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Porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease that threatens the global swine industry. Recent studies have focused on the damage that PRRSV causes to the reproductive system of male pigs, although pathological research is lacking. Therefore, we examined the pathogenic mechanisms in male piglets infected with PRRSV. Gross and histopathological changes indicated that PRRSV affected the entire reproductive system, as confirmed via immunohistochemical analysis. PRRSV infected Sertoli cells and spermatogonia. To test the new hypothesis that PRRSV infection in piglets impairs blood – testis barrier (BTB) development, we investigated the pathology of PRRSV damage in the BTB. PRRSV infection significantly decreased the quantity and proliferative capacity of Sertoli cells constituting the BTB. Zonula occludens-1 and β-catenin were downregulated in cell – cell junctions. Transcriptome analysis revealed that several crucial genes and signalling pathways involved in the growth and development of Leydig cells, Sertoli cells, and tight junctions in the testes were downregulated. Apoptosis, necroptosis, inflammatory, and oxidative stress-related pathways were activated, whereas hormone secretion-related pathways were inhibited. Many Sertoli cells and spermatogonia underwent apoptosis during early differentiation. Infected piglets exhibited disrupted androgen secretion, leading to significantly reduced testosterone and anti-Müllerian hormone levels. A cytokine storm occurred, notably upregulating cytokines such as tumour necrosis factor-α and interleukin-6. Markers of oxidative-stress damage (i.e. H2O2, malondialdehyde, and glutathione) were upregulated, whereas antioxidant-enzyme activities (i.e. superoxide dismutase, total antioxidant capacity, and catalase) were downregulated. Our results demonstrated that PRRSV infected multiple organs in the male reproductive system, which impaired growth in the BTB.

Lipid-coated perfluorocarbon nanodroplets (lp-NDs) hold great promise in bio-medicine as vehicles for drug delivery, molecular imaging and vaccine agents. However, their clinical utility is restricted by limited targeted accumulation, attributed to the innate immune system (IIS), which acts as the initial defense mechanism in humans. This study aimed to optimize lp-ND formulations to minimize non-specific clearance by the IIS. Ginsenosides (Gs), the principal components of Panax ginseng, possessing complement inhibition ability, structural similarity to cholesterol, and comparable fat solubility to phospholipids, were used as promising candidate IIS inhibitors. Two different types of ginsenoside-based lp-NDs (Gs lp-NDs) were created, and their efficacy in reducing IIS recognition was examined. The Gs lp-NDs were observed to inhibit the adsorption of C3 in the protein corona (PC) and the generation of SC5b-9. Adding Gs to lp-NDs reduced complement adsorption and phagocytosis, resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs. These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants, potentially reducing non-specific clearance by the IIS and improving lifespan.

Accurate diagnosis of plant diseases is crucial for crop health. This study introduces the EDA–ViT model, a Vision Transformer (ViT)-based approach that integrates adaptive entropy-based data augmentation for diagnosing custard apple (Annona squamosa) diseases. Traditional models like convolutional neural network and ViT face challenges with local feature extraction and large dataset requirements. EDA–ViT overcomes these by using a multi-scale weighted feature aggregation and a feature interaction module, enhancing both local and global feature extraction. The adaptive data augmentation method refines the training process, boosting accuracy and robustness. With a dataset of 8226 images, EDA–ViT achieved a classification accuracy of 96.58%, an F1 score of 96.10%, and a Matthews Correlation Coefficient (MCC) of 92.24%, outperforming other models. The inclusion of the Deformable Multi-head Self-Attention (DMSA) mechanism further enhanced feature capture. Ablation studies revealed that the adaptive augmentation contributed to a 0.56% accuracy improvement and a 0.34% increase in MCC. In summary, EDA–ViT presents an innovative solution for custard apple disease diagnosis, with potential applications in broader agricultural disease detection, ultimately aiding precision agriculture and crop health management.

Abstract Spinal muscular atrophy is an autosomal recessive neuromuscular disease caused by mutations in the multifunctional protein Survival of Motor Neuron, or SMN. Within the nucleus, SMN localizes to Cajal bodies, which are associated with nucleoli, nuclear organelles dedicated to the first steps of ribosome biogenesis. The highly organized structure of the nucleolus can be dynamically altered by genotoxic agents. RNAP1, Fibrillarin, and nucleolar DNA are exported to the periphery of the nucleolus after genotoxic stress and, once DNA repair is fully completed, the organization of the nucleolus is restored. We find that SMN is required for the restoration of the nucleolar structure after genotoxic stress. During DNA repair, SMN shuttles from the Cajal bodies to the nucleolus. This shuttling is important for nucleolar homeostasis and relies on the presence of Coilin and the activity of PRMT1.

