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The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents. [ABSTRACT FROM AUTHOR]

Tyrosyl-DNA phosphodiesterase 2 (TDP2) plays an important role in the repair of DNA damage induced by Topoisomerase II (TOP2), and is a potential anticancer target. In this work, we established an efficient and precise fluorescence assay for TDP2 inhibitor discovery based on FRET technique. The sequent screening of our natural product library led to the identification of a new TDP2 inhibitor 3 (8.6 ± 0.35 μM), which showed synergistic effect with etoposide in HCT116 and DU145 cell lines. The possible binding mode of 3 with TDP2 protein was also studied. [Display omitted] • A TDP2 screening assay is established based on FRET technique. • The TDP2 assay is suitable for high throughput screening. • A seco-steroid 3 is identified as novel TDP2 inhibitor. • TDP2 inhibitor 3 shows synergistic effect with etoposide. [ABSTRACT FROM AUTHOR]

[Display omitted] • BmLV is originated from a plant virus. • BmLV can enter nontarget cells with transient propagation. • The Imd and RNAi pathways are activated by BmLV infection. • The transient propagation of BmLV is mediated by dysregulation of gene expression. Bombyx mori latent virus (BmLV), a novel positive-strand RNA virus was first identified in the B. mori cultured BmN cell line. Whether the infectivity of BmLV to silkworm larvae and non-silkworm cells is connected with dysregulation of gene expression are not well understood. A complete sequence of BmLV genomic RNA was identified and revealed that a fragment with 495 nt in length was deleted from the RNA-dependent RNA polymerase (RdRp) gene in some BmLV genomic RNAs. Studies on the infectivity of BmLV to nontarget cells showed that BmLV can infect silkworm larvae, Spodoptera frugiperda Sf-9 and H1299 lung cancer cells with transient propagation. The dysregulation of gene expression of Sf-9 cells followed by BmLV infection was analyzed. Out of 743 differentially expressed genes (DEGs), 300 were upregulated and 443 were downregulated. Gene Ontology (GO) analysis indicated the DEGs were enriched into oxidoreductase activity for CH-NH 2 group donors, glutamate biosynthetic process, response to stress and proteasome core complex. KEGG enrichment analysis showed that DEGs were mainly enriched into sulfur metabolism, RNA degradation, proteasome, pentose and glucuronate interconversions. Undesirable nutrients and temperature factors contributed to the propagation of BmLV in Sf-9 cells. Additionally, the Imd and RNAi pathways were activated by BmLV infection without stimulating Toll and JAK-STAT pathways. Therefore, it is suggested that BmLV is originated from plants, which can enter nontarget cells with transient propagation. The transient infection of BmLV may not only be regulated by Imd and RNAi immune pathways but also mediated by dysregulation of gene expression. [ABSTRACT FROM AUTHOR]

This work reports on the synthesis, mechanical, and thermal properties of in situ AlN/Al-12Si composite through laser powder bed fusion (LPBF) by blending Al-12Si powder with 5 vol% nano-sized BN particles. Incorporating nano-BN particles results in (i) formation of thermally stable AlN phase, preventing Si diffusion and breakdown of cellular structure, (ii) improvement of compressive yield strength (CYS), and (iii) reduction in coefficients of thermal expansion (CTE) and thermal conductivity. In addition, compared to Al-12Si alloy, the composite exhibits grain refinement from 38.8 to 1.2 μm in size, and the alteration of columnar grains (Al-12Si) to equiaxed grains (AlN/Al-12Si). At annealing temperatures above 573 K, the CYS of the unadulterated Al-12Si alloy had a ∼ 2.1 times greater reduction (from 285 to 200 MPa) compared to that of the composites (from 301 to 260 MPa). The formation of the AlN phase mitigates the significant reduction in CYS. The CTE of Al-12Si and AlN/Al-12Si are 27.3 × 10−6 K−1 and 24.3 × 10−6 K−1 respectively. There is good agreement between the measured CYS results and the calculated strengthening mechanisms. This work offers both theoretical insights and experimental data to support the use of LPBF AlN/Al-12Si composite in low- and moderate-temperature applications. • Novel in situ AlN/Al-12Si composite is successfully fabricated by laser powder bed fusion. • AlN phase generate from the reaction between BN particle and Al-12Si during laser melting. • AlN/Al-12Si composites have a higher compressive yield strength and lower thermal conductivity. • AlN phase leads to the grain refinement, improving the compressive yield strength. • AlN phase mitigates the reduction in coefficients of thermal expansion at medium temperature. [ABSTRACT FROM AUTHOR]

• WBSCR22 expression was upregulated in glioma tissues. • Overexpression of WBSCR22 promotes glioma cell proliferation, migration and invasion. • WBSCR22 may serve as the potential therapeutic target for glioma therapy. Human WBSCR22 is involved in cancer proliferation, invasion and metastasis; however, its function in glioma remains unexplored. In our research, we aimed to investigate the role of WBSCR22 in the development of glioma and its possible molecular mechanisms. Using bioinformatic analysis of public datasets, we determined that WBSCR22 overexpression in glioma specimens was correlated with an unfavorable patient prognosis. Our results revealed that WBSCR22 was highly expressed in glioma cell lines. The loss of WBSCR22 inhibited the growth, invasion and migration of glioma cells, while WBSCR22 overexpression produced the opposite effects. Moreover, we found that WBSCR22 downregulation reduced the phosphorylation of Akt and GSK3β and decreased the levels of β-catenin and CyclinD1 in glioma cells. The opposite effects were observed when WBSCR22 was overexpressed. Additionally, we verified with a dual-luciferase reporter assay that WBSCR22 was a direct target of miR-146b-5p. Furthermore, overexpression of miR-146b-5p suppressed WBSCR22 mRNA and protein expression. Notably, the restoration of WBSCR22 expression remarkably reversed the effects of miR-146b-5p overexpression on cell survival, apoptosis and the cell cycle in glioma cells. Collectively, our findings revealed a tumor-promoting role for WBSCR22 in glioma cells, thus providing molecular evidence for WBSCR22 as a novel therapeutic target in glioma. [ABSTRACT FROM AUTHOR]

Accurate communication at the stigma surface is required to promote plants' own pollen and reject foreign pollen. Liu et al. have now discovered an autocrine signaling pathway at the surface of arabidopsis stigmatic papillae, accumulating ROS. Downregulation of ROS production via an antagonistic peptide from the pollen coat promotes pollen hydration and germination. [ABSTRACT FROM AUTHOR]

mtDNA COII gene sequences were identified and analyzed using different types of software, namely, MEGA5.0, DNAMAN, and DnaSP5.0 in four Chinese provinces, namely, Sichuan, Zhejiang, Guizhou and Shanghai. Analysis of molecular genetic variation and its genetic structure and differentiation, combined with NJ tree, MP tree analysis and analysis of molecular variance (AMOVA), at Fst = 0.0582 conclude that the genetic differentiation is low, gene flow is Nm = 8.0911, and gene exchange is sufficient. However, for the geographic populations of Pseudoregma bambucicola in the four provinces, their gene exchange is relatively weak at Nm = 0.8284, whereas the genetic differentiation is high at Fst = 0.3764. Based on the data, total nucleotide diversity between the populations is 0.00158 ± 0.00021. The results showed that the total population of Tajima's D and Fu's Fs results are D = −0.885 and Fs = 0.226, respectively. The experimental numerical results showed that this total population is not significant (P > 0.10), indicating that nine different geographic populations are short-term. No expansion occurred in the internal population. This study provided a theoretical and practical basis for the comprehensive prevention and control of P. bambucicola. [ABSTRACT FROM AUTHOR]

• Hydrophobic association hydrogel (HA-gel) was synthesized by micellar copolymerization. • HA-gel is a kind of permanently cross-linked hydrogel and the swelling ratio of HA-gels is high. • All the HA-gels exhibit "swelling overshoot" phenomenon obviously. Hydrophobic association hydrogels (HA-gels) were successfully synthesized from octylphenol polyoxyethylene (7) acrylate (OP-7-AC) and sodium dodecylsulfate (SDS) and their swelling behaviors were studied. Swelling test indicates that the swelling ratio and swelling rate of hydrogel go down first then go up with increased content of SDS. HA-gels exhibited a special "swelling overshoot" phenomenon because of the dissolution of non-gel compositions and surplus SDS. Diffusion of water molecules or the extension of network chains played a major role in the beginning of swelling process of xerogel. With OP-7-AC content increased, swelling ratio of hydrogel and xerogel increased and the "swelling overshoot" became more obvious. At the beginning of swelling, the gel loss increased sharply and then tended to be constant. The gel loss increased with the increase in SDS and OP-7-AC content. The results indicate that SDS and OP-7-AC contents have great effects on the swelling ratio and stability of HA-gels. [ABSTRACT FROM AUTHOR]

• The influence of cognitive activity avoiding emotion on sleep is investigated. • No differences in macro-sleep and sleep spindles characteristics between conditions. • Deep neural network model achieved 96% accuracy in differentiating conditions. • Our findings suggest a weak but positive effect of cognitive activity on sleep. Understanding the influence of cognitive activity on subsequent sleep has both theoretical and applied implications. This study aims to investigate the effect of pre-sleep cognitive activity, in the context of avoiding emotional interference, on macro-sleep and sleep spindles. In a within-subjects design, participants' sleep electroencephalography was collected in both the with and without pre-sleep cognitive activity conditions. Subsequent macro-sleep (i.e., sleep stage distribution and sleep parameters) and spindle characteristics (i.e., density, amplitude, duration, and frequency) were analyzed. In addition, a novel machine learning framework (i.e., deep neural network, DNN) was used to discriminate between cognitive activity and control conditions. There were no significant differences in macro-sleep and sleep spindles between the cognitive activity and control conditions. Spindles-based DNN models achieved over 96% accuracy in differentiating between the two conditions, with fast spindles performing better than full-range and slow spindles. These results suggest a weak but positive effect of pre-sleep cognitive activity on subsequent sleep. It sheds light on a possible low-cost and easily accessible sleep intervention strategy for clinical and educational purposes. [ABSTRACT FROM AUTHOR]

Bombyx mori cypovirus (BmCPV) enters permissive cells via clathrin-mediated endocytosis pathway. However, the distinct entry mechanism for BmCPV is still ambiguous. The aim of this study is to investigate the role of gangliosides and cholesterol in BmCPV cell entry. The number of BmCPV virions attached to the cell surface and the expression level of BmCPV vp 1 gene was significantly decreased by digestion of terminal sialic acids in gangliosides with neuraminidase (NA). Preincubation of different concentration of ganglioside GM1, GM2 or GM3 with BmCPV prior to infection, the reduction of BmCPV infectivity was found by GM2-treated in a dose-depend manner. BmCPV virions were found to colocalize with GM2 in the cell surface. The infectivity of BmCPV was reduced by anti-GM2 antibody treatment cells. Moreover, BmCPV infection was impaired by depletion of membrane cholesterol with MβCD, but the inhibitory effect of MβCD was restored by supplementing with cholesterol. The number of viral particles attached on the BmN cells was significantly decreased by pretreated with MβCD, and BmCPV infection was inhibited by silencing the expression of 3-hydroxy-3-methylglutaryl-CoA reductase gene ( Hmg -r) in cholesterol biosynthesis pathway. These results indicate that ganglioside GM2 and cholesterol in membrane lipid rafts are essential for BmCPV attachment to cell surface for its cell entry. [ABSTRACT FROM AUTHOR]

Both leica microscopic camera system and scanning electron microscopy was used to observe and characterize the feet, back, abdomen, antennae and mouthparts of the Pseudoregma bambucicola from the bamboo, Bambusa multiplex . The possible functions of all the external morphological characteristics of the P. bambucicola were described and discussed in detail, which offers a basis for further enriching the biology, phylogeny and ecological niche of the P. bambucicola . Moreover, the morphological results should contribute to morphological identification and differentiation of the P. bambucicola from other aphids in the same family. [ABSTRACT FROM AUTHOR]

Sogatella furcifera is a major rice pest that exhibits wing dimorphism. The methylation-sensitive representational difference analysis (MS-RDA) is widely used in plants and some animals to identify methylation differences in genomic DNA regions. However the method has been applied to insects very less. The objective of the current research was to monitor differential cytosine methylations at CCGG sequences in macropterous and brachypterous adults of female S. furcifera to determine the association between gene methylation and wing phenotypes using MS-RDA. After the second subtractive hybridization, two differentially methylated DNA fragments were obtained. These DNA fragments were then cloned into the pGEM-T vector and sequenced. One fragment from the positive hybridization was 464 bp, and highly similar to the 18S ribosomal RNA (rRNA) genes from some animals. Another fragment from the reverse hybridization was 453 bp, and homologous to the 28S rRNA gene of S. furcifera with a similarity rate as high as 99%. These results provide potential evidence that DNA methylation of rRNA genes may be related to wing phenotype variations in S. furcifera , and will facilitate future studies on the epigenetic mechanisms of insect wing polymorphism. [ABSTRACT FROM AUTHOR]

BACKGROUND: To investigate the therapeutic value of enhanced external counterpulsation (EECP) on recovery of cerebral blood flow following cardiac arrest (CA) and successful resumption of spontaneous circulation (ROSC) by cardiopulmonary resuscitation. METHODS: CA models were conducted using beagle dogs induced by alternating current. After successful ROSC by cardiopulmonary resuscitation, 16 dogs were randomly divided into the EECP and control group (n = 8 per group). Dogs underwent dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging at baseline prior to CA and during the 3 days following ROSC. Mean blood pressure, right common carotid artery blood flow, intracranial microcirculation and blood lactate levels were measured. Neurological outcome was assessed by the neurologic deficit score. Hematoxylin-eosin staining and transmission electron microscopy were performed for morphology and microconstruction of the cerebral cortex. RESULTS: The EECP group exhibited a significant elevation in right common carotid artery blood flow, intracranial microcirculation and a substantial decrease in blood lactate levels relative to the control group. Relative cerebral blood flow and volume were higher in the EECP group during the 3 days. Apparent diffusion coefficients were significantly higher in the EECP group on the first and third days. After ROSC, the neurologic deficit score was significantly higher in the control group compared to those in the EECP group during the three days of experiment. The cell swelling of neurons and increase of mitochondrial mass were more pronounced in the control group. CONCLUSION: EECP is beneficial for recovery of cerebral blood flow and attenuation of ischemic cerebral edema following CA and successful ROSC. [ABSTRACT FROM AUTHOR]

Summary: Infantile hemangioma is the most common tumor of infancy and the mechanism leading to proliferation hemangiomas formation is poorly understood and currently no successful treatment modality exists. We hypothesize that EPCs formed during proliferation hemangiomas, as the result of vascular endothelial growth factor (VEGF) stimulation through MMP9, play the major role in the control of cell proliferation and capillary-like vessels production. Accepting the hypothesis to be correct, a therapy that inhibits EPC mobilization and proliferation can be used to prevent the proliferation hemangiomas formation. Current therapies are only partially effective and safe because they could not eliminate all the relative factors of proliferation hemangiomas formation at all, such as: EPCs in the peripheral blood, and at the same time inducing death (apoptosis and necrosis) of other normal cells. A more efficient prevention of proliferation hemangiomas could be achieved using specific drugs or biologic methods that inhibit EPC mobilization and proliferation. Therapy based on gene therapy, capable to specifically inhibit VEGF and MMP9 expression in gene level, can be possibly effective. [Copyright &y& Elsevier]

Stark's sampling theorems in polar coordinates have important significance in the field of medical imaging. However, the direct use of Stark's results may mislead as in most real-world scenarios the jitter occurs in azimuth due to uncertainty of sampling at the medical imaging system transmitter end. On the basis of the classical Stark's interpolation formulae, this paper addresses the image reconstruction problem when the sample data are collected on nonuniform polar radius and polar azimuth lattices, where the sample points are normalized zeros of Bessel functions in radius while random jittered ones in azimuth that are clustered around uniform points with a given probability distribution. By using the existing basis functions found in Stark's formulae, it follows a biased estimate of the original angularly periodic images that are bandlimited both to the highest frequency and in the Fourier transform or the Hankel transform domain. With the newly designed angular generating functions, there are a kind of unbiased estimators whose variance approaches zero as the jitter becomes less and less pronounced. [ABSTRACT FROM AUTHOR]

Lifelong learning facilitates active ageing, and intragenerational learning—the process by which older adults learn from their peers—is an effective means of achieving this goal. The present research aims to elucidate the mechanisms and differences between intergenerational and intragenerational learning models for older adults as evidenced by brain-to-brain synchrony. Fifty-six instructor-learner dyads completed a study comparing intergenerational and intragenerational learning models, as well as task difficulty. The study utilized a block puzzle task and functional near-infrared spectroscopy (fNIRS) for hyperscanning. The instructor-learner dyads showed greater interpersonal neural synchrony (INS) and learning acquisition in the intragenerational learning model in the difficult task condition (t (54) = 3.49, p < 0.01), whereas the two learning models yielded similar results in the easy condition (t (54) = 1.96, p = 0.06). In addition, INS and self-efficacy mediated the association between learning models and learning acquisition in older adults (b = 0.14, SEM = 0.04, 95 % CI [0.01 0.16]). This study is the first to provide evidence of interbrain synchrony in an investigation of the intragenerational learning model in older adults. Our findings suggest that intra-learning is as effective as traditional inter-learning and may be more effective in certain contexts, such as difficult tasks. Encouraging intra-learning in community service or educational activities can effectively mitigate the challenge of limited volunteers and enhance learning acquisition among older adults. • Intragenerational learning is as effective as intergenerational learning. • Greater interpersonal neural synchrony (INS) and learning acquisition in the intra-learning. • This effect was moderated by task difficulty. • INS and self-efficacy mediated the association between learning models and acquisition. • This finding encourages intra-learning in community service or educational activities. [ABSTRACT FROM AUTHOR]

Chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), are ubiquitous alternatives to perfluorooctane sulfonate (PFOS), a widely used poly- and perfluoroalkyl substance (PFAS). Despite in vivo and in vitro evidence of metabolic toxicity, no study has explored associations of Cl-PFESAs concentrations with metabolic syndrome (MetS) in a human population. To help address this data gap, we quantified 32 PFAS, including 2 PFOS alternative Cl-PFESAs (6:2 and 8:2 Cl-PFESAs) in serum from 1228 adults participating in the cross-sectional Isomers of C8 Health Project in China study. The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS and its various components were estimated using individual PFAS as a continuous or categorical predictor in multivariate regression models. The association between the overall mixture of PFAS and MetS was examined using probit Bayesian Kernel Machine Regression (BKMR-P). Greater serum PFAS concentrations were associated with higher odds of MetS and demonstrated a statistically significant dose-response trend (P for trend < 0.001). For example, each ln-unit (ng/mL) increase in serum 6:2 Cl-PFESA was associated with a higher prevalence of MetS (OR = 1.52, 95% CI: 1.25, 1.85). MetS was also 2.26 (95% CI: 1.59, 3.23) times more common in the highest quartile of serum 6:2 Cl-PFESA concentration than the lowest, and particularly high among women (OR = 6.41, 95% CI: 3.65, 11.24). The BKMR-P analysis showed a positive association between the overall mixture of measured PFAS and the odds of MetS, but was only limited to women. While our results suggest that exposure to Cl-PFESAs was associated with MetS, additional longitudinal studies are needed to more definitively address the potential health concerns of these PFOS alternatives. [Display omitted] • The first study on the associations of Cl-PFESAs concentrations with metabolic syndrome (MetS). • Higher serum PFOS alternatives were associated with higher odds of MetS in adults. • Probit Bayesian Kernel Machine Regression (BKMR-P) analysis shows a positive association between PFAS mixture and MetS. • Females were more sensiive to serum PFOS alternatives than males. Cl-PFESAs and a mixture of PFAS were positively associated with MetS in adults, with stronger associations in women than men. [ABSTRACT FROM AUTHOR]

To evaluate the response to neoadjuvant therapy in patients with colorectal liver metastases (CRLMs) using ultrasound(US) and contrast-enhanced ultrasound(CEUS), with correction to the tumor regression grade (TRG) of pathological results. This study included patients with resectable CRLMs admitted from February to December 2022. After at least 4 cycles neoadjuvant therapy, all the patients received US and CEUS examinations within two weeks before hepatectomy. CEUS clips were postprocessed with color parameter imaging (CPI) and microflow imaging (MFI) analysis. Logistic regression analyses were used to develop an evaluation Nomogram. Ultrasound-based model was constructed to discriminate between the response (TRG1/2/3) and nonresponse (TRG4/5) groups at the lesion level. The model's predictive ability was evaluated using the C index and calibration curve, with decision curve analysis assessing the Nomogram's added value. The study analyzed 105 CRLM lesions (the lesion with the highest diameter analyzed for each patient), with 43.8% showing a response to therapy. Univariate analysis identified calcification on US (p = 0.039), CEUS enhancement degree (p < 0.001), CEUS enhancement pattern (p<0.001), CEUS washout type (p < 0.001), CEUS necrosis (p < 0.001), CPI feeding artery (p = 0.003) and MFI pattern (p < 0.001) were significantly associated with TRG. The multivariate analysis showed CEUS enhancement pattern (p = 0.026), CEUS washout type (p = 0.018) and CEUS necrosis (p = 0.005) were independently associated with the neoadjuvant therapy response. A Nomogram with the three independent predictors was developed, with an AUC of 0.898. The ultrasound-based model provided accurate evaluation of pathological tumor response to preoperative chemotherapy in patients with CRLM, and may help to decide the individualized treatment strategy. [ABSTRACT FROM AUTHOR]

Water is often chlorinated to protect public health, but chlorination causes harmful disinfection byproducts to form. Currently available in vitro assays generally determine non-volatile disinfection byproduct (NVDBP) toxicities because of the limitation of pretreatments used, but chemical analyses and regulations are focused on volatile disinfection byproducts (VDBPs) such as trihalomethanes. The gap of VDBP toxicities have been of concern for some time. In this study, we extracted VDBPs from two chlorinated effluent organic matters and one chlorinated natural organic matter, using a helium aeration–liquid nitrogen condensation system, and systematically assessed the VDBP and NVDBP toxicities to mammalian cells. VDBPs accounted for 10%–20% of the total organic halogen concentrations in three chlorinated water samples. VDBPs were much less cytotoxic, caused fewer DNA double-strand breaks, induced less reactive oxygen species and DNA/RNA oxidative damage marker of 8-hydroxyl(deoxy)guanosine in cells than did NVDBPs. Moreover, by collecting the VDBPs, toxicity measurement of the full range of DBPs was achieved. Cytotoxicity, reactive oxygen species and 8-hydroxyl(deoxy)guanosine levels were significantly higher for cells exposed to the mixture of VDBPs and NVDBPs than only NVDBPs, but not by large percentages (20%–30% for cytotoxicity), suggesting NVDBPs mainly contributed to the toxicity of chlorinated water. Our study suggested that future research should focus more on NVDBP toxicity and identifying toxicity drivers from NVDBPs. Image 1 • VDBPs contributed to small proportions of the TOX concentration. • VDBPs showed lower cytotoxicity, genotoxicity and induce less oxidative stress than NVDBPs. • The VDBP and NVDBP mixture induced higher cytotoxicity and oxidative stress than NVDBPs. • The toxicity caused by unknown VDBPs was relatively low. [ABSTRACT FROM AUTHOR]

• At least seven alternative splicing isoforms of BmYki were identified. • S97 phosphorylation contributes to the cellular location of BmYki1. • BmYki3 plays a major positive regulatory role in Hippo signaling pathway. • BmYki2 plays a role of microregulation and balance in Hippo signaling pathway. • BmYki1 plays a secondary positive regulatory role in the Hippo signaling pathway. Yorki (Yki), a transcriptional co-activator that is a key component of the Hippo pathway, induces the transcription of a number of targets that promote cell proliferation and survival. Bombyx mori Yki3 (BmYki3), with 445 amino acid residues, facilitates cell migration and cell division, and enlarges cultured cell and wing disc size. In this study, cellular localization, transcriptional co-activator activity, cell migration, cell cycle, and cell size were characterized in alternative isoforms of BmYki. BmYki1 and BmYki3 are mainly located in the cytoplasm and nucleus, respectively, while, BmYki2 is located in both the cytoplasm and nucleus. The mutation BmYki1S97A (S97mutated to A) was transported from the cytoplasm to nucleus. Cell migration, cell cycle, and cell size could be enhanced by BmYki, however, the effect of BmYki1 and BmYki2 on cell proliferation was less compared to BmYki3. Moreover, wing discs could be enlarged by overexpressing BmYki1 or BmYki2 isoforms. Dual-luciferase reporter assay showed that BmYki3 had the highest activity to B. mori ovarian tumor gene. In BmN cells overexpressing one of the BmYki isoforms, expression levels of kibra ortholog (kibra), inhibitor of apoptosis protein (iap), four-jointed (fj), expanded (ex), crumbs (crb) and BMP and activin membrane-bound inhibitor homolog (Bmpr) genes were upregulated, while those of α-catenin (α-cat), decapentaplegic (dpp), serrate (serr) and signal transducer and activator of transcription (stat) genes were down-regulated. There was some difference in the regulation of gene expression between different isoforms. These results suggested that the activity of BmYki isoforms was different in the silkworm. [ABSTRACT FROM AUTHOR]

The development of artificial devices that mimic the highly efficient and sophisticated photosystems found in nature is a subject worthy of in-depth study. Two calixarene D-π-A dyes, C4-CZSTP and C4-CZBTP, containing an N-methylcarbazole group as a secondary auxiliary electron donor, are synthesized on the basis of our previously reported calixarene dye C4-BTP. These dyes are then cooperated with Ni-deposited g-C 3 N 4 to prepare ternary photocatalysts, denoted as C4-CZSTP/Ni/g-C 3 N 4 , C4-CZBTP/Ni/g-C 3 N 4 and C4-BTP/Ni/g-C 3 N 4 , and their photocatalytic performances are evaluated under visible light irradiation. The optimized 4.0 wt% C4-CZSTP/Ni/g-C 3 N 4 sample gives a remarkable H 2 evolution rate of 5552 μmol g−1 h−1, representing one of the highest records among the reported analogous systems based on g-C 3 N 4. And after an extended test of 49 h, a total H 2 yield of 63.57 mmol g−1 is obtained, corresponding to a turnover number (TON) based on C4-CZSTP moles (TON C4-CZSTP) of 3180. This performance can be attributed to the enhanced light-harvesting and photoelectron conversion of the as-prepared calixarene dyes, the adjusted energy levels and the effective cooperation of the three components. The optimal performance of C4-CZSTP/Ni/g-C 3 N 4 among the three dye-sensitized systems is due to its higher lowest unoccupied molecular orbital (LUMO) value, i.e. stronger electronic driving force from the excited dye to g-C 3 N 4. This study provides an interesting example for the design and preparation of a low-cost, high-efficiency and noble metal-free photocatalytic system for solar fuel production. Carbazole-based calix [4]arene dye-sensitized Ni/g-C 3 N 4 photocatalysts exhibit high visible-light photocatalytic hydrogen production activity and good stability during the long-term tests. [Display omitted] • Carbazole-based calixarene dyes are first designed and synthesized. • Non-noble metal nickel-decorated g-C 3 N 4 coupled with calixarene dyes are first prepared. • The hybrid photocatalysts exhibit high H 2 production activity and good durability. • The relationship between structures, properties and performances of catalysts is systematically investigated. • The electron transfer mechanism of the calixarene dye/Ni/g-C 3 N 4 system is intensively studied. [ABSTRACT FROM AUTHOR]

Computer-aided color parameter imaging (CPI) is a novel technique for contrast-enhanced ultrasound (CEUS) that can highlight hemodynamic features of focal lesions. The purpose of the study was to investigate the role of CPI in evaluation of hepatocellular carcinoma (HCC) hemodynamic features and prognosis after radiofrequency ablation (RFA). One hundred twenty-one patients with HCC underwent CEUS with CPI analysis before RFA. Eighty-nine patients had pathologically proven well- to moderately differentiated HCC (WM-HCC), and 32 patients had poorly differentiated or undifferentiated HCC (PU-HCC). Perfusion features of CEUS and contrast-enhanced computed tomography/magnetic resonance imaging were compared with CPI parameters for WM-HCC and PU-HCC. The results indicated that 67.4% of WM-HCC had a centrifugal perfusion CPI pattern, whereas 84.4% of PU-HCC tumors had a centripetal pattern (p < 0.001, odds ratio = 11.2). The specificity, sensitivity and accuracy of the CPI perfusion pattern regarding HCC pathological grade were higher than those with routine CEUS (84.4% vs. 9.4%, p < 0.001; 67.4% vs. 3.4%, p < 0.001; 71.9% vs. 5.0%, p < 0.001). Moreover, multivariable analysis revealed that the CPI perfusion pattern was an independent risk factor for progression-free survival post-RFA (centripetal group: 28.3 ± 4.1 mo vs. centrifugal group: 45.8 ± 4.4 mo, p = 0.002). A novel CPI technique for CEUS could non-invasively provide valuable hemodynamic information and predict prognosis for HCC patients treated by RFA. [ABSTRACT FROM AUTHOR]

To enhance deep learning-based automated interictal epileptiform discharge (IED) detection, this study proposes a multimodal method, vEpiNet, that leverages video and electroencephalogram (EEG) data. Datasets comprise 24 931 IED (from 484 patients) and 166 094 non-IED 4-second video-EEG segments. The video data is processed by the proposed patient detection method, with frame difference and Simple Keypoints (SKPS) capturing patients' movements. EEG data is processed with EfficientNetV2. The video and EEG features are fused via a multilayer perceptron. We developed a comparative model, termed nEpiNet, to test the effectiveness of the video feature in vEpiNet. The 10-fold cross-validation was used for testing. The 10-fold cross-validation showed high areas under the receiver operating characteristic curve (AUROC) in both models, with a slightly superior AUROC (0.9902) in vEpiNet compared to nEpiNet (0.9878). Moreover, to test the model performance in real-world scenarios, we set a prospective test dataset, containing 215 h of raw video-EEG data from 50 patients. The result shows that the vEpiNet achieves an area under the precision–recall curve (AUPRC) of 0.8623, surpassing nEpiNet's 0.8316. Incorporating video data raises precision from 70% (95% CI, 69.8%–70.2%) to 76.6% (95% CI, 74.9%–78.2%) at 80% sensitivity and reduces false positives by nearly a third, with vEpiNet processing one-hour video-EEG data in 5.7 min on average. Our findings indicate that video data can significantly improve the performance and precision of IED detection, especially in prospective real clinic testing. It suggests that vEpiNet is a clinically viable and effective tool for IED analysis in real-world applications. • Propose a multimodal deep learning-based diagnosis model to extract features from both EEG and video signals. • Introduce a novel patient detection algorithm that is able to accurately identify patient targets in videos/images. • Design a method to integrate the features extracted from the electrodes and the video. • Invent a visual IED detection software that utilizes the proposed multimodal model to present the detection results in prospective testing visually. [ABSTRACT FROM AUTHOR]

Bombyx mori cypovirus (BmCPV), a member of the family Reoviridae, is a model of Cypovirus, has a 10 segmented double-stranded RNA genome. However, so far, only one viral small peptide vSP27 with negative regulation on viral infection was identified; the mechanisms underlying host-BmCPV interaction are still unknown. Here, we identified that vSP27 was translated from a BmCPV derived circular RNA (circRNA-vSP27). Subsequently, results showed that vSP27 induced generation of ROS activated the NF-κB signaling pathway, induced the expression of antimicrobial peptides, and suppressed BmCPV infection. On the other hand, we identified a nuclear protein Akirin that could hijack vSP27, positively regulate the NF-κB pathway, and lead to inhibiting the viral infection. Altogether, our data suggested that BmCPV derived circRNA-vSP27 with small peptide translation activity may be employed by the host immunity in defense against the BmCPV infection. [ABSTRACT FROM AUTHOR]

To investigate the degradation efficiency of conditioners and commercial microbial agents on estrogens (E1, 17α-E2, 17β-E2, E3, EE2, and DES) in the composting process of dairy manure, seven different treatments (RHB-BF, OSP-BF, SD-BF, MR-BF, MR-FS, MR-EM, and MR-CK) under forced ventilation conditions were composted and monitored regularly for 30 days. The results indicated that the removal rates of estrogens in seven treatments ranged from 95.35% to 99.63%, meanwhile the degradation effect of the composting process on 17β-Estradiol equivalent (EEQ) was evaluated, and the removal rate of ΣEEQ ranged from 96.42% to 99.72%. With the combined addition of rice husk biochar (RHB) or oyster shell powder (OSP) and bio-bacterial fertilizer starter cultures (BF), namely RHB-BF and OSP-BF obviously promoted the rapid degradation of estrogens. 17β-E2 was completely degraded on the fifth day of composting in OSP-BF. Microbial agents have some promotional effect and enhances the microbial degradation of synthetic estrogen (EE2, DES). According to the results of RDA, pH and EC were the main environmental factors affecting on the composition and succession of estrogen-related degrading bacteria in composting system. As predominant estrogens-degrading genera, Acinetobacter, Bacillus, and Pseudomonas effected obviously on the change of estrogens contents. The research results provide a practical reference for effective composting of dairy manure to enhancing estrogens removal and decreasing ecological risk. [Display omitted] • Conditioners and microbial agents could enhance estrogens degradation (>95% removal). • Conditioner OSP presented excellent removal effect (99.63%) on the estrogens in composting. • The addition of microbial agents promoted the degradation of synthetic estrogens (EE2, DES). • PH/EC dominantly effected on the composition and succession of estrogens-degrading genera. • Predominant genera for estrogens degradation were Acinetobacter, Bacillus, and Pseudomonas. [ABSTRACT FROM AUTHOR]

Abstract Bombyx mori cypovirus (BmCPV) is one of the most infectious pathogen in sericulture and a member of the family Reoviridae. It specifically infects the midgut of silkworm. The BmCPV genome consists of 10 dsRNAs segments (S1–S10), which have generally been assumed to be monocistronic. In this study, a small open reading frame encoding the peptide S5-sORF, containing 27 amino acid residues, was predicted in a region of the negative (−) strand of BmCPV segment S5. An immunofluorescence assay detected S5-sORF in the cytoplasm and nuclei of BmCPV-infected cells, and it was also detected in the virion with western blotting, suggesting that S5-sORF may be assembled into the BmCPV virion. Viral gene expression was inhibited by overexpressed S5-sORF, and viral multiplication was dose-dependently suppressed by the S5-sORF peptide. A viable recombinant virus, BmCPV-S5-sORFmut, in which the start codon (ATG) of S5-sORF was mutated to a stop codon (TGA), was generated with reverse genetics. The proliferation of BmCPV was increased by the abolition of S5-sORF expression. Furthermore, the RNA transcript of S5-sORF and small peptide of S5-sORF were involved in BmCPV replication. The expression of genes related to the innate immune pathways and apoptosis in the silkworm were not significantly affected by S5-sORF overexpression. Our results suggest that a viral nucleotide sequence is utilized by the host to generate an antiviral peptide, which may be a novel strategy protecting the host from viral infection. Highlights • Small open reading frame (sORF) was found on the negative strand of BmCPV segment 5. • S5-sORF peptide was encoded by sORF and it was detected in the virion of BmCPV. • S5-sORF peptide was distributed in the cytoplasm and nuclei of BmCPV-infected cells. • The expressions of viral genes were inhibited by overexpression of S5-sORF. • RNA and small peptide of S5-sORF suppressed the replication of BmCPV. [ABSTRACT FROM AUTHOR]

Patients envenomed by snakes from the Viperidae and Elapidae families in China often have varying degrees of local tissue necrosis. Due to the relative clinical characteristics of local tissue necrosis and ulceration following envenoming, this study has analyzed the proteome of six snake venoms from the Viperidae and Elapidae family, and the toxin profiles of each snake were compared and correlated with the clinical manifestations that follow cytotoxic envenoming. Deinagkistrodon acutus and Naja atra envenomation induce severe ulceration, which is absent in Bungarus multicinctus envenomation and mild in the other three vipers. It is interesting to note that the proportion of c-type lectins (CTL) (20.63%) in Deinagkistrodon acutus venom was relatively high, which differs from the venom of other vipers. In addition, three-fingered toxin (3FTx) (2.15%) is present in the venom of Deinagkistrodon acutus , but has not been detected in the remaining three vipers. Snake venom metalloprotease (SVMP) (34.4%–44.7%), phospholipase A 2 (PLA 2) (9.81%–40.83%), and snake venom serine protease (SVSP) (9.44%–16.2%) represent the most abundant families of toxin in Viperidae venom. The Elapidae venom proteome was mainly composed of neurotoxins and cytotoxins, including 3FTx (39.28%–60.08%) and PLA 2 (8.24%–58.95%) toxins, however, the proportion of CRISPS (26.36%) in Naja atra venom was relatively higher compared to Bungarus multicinctus venom. Significant differences in SVMP, SVSP, and 3FTx expression levels exist between the Viperidae and the Elapidae family. The main toxins responsible for the development of tissue necrosis and ulcerations following Viperidae envenoming are hematotoxins (SVSMP, SVSP) and myotoxins (PLA 2). Deinagkistrodon acutus venom contains high levels of CTL and traces of 3FTx, leading to more severe local necrosis. However, Naja atra venom can also cause severe local necrosis through the effects of myotoxin (3FTx, CRISP, PLA 2). Bungarus multicinctus venom does not contain myotoxins, resulting in pure systemic neurological manifestations no obvious necrosis of local tissue in patients. [Display omitted] • We analyzed the proteome of six snakes from the Viperidae and Elapidae family in China. • The toxin profiles were compared and correlated with the clinical manifestations that follow cytotoxic envenoming. • The main toxins responsible for tissue necrosis following Viperidae envenoming are hematotoxins and cytotoxins. • Deinagkistrodon acutus venom contains c-type lectin and three-fingered toxin, leading to more severe local necrosis. • Naja atra venom can cause severe local necrosis through the effects of cytotoxins. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are produced by the stimulated humoral immune system. Most mature AMPs contain less than 50 amino acid residues. Some of them are generated from proproteins upon microbial challenges. Here, we report the antimicrobial activities of a proline-rich proprotein, named SlLebocin1 (SlLeb1), from the tobacco cutworm Spodoptera litura . SlLebocin1 cDNA contains a 477-bp open reading frame (ORF). It is mainly expressed in hemocytes and the midgut in naïve larvae. The transcript level was significantly induced in hemocytes but repressed in the midgut and fat body by bacterial challenges. The proprotein contains 158 amino acids with 3 RXXR motifs that are characteristic of some Lepidopteral lebocin proproteins. Four peptides corresponding to the predicted processed fragments were synthesized chemically, and their antimicrobial activities against two Gram-negative and two Gram-positive bacterial strains were analyzed. The peptides showed differential antimicrobial activities. For Escherichia coli and Bacillus subtilis , only the C-terminal fragment (124–158) showed strong inhibitory effects. For Staphylococcus aureus , all peptides showed partial inhibitions. None of them inhibited Serratia marcescens . Bacterial morphologies were examined by the scanning electron microscopy and confocal laser scanning microscopy. The antimicrobial peptides either disrupted cellular membrane or inhibited cell division and caused elongated/enlarged morphologies. The results may provide ideas for designing novel antibiotics. [ABSTRACT FROM AUTHOR]

Highlights • circRNA was a novel non-coding RNA in insect. • 353 significantly differentially expressed circRNAs were found. • The expression level of circRNAs was affacted by BmNPV. infection. • circRNAs maybe a kind of new immune regulatory molecule. Abstract Thus far, no systematic studies have examined circRNA expression profiles in the silkworm following B.mori nucleopolyhedrovirus (BmNPV) infection. To explore the expression patterns of circRNAs in the silkworm midgut following BmNPV infection, circRNAs in normal midguts and BmNPV-infected midguts were analyzed by high-throughput sequencing. A total of 353 circRNAs were significantly differentially expressed, of which 241 were upregulated and 112 were downregulated following infection. GO annotation and KEGG pathways analyses of these circRNAs showed that many key immunity pathways and metabolism pathways were enriched in the BmNPV-infected midguts. The potential roles of the predicted targets of the miRNAs that interacted with the circRNAs showed that ubiquitin, apoptosis, and endocytosis signaling pathways were enriched significantly by BmNPV infection. [ABSTRACT FROM AUTHOR]

The simultaneous anammox and denitrification (SAD) process is an emerging treatment for wastewaters containing nitrogen pollution and organics. However, there is little research on the effect of organic matter types on the SAD process. In this study, two reactors, one with glucose (R1) and the other with acetate (R2), were used to investigate the effects of different carbon sources and C/N ratios on the SAD process. The nitrogen removal performance, functional gene abundance, biomass activity and microbial community structures of the two reactors were analyzed and compared. Results showed that a desirable nitrogen removal efficiency (NRE) was obtained at the C/N ratio of 1.2 in R1, whereas a similar NRE could be achieved at a C/N ratio of 0.8 in R2, which was more susceptible to a high C/N ratio. Moreover, at high C/N ratios, the microbial species diversity of R1 was higher than that of R2. High-throughput sequencing analysis revealed that anammox bacteria predominated at low COD, but denitrifying bacteria grew rapidly at high C/N ratio. Removal of NO 3 − -N in the glucose-driven reactor appeared to be more depended on other heterotrophic bacteria other than denitrification bacteria. In general, the glucose-driven reactor was more stable and resistant to high C/N ratios during the SAD process than the acetate-driven one. Results of this study provide information for practical treatment of wastewater with high nitrogen contents. [ABSTRACT FROM AUTHOR]

The genome of Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) contains 10 double stranded RNA segments (S1–S10). The segment 7 (S7) encodes 50 kDa protein which is considered as a structural protein. The expression pattern and function of p50 in the virus life cycle are still unclear. In this study, the viral structural protein 7 (VP7) polyclonal antibody was prepared with immunized mouse to explore the presence of small VP7 gene-encoded proteins in Bombyx mori cytoplasmic polyhedrosis virus. The expression pattern of vp7 gene was investigated by its overexpression in BmN cells. In addition to VP7, supplementary band was identified with western blotting technique. The virion, BmCPV infected cells and midguts were also examined using western blotting technique. 4, 2 and 5 bands were detected in the corresponding samples, respectively. The replication of BmCPV genome in the cultured cells and midgut of silkworm was decreased by reducing the expression level of vp7 gene using RNA interference. In immunoprecipitation experiments, using a polyclonal antiserum directed against the VP7, one additional shorter band in BmCPV infected midguts was detected, and then the band was analyzed with mass spectrum (MS), the MS results showed thatone candidate interacted protein (VP7 voltage-dependent anion-selective channel-like isoform, VDAC) was identified from silkworm. We concluded that the novel viral product was generated with a leaky scanning mechanism and the VDAC may be an interacted protein with VP7. [ABSTRACT FROM AUTHOR]

The activation of hepatic stellates cells (HSCs) is well believed to play a pivotal role in the development of liver fibrosis. MicroRNA-145 (miR-145) is known to suppress the progression of hepatocellular carcinoma, and is previously reported to be associated with Wnt/β-catenin pathway, but its role in the progression of hepatic fibrosis and activation of HSCs remains unknown and is warranted for investigation. In the present study, we found that the expression of miR-145 is significantly down-regulated in vivo in CCl 4 -induced mice liver fibrosis as well as in transforming growth factor-β1 (TGF-β1) induced HSC-T6 cell lines and human hepatic stellate cell line LX-2 in vitro . Furthermore, over-expression of miR-145 inhibited TGF-β1-induced the activation and proliferation of HSC-T6 cells in vitro . Mechanistically, we identified that zinc finger E-box-binding homeobox 2 (ZEB2), a key mediator of epithelial-to-mesenchymal transition, acted as a functional downstream target for miR-145. Interestingly, ZEB2 was shown to be involved in the TGF-β1-induced HSCs activation by regulating Wnt/β-catenin signaling pathway. Taken together, our results revealed the critical regulatory role of miR-145 in HSCs activation and implied miR-145 as a potential candidate for therapy of hepatic fibrosis by regulation of Wnt/β-catenin through targeting ZEB2. [ABSTRACT FROM AUTHOR]

Transforming growth factor (TGF)-β superfamily members inhibit Bombyx mori nucleohedrovirus (BmNPV) multiplication in silkworm are not determined. In this study, we first found that BmNPV RNA transcription and protein expression level were regulated by TGF-β members, Decapentaplegic (Bmdpp) and Dawdle (Bmdaw) in the domesticated silkworm, B. mori and silkworm ovary-derived cells. Furthermore, subcellular localization showed that Bmdpp and Bmdaw were mainly presented in cytomembrane of the cultured BmN cells. Tissues expression pattern analysis found that the highest expression levels of Bmdpp and Bmdaw genes were in the hemocyte of fifth instar larvae. During the immune response, the expression level of Bmdpp gene was elevated and Bmdaw gene was declined in BmNPV infected BmN cells and silkworm. The multiplication of BmNPV was inhibited by overexpression of Bmdpp and Bmdaw genes in BmN cells. RNA interference experiments found that the multiplication of BmNPV was raised with specific siRNAs of Bmdpp and Bmdaw genes in BmN cells. The antiviral immune pathways were not significantly regulated by the TGF-β superfamily members. Taken together, these findings provided a clue to understand the function of Bmdpp and Bmdaw gene in response to the BmNPV infection in silkworm. [ABSTRACT FROM AUTHOR]