted apoptosis, and regulated the cell cycle of HBMECs compared with the controls (P P ConclusionOur results indicate that miR-550a-3-5p and YAP1 may be novel potential targets for controlling brain metastasis.

While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA - comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA - language correlations, while sex had a moderating effect on the FA - comprehension correlation of the arcuate fasciculus, and age influenced the FA - naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.

Colibactin is synthesized by a 54-kb genomic island, leads to toxicity in eukaryotic cells, and plays a vital role in many diseases, including neonatal sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is speculated to be an armory of extraintestinal pathogenic Escherichia coli and can be a potential zoonotic bacterium that threatens human and animal health. In this study, the APEC XM meningitis mouse model was successfully established to investigate the effect of colibactin in in vivo infection. The clbH-deletion mutant strain induced lower γ-H2AX expression, no megalocytosis, and no cell cycle arrest in bEnd.3 cells, which showed that the deletion of clbH decreased the production of colibactin in the APEC XM strain. The deletion of clbH did not affect the APEC XM strain’s ability of adhering to and invading bEnd.3 cells. In vitro, the non-colibactin-producing strain displayed significantly lower serum resistance and it also induced a lower level of cytokine mRNA and few disruptions of tight junction proteins in infected bEnd.3 cells. Meningitis did not occur in APEC ΔclbH-infected mice in vivo, who showed fewer clinical symptoms and fewer lesions on radiological and histopathological analyses. Compared with the APEX XM strain, APEC ΔclbH induced lower bacterial colonization in tissues, lower mRNA expression of cytokines in brain tissues, and slight destruction of the brain blood barrier. These results indicate that clbH is a necessary component for the synthesis of genotoxic colibactin, and colibactin is related to the development of meningitis induced by APEC XM.

Background Ischemic heart disease and the resulting heart failure continue to carry high morbidity and mortality, and a breakthrough in our understanding of this disorder is needed. The adult spiny mouse (Acomys cahirinus) has evolved the remarkable capacity to regenerate full-thickness skin tissue, including microvasculature and cartilage, without fibrosis or scarring. We hypothesized that lack of scarring and resulting functional regeneration also applies to the adult Acomys heart. Methods and results We compared responses of the Acomys heart to CD1 outbred Mus heart following acute left anterior descending coronary artery ligation to induce myocardial infarction. Both Acomys and Mus hearts showed decreased ejection fraction (EF) after ligation. However, Acomys hearts showed significant EF recovery to pre-ligation values over four weeks. Histological analysis showed comparable infarct area 24-h after ligation with a similar collateral flow in both species' hearts, but subsequently, Acomys displayed reduced infarct size, regenerated microvasculature, and increased cell proliferative activity in the infarcted area. Conclusions These observations suggest that adult Acomys displays remarkable cardiac recovery properties after acute coronary artery occlusion and may be a useful model to understand functional recovery better. Translational perspective Adult Acomys provides a novel mammalian model to further investigate the cardioprotective and regenerative signaling mechanisms in adult mammals. This opens the door to breakthrough treatment strategies for the injured myocardium and help millions of patients with heart failure secondary to tissue injury with irreversible damage.

Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP), an RNA-binding protein that can regulate the translation of specific mRNAs. In this study, we developed an FXS human forebrain organoid model and observed that the loss of FMRP led to dysregulated neurogenesis, neuronal maturation and neuronal excitability. Bulk and single-cell gene expression analyses of FXS forebrain organoids revealed that the loss of FMRP altered gene expression in a cell-type-specific manner. The developmental deficits in FXS forebrain organoids could be rescued by inhibiting the phosphoinositide 3-kinase pathway but not the metabotropic glutamate pathway disrupted in the FXS mouse model. We identified a large number of human-specific mRNAs bound by FMRP. One of these human-specific FMRP targets, CHD2, contributed to the altered gene expression in FXS organoids. Collectively, our study revealed molecular, cellular and electrophysiological abnormalities associated with the loss of FMRP during human brain development.

N-myc downstream-regulated gene 1 (NDRG1) is a key regulator that interacts with many classic tumor signaling pathways, including some molecules downstream of the epidermal growth factor receptor (EGFR). However, whether NDRG1 is involved in the mechanism of resistance to cetuximab (CTX), the first monoclonal antibody targeting the EGFR has not been reported. Here, we found that NDRG1 enhanced the sensitivity of CTX in colorectal cancer (CRC) cell lines. Afterwards, we determined the underlying mechanism of this phenomenon. We demonstrated that NDRG1 inhibited the expression of EGFR; blocked EGFR phosphorylation and reduced the EGFR distribution in the cell membrane, cytoplasm and nucleus. And then, NDRG1 suppressed the EGFR downstream signaling: RAS/RAF/ERK and PI3k/AKT/mTOR pathways. Moreover, we discovered that NDRG1 attenuated the endocytosis and degradation of EGFR induced by caveolin-1 (Cav1). Additionally, our findings were further observed in an animal model and human tissues. Our results represent a potentially significant discovery that explains the mechanisms of NDRG1 in CTX resistance. NDRG1 could be a promising biomarker to predict optimum responses to CTX, and a key target to enhance CTX activity in the treatment of metastatic CRC (mCRC).

We aimed to compare the clinical data, laboratory findings, and imaging characteristics of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and aquaporin 4 antibody (AQP4)-positive neuromyelitis optica spectrum disorder (NMOSD), as detailed comparative analyses of laboratory data for both diseases are rare. Our retrospective study compared the clinical data, laboratory findings, and imaging characteristics of 118 AQP4-positive patients with first-episode NMOSD and 25 patients with first-episode MOGAD. Logistic regression was used to determine the factors that differentiated MOGAD and AQP4-positive NMOSD. There were significant differences in age, symptoms, recurrence rate, laboratory indicators, and imaging examinations between patients with MOGAD and patients with AQP4-positive NMOSD. Patients with MOGAD were younger and had higher levels of uric acid than those with AQP4-positive NMOSD. The proportion of cortical gray matter/juxtacortical white matter lesions was significantly higher in the MOGAD group than in the NMOSD group. Logistic regression revealed that young age [odds ratio (OR) = 0.947, 95% confidence interval (CI) = 0.905–0.99], high uric acid level (OR = 1.016, 95% CI = 1.006–1.027), and cortical gray matter/juxtacortical white matter involvement (OR = 3.889, 95% CI = 1.048–14.442) were significantly related to MOGAD. The multivariate analysis of the present study demonstrated that age, uric acid level, and the presence of lesions in the cortical gray matter/juxtacortical white matter can aid in distinguishing patients with AQP4-positive NMOSD from those with MOGAD. These factors may also aid in determining which patients should be tested for antibodies.

Background: Epigenetic regulation concerning histone lysine methylation and demethylation play a crucial role in cerebral ischemic injury. Dysregulation of histone methylation modifiers has been identified in cerebral ischemia. However, the function and the underlying mechanisms of histone demethylase KDM4A on neuroinflammation and functional recovery in ischemic stroke remains unclear. Methods: In the present study, the rat model of transient middle cerebral artery occlusion (MCAO) was established, and the expression level of KDM4A was assessed in brain tissues. KDM4A inhibition was carried out by intrathecal injection with Lv-shKDM4A, and then pro-inflammatory cytokines and neurological functional tests were assessed. Results: We demonstrated that rats subjected to MCAO showed a markedly increased expression of KDM4A, pro-inflammatory cytokines IL-1β and TNF-α, and vascular endothelial growth factor (VEGF), whereas KDM4A inhibition repressed the expression of IL-1β, TNF-α and VEGF both in MCAO and oxygen-glucose deprivation (OGD) models. Furthermore, KDM4A inhibition showed a marked improvement in spatial learning and sensorimotor function, as suggested by mNSS and foot-fault test, respectively. Mechanistically, KDM4A inhibition repressed NF-κB signaling activation in microglia as indicated by decreased expression and nuclear translocation of p65 in vitro and in vivo. The effects of KDM4A overexpression on exacerbating neuroinflammation was inhibited by additional treatment of NF-κB inhibitor (JSH-23). Conclusion:: The current results demonstrated KDM4A inhibition improves functional recovery in ischemic stroke by repressing NF-κB activation and subsequent neuroinflammation.

Stereocilia are actin-based cell protrusions of inner ear hair cells that play an essential role in mechano-electrical transduction (MET). Stereocilia are organized into several rows of increasing heights with the MET protein complex localized at the tips of shorter row stereocilia. At the tips of shorter row mechanotransducing stereocilia also resides a so-called "row 2 protein complex" whose dysfunction causes degeneration of the mechanotransducing stereocilia. In the present work, we show that BAIAP2L2 is localized at the tips of shorter row stereocilia in neonatal and adult mouse cochlear hair cells. Baiap2l2 inactivation causes degeneration of the mechanotransducing stereocilia, which eventually leads to profound hearing loss in mice of either sex. Consistently, electrophysiology and FM 1-43FX dye uptake results confirm that MET currents are compromised in Baiap2l2 knockout mice. Moreover, BAIAP2L2 binds to known row 2 complex components EPS8L2, TWF2, and CAPZB2, and the stereociliary tip localization of CAPZB2 is dependent on functional BAIAP2L2. Interestingly, BAIAP2L2 also binds to CIB2, a known MET complex component, and the stereociliary tip localization of BAIAP2L2 is abolished in Cib2 knockout mice. In conclusion, our present data suggest that BAIAP2L2 is a row 2 complex component, and is required for the maintenance of mechanotransducing stereocilia. Meanwhile, specific MET components such as CIB2 might play a direct role in stereocilia maintenance through binding to BAIAP2L2.

Streptococcus suis is an important zoonotic pathogen. An increase in multi-drug-resistant strains has led to poor performance of traditional antibiotic therapies. Thus, alternative antibacterial agents are urgently needed. In this study, we identified a recombined and expressed lysin PlyARI derived from the novel serotype S. suis (Chz) prophage PhiARI0460-1. The recombinant PlyARI at a concentration of 10 µg/mL showed high bacteriolytic activity against 30 S. suis isolates. The minimum inhibitory concentration (MIC) of PlyARI against S. suis was found to be as low as 2 µg/mL, and the lytic efficiency could be maintained between the range of pH 4 and 12. Additionally, in a mouse infection model, a dose of 0.5 mg of PlyARI protected 10 out of 10 mice that were challenged with highly virulent S. suis strain HA9801. Furthermore, the binding specificity of PlyARI was evaluated by constructing a green fluorescent protein (GFP-ARIb), where GFP was fused with the PlyARI-SH3b (cell wall-binding domain, CBD), revealing a high affinity to S. suis, Staphylococcus aureus, and Streptococcus equi along with exhibiting a medium affinity to Streptococcus pneumoniae as well as Streptococcus agalactiae. Overall, our findings indicated that PlyARI may be an alternative antibacterial agent that was useful in treating and possibly the prevention of Streptococcal infections.

Programmed cell death ligend-1 (PD-L1) expression by immunohistochemistry (IHC) assays is a predictive marker of anti-PD-1/PD-L1 therapy response. With the popularity of anti-PD-1/PD-L1 inhibitor drugs, quantitative assessment of PD-L1 expression becomes a new labor for pathologists. Manually counting the PD-L1 positive stained tumor cells is an obviously subjective and time-consuming process. In this paper, we developed a new computer aided Automated Tumor Proportion Scoring System (ATPSS) to determine the comparability of image analysis with pathologist scores. A three-stage process was performed using both image processing and deep learning techniques to mimic the actual diagnostic flow of the pathologists. We conducted a multi-reader multi-case study to evaluate the agreement between pathologists and ATPSS. Fifty-one surgically resected lung squamous cell carcinoma were prepared and stained using the Dako PD-L1 (22C3) assay, and six pathologists with different experience levels were involved in this study. The TPS predicted by the proposed model had high and statistically significant correlation with sub-specialty pathologists’ scores with Mean Absolute Error (MAE) of 8.65 (95% confidence interval (CI): 6.42–10.90) and Pearson Correlation Coefficient (PCC) of 0.9436 ($$p < 0.001$$ p < 0.001 ), and the performance on PD-L1 positive cases achieved by our method surpassed that of non-subspecialty and trainee pathologists. Those experimental results indicate that the proposed automated system can be a powerful tool to improve the PD-L1 TPS assessment of pathologists.

Background: Rare variants play an essential role in the etiology of cancer. In this study, we aim to characterize rare germline variants that impact the risk of cancer. Methods: We performed a genome-wide rare variant analysis using germline whole exome sequencing (WES) data derived from the Geisinger MyCode initiative to discover cancer predisposition variants. The case–control association analysis was conducted by binning variants in 5,538 patients with cancer and 7,286 matched controls in a discovery set and 1,991 patients with cancer and 2,504 matched controls in a validation set across nine cancer types. Further, The Cancer Genome Atlas (TCGA) germline data were used to replicate the findings. Results: We identified 133 significant pathway–cancer pairs (85 replicated) and 90 significant gene–cancer pairs (12 replicated). In addition, we identified 18 genes and 3 pathways that were associated with survival outcome across cancers (Bonferroni P < 0.05). Conclusions: In this study, we identified potential predisposition genes and pathways based on rare variants in nine cancers. Impact: This work adds to the knowledge base and progress being made in precision medicine.

Human protothecosis is a rare infection caused by Prototheca spp., which are environmental achloric algae ubiquitously existing in nature. Members of the genus of Prototheca usually cause localized infection that affects the skin or wounds. Systemic infection is extremely rare and tends to occur in immunocompromised patients. Here, we report a case of cutaneous protothecosis and meningitis due to Prototheca wickerhamii in an immunocompetent teenager who obtained full-body tattoos at the time of infection. To the best of our knowledge, this is the first description of P. wickerhamii isolated from both skin tissue and cerebrospinal fluid. The data contained in this report will increase our understanding of this pathogen and elucidate the most optimal treatment.

How the suitable distribution of a given grassland type will respond to policy implementation and climate change is a prerequisite and the basis for effective grassland management and sustainable development. The maximum entropy (MaxEnt) model as a comprehensive evaluation method at species level was successfully used to simulate the temporal and spatial changes in the geographical distribution of Kobresia meadow in China’s Three-River Headwaters (TRH) region under the context of policy implementation and climate change. There were three main findings. First, there are the six dominant environmental variables affecting the distribution of Kobresia meadow (these being elevation, precipitation variation coefficient, March precipitation, April precipitation, April minimum temperatures, and May minimum temperatures: their threshold values are 3500–4000 m, 86–100, 8.5 mm, 12 mm, –3.5°C and 1.5°C, respectively, which indicate the most suitable conditions for Kobresia meadow distribution). Second, under current (2005–2014) climate conditions, the suitable distribution of Kobresia meadow gradually decreases from east to west, with the largest area in the east. Implementation of the ecological conservation policy in the TRH has greatly improved the ecological environment in lower elevation and high population areas. This has benefited the growth of Kobresia meadow and enlarged its suitable areas. Third, compared with the current distribution, areas suitable for Kobresia meadow will increase by 25.4–33.0% in the 2050s (2041–2060) and 17.4–33.0% in the 2070s (2061–2080) under four Representative Concentration Pathway (RCP) scenarios. More importantly, from the 2050s to the 2070s, areas suitable for Kobresia meadow will decrease or stabilise, bringing new challenges for protection and utilisation.

The low temperature, drought, high salt, and other environments influence crop production and development directly, so the gene cloning method has become an effective biological means. In order to effectively improve the cloning effect, a gene cloning method for Conringia planisiliqua based on mRNA differential display technology was proposed. Based on mRNA differential display technology, the gene of Conringia planisiliqua was transcribed. The present study expects gene cloning to be better than the traditional method. This will lay the basis for gene cloning and functional verification of the transcription and disease-resistant proteins in Conringia planisiliqua. According to homologous identification results, the homologous drought-resistant genes were determined and screened. The data of Conringia planisiliqua in the existing biological database were used to extract ESTs data of Conringia planisiliqua. Then, the heating environment was established and the concept of integral function was introduced to express the influence of growth environment of different genomes. The mass, momentum, energy, and turbulent flow situation of stress-resistant gene of Conringia planisiliqua during the growth were satisfied. Finally, the data search was carried out in the NCBI database and gene cloning was achieved by ESTs data sequence. Experimental results show that the proposed method can effectively reduce the gene data fitting and improve the quantity of gene fragments cloned in a cycle, so the overall cloning effect is better.

Granulosa cells (GCs) play a crucial role in follicular development and atresia. Previous studies have showed that GCs in the form of monolayer influenced in vitro maturation (IVM) of oocytes. However, the effects of GCs in the form of conditioned medium and monolayer on IVM and development competence of buffalo oocytes remain unclear. In the present study, we examined the impacts of GC-conditioned medium (GCCM) and monolayer GC on maturation efficiency and embryo development of buffalo oocytes after parthenogenetic activation (PA). Our results showed that GCCM that was collected on day 2 and added to IVM medium at a 20% proportional level (2 days and 20%) exerted significant negative effects on IVM rate (41.6% vs. 44.5%), but significantly enhanced embryo development (oocyte cleavage, 81.3% vs. 69.3%; blastocyst formation, 36.3% vs. 29.3%) of buffalo oocytes after PA compared with the control group. Furthermore, monolayer GC significantly reduced both maturation efficiency (40.2% vs. 44.5%) and embryo development (oocyte cleavage, 60.6% vs. 69.3%; blastocyst formation, 20.6% vs. 29.3%) of buffalo oocytes after PA compared to the control group. Our study indicated that GCs in the form of GCCM (2 days and 20%) and monolayer GC had different effects on IVM and subsequent parthenogenetic development of buffalo oocytes.

Mycoplasma hyorhinis infects pigs causing polyserositis and polyarthritis, and has also been reported in a variety of human tumor tissues. The occurrence of disease is often linked with the systemic invasion of the pathogen. Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), one of the key enzymes of glycolysis, was reported as a surface multifunctional molecule in several bacteria. Here, we investigated whether GAPDH could manifest binary functions; as an adhesin to promote colonization as well as a plasminogen receptor functioning in extracellular matrix (ECM) degradation to promote systemic invasion. The surface localization of GAPDH was observed in M. hyorhinis with flow cytometry and colony blot analysis. Recombinant GAPDH (rGAPDH) was found to be able to bind porcine-derived PK-15 and human-derived NCI-H292 cells. The incubation with anti-GAPDH antibody significantly decreased the adherence of M. hyorhinis to both cell lines. To investigate its function in recruiting plasminogen, firstly, the interaction between rGAPDH and plasminogen was demonstrated by ELISA and Far-Western blot assay. The activation of the rGAPDH-bound plasminogen into plasmin was proved by using a chromogenic substrate, and furtherly confirmed to degrade extracellular matrix by using a reconstituted ECM. Finally, the ability of rGAPDH to bind different ECM components was demonstrated, including fibronectin, laminin, collagen type IV and vitronectin. Collectively, our data imply GAPDH as an important adhesion factor of M. hyrohinis and a receptor for hijacking host plasminogen to degrade ECM. The multifunction of GAPDH to bind both plasminogen and ECM components is believed to increase the targeting of proteolysis and facilitate the dissemination of M. hyorhinis.

Skeletal muscle development is a complex and highly orchestrated biological process mediated by a series of myogenesis regulatory factors. Numerous studies have demonstrated that circular RNAs (circRNAs) are involved in muscle differentiation, but the exact molecular mechanisms involved remain unclear. Here, we analyzed the expression of circRNAs at the adult and embryo development stages of cattle musculus longissimus. A stringent set of 1,318 circRNAs candidates were identified, and we found that 495 circRNAs were differentially expressed between embryonic and adult tissue libraries. We subsequently focused on one of the most downregulated circRNAs (using the adult stage expression as control), and this was named muscle differentiation-associated circular RNA (circMYBPC1). With RNA binding protein immunoprecipitation (RIP) and RNA pull-down assays, circMYBPC1 was identified to promote myoblast differentiation by directly binding miR-23a to relieve its inhibition on myosin heavy chain (MyHC). In addition, RIP assays demonstrated that circMYBPC1 could directly bind MyHC protein. In vivo observations also suggested that circMYBPC1 may stimulate skeletal muscle regeneration after muscle damage. These results revealed that the novel non-coding circRNA circMYBPC1 promotes differentiation of myoblasts and may promote skeletal muscle regeneration. Our results provided a basis for in-depth analysis of the role of circRNA in myogenesis and muscle diseases., Graphical abstract, Chen et al. identified circRNAs related to Angus cattle muscle development through RNA-seq and described the discovery and characterization of a new circular RNA, circMYBPC1, in bovine skeletal muscle. Through molecular biology experiments, they found that circMYBPC1 interacts with miR-23a and MyHC proteins to promote muscle differentiation.

Past researches have shown that pluripotency maintenance of naive and primed-state pluripotent stem cells (PSCs) depends on different signaling pathways, and naive-state PSCs possess the ability to produce chimeras when they are introduced into a blastocyst. Considering porcine is an attractive model for preclinical studies, many researches about pig induced pluripotent stem cells (piPSCs) have been reported. Some cytokines and small molecule compounds could transform primed piPSCs into naive state. However, there are no suitable culture conditions for generation of naive-state piPSCs with high efficiency; other small molecule compounds need further exploration. In this study, we investigated whether p38 MAPK and JNK signal pathway inhibitor SB203580 and SP600125 could be of benefit for acquiring naive-state piPSCs. By comparing reprogramming efficiencies under conditions of different donor cells and culture environment, we found that porcine bone marrow mesenchymal stem cells (PBMSCs) have higher efficiency on piPSC induction, and the culture condition of CHIR99021+PD0325901(2i)+Lif+bFGF is more suitable for subculturing of piPSCs. Our results also indicate that SB203580 and SP600125 could promote reprogramming of PBMSCs into naive-like state piPSCs. These results provide guidance for choosing donor cells, culture conditions, and research of different state iPSCs during the process of reprogramming pig somatic cells.

Human gut microbiota modulates normal physiological functions, such as maintenance of barrier homeostasis and modulation of metabolism, as well as various chronic diseases including type 2 diabetes and gastrointestinal cancer. Despite decades of research, the composition of the gut microbiota remains poorly understood. Here, we established an effective extraction method to obtain high quality gut microbiota genomes, and analyzed them with third-generation sequencing technology. We acquired a large quantity of data from each sample and assembled large numbers of reliable contigs. With this approach, we constructed tens of completed bacterial genomes in which there were several new bacteria species. We also identified a new conditional pathogen, Enterococcus tongjius, which is a member of Enterococci. This work provided a novel and reliable approach to recover gut microbiota genomes, facilitating the discovery of new bacteria species and furthering our understanding of the microbiome that underlies human health and diseases.

Sepsis is a deadly clinical condition. Allylpyrocatechol is bioactive flavonoid that has shown promising anti-inflammatory and antioxidant activity. The effects of allylpyrocatechol on sepsis-induced lung injury have not been fully established. This study investigated the effects of allylpyrocatechol in a mouse model of sepsis-induced lung injury. RAW264.7 macrophages were used for in vitro studies. A mouse model of sepsis was established by cecal ligation and puncture (CLP). The PaO2/FiO2 ratio was measured in conjunction with lung tissue histology, and edema was determined by the wet:dry tissue ratio. ELISA was performed to analyze levels of IL-6, TNF-α, NOx, and HMGB1. Malondialdehyde (MDA) levels were measured to determine lipid peroxidation status. Protein expression was investigated via Western blotting analyses. Molecular docking studies were done to study the affinity of SIRT1 with Allylpyrocatechol. It was observed that Allylpyrocatechol inhibited the production of HMGB1 and suppressed pro-inflammatory responses in macrophages treated with bacterial lipopolysaccharide (LPS) in vitro, and in CLP sepsis mice in vivo. Moreover, it ameliorated the reduction of SIRT1 levels in both LPS-treated macrophages and CLP mice, alleviated sepsis-induced lung edema, reduced lipid peroxidation, improved lung tissue histology findings, reduced mortality, and improved the PaO2/FiO2 ratio in CLP mice. Allylpyrocatechol caused significant reductions in serum levels of IL-6, nitric oxide, TNF-α, and HMGB1, as well as nuclear translocation of inducible nitric oxide synthase, SIRT1, and HMGB1 in lungs of CLP mice. Molecular docking analysis suggested affinity of SIRT1 with Allylpyrocatechol. The findings suggest that Allylpyrocatechol protects mice against lung injury via SIRT1-mediated suppression of HMGB1 nuclear translocation and p-p65 activation.

Cancer-associated fibroblasts (CAFs) can promote the development and metastasis of prostate cancer partly by mediating tumor-associated inflammation. An increasing amount of studies have focused on the functional interactions between CAFs and immune cells in the tumor microenvironment (TME). We previously reported that G protein-coupled receptor 30 (GPR30) was highly expressed in prostate CAFs and plays a crucial role in prostate stromal cell activation. However, the effect and underlying mechanism of GPR30 expression in prostate CAFs affecting the interaction between CAFs and tumor-associated macrophages (TAMs) need further elucidation. Here, we found that, compared with CAF-shControl, CAF-shGPR30 inhibited macrophage migration through transwell migration assays, which should be attributed to the decreased expression of C-X-C motif chemokine ligand 12 (CXCL12). In addition, macrophages treated with a culture medium of CAF-shGPR30 exhibited attenuated M2 polarization with downregulated M2-like markers expression. Moreover, macrophages stimulated with a culture medium of CAF-shGPR30 were less efficient in promoting activation of fibroblast cells and invasion of PCa cells. Finally, cocultured CAF-shGPR30 and macrophages suppressed PCa cell invasion compared to cocultured CAF-shControl and macrophages by decreasing interleukin-6 (IL-6) secretion, and this effect could be abrogated with rescue expression of IL-6. Our results pinpoint the function of GPR30 in prostate CAFs on regulating the CAF-TAM interaction in the TME and provide new insights into PCa therapies via regulating TME.

In pregnant sows, heat stress (HS) not only affects sows, but also has long-term effects on offspring growth. However, it is still unclear how HS in pregnant sows influences offspring skeletal muscle development. In this study, 12 sows with similar body conditions were assigned into either a control (CON) or an HS group. The CON sows were housed at 18-22 ℃, and the sows in the HS group were housed at 28-32 ℃ from day 85 to 114 of pregnancy. The results showed that maternal HS decreased the total protein content (P 0.05) and prolactin level (P 0.05), yet increased the triglyceride content (P 0.05) of milk. The piglets of both groups had similar body weight and longissimus dorsi (LD) muscle weight at birth, but body weight (P 0.05) and LD weight (P 0.05) was significantly lower at weaning age in the HS group. Increased expression of myostatin (MSTN) (P 0.05) and its receptor (P 0.05) in the LD of HS piglets was observed at weaning. The following decreased in HS piglets: expression of serine/threonine-specific protein kinase (P 0.05), the mammalian target of rapamycin (P 0.05), and glycogen synthase kinase-3β (P 0.05) signal pathway-involved proteins. The results indicated that maternal HS during late pregnancy influenced offspring LD muscle growth via the activated MSTN pathway. This effect may be related to sow's milk composition.

Background Myelin and lymphocyte protein 2 (MAL2) is a proven oncogene in some human tumors. However, currently, little is known about the function of MAL2 in prostate adenocarcinoma (PRAD). This study sought to investigate the role of MAL2 on PRAD progression. Methods MAL2 expression in PRAD was first analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA) database. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay and Western blot assay were used to detect the expression of MAL2 in PRAD tissues and cell lines. Additionally, immunohistochemistry (IHC) straining was used to detect the expression of MAL2 in PRAD pathological tissues. The Cell Counting Kit-8 (CCK-8) assay, clone formation assay and Flow cytometry were performed to investigate the effect of MAL2 on PRAD cell proliferation and cell apoptosis. Cell migration and invasion were measured by Transwell assay. The effect of MAL2 on epithelial-mesenchymal transition (EMT) progression and the Notch signaling pathway in PRAD was also investigated. Results MAL2 was discovered to be obviously upregulated in PRAD tissues and cell lines. The upregulation of MAL2 was closely associated with tumor, nodes and metastases (TNM) stage, the Gleason score and metastasis of PRAD patients, and affected the prognosis of PRAD patients. Functionally, the depletion of MAL2 suppressed cell proliferation, migration, invasion, and EMT progression, and promoted cell apoptosis of PRAD cells. In an in vivo experiment, MAL2 knockdown significantly suppressed tumor growth in mice. Further, inhibiting the Notch pathway reversed the effect of MAL2 knockdown on PRAD progression. Conclusions In sum, MAL2 was found to be upregulated in PRAD, and appears to act as a carcinogen in PRAD. Additionally, MAL2 appears to regulate PRAD progression through the Notch signaling pathway.

As antimicrobial agents, essential oils (EOs) have been used by more and more companies as alternatives to traditional chemicals. In the study, seven EOs from Pinus massoniana, cinnamon, Star anise, Litsea cubeba, Cinnamomum camphora, Lemon eucalyptus, and Camphor from Guangxi were researched for their antifungal performances and chemical components. With the help of the diffusion in a disc way as well as the minimum inhibitory concentration (MIC) to three fungi, the antifungal impacts and the bamboo slices anti-mold tests of these EOs were studied. The compositions of these oils were identified. Litsea cubeba EO, Anise EO, and Cinnamon EO exhibited super antifungal activity against Trichoderma viride, Aspergillus niger, and Penicillium citrinum. Treated by Cinnamon EO, Anise EO, or Litsea cubeba EO, few molds were observed on the surface of bamboo chips, which showed that these EOs had a good antifungal effect on molds of bamboo. Antifungal effect of seven essential oils on bamboo

We read with great interest the recent article published in Gut in which Yeoh et al demonstrated that gut microbiota composition of recovered patients with COVID-19 remained significantly distinct from uninfected controls.1 Persisting symptoms, also known as ‘long COVID-19’, have been reported in a significant proportion of patients following hospital discharge.2 3 Gut dysbiosis might link to long COVID-19 risks.1 Few studies have focused on the recovery process of gut microbiota following SARS-CoV-2 infection. Here, we conducted a prospective study to longitudinally monitor alterations of gut microbiota in patients with COVID-19 using 16S rDNA sequencing (detailed methods in online supplementary materials). Faecal microbiota was monitored at three timepoints, acute phase (from illness onset to viral clearance), convalescence (from viral clearance to 2 weeks after hospital discharge), postconvalescence (6 months after hospital discharge).### Supplementary data [gutjnl-2021-324090supp001.pdf] The gut microbiota richness, measured by Chao 1 index, was obviously lower (p

Ni2+-functionalized porous ceramic/agarose composite beads (Ni-NTA Cerose) can be used as carrier materials to immobilize enzymes harboring a metal affinity tag. Here, a 6×His-tag fusion alcohol dehydrogenase Mu-S5 and glucose dehydrogenase from Bacillus megaterium (BmGDH) were co-immobilized on Ni-NTA Cerose to construct a packed bed reactor (PBR) for the continuous synthesis of the chiral intermediate (S)-(4-chlorophenyl)-(pyridin-2-yl) methanol [(S)-CPMA]. NADPH recycling and in situ product adsorption was achieved simultaneously by assembling a D101 macroporous resin column after the PBR. Using an optimum enzyme activity ration of 2:1 (Mu-S5: BmGDH) and hydroxypropyl-β-cyclodextrin as co-solvent, a space-time yield of 1,560 g/(L·d) could be achieved in the first three days at a flow rate of 5 mL/min and substrate concentration of 10 mM. With simplified selective adsorption and extraction procedures, (S)-CPMA was obtained in 84% isolated yield.

Several clinical studies have reported that hearing loss is correlated with autism in children. However, little is known about the underlying mechanism between hearing loss and autism. p21-activated kinases (PAKs) are a family of serine/threonine kinases that can be activated by multiple signaling molecules, particularly the Rho family of small GTPases. Previous studies have shown that Pak1 mutations are associated with autism. In the present study, we take advantage of Pak1 knockout (Pak1-/-) mice to investigate the role of PAK1 in hearing function. We find that PAK1 is highly expressed in the postnatal mouse cochlea and that PAK1 deficiency leads to hair cell (HC) apoptosis and severe hearing loss. Further investigation indicates that PAK1 deficiency downregulates the phosphorylation of cofilin and ezrin-radixin-moesin and the expression of βII-spectrin, which further decreases the HC synapse density in the basal turn of cochlea and disorganized the HC stereocilia in all three turns of cochlea in Pak1-/- mice. Overall, our work demonstrates that the autism-related gene Pak1 plays a crucial role in hearing function. As the first candidate gene linking autism and hearing loss, Pak1 may serve as a potential target for the clinical diagnosis of autism-related hearing loss.

Bone marrow-derived mesenchymal stem cells (BMSCs) from livestock are valuable resources for animal reproduction and veterinary therapeutics. Previous studies have shown that BMSCs were prone to ma...

Several studies have indicated that the oral and gut microbiota may exhibit differences in patients with cirrhosis. Less is known about the microbiota in the stomach, which is located between the oral cavity and the intestinal tract. In this study, the gastric mucosal microbiota of patients with liver cirrhosis and controls were analyzed with 16S ribosomal RNA (rRNA) pyrosequencing. Cirrhotic patients had significantly lower Helicobacter pylori (H. pylori) infection rates, as confirmed by both the histological method and the pyrosequencing method. In H. pylori-negative subjects, gastric bacterial communities of healthy and cirrhosis cohorts were clustered into four clusters based on bacterial compositions: Cluster_1 and Cluster_2 (mostly cirrhosis), Cluster_3 (mostly healthy), and Cluster_4 (around half of each). Compositional and functional differences were observed among these different clusters. At the genus level, Cluster_1 and Cluster_2 showed enrichment of Neisseria and Streptococcus, respectively. Functionally, Cluster_2 was characterized as depleted of genetic information processing, as well as of modules related to glycan biosynthesis and metabolism. Patients in Cluster_2 had more severe gastrointestinal symptoms and a higher rate of previous endoscopic variceal ligation (EVL) therapy than patients in other clusters. Our findings suggest that the colonization of both H. pylori and non-H. pylori is influenced in liver cirrhosis. Although the H. pylori-negative gastric mucosal microbiota showed considerable heterogeneity, associations between specific gastric microbiota and clinical characteristics could be observed. Previous EVL therapy might lead to a distinct structure of the gastric mucosal microbiota, thus aggravating the gastrointestinal symptoms in H. pylori-negative cirrhotic patients.

Cultivated grapevine (Vitis) is a highly valued horticultural crop, and cold stress affects its growth and productivity. Wild Amur grape (Vitis amurensis) PAT1 (Phytochrome A signal transduction 1, VaPAT1) is induced by low temperature, and ectopic expression of VaPAT1 enhances cold tolerance in Arabidopsis (Arabidopsis thaliana). However, little is known about the molecular mechanism of VaPAT1 during the cold stress response in grapevine. Here, we confirmed the overexpression of VaPAT1 in transformed grape calli enhanced cold tolerance. Yeast two-hybrid and bimolecular fluorescence complementation assays highlighted an interaction between VaPAT1 with INDETERMINATE-DOMAIN 3 (VaIDD3). A role of VaIDD3 in cold tolerance was also indicated. Transcriptome analysis revealed VaPAT1 and VaIDD3 overexpression and cold treatment coordinately modulate the expression of stress-related genes including lipoxygenase 3 (LOX3), a gene encoding a key jasmonate biosynthesis enzyme. Co-expression network analysis indicated LOX3 might be a downstream target of VaPAT1. Both electrophoretic mobility shift and dual luciferase reporter assays showed the VaPAT1-IDD3 complex binds to the IDD-box (AGACAAA) in the VaLOX3 promoter to activate its expression. Overexpression of both VaPAT1 and VaIDD3 increased the transcription of VaLOX3 and JA levels in transgenic grape calli. Conversely, VaPAT1-SRDX (dominant repression) and CRISPR/Cas9-mediated mutagenesis of PAT1-ED causing the loss of the C-terminus in grape calli dramatically prohibited the accumulation of VaLOX3 and JA levels during cold treatment. Together, these findings point to a pivotal role of VaPAT1 in the cold stress response in grape by regulating JA biosynthesis.

The anthocyanin synthetic pathway is regulated centrally by an MYB-bHLH-WD40 (MBW) complex. Anthocyanin pigmentation is an important fruit quality trait in red-fleshed kiwifruit; however, the underlying regulatory mechanisms involving the MBW complex are not well understood. In this study, one R2R3MYB (AcMYBF110 expressed in fruit characteristically), one bHLH (AcbHLH1), two upstream regulators of AcbHLH1 (AcbHLH4 and AcbHLH5), and one WDR (AcWDR1) are characterized as being involved in the regulation of anthocyanin synthesis in kiwifruit. AcMYBF110 plays an important role in the regulation of anthocyanin accumulation by specifically activating the promoters of several anthocyanin pathway genes including AcCHS, AcF3'H, AcANS, AcUFGT3a, AcUFGT6b, and AcGST1. Coexpression of AcbHLH1, AcbHLH4, or AcbHLH5 together with AcMYBF110 induces much greater anthocyanin accumulation in both tobacco leaves and in Actinidia arguta fruit compared with AcMYBF110 alone. Moreover, this activation is further enhanced by adding AcWDR1. We found that both AcMYBF110 and AcWDR1 interact with all three AcbHLH factors, while AcMYBF110 also interacts with AcWDR1 to form three different MBW complexes that have different regulatory roles in anthocyanin accumulation of kiwifruit. The AcMYBF110-AcbHLH1-AcWDR1 complex directly targets the promoters of anthocyanin synthetic genes. Other features of the regulatory pathways identified include promotion of AcMYBF110, AcbHLH1,and AcWDR1 activities by this MBW complex, providing for both reinforcement and feedback regulation, whereas the AcMYBF110-AcbHLH4/5-AcWDR1 complex is indirectly involved in the regulation of anthocyanin synthesis by activating the promoters of AcbHLH1 and AcWDR1 to amplify the regulation signals of the first MBW complex.