To solve the problem of efficient extraction of coal liquefied oil residue, the extractants with different properties, such as aliphatic hydrocarbon, aromatic hydrocarbon, oxygen-containing compounds, and simulated coking benzene, were selected for the extraction of coal liquefied oil residue. And the effects of solubility and polarity parameters of extractants on extraction rate and extract components were investigated. The results show that with the increase in solubility and polarity parameters of extractants, the extraction rate for coal liquefied oil residue increased and then decreased. The influence of the solubility parameter of extractants on the extraction performance was mainly reflected in their matching degree with the solubility parameter of the extractable components. The effect of the polarity parameter of the extractants was mainly the breaking of the associated structure of coal liquefied oil residue. When the solubility parameters of the extracts and extractants were close, the extraction performance was good, such as aromatic hydrocarbon and tetrahydrofuran. The main components of these extracts were polycyclic aromatic hydrocarbons. The extractants with larger polar parameters were more likely to destroy the associated structure of coal liquefied oil residue, resulting in higher contents of N and S elements in acetone, ethanol, and methanol extracts. Simulated coking benzene was a good solvent for extracting coal liquefied oil residue, which was easy to be recovered from solution, and the extraction rate of coal liquefied oil residue could reach more than 50%.

This study aimed to assess liver fibrosis in rabbits by deep learning models based on acoustic nonlinearity maps. Injection of carbon tetrachloride was used to induce liver fibrosis. Acoustic nonlinearity maps, which were built by data of echo signals, were used as input data for deep learning model. Convolutional neural network (CNN), CNN combined with support vector machine (SVM), CNN combined with random forest and CNN combined with logistic regression were used as deep learning model. Nested 10-fold cross-validation was used to search hyperparameters and evaluate performance of models. Histologic examination of liver specimens of the rabbits was performed to evaluate the fibrosis stage. Receiver operator characteristic curve and area under curve (AUC) were used for estimating the probability of the correct prediction of liver fibrosis stages. A total of 600 acoustic nonlinearity maps were used. Model of CNN combined with SVM demonstrated the best diagnostic performance compared with all other methods for diagnosis of significant fibrosis (≥F2, AUC = 0.82), advanced fibrosis (≥F3, AUC = 0.88) and cirrhosis (F4, AUC = 0.90). Model of CNN showed the second highest AUCs. The deep learning model based on acoustic nonlinearity maps demonstrated potential for evaluation of liver fibrosis.

The effects of four aliphatic hydrocarbon extractants (n-hexane, cyclohexane, petroleum ether, and n-heptane) on the extraction rate and properties of extracts from coal liquefaction residue were investigated by Soxhlet extraction experiments. The results show that the molecular structure, viscosity, and boiling point of extractants affected extraction rate, and the extraction rates of four extractants were in the following order: cyclohexane, petroleum ether, n-hexane, n-heptane. As for the composition of extracts, the extracts of n-hexane, cyclohexane, and petroleum ether were mainly composed of aliphatic hydrocarbons, while the extracts of n-heptane were dominated by polycyclic aromatic hydrocarbons with a relative content of 94.1%, among which pyrene substances accounted for 53.3%. The n-heptane extracts of coal liquefaction residue were further sequentially eluted by column chromatography, and their compositions were analyzed. As the elution proceeded, the main components in petroleum ether eluate gradually changed from aliphatic hydrocarbons to polycyclic aromatic hydrocarbons, and the ring number of polycyclic aromatic hydrocarbons gradually increased. The petroleum ether/carbon disulfide eluate could be enriched with 59.7% of benzo[ghi]perylene. Later, dibutyl phthalate with a relative content of 50.7% could be enriched by petroleum ether/ethyl acetate as eluent. The separation of different substances in n-heptane extracts was achieved by ethyl acetate and methanol, and the methanol eluate mainly contained lipids, phenols, and alcohols. The separation and detection of extracts were basically achieved by this method.

Abstract Background Porcine deltacoronavirus (PDCoV) is a new pathogenic porcine intestinal coronavirus, which has appeared in many countries since 2012. PDCoV disease caused acute diarrhea, vomiting, dehydration and death in piglets, resulted in significant economic loss to the pig industry. However, there is no commercially available vaccine for PDCoV. In this study, we constructed recombinant pseudorabies virus (rPRVXJ-delgE/gI/TK-S) expressing PDCoV spike (S) protein and evaluated its safety and immunogenicity in mice. Results The recombinant strain rPRVXJ-delgE/gI/TK-S obtained by CRISPR/Cas gE gene editing technology and homologous recombination technology has genetic stability in baby hamster syrian kidney-21 (BHK-21) cells and is safe to mice. After immunizing mice with rPRVXJ-delgE/gI/TK-S, the expression levels of IFN-γ and IL-4 in peripheral blood of mice were up-regulated, the proliferation of spleen-specific T lymphocytes and the percentage of CD4+ and CD8+ lymphocytes in mice spleen was increased. rPRVXJ-delgE/gI/TK-S showed good immunogenicity for mice. On the seventh day after booster immunity, PRV gB and PDCoV S specific antibodies were detected in mice, and the antibody level continued to increase, and the neutralizing antibody level reached the maximum at 28 days post- immunization (dpi). The recombinant strain can protect mice with 100% from the challenge of virulent strain (PRV XJ) and accelerate the detoxification of PDCoV in mice. Conclusion The recombinant rPRVXJ-delgE/gI/TK-S strain is safe and effective with strong immunogenicity and is expected to be a candidate vaccine against PDCoV and PRV.

The increase in drug-resistant bacteria is a world-wide health issue that demands the development of alternatives to standard antibiotic treatments. In this study, the authors synthesise a hedgehog artificial macrophage with heme-mimetic catalytic centres, and peroxidase- and haloperoxidase-mimicking activities, for the treatment of methicillin-resistant Staphylococcus aureus.

Background: Lipid and polymer microbubbles (MBs) are widely used as ultrasound contrast agents in clinical diagnosis, and possess great potential in ultrasound-mediated therapy due to their drug loading function. However, overcoming the limitations of stability and echo enhancement of MBs are still a considerable challenge.Methods: A series novel block, graft and block-graft copolymers was proposed and prepared in this work, and these copolymers were used as shells to encapsulate perfluoropentane as ultrasound contrast agents. First, block, graft and block-graft copolymers with different topological structures were prepared. Then, these copolymers were prepared into block copolymer phase-transition MBs, graft copolymer phase-transition MBs, and block-graft copolymer phase-transition MBs, respectively. Finally, the dexamethasone was used for drug-loaded phase-transition microbubbles model to explore the potential of theranostic microbubbles.Results: Finally, these three resulting copolymer MBs with average size of 4–5 μm exhibited well enhancement of ultrasound imaging under the influence of different frequencies and mechanical index, and they exhibited a longer contrast-enhanced ultrasound imaging time and higher resistance to mechanical index compared with SonoVue in vitro and in vivo. In vitro drug release results also showed that these copolymer MBs could encapsulate dexamethasone drugs, and the drug release could be enhanced by ultrasonic triggering. These copolymer MBs were therapeutic MBs for targeted triggering drug release.Conclusion: Therefore, the feasibility of block, graft, and block-graft copolymers as ultrasonic contrast agents was verified, and their ultrasonic enhancement performance in vitro and in vivo was compared. The ultrasound contrast agents developed in this work have excellent development potential in comprehensive diagnosis and treatment.

Background: In recent years, with the change in human dietary habits, hyperlipidemia (HLP) has become a common chronic disease. Hyperlipidemia is closely related to the incidence of cardiovascular diseases. Due to the increasing incidence and mortality from cardiovascular diseases, it is imperative to develop new medications for reducing lipid levels. With the aim of discovering new treatment options for hyperlipidemia, we conducted a multi-omics analysis of a potential endogenous bile acid compound. Methods: Two hyperlipidemia models were established by feeding rats and mice with a high-fat diet. Serum and fecal specimens of rats with hyperlipidemia were collected. Through the combined analysis of lipid metabolism sequencing, 16S RNA intestinal flora sequencing, and bile acid targeted metabolism sequencing, taurohyodeoxycholic acid (THDCA) was found to be a potential lipid-lowering compound. A mouse hyperlipidemia model was developed to verify the anti-hyperlipidemia function of THDCA. Results: Analysis of serum lipid metabolites revealed that the synthesis of bile acid was one of the metabolic pathways that showed significant alterations. 16S RNA sequencing of intestinal flora also found that high-fat diet intake greatly influenced both primary and secondary bile acid biosynthesis. Analysis of bile acid metabolites in the serum and liver tissue found that THDCA in the secondary bile acids is a potential biomarker of hyperlipidemia. Verification experiments in mice confirmed the beneficial function of THDCA in lowering abnormal lipid levels induced by a high-fat diet. Conclusions: THDCA has been identified as a biomarker of hyperlipidemia and has shown potential for the treatment of hyperlipidemia.

Objective: To demonstrate the effectiveness of Huangqin decoction (Huangqin Tang in Chinese, HQT) combined with Radix Actinidiae chinensis (Tengligen in Chinese, TLG) under the guidance of “dampness–heat theory” in preventing and treating colorectal cancer (CRC) with dampness–heat accumulation and to preliminarily reveal its mechanism.Methods: The mice model of CRC was established by intraperitoneal injection of AOM combined with consumption of 2.5% DSS solution, and celecoxib, HQT, TLG, and their combination (HQT + TLG) were administered at the same time. The physical signs and death of the mice were observed daily. At the end of the experiment, the colorectal tissue was dissected, and the tumor was observed and counted. HE staining and Masson’s staining were used to observe the histopathological changes of colon. Expression levels of TNF-α, IL-6, and IL-10 in colorectal tissue were detected by ELISA, and the expression of TNF-α was observed by immunofluorescence. TUNEL assay was used to observe the apoptosis of tumor tissues, and immunohistochemistry was used to observe the expression of Ki-67 and occludin. The mRNA expression levels of claudin-1, occludin, ZO-1, and IL-6 and IL-17 were detected by RT-PCR, and occludin, ZO-1, NF-κB, and STAT3 protein levels were detected by Western blot. The composition of intestinal flora was analyzed by 16S rRNA.Results: HQT + TLG could significantly reduce the mortality of model mice and improve the intestinal mucosal inflammatory cell infiltration and high-grade intraepithelial neoplasia in model mice. All administration groups show a great reduction in the levels of IL-6 and TNF-α in the colorectal tissues of model mice, and increase in the level of IL-10, the total number of CD3+ T cells, the proportion of CD3+CD4+ T cells, and the ratio of CD4/CD8. HQT and HQT + TLG could significantly change the composition of intestinal flora and increase the abundance of Firmicutes and Patescibacteria.Conclusion: HQT and TLG combination has a good effect on inhibiting AOM-DSS-induced CRC. This function may be related to improving the composition of the intestinal flora, regulating the proportion of T-cell subsets in colorectal lymphoid tissue to improve inflammatory response, and downregulating the expression of claudin-1, inhibiting the activation of IL-6/STAT3 signaling pathway to improving abnormal hyperplasia.

Abstract Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating viral diseases in the global pig industry, including China. Recently, we successfully isolated a porcine reproductive and respiratory syndrome virus (PRRSV) from lung tissue and peripheral blood of piglets at a farm from Dujiangyan in Sichuan, China, and named it the DJY‐19 strain. The full‐length genome sequence of DJY‐19 shared 86.8%–94.1% nucleotide similarity with NADC30‐like and NADC30 PRRSV strains. We compared the open reading frame (ORF) 5 gene of DJY‐19 with 34 PRRSV strains from Genbank. Phylogenetic analysis showed that DJY‐19 clustered with NADC30 strains, characterized by a predicted 131‐amino‐acid deletion in the nonstructural protein (NSP) 2. The results of homology analysis showed that the homology between DJY‐19 and NADC30 (JN654459.1) strains was the highest (95.9%), whereas homology with other domestic strains was lower (80.9%–92.6%). Furthermore, we identified four recombination breakpoints in the DJY‐19 genome; they separated the DJY‐19 genome into four regions. The 8106–9128 nucleotide (nt) region of DIY‐19 was highly similar to the TJ strain, and the 12106–12580 nt region of DIY‐19 was highly similar to the JXA1‐R strain. Our findings demonstrate that DJY‐19 arose from the recombination of North America NADC30 strain and TJ strain and JXA1‐R in China. The application of multiple attenuated vaccine strains has led to complex recombination of PRRSV strains in China. This study provides a theoretical basis for making a more reasonable PRRS virus control and prevention strategy.

Christian, especially Protestant, identity is often framed through the lens of belief, particularly belief understood as an interior orientation. Through an examination of the non-denominational Protestant group, the ‘Little Flock’, founded by Watchman Nee in the early 20th century, we trace enduring aspects of Little Flock theology in contemporary Chinese Protestant practice. In particular, we attend to conceptions of and debates surrounding belief and how to determine the quality of one’s faith—whether or not one might be considered not just a Christian, but a ‘good’ one.

MicroRNAs (miRNAs) are important regulators in the process of cardiac hypertrophy and heart failure. Previous studies have shown that miR-199a is upregulated in pressure-overload cardiac hypertrophy and that inhibition of miR-199a attenuates cardiac hypertrophy in vitro. However, the therapeutic role of anti-miR-199a treatment in the cardiac hypertrophy in vivo model is less known. Here, we show an efficient and useful method to treat mouse cardiac hypertrophy and restore cardiac function through injection of adeno-associated virus (AAV)-mediated anti-miR-199a tough decoys (TuDs). RNA-seq transcriptome analysis indicated that genes related to cytoplasmic translation and mitochondrial respiratory chain complex assembly were upregulated in anti-miR-199a-treated recovered hearts. We further validated that PGC-1α is the direct target of miR-199a involved in the therapeutic effect and the regulation of the PGC-1α/ERRα axis and that the downstream pathway of mitochondrial fatty acid oxidation and oxidative phosphorylation constitute the underlying mechanism of the restored mitochondrial structure and function in our anti-miR-199a-treated mice. Our study highlights the important regulatory role of miR-199a in cardiac hypertrophy and the value of the AAV-mediated miRNA delivery system.

Abstract Background The mortality of critically ill patients with COVID-19 is high, particularly among those receiving mechanical ventilation (MV). Despite the high number of patients treated worldwide, data on respiratory mechanics are currently scarce and the optimal setting of MV remains to be defined. This scoping review aims to provide an overview of available data about respiratory mechanics, gas exchange and MV settings in patients admitted to intensive care units (ICUs) for COVID-19-associated acute respiratory failure, and to identify knowledge gaps. Main text PubMed, EMBASE, and MEDLINE databases were searched from inception to October 30, 2020 for studies providing at least one ventilatory parameter collected within 24 h from the ICU admission. The quality of the studies was independently assessed using the Newcastle–Ottawa Quality Assessment Form for Cohort Studies. A total of 26 studies were included for a total of 14,075 patients. At ICU admission, positive end expiratory pressure (PEEP) values ranged from 9 to 16.5 cm of water (cmH2O), suggesting that high levels of PEEP were commonly used for setting MV for these patients. Patients with COVID-19 are severely hypoxemic at ICU admission and show a median ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ranging from 102 to 198 mmHg. Static respiratory system compliance (Crs) values at ICU admission were highly heterogenous, ranging between 24 and 49 ml/cmH2O. Prone positioning and neuromuscular blocking agents were widely used, ranging from 17 to 81 and 22 to 88%, respectively; both rates were higher than previously reported in patients with “classical” acute respiratory distress syndrome (ARDS). Conclusions Available data show that, in mechanically ventilated patients with COVID-19, respiratory mechanics and MV settings within 24 h from ICU admission are heterogeneous but similar to those reported for “classical” ARDS. However, to date, complete data regarding mechanical properties of respiratory system, optimal setting of MV and the role of rescue treatments for refractory hypoxemia are still lacking in the medical literature.

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) is a serious viral disease of swine. At present, there are vaccines for the control of PRRSV infection, but the effect is not satisfactory. The recombination of attenuated vaccines causes significant difficulties with the prevention and control of PRRSV. Type III interferons (IFNs), also called IFN-λs, were newly identified and showed potent antiviral activity within the mucosal surface and immune organs. Results Therefore, primary porcine alveolar macrophages (PAMs) were used for this investigation. To this end, we found that the replication of PRRSV in PAMs was significantly reduced after pre-treatment with IFN-λ3, and such inhibition was dose- and time-dependent. The plaque formation of PRRSV abrogated entirely, and virus yields were reduced by four orders of magnitude when the primary PAMs were treated with IFN-λ3 at 1000 ng/ml. In addition, IFN-λ3 in our study was able to induce the expression of interferon-stimulated genes 15 (ISG15), 2′-5′-oligoadenylate synthase 1 (OAS1), IFN-inducible transmembrane 3 (IFITM3), and myxoma resistance protein 1(Mx1) in primary PAMs. Conclusions IFN-λ3 had antiviral activity against PRRSV and can stimulate the expression of pivotal interferon-stimulated genes (ISGs), i.e., ISG15, Mx1, OAS1, and IFITM3. So, IFN-λ3 may serve as a useful antiviral agent.

Imidazolopiperazines (IZPs) are a class of compounds under clinical development for malaria, but their mechanism of action is unclear. Here, the authors show that IZPs inhibit the parasite’s secretory pathway, affecting protein trafficking and export.

With regards to the Sinicization of Christianity (基督教中國化), there has always been a tension between “Chinese Christians” (中國(人)基督徒) and “Christian Chinese” (基督徒中國人). This paper intends to respond to this tension through the analysis of The Jesus Family (耶穌家庭), an important representative of the indigenous church movement in modern China. The Jesus Family had its own unique theological propositions and ecclesial practices. Particularly noteworthy was its emphasis on the living community of believers. Below, we present research on The Jesus Family, analyzed from two distinct aspects: those of “Jesus” and “family”. If the return to “Jesus” reflected the movement’s restorationist theological position, the “family” can be seen as reflecting the movement’s sociological advocacy for the practice of communitarian Christian principles. We argue that these aspects of The Jesus Family—emphasizing the values of personal intimacy with Jesus alongside communitarian principles—were key to its flourishing precisely within the unique context of modern Chinese social turmoil and history. In this light, The Jesus Family—both in its theological and sociological dimension—eludes simple classification as the product of “Chinese traditions” or “Christian orthodoxy.” Rather, it appears as the product of the interaction between the two, and we argue that in this, one sees also how the process of the Sinicization of Christianity relies on both traditional Chinese culture and Christian orthodoxy as inseparable and playing mutually interdependent roles.

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with very few treatment options. Although tumor-targeted nanomedicines hold great promise for the treatment of TNBC, the tumor microenvironment (TME) continues to be a major cause of failure in nanotherapy and immunotherapy. To overcome this barrier, we designed a new synergistic cascade strategy (SCS) that uses mild hyperthermia and smart drug delivery system (SDDS) to alter TME resistance in order to improve drug delivery and therapeutic efficacy of TNBC.Methods: Mild hyperthermia was produced by microwave (MW) irradiation. SDDS were formulated with thermosensitive polymer-lipid nanoparticles (HA-BNPs@Ptx), composed of polymer PLGA, phospholipid DPPC, hyaluronic acid (HA, a differentiation-44-targeted molecule, also known as CD44), 1-butyl-3-methylimidazolium-L-lactate (BML, a MW sensitizer), and paclitaxel (Ptx, chemotherapy drug). 4T1 breast tumor-bearing mice were treated with two-step MW combined with HA-BNPs@Ptx. Tumors in mice were pretreated with first MW irradiation prior to nanoparticle injection to modify and promote TME and promoting nanoparticle uptake and retention. The second MW irradiation was performed on the tumor 24 h after the injection of HA-BNPs@Ptx to produce a synergistic cascade effect through activating BML, thus, enhancing a hyperthermia effect, and instantly releasing Ptx at the tumor site.Results: Multifunctional CD44-targeted nanoparticles HA-BNPs@Ptx were successfully prepared and validated in vitro. After the first MW irradiation of tumors in mice, the intratumoral perfusion increased by two times, and the nanoparticle uptake was augmented by seven times. With the second MW irradiation, remarkable antitumor effects were obtained with the inhibition rate up to 88%. In addition, immunohistochemical analysis showed that SCS therapy could not only promote tumor cell apoptosis but also significantly reduce lung metastasis.Conclusion: The SCS using mild hyperthermia combined with SDDS can significantly improve the efficacy of TNBC treatment in mice by modifying TME and hyperthermia-mediated EPR effects.

This paper foregrounds the Turnerian experiences of pilgrims themselves, for whom pilgrimage is perhaps first and foremost the process of experiencing faith with their whole body and mind. At the Chinese Catholic pilgrimage site of Sheshan, located in western Shanghai, multiple meanings and possibilities are written onto the body of the pilgrim as it interacts with sacred materialities. In the process, the pilgrim materially orients themselves towards the transcendent other and to people and events throughout time. The boundary between subject and object is increasingly blurred in the pilgrim’s imagination, and pilgrimage becomes a ‘porous’ mind-body experience for them. In the process, as pilgrims repeatedly physically enact doctrine and doctrinal texts in the course of pilgrimage—while simultaneously rooting them in their own personal lives—Sheshan is, through the concrete actions of worshippers layered up over time, continually being re-made as sacred.

Abstract Background Pseudorabies virus (PRV, or suid herpesvirus, SuHV-1), a member of the herpesvirus family, has an extremely broad host range and threatens the pig industry in China. PRV can evade host innate immunity and infect the kidney, lung, brain and other tissues. At the same time, many studies have reported that microRNA (miRNA) can affect the replication of viruses by regulating gene expression levels. Results Here, to identify changes in miRNA expression and post-transcriptional regulation associated with PRV infection in the lung, spleen, and olfactory bulb, we sequenced small RNAs in tissues of rats infected or uninfected with PRV strain XJ (PRV-XJ). Sixty-one, 199 and 29 differentially-expressed miRNAs were identified in the lung, spleen, and olfactory bulb, respectively, of infected compared with uninfected rats. Among the miRNAs differentially-expressed in PRV-infected rats, 36, 171, and 15 miRNAs showed tissue-selective expression in the olfactory bulb, lung and spleen, respectively. All differentially-expressed miRNAs were analyzed for their GO functional annotations and KEGG pathway associations . Conclusions In PRV-XJ-infected rats, miRNAs were differentially expressed in the lung, spleen and olfactory bulb. These miRNAs were involved in regulating various pathways of the nervous, respiratory and immune systems, and may affect the tissue tropism of the virus and play pivotal roles in viral infection and proliferation.

Although pesticide intermediates are a kind of typical toxic pollutant in contaminated sites, the remediation of these contaminants in groundwater and soils is of limited concern. In the present study we investigated the performance of a novel heterogeneous oxidation system, biochar supported nanoscaled-zero valent iron (nZVI/BC) activated persulfate (PS), in the oxidative degradation of nitrochlorobenzene (NCB), a typical pesticide intermediate. Peanut shell based nZVI/BC was prepared and used as the PS activator. The degradation kinetics of m-, p-, and o-NCB isomers in the aqueous phase were investigated. The effects of BC/nZVI composition (Fe/BC mass ratio), the amount of BC/nZVI and PS, and initial contaminant concentration on NCB removal were also examined. Results suggest that over 90% removals of three NCB isomers could be obtained by the nZVI/BC activated PS system at initial NCB concentration of 10 mg L−1. The combination of nZVI/BC composite and PS showed superior performance to PS alone. The optimal treatment condition was supposed as the Fe: BC ratio of 1:1, Fe amount of 6 mmol L−1, and the mole ratio of Fe to perfulfate of 1:1.

Hyperlipidemia is a common metabolic disorder and regarded as one of the main risk factors for cardiovascular disease. The gut microbiota has been identified as a potential contributor to hyperlipidemia as it can greatly regulate bile acid metabolism. Linderae radix is a natural medicine widely used in the treatment of a variety of diseases and is also a common drug for hyperlipidemia. Recently, the lipid-lowering effect of Linderae radix are receiving increasing attention but the underlying mechanism remains unknown. The study aimed to investigate the effects of Linderae radix ethanol extract (LREE) on gut microbiota in rats with hyperlipidemia syndrome. We established a hyperlipidemia rat model using a high-fat diet and used LREE as the intervention. Blood lipid levels and pathological examination were measured to assess the effects of LREE on hyperlipidemia. The gut microbiota was determined by 16s rDNA sequencing and the bile acid metabolism-related proteins were detected by western blot to discover the underlying correlations. The results show that LREE lowered TC, TG, and LDL levels effectively, and it also alleviated liver injury by reducing ALT and AST activity. Meanwhile, LREE improved gut microbiota disturbance caused by HFD via increasing intestinal microbiota diversity and changing the abundance of the Firmicutes, Bacteroidetes, and Actinobacteria. In addition, LREE can increase bile acid reabsorption and promote fecal excretion through farnesoid X receptor (FXR), apical sodium-dependent bile acid transporter (ASBT), organic solute transporter alpha (OST-α), and cytochrome P450 family 7 Subfamily A Member 1 (CYP7A1) thus restoring abnormal bile acid metabolism caused by hyperlipidemia.

We sequenced the complete genome of the pseudorabies virus (PRV) FJ epidemic strain, and we studied the characteristics and the differences compared with the classical Chinese strain and that of other countries. Third-generation sequencing and second-generation sequencing technology were used to construct, sequence, and annotate an efficient, accurate PRV library. The complete FJ genome was 143,703 bp, the G+C content was 73.67%, and it encoded a total of 70 genes. The genetic evolution of the complete genome and some key gene sequences of the FJ strain and PRV reference strains were analyzed by the maximum likelihood (ML) method of MEGA 7.0 software. According to the ML tree based on the full-length genome sequences, PRV FJ strain was assigned to the branch of genotype II, and it showed a close evolutionary relationship with PRV epidemic variants isolated in China after 2011. The gB, gC, gD, gH, gL, gM, gN, TK, gI, and PK genes of the FJ strain were assigned to the same branch with other Chinese epidemic mutants; its gG gene was assigned to the same branch with the classic Chinese Fa and Ea strains; and its gE gene was assigned to a relatively independent branch. Potential recombination events were predicted by the RDP4 software, which showed that the predicted recombination sites were between 1694 and 1936 bp, 101,113 and 102,660 bp, and 107,964 and 111,481 bp in the non-coding region. This result broke the previously reported general rule that pseudorabies virus recombination events occur in the gene coding region. The major backbone strain of the recombination event was HLJ8 and the minor backbone strain was Ea. Our results allowed us to track and to grasp the recent molecular epidemiological changes of PRV. They also provide background materials for the development of new PRV vaccines, and they lay a foundation for further study of PRV.

ABSTRACT Resistance profiles of houseflies (Gol-RR) collected from a field in Golmud city, Qinghai province, China, were determined for seven insecticides using topical bioassays. Resistance ratios of >1219.51, 153.17, >35.43, 6.12, 3.24, 1.73, and 0.86-fold were obtained for propoxur, cypermethrin, imidacloprid, indoxacarb, chlorpyrifos, fipronil, and chlorfenapyr, respectively, relative to a laboratory susceptible strain (SS). Synergism experiments showed that piperonyl butoxide (PBO), triphenylphosphate (TPP), and diethyl maleate (DEM) increased propoxur toxicity by >105.71, >7.88, and >5.15-fold in the Gol-RR strain, compared with 5.25, 2.00, and 1.39-fold in the SS strain, indicating the involvement of P450 monooxygenases, esterases, and glutathione-S-transferase in conferring resistance. Although cypermethrin resistance was significantly suppressed with PBO, TPP, and DEM in the Gol-RR strain, the synergistic potential of these agents to cypermethrin was similar in the SS strain, demonstrating that metabolism-mediated detoxification was not important for conferring resistance to cypermethrin in the Gol-RR strain. However, the three agents did not act synergistically with imidacloprid, indicating that other mechanisms may be responsible for the development of resistance to this insecticide. Acetylcholinesterase (AChE) activity was 13.70-fold higher in the Gol-RR than in the SS strain, suggesting the properties of the AChE enzyme were altered in the Gol-RR strain. Thus, rotation of chlorfenapyr insecticide with other agents acting through a different mode with minimal/no resistance could be an effective resistance management strategy for housefly.

Abstract Background The complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Here, we infected specific pathogen-free Mus musculus with App serotype 7 by intranasal inoculation to construct an acute hemorrhagic pneumonia infection model and isolated the infected lungs for analysis of the interactions by dual RNA-seq. Results Four cDNA libraries were constructed, and 2428 differentially expressed genes (DEGs) of the host and 333 DEGs of App were detected. The host DEGs were mainly enriched in inflammatory signaling pathways, such as the TLR, NLR, RLR, BCR and TCR signaling pathways, resulting in large-scale cytokine up-regulation and thereby yielding a cytokine cascade for anti-infection and lung damage. The majority of the up-regulated cytokines are involved in the IL-23/IL-17 cytokine-regulated network, which is crucial for host defense against bacterial infection. The DEGs of App were mainly related to the transport and metabolism of energy and materials. Most of these genes are metabolic genes involved in anaerobic metabolism and important for challenging the host and adapting to the anaerobic stress conditions observed in acute hemorrhagic pneumonia. Some of these genes, such as adhE, dmsA, and aspA, might be potential virulence genes. In addition, the up-regulation of genes associated with peptidoglycan and urease synthesis and the restriction of major virulence genes might be immune evasion strategies of App. The regulation of metabolic genes and major virulence genes indicate that the dominant antigens might differ during the infection process and that vaccines based on these antigens might allow establishment of a precise and targeted immune response during the early phase of infection. Conclusion Through an analysis of transcriptional data by dual RNA-seq, our study presents a novel global view of the interactions of App with its host and provides a basis for further study.

Background: Veratrum nigrum (Liliaceae) is perennial medicinal plant widely used to treat various conditions. To de­ter­mine its insecticidal properties against the German cockroach (Blattella germanica), several laboratory tests were car­ried out. Methods: A 4kg dry sample of V. nigrum root was purchased from the medicinal material market in Yunnan Province in 2015, China. In contact toxicity tests, V. nigrum alkaloidal extract was topically applied to the abdomen of cockroaches using a micro-applicator. In vitro acetylcholinesterase (AChE) activity tests were performed using a modified Ellman method. Results: Veratrum nigrum alkaloidal extract was toxic to male adults and 4th nymphs cockroaches, with median lethal dose (LD50) values of 14.90µg/insect, 14.21µg/insect for adults and 41.45µg/insect, 39.01µg/insect for 4th nymphs after 24h and 48h exposure, respectively. There was a significant difference between adults and nymphs in terms of tolerance to V. nigrum alkaloidal extract. There was no significant difference in mortalities at 24h and 48h, the lethal effect of V. nigrum alkaloidal extract on German cockroach was quick. AChE activity tests showed that V. nigrum alkaloidal extract had an excellent inhibitory effect on AChE: inhibition in the 4th nymphs and male adults had 50% inhibiting concentra­tion (IC50) values of 3.56mg/ml and 5.78mg/ml respectively. The inhibitory effect of AChE activity was positively cor­related with inhibitory time (0–20min), at a concentration of 1mg/ml, inhibition of nymph and adult AChE activity had 50% inhibiting time (IT50) values of 8.34min and 16.75min, respectively. Conclusion: V. nigrum may be explored as a potential natural insecticide for control of the German cockroach.

Prayers in Christianity are often considered to be a theological or pastoral topic; while social scientific studies generally tend to reduce them, like prayers in other religious contexts, to the status of psychological responses bringing comfort to the practitioner, or a collective construction connected with social and cultural institutions. However, what prayer actually is, and what it means to Christians who practise it remains an open issue for further, more intensive and thorough study. Based on fieldwork in an urban church in China, this article provides some perspectives on contemporary Chinese Christians and their prayer life, attempting to elaborate its possible significance, especially in terms of subject-formation processes within these Christians. Meanwhile, this article argues that, in working towards a better understanding of Christians, it is more efficacious to take ‘Christians’ as those who are, rather than a given or acquired identity, or a status of being, engaged in a process of becoming through a practice, or set of practices, which in this case is prayer,. Moreover, in the case of this Chinese Christian church, the practise of prayer also indicates some reflections on the cultural and religious diversity of contemporary Chinese society.

Studies of digital religion frequently take democratic regime settings and developed economic contexts for granted, leaving regime and economic development levels as background factors (Campbell 2013). However, in China, the role of the authoritarian state, restrictions on religion, and rapid social change mean that online and offline religious practices will develop in distinct ways. This article analyzes the 2019 Bible handcopying movement promoted through China’s most popular social media WeChat as a way to commemorate the hundredth anniversary of the publication of China’s most widely used translation of the Bible. Drawing on interviews by and communication with the movement’s founder, the co-authors participated in and collected postings from a 500-member WeChat group from March to August 2019. We argue that while offline handcopying is an innovation in religious practice due to Chinese cultural and historical traditions, the online group constitutes a micro-scale “alter-public” (Chen 2015; Warner 2002), a site for religious discussion, prayer, and devotion that strengthens an “alternative” Protestant identity alongside that of Chinese citizen of the People’s Republic of China.

Toxicity and horizontal transmission of 1% fipronil dust of activated carbon were measured using the subterranean termite Coptotermes formosanus Shiraki in laboratory conditions. 1% fipronil dust of activated carbon has delayed toxicity towards C. formosanus compared with 0.5% fipronil dust of French chalk; knockdown times KT50 and KT90 were delayed by >9 and >15 h respectively. Furthermore, 1% fipronil dust of activated carbon showed excellent primary and secondary horizontal transfer levels. In primary horizontal transfer, recipient mortalities reached 100% by 24, 48 and 72 h at donor-recipient ratios of 1:1, 1:5 and 1:10, respectively. High transfer efficacies were also found if donor-recipient ratios were greatly increased: mortality reached 100% at 9 d at ratio 1:25 and >90% at 12 d at 1:50. In secondary horizontal transfer, the toxicant transmitting ability of C. formosanus was greater when the primary horizontal transfer ratio was lower, and the highest transfer efficacy was found with a donor-recipient ratio of 1:1 - recipient mortalities reached 100% at 5 d and 11 d, respectively. Application of 1% fipronil dust of activated carbon overcomes the problem that that too high a concentration kills termites before they can contaminate their nestmates, while a lower concentration may not supply a sufficient dose for effective transfer from treated to untreated termites; this preparation has delayed toxicity, dose-dependent toxicity in horizontal transfer and high efficacy to control C. formosanus.

The flavonoid phlorhizin is abundant in the leaves of Sweet Tea(ST, Lithocarpus Polystachyus Rehd). Phlorhizinwas preparatively separated and purified from a crude ST extract containing 40% total flavonoids by static adsorption and dynamic desorption on ADS-7 macroporous resin and neutral alumina column chromatography. Only water and ethanol were used as solvents and eluants throughout the whole separation and purification process. Using a phlorhizin standard as the reference compound, the target compound separated from the crude ST extracts was analyzed by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and electrosprayionization mass spectrometry (EIS-MS) and identified as 99.87% pure (by HPLC-UV) phlorhizin. The results showed that 10g of the targetcompound could be obtained from 40g of the crude extracts in a single operation, indicating a 40% recovery. Therefore, this represents an efficientand environmentally-friendly technology for separating and purifying phlorhizinfrom ST leaves.

The convertible bonds usually have multiple additional provisions that make their pricing problem more difficult than straight bonds and options. This paper uses the binary tree method to model the finance market. As the underlying stock prices and the interest rates are important to the convertible bonds, we describe their dynamic processes by different binary tree. Moreover, we consider the influence of the credit risks on the convertible bonds that is described by the default rate and the recovery rate; then the two-factor binary tree model involving the credit risk is established. On the basis of the theoretical analysis, we make numerical simulation and get the pricing results when the stock prices are CRR model and the interest rates follow the constant volatility and the time-varying volatility, respectively. This model can be extended to other financial derivative instruments